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Sample records for pump inhibitor tinidazole

  1. Tinidazole

    MedlinePlus

    Tinidazole is used to treat trichomoniasis (a sexually transmitted disease that can affect men and women), giardiasis (an infection of the intestine that can cause diarrhea, gas, and stomach cramps), and amebiasis (an ...

  2. Proton pump inhibitors

    MedlinePlus

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

  3. Proton pump inhibitors and pain.

    PubMed

    Smith, Howard S; Dhingra, Reena; Ryckewaert, Lori; Bonner, Dave

    2009-01-01

    There may be a relationship between proton pump inhibitors (PPIs) and iron absorption. PPIs may decrease the amount of iron absorbed gastrointestinally specifically due to alteration of the pH in the duodenum. Restless legs syndrome (RLS) is a sensorimotor disorder that includes an urge to move legs, accompanied or caused by uncomfortable and unpleasant sensations in the legs; the urge to move begins or worsens during periods of rest or inactivity, the urge to move is partially or totally relieved by movement, and the urge is worse or only occurs at night. In the majority of the restless leg syndrome population, the sensation is deep seated, often described as being in the shin bones, and most commonly felt between the knee and ankle. It may be described as a creepy, shock-like, tense, electric, buzzing, itchy, or even numb sensation. A subpopulation of this restless leg syndrome patient population experiences restless leg syndrome associated pain (RLSAP) that has been described as a deep "achy pain." This pain has not been found to be relieved by many of the typical over the counter analgesics. Often, constant movement of the legs appears to be the only remedy, as these sensations usually appear during periods of rest. Furthermore, there appears to be an association between iron deficiency and those suffering from Restless Leg Syndrome (RLS). The authors theorize that there may be a possible correlation between PPIs and the symptoms (e.g. pain) associated with RLS. The authors propose that PPIs, such as omeprazole, may interfere with iron absorption in certain patients and that a subpopulation of patients who develop significant iron deficiency characterized by low serum ferritin levels while on PPIs may also develop RLS-like symptoms (including RLSAP). While there is no robust direct evidence to support any associations of PPIs and iron deficiency or PPIs associated with RLS-like symptoms (including RLSAP), it is hoped that this manuscript may spark research

  4. [Myoclonic encephalopathy associated with proton pump inhibitors].

    PubMed

    Boulliat, J; Polard, E; Colin, F; Bentué-Ferrer, D; Allain, H

    2004-03-01

    Two men (66 and 73 Years) with a cardiovascular history were hospitalized for rapid onset encephalopathy associated with myoclonia and an extrapyramidal syndrome. On the basis of the French Pharmacovigilance system, this symptomatology has been attributed to the coadministration of a proton pump inhibitor, lansoprazole (15mg/day) with levodopa. Lansoprazole withdrawal led to a normalisation of the situation. PMID:15037850

  5. Tinidazole

    MedlinePlus

    ... infection of the intestine that can cause diarrhea, gas, and stomach cramps), and amebiasis (an infection of the intestine that can cause diarrhea, gas, and stomach cramps and can spread to other ...

  6. Can proton pump inhibitors accentuate skin aging?

    PubMed

    Namazi, Mohammad Reza; Jowkar, Farideh

    2010-02-01

    Skin aging has long been important to human beings and in recent years this field has received tremendous attention by both researchers and the general population. Cutaneous aging includes two distinct phenomena, intrinsic aging and photoaging, and is characterized mainly by the loss of collagen fibers from dermis. Proton pump inhibitors (PPIs) are widely prescribed gastric acid-reducing agents that are usually consumed for long periods in some conditions such as gastroesophageal reflux disease. We suggest that PPIs can accentuate skin aging by two mechanisms. First, through increasing intralysosomal PH, PPIs can suppress transforming growth factor-beta (TGFbeta) processing and consequently decrease its secretion. Second, through inhibiting MNK, a P-type ATPase with steady-state localization at the trans-Golgi network, PPIs can hamper copper transport and consequently curb lysyl oxidase activity. PMID:20470945

  7. Proton pump inhibitors decrease melanogenesis in melanocytes

    PubMed Central

    BAEK, SEUNG-HWA; LEE, SANG-HAN

    2015-01-01

    Proton pump inhibitors (PPIs) are widely used as inhibitors of gastric juice secretion for treatment of gastroesophageal reflux disease. However, there are no previous studies of the effects on melanogenesis resulting from PPI treatments. Therefore, the aim of the present study was to investigate the effects of PPIs on melanogenesis in melan-a cells derived from immortalized mouse melanocytes. Tyrosinase activity and copper-chelating activity were measured spectrophotometrically. In addition, the melanin content and viability of melan-a cells treated with PPIs were assessed and the mRNA levels of melanogenesis-associated genes were measured by reverse transcription-polymerase chain reaction. Treatment with rabeprazole, but not the other PPIs tested, resulted in strong, dose-dependent inhibition of mushroom tyrosinase (TYR). By contrast, each of the PPIs tested exhibited copper-chelating activity. Treatment of melan-a cells with 100 µM concentrations of the PPIs resulted in significantly reduced melanin synthesis and reduced expression of several melanogenesis-associated genes, including TYR, TYR-related protein-1 (TRP-1) and TRP-2, and microphthalmia-associated transcription factor, but did not result in cytotoxic effects. These results suggest that PPIs inhibit melanin biosynthesis in melan-a cells via the downregulation of melanogenesis-associated genes. Furthermore, the findings indicate that PPIs in general could be utilized as skin-whitening agents and/or as biomaterial for treating hyperpigmentation disorders. PMID:26405553

  8. Proton Pump Inhibitors and the Prescribing Cascade.

    PubMed

    Rababa, Mohammad; Al-Ghassani, Amal Ali; Kovach, Christine R; Dyer, Elaine M

    2016-04-01

    HOW TO OBTAIN CONTACT HOURS BY READING THIS ARTICLE Instructions 1.3 contact hours will be awarded by Villanova University College of Nursing upon successful completion of this activity. A contact hour is a unit of measurement that denotes 60 minutes of an organized learning activity. This is a learner-based activity. Villanova University College of Nursing does not require submission of your answers to the quiz. A contact hour certificate will be awarded once you register, pay the registration fee, and complete the evaluation form online at http://goo.gl/gMfXaf. To obtain contact hours you must: 1. Read the article, "Proton Pump Inhibitors and the Prescribing Cascade" found on pages 23-31, carefully noting any tables and other illustrative materials that are included to enhance your knowledge and understanding of the content. Be sure to keep track of the amount of time (number of minutes) you spend reading the article and completing the quiz. 2. Read and answer each question on the quiz. After completing all of the questions, compare your answers to those provided within this issue. If you have incorrect answers, return to the article for further study. 3. Go to the Villanova website listed above to register for contact hour credit. You will be asked to provide your name; contact information; and a VISA, MasterCard, or Discover card number for payment of the $20.00 fee. Once you complete the online evaluation, a certificate will be automatically generated. This activity is valid for continuing education credit until March 31, 2019. CONTACT HOURS This activity is co-provided by Villanova University College of Nursing and SLACK Incorporated. Villanova University College of Nursing is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. ACTIVITY OBJECTIVES 1. Describe the prescribing cascade of proton pump inhibitors (PPI) in nursing home residents. 2. Identify the statistically

  9. Antiplatelet agents and proton pump inhibitors – personalizing treatment

    PubMed Central

    Lin, Eugene; Padmanabhan, Rajiv; Moonis, Majaz

    2010-01-01

    Introduction: Antiplatelet therapy remains one of the cornerstones in the management of non-cardioembolic ischemic stroke. However, a significant percentage of patients have concomitant gastroesophageal reflux or peptic ulcer disease that requires acid-reducing medications, the most powerful and effective being the proton pump inhibitors (PPIs). Antiplatelet efficacy, at least in vivo, and particularly for clopidogrel, has been shown to be reduced with concomitant proton pump inhibitor use. Whether this is clinically relevant is not clear from the limited studies available. Methods: We conducted an extensive review of studies available on Medline related to pharmacodynamic interactions between the antiplatelet medications and proton pump inhibitors as well as clinical studies that addressed this potential interaction. Results: Based on the present pharmacodynamic and clinical studies we did not find a significant interaction that would reduce the efficacy of antiplatelet agents with concomitant user of proton pump inhibitors. Conclusions: Patients on antiplatelet agents after a transient ischemic attack or ischemic stroke can safely use aspirin, and extended release dipyridamole/aspirin with proton pump inhibitors. Patients on clopidogrel may use other acid-reducing drugs besides proton pump inhibitors. In rare cases where proton pump inhibitors and clopidogrel have to be used concurrently, careful close monitoring for recurrent vascular events is required. PMID:23226046

  10. Antiplatelet drug interactions with proton pump inhibitors

    PubMed Central

    Scott, Stuart A; Obeng, Aniwaa Owusu; Hulot, Jean-Sébastien

    2014-01-01

    Introduction Non-aspirin antiplatelet agents (e.g., clopidogrel, prasugrel, ticagrelor) are commonly prescribed for the prevention of recurrent cardiovascular events among patients with acute coronary syndromes (ACS) and/or those undergoing percutaneous coronary intervention (PCI). In addition, combination therapy with proton pump inhibitors (PPIs) is often recommended to attenuate gastrointestinal bleeding risk, particularly during dual antiplatelet therapy (DAPT) with clopidogrel and aspirin. Importantly, a pharmacological interaction between clopidogrel and some PPIs has been proposed based on mutual CYP450-dependent metabolism, but available evidence is inconsistent. Areas covered This article provides an overview of the currently approved antiplatelet agents and PPIs, including their metabolic pathways. Additionally, the CYP450 isoenzyme at the center of the drug interaction, CYP2C19, is described in detail, and the available evidence on both the potential pharmacological interaction and influence on clinical outcomes are summarized and evaluated. Expert opinion Although concomitant DAPT and PPI use reduces clopidogrel active metabolite levels and ex vivo-measured platelet inhibition, the influence of the drug interaction on clinical outcomes has been conflicting and largely reported from non-randomized observational studies. Despite this inconsistency, a clinically important interaction cannot be definitively excluded, particularly among patient subgroups with higher overall cardiovascular risk and potentially among CYP2C19 loss-of-function allele carriers. PMID:24205916

  11. Are proton pump inhibitors really so dangerous?

    PubMed

    Savarino, Vincenzo; Dulbecco, Pietro; Savarino, Edoardo

    2016-08-01

    For decades, millions of patients with acid-related disorders have had their acid inhibited effectively and safely first with H2-receptor antagonists (H2RAs) and then with proton pump inhibitors (PPI). As with any pharmacological agent, PPIs have been reported to be associated with some adverse events, but several recent large-scale observational studies have evidenced new and serious abnormalities generally linked to their chronic use. However, these studies have often important limitations for their frequent retrospective design and other methodological drawbacks, such as selection biases of the analyzed populations and the presence of various confounding factors. Overall, although the conclusions of these pharmacovigilant investigations must be taken into account and can generate important hypotheses for future research, they do not have to create panic among patients and alarmism among physicians. On considering the weakness of these studies, we suggest physicians should not refrain from continuing to use PPIs, if these drugs are given for medical indications clearly established in the literature and, more importantly, they should not be induced to shift to H2RAs, a class of antisecretory agents that are much less effective than PPIs. A return to the past is potentially dangerous for the patients, taking into account the well-known success of PPIs in the wide spectrum of all acid-related conditions. PMID:27321544

  12. Proton pump inhibitors and risk of dementia

    PubMed Central

    Thongprayoon, Charat; Panjawatanan, Panadeekarn; Ungprasert, Patompong

    2016-01-01

    Background Proton pump inhibitors (PPIs) are one of the most commonly prescribed medications. Recent studies have raised a concern over increased risk of dementia among PPIs users but the results of those studies were inconsistent. We conducted this systematic review and meta-analysis to summarize all available data. Methods A literature search was performed in MEDLINE and EMBASE database from inception to April 2016. Observational studies that reported risk of dementia among PPIs users compared with non-users were included. Point estimates were extracted from individual studies and pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random-effect, generic inverse variance method. Results Four studies were included in the analysis. Pooled RR of dementia among PPIs users compared with non-users was 1.08 (95% CI, 0.82–1.43). Sensitivity analysis including only cohort studies demonstrated a higher risk with pooled RR of 1.44 (95% CI, 1.36–1.52). Conclusions Our study demonstrated an increased risk of dementia among PPIs users. Whether this association is causal requires further investigations. PMID:27429966

  13. Proton pump inhibitors affect the gut microbiome

    PubMed Central

    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

    2016-01-01

    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 promoting colonisation by pathogens. In this study, we investigated the influence of PPI use on the gut microbiome. Methods 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. Results 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 <0.05). Multiple oral bacteria were over-represented in the faecal 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. Conclusions 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. PMID:26657899

  14. Multimorbidities and Overprescription of Proton Pump Inhibitors in Older Patients

    PubMed Central

    Delcher, Anne; Hily, Sylvie; Boureau, Anne Sophie; Chapelet, Guillaume; Berrut, Gilles; de Decker, Laure

    2015-01-01

    Objectives To determine whether there is an association between overprescription of proton pump inhibitors (PPIs) and multimorbidities in older patients. Design Multicenter prospective study. Setting Acute geriatric medicine at the University Hospital of Nantes and the Hospital of Saint-Nazaire. Participants Older patients aged 75 and over hospitalized in acute geriatric medicine. Measurements Older patients in acute geriatric medicine who received proton pump inhibitors. Variables studied were individual multimorbidities, the burden of multimorbidity evaluated by the Cumulative Illness Rating Scale, age, sex, type of residence (living in nursing home or not), functional abilities (Lawton and Katz scales), nutritional status (Body Mass Index), and the type of concomitant medications (antiaggregant, corticosteroids’, or anticoagulants). Results Overprescription of proton pump inhibitors was found in 73.9% older patients. In the full model, cardiac diseases (odds ratio [OR] = 4.17, p = 0.010), metabolic diseases (OR = 2.14, p = 0.042) and corticosteroids (OR = 5.39, p = 0.028) were significantly associated with overprescription of proton pump inhibitors. Esogastric diseases (OR = 0.49, p = 0.033) were negatively associated with overprescription of proton pump inhibitors. Conclusion Cardiac diseases and metabolic diseases were significantly associated with overprescription of proton pump inhibitors. PMID:26535585

  15. Long Term Proton Pump Inhibitor Use and Gastrointestinal Cancer

    PubMed Central

    Graham, David Y.; Genta, Robert M.

    2010-01-01

    Proton pump inhibitors profoundly affect the stomach and have been associated with carcinoid tumors in female rats. There is now sufficient experience with this class of drugs to allow reasonable estimation of their safety in terms of cancer development. Long term proton pump inhibitor use is associated with an increase in gastric inflammation and development of atrophy among those with active Helicobacter pylori infections. The actual risk is unknown but is clearly low. However, it can be markedly reduced or eliminated by H. pylori eradication leading to the recommendation that patients considered for long term proton pump inhibitor therapy be tested for H. pylori infection and if present, it should be eradicated. Oxyntic cell hyperplasia, glandular dilatations, and fundic gland polyps may develop in H. pylori-uninfected patients, but these changes are believed to be reversible and without significant cancer risk. PMID:19006608

  16. Tinidazole in the prophylaxis of post-appendicectomy infections.

    PubMed

    Salo, J; Silvennoinen, E; Hulkko, A; Ervasti, E; Holopainen, O

    1981-01-01

    A total of 223 consecutive suspected appendicitis patients were treated preoperatively with parenteral tinidazole or physiological saline (control group). An infusion of 500 mg tinidazole was given to 110 patients over 30 minutes beginning about 30 minutes before the start of the operation, the control group comprised 111 patients. Postoperative infections were diagnosed in three patients in the group receiving tinidazole (3%) and in 17 patients in the control group (15%). The difference was statistically significant. There were no side-effects due to the drugs. Tinidazole appears to be well suited to the prophylaxis of post-appendicectomy infections. PMID:7032413

  17. Histamine 2 Receptor Antagonists and Proton Pump Inhibitors.

    PubMed

    Brinkworth, Megan D; Aouthmany, Mouhammad; Sheehan, Michael

    2016-01-01

    Within the last 50 years, the pharmacologic market for gastric disease has grown exponentially. Currently, medical management with histamine 2 receptor antagonist and proton pump inhibitors are the mainstay of therapy over surgical intervention. These are generally regarded as safe medications, but there are growing numbers of cases documenting adverse effects, especially those manifesting in the skin. Here we review the pharmacology, common clinical applications, and adverse reactions of both histamine 2 receptor antagonists and proton pump inhibitors with a particular focus on the potential for allergic reactions including allergic contact dermatitis. PMID:27172303

  18. Development of efflux pump inhibitors in antituberculosis therapy.

    PubMed

    Song, Lele; Wu, Xueqiong

    2016-06-01

    Resistance and tolerance to antituberculosis (anti-TB) drugs, especially the first-line drugs, has become a serious problem in anti-TB therapy. Efflux of antimicrobial agents via bacterial efflux pumps is one of the main reasons for drug resistance. Efflux pump inhibitors (EPIs) bind to efflux pumps to inhibit drug efflux and thus enhance the drug effect and reduce drug resistance. Studies on EPIs targeting the efflux pumps of Mycobacterium tuberculosis (Mtb) help to understand Mtb resistance and to identify the potential drug target and are of significance in guiding the development of new anti-TB drugs and optimal combinations. Currently, there are many potential EPIs under study, but none of them has been used clinically for anti-TB therapy. In this article, we will provide an overview on the current development of EPIs targeting the efflux pumps of Mtb and discuss their potential clinical applications. PMID:27211826

  19. Dexlansoprazole – a new-generation proton pump inhibitor

    PubMed Central

    Radwan, Piotr

    2015-01-01

    Dexlansoprazole modified release (MR) is an R-enantiomer of lansoprazole and a new-generation proton pump inhibitor exhibiting high efficacy in the treatment of symptoms and lesions associated with erosive oesophagitis caused by gastroesophageal reflux disease (GERD). The dual release of the active ingredient – in the duodenum and the small intestine – makes it possible to achieve two peak concentrations at various times, within two and five hours of administration. Dexlansoprazole MR ensures the longest maintenance of drug concentration in the plasma of all known proton pump inhibitors, and the longest proton pump inhibitory effect. The basic indications for the drug include all forms of gastroesophageal reflux disease, especially with night-time heartburn and sleep disorders resulting from GERD. Dexlansoprazole can be taken regardless of meal times. It has a good safety profile and carries a low risk of adverse interactions with other drugs. PMID:26759624

  20. Current Advances in Developing Inhibitors of Bacterial Multidrug Efflux Pumps.

    PubMed

    Mahmood, Hannah Y; Jamshidi, Shirin; Sutton, J Mark; Rahman, Khondaker M

    2016-01-01

    Antimicrobial resistance represents a significant challenge to future healthcare provision. An acronym ESKAPEE has been derived from the names of the organisms recognised as the major threats although there are a number of other organisms, notably Neisseria gonorrhoeae, that have become equally challenging to treat in the clinic. These pathogens are characterised by the ability to rapidly develop and/or acquire resistance mechanisms in response to exposure to different antimicrobial agents. A key part of the armoury of these pathogens is a series of efflux pumps, which effectively exclude or reduce the intracellular concentration of a large number of antibiotics, making the pathogens significantly more resistant. These efflux pumps are the topic of considerable interest, both from the perspective of basic understanding of efflux pump function, and its role in drug resistance but also as targets for the development of novel adjunct therapies. The necessity to overcome antimicrobial resistance has encouraged investigations into the characterisation of resistance-modifying efflux pump inhibitors to block the mechanisms of drug extrusion, thereby restoring antibacterial susceptibility and returning existing antibiotics into the clinic. A greater understanding of drug recognition and transport by multidrug efflux pumps is needed to develop clinically useful inhibitors, given the breadth of molecules that can be effluxed by these systems. This review discusses different bacterial EPIs originating from both natural source and chemical synthesis and examines the challenges to designing successful EPIs that can be useful against multidrug resistant bacteria. PMID:26947776

  1. An overview of bacterial efflux pumps and computational approaches to study efflux pump inhibitors.

    PubMed

    Jamshidi, Shirin; Sutton, J Mark; Rahman, Khondaker M

    2016-02-01

    Micro-organisms express a wide range of transmembrane pumps known as multidrug efflux pumps that improve the micro-organism's ability to survive in severe environments and contribute to resistance against antibiotic and antimicrobial agents. There is significant interest in developing efflux inhibitors as an adjunct to treatment with current and next generation of antibiotics. A greater understanding of drug recognition and transport by multidrug efflux pumps is needed to develop clinically useful inhibitors, given the breadth of molecules that can be effluxed by these systems. We summarize some structural and functional data that could provide insights into the inhibition of transport mechanisms of these intricate molecular nanomachines with a focus on the advances in computational approaches. PMID:26824720

  2. Spectrophotometric Determination of Certain Benzimidazole Proton Pump Inhibitors

    PubMed Central

    Syed, A. A.; Syeda, Ayesha

    2008-01-01

    Spectrophotometric method for the determination of certain proton pump inhibitors belonging to the benzimidazole class of compounds has been developed. The method is based on the reaction of omeprazole, lansoprazole, pantoprazole, rabeprazole and esomeprazole with iron (III) and subsequent reaction with ferricyanide under neutral condition which yields Prussian blue product with maximum absorption at 720–730 nm. The commonly encountered excipients and additives that often accompany pharmaceutical preparations did not interfere with the determination. The method was applied for the determination of omeprazole, lansoprazole, pantoprazole, rabeprazole and esomeprazole in pharmaceutical preparations and no difference was found statistically. Thus, the spectrophotometric method can be applied as inexpensive, rapid, easy, accurate and precise method for the routine analysis of the five proton pump inhibitors in pharmaceutical preparations. PMID:20046782

  3. Inhibitors of Bacterial Multidrug Efflux Pumps Potentiate Antimicrobial Photoinactivation▿

    PubMed Central

    Tegos, George P.; Masago, Kayo; Aziz, Fatima; Higginbotham, Andrew; Stermitz, Frank R.; Hamblin, Michael R.

    2008-01-01

    Antimicrobial photodynamic inactivation (APDI) combines a nontoxic photoactivatable dye or photosensitizer (PS) with harmless visible light to generate singlet oxygen and reactive oxygen species that kill microbial cells. Cationic phenothiazinium dyes, such as toluidine blue O (TBO), are the only PS used clinically for APDI, and we recently reported that this class of PS are substrates of multidrug efflux pumps in both gram-positive and gram-negative bacteria. We now report that APDI can be significantly potentiated by combining the PS with an efflux pump inhibitor (EPI). Killing of Staphylococcus aureus mediated by TBO and red light is greatly increased by coincubation with known inhibitors of the major facilitator pump (NorA): the diphenyl urea INF271, reserpine, 5′-methoxyhydnocarpin, and the polyacylated neohesperidoside, ADH7. The potentiation effect is greatest in the case of S. aureus mutants that overexpress NorA and least in NorA null cells. Addition of the EPI before TBO has a bigger effect than addition of the EPI after TBO. Cellular uptake of TBO is increased by EPI. EPI increased photodynamic inactivation killing mediated by other phenothiazinium dyes, such as methylene blue and dimethylmethylene blue, but not that mediated by nonphenothiazinium PS, such as Rose Bengal and benzoporphyrin derivative. Killing of Pseudomonas aeruginosa mediated by TBO and light was also potentiated by the resistance nodulation division pump (MexAB-OprM) inhibitor phenylalanine-arginine beta-naphthylamide but to a lesser extent than for S. aureus. These data suggest that EPI could be used in combination with phenothiazinium salts and light to enhance their antimicrobial effect against localized infections. PMID:18474586

  4. Clinical relevance of clopidogrel-proton pump inhibitors interaction

    PubMed Central

    Bouziana, Stella D; Tziomalos, Konstantinos

    2015-01-01

    Clopidogrel is a widely used antiplatelet agent for the secondary prevention of cardiovascular events in patients with stable coronary heart disease, acute coronary syndromes and ischemic stroke. Even though clopidogrel is safer than aspirin in terms of risk for gastrointestinal (GI) bleeding, the elderly, and patients with a history of prior GI bleeding, with Helicobacter pylori infection or those who are also treated with aspirin, anticoagulants, corticosteroids or nonsteroidal anti-inflammatory drugs are at high risk for GI complications when treated with clopidogrel. Accordingly, proton pump inhibitors are frequently administered in combination with clopidogrel to reduce the risk for GI bleeding. Nevertheless, pharmacodynamic studies suggest that omeprazole might attenuate the antiplatelet effect of clopidogrel. However, in observational studies, this interaction does not appear to translate into increased cardiovascular risk in patients treated with this combination. Moreover, in the only randomized, double-blind study that assessed the cardiovascular implications of combining clopidogrel and omeprazole, patients treated with clopidogrel/omeprazole combination had reduced risk for GI events and similar risk for cardiovascular events than patients treated with clopidogrel and placebo. However, the premature interruption of the study and the lack of power analysis in terms of the cardiovascular endpoint do not allow definite conclusions regarding the cardiovascular safety of clopidogrel/omeprazole combination. Other proton pump inhibitors do not appear to interact with clopidogrel. Nevertheless, given the limitations of existing observational and interventional studies, the decision to administer proton pump inhibitors to patients treated with clopidogrel should be individualized based on the patient’s bleeding and cardiovascular risk. PMID:25949846

  5. The Proton Pump Inhibitor Non-Responder: A Clinical Conundrum

    PubMed Central

    Hussain, Zilla H; Henderson, Emily E; Maradey-Romerao, Carla; George, Nina; Fass, Ronnie; Lacy, Brian E

    2015-01-01

    Gastroesophageal reflux disease (GERD) is a highly prevalent chronic condition where in stomach contents reflux into the esophagus causing symptoms, esophageal injury, and subsequent complications. Proton pump inhibitors (PPI) remain the mainstay of therapy for acid suppression. Despite their efficacy, significant proportions of GERD patients are either partial or non-responders to PPI therapy. Patients should be assessed for mechanisms that can lead to PPI failure and may require further evaluation to investigate for alternative causes. This monograph will outline a diagnostic approach to the PPI non-responder, review mechanisms associated with PPI failure, and discuss therapeutic options for those who fail to respond to PPI therapy. PMID:26270485

  6. [Physiological functions of endoplasmic and sarcoplasmic reticulum Ca pump and pharmacology of inhibitors of the pump].

    PubMed

    Watanabe, M; Shigekawa, M

    1993-09-01

    This review is derived from the symposium held at the 66th Annual Meeting of the Japanese Pharmacological Society (March, 1993). The symposium consisted of six invited papers whose general theme was the application of recently found ATPase inhibitors selective to SR- and ER-Ca(2+)-ATPase to the analyses of the physiological and pharmacological roles of endoplasmic and sarcoplasmic reticulum Ca stores. Inhibitors used were: thapsigargin, cyclopiazonic acid, 2,5-di-(t-butyl)-1,4-benzohydroquinone and 3',3",5',5"-tetraiodosulfophthalein. Gingerol was found to facilitate the action of the ATPase. In either smooth, cardiac or skeletal muscle, sympathetic neurons or several cell lines these inhibitors affected a variety of cell functions and conditions such as contraction, ionic conductance and excitability of the plasma membrane, regulation of intracellular free Ca2+ concentration, transport of viral glycoprotein to the cell surface. Many of these studies utilized either single or cultured cell preparations or skinned muscle. These inhibitors were shown to be useful tools for investigating the SR and ER functioning as Ca sources or Ca sequestrating pumps, and further for estimating the contribution of ER or SR to regulating the flux of Ca2+ and other ions through the plasma membrane. Results of analyses using these inhibitors are discussed. PMID:8406230

  7. Helicobacter pylori urease inhibition by rabeprazole, a proton pump inhibitor.

    PubMed

    Tsuchiya, M; Imamura, L; Park, J B; Kobashi, K

    1995-08-01

    We investigated the inhibitory effects of four gastric proton pump inhibitors (PPIs): rabeprazole, a novel benzimidazole PPI, omeprazole, lansoprazole and AG-2000, on the urease activity of Helicobacter pylori (H. pylori). Their 50% inhibitory concentrations (I50s) were found to be 0.29, 5.4, 9.3 and 0.3 microM respectively. Rabeprazole and omeprazole were also potent inhibitors of Jack bean and Proteus mirabilis cellular ureases. The thioether derivative of rabeprazole, one of its metabolites, had no inhibitory effect on H. pylori urease, despite being reported as a more potent inhibitor of H. pylori growth than rabeprazole. The inhibitory effect of rabeprazole was prevented completely and reversed considerably by the addition of sulfhydryl compounds, such as beta-mercaptoethanol, glutathione and dithiothreitol. Moreover, the addition of beta-mercaptoethanol recovered the urease activity inhibited by rabeprazole. From these results, we expected that rabeprazole inhibited H. pylori urease activity by forming disulfide bonds between it and the active site of the enzyme. PMID:8535394

  8. Proton pump inhibitor prescription abuse and sepsis in cirrhosis

    PubMed Central

    Picardi, Antonio; Vespasiani-Gentilucci, Umberto

    2016-01-01

    Proton pump inhibitors (PPIs) represent one of the most extensively prescribed classes of drugs in general and in patients with liver cirrhosis. Many prescriptions are made without a clear adherence to standard indications. As a class of ordinarily well tolerated drug, PPIs are not free of side-effects and concerns have been raised about a possible role for PPIs in predisposing patients to an increased risk of bacterial infections and sepsis. As evidences of different power are accumulating on this topic, prospective studies are needed to reach a more universal agreement, but definitely more attention is needed by prescribers in being more adherent to the few recognized indications for the use of PPIs, particularly in patients with liver cirrhosis. Otherwise, doctors could run the risk of being accused of “abused” prescription. PMID:26855807

  9. [Proton pump inhibitors: not as safe as they seem].

    PubMed

    van Herwaarden, N; Bos, J M; Veldman, B; Kramers, C

    2016-01-01

    - Proton pump inhibitors (PPIs) are among the most widely used drugs worldwide. However, some patients use them without a good indication.- Although PPIs are generally safe, there is an increasing number of signals of potentially serious side effects.- This article gives an overview of the incidence and prevalence of the following side effects: gastroenteritis, respiratory tract infections, hypomagnesaemia, renal function disorders, vitamin B12 and iron deficiency, dementia, osteoporosis and fractures.- It is important to prescribe a PPI only when there is a good indication for use. Patients with chronic PPI use should be checked periodically to see whether there is still an indication.- If any of the listed side effects should occur, it is advisable to consider PPI as a possible cause. PMID:27438396

  10. Ocular Side Effect of Tinidazole: A Rare Case Report

    PubMed Central

    Kauser, Hina; Qadir, Maniah; Anwar, Waseem

    2014-01-01

    Ocular side effects in the form of punctate epithelial erosions with the use of tinidazole - a 5-nitroimidazole group of drugs is very rare. A 32-year-old male was prescribed tablet tinidazole for the treatment of amoebiasis but developed adverse effects in the form of blisters on both upper and lower lips with itching and burning sensation, itching and burning on penile and anal area associated with punctate epithelial erosions of cornea of both the eyes. All these are rare manifestations but punctate epithelial erosions of cornea has never been reported in the literature so far. Punctate epithelial erosions of cornea have not previously been reported and should be added to the list of complications of tinidazole. Hence, this case is being reported. PMID:25657970

  11. Ocular side effect of tinidazole: a rare case report.

    PubMed

    Kauser, Hina; Qadir, Maniah; Anwar, Waseem

    2014-01-01

    Ocular side effects in the form of punctate epithelial erosions with the use of tinidazole - a 5-nitroimidazole group of drugs is very rare. A 32-year-old male was prescribed tablet tinidazole for the treatment of amoebiasis but developed adverse effects in the form of blisters on both upper and lower lips with itching and burning sensation, itching and burning on penile and anal area associated with punctate epithelial erosions of cornea of both the eyes. All these are rare manifestations but punctate epithelial erosions of cornea has never been reported in the literature so far. Punctate epithelial erosions of cornea have not previously been reported and should be added to the list of complications of tinidazole. Hence, this case is being reported. PMID:25657970

  12. [Proton pump inhibitors and clopidogrel: a hazardous association?].

    PubMed

    Szymezak, J; Gaussem, P

    2013-02-01

    Proton pump inhibitors (PPI) and antiplatelet agents, especially aspirin and clopidogrel, are among the most prescribed medications worldwide. Their co-administration is justified by the increased risk of gastrointestinal bleeding related to the antiplatelet therapy. The issue of the interaction between PPI and clopidogrel has been raised with the emergence of the concept of "high on-clopidogrel platelet reactivity" (or "clopidogrel resistance") together with the discovery of the role of CYP2C19 isoform in the pharmacokinetics of those two medications. Indeed, CYP2C19 is involved in the conversion of the clopidogrel pro-drug into its active metabolite and is involved in the metabolisation of PPI into inactive metabolites, acting as substrates/inhibitors of CYP2C19. Despite their heterogeneity, most pharmacodynamic studies have shown a decreased clopidogrel antiplatelet effect when associated to PPI, especially those with the highest CYP2C19 inhibiting activity (omeprazole, lansoprazole, rabeprazole). On the other hand, clinical studies are inconclusive. Retrospective studies have shown an increased risk of major cardiovascular events or mortality when clopidogrel and PPI are associated in comparison with clopidogrel alone, particularly in the patients with the higher cardiovascular risk. However, the two prospective randomized studies published so far did not find any interaction and confirmed the benefit of PPI on the gastrointestinal bleeding. As a conclusion, as the clinical studies are not conclusive, the French health authorities have recently removed the alert about this interaction. PPI and clopidogrel can thus be co-prescribed. PMID:23200799

  13. Hypomagnesemia Induced by Long-Term Treatment with Proton-Pump Inhibitors

    PubMed Central

    Janett, Simone; Camozzi, Pietro; Peeters, Gabriëlla G. A. M.; Lava, Sebastiano A. G.; Simonetti, Giacomo D.; Goeggel Simonetti, Barbara; Bianchetti, Mario G.; Milani, Gregorio P.

    2015-01-01

    In 2006, hypomagnesemia was first described as a complication of proton-pump inhibitors. To address this issue, we systematically reviewed the literature. Hypomagnesemia, mostly associated with hypocalcemic hypoparathyroidism and hypokalemia, was reported in 64 individuals on long-term proton-pump inhibitors. Hypomagnesemia recurred following replacement of one proton-pump inhibitor with another but not with a histamine type-2 receptor antagonist. The association between proton-pump inhibitors and magnesium metabolism was addressed in 14 case-control, cross-sectional studies. An association was found in 11 of them: 6 reports found that the use of proton-pump inhibitors is associated per se with a tendency towards hypomagnesemia, 2 found that this tendency is more pronounced in patients concurrently treated with diuretics, carboplatin, or cisplatin, and 2 found a relevant tendency to hypomagnesemia in patients with poor renal function. Finally, findings likely reflecting decreased intestinal magnesium uptake were observed on treatment with proton-pump inhibitors. Three studies did not disclose any relationship between magnesium metabolism and treatment with histamine type-2 receptor antagonists. In conclusion, proton-pump inhibitors may cause hypomagnesemia. In these cases, switching to a histamine type-2 receptor antagonist is advised. PMID:26064102

  14. Clinical evidence of interaction between clopidogrel and proton pump inhibitors

    PubMed Central

    Lin, Shoa-Lin; Chang, Hui-Min; Liu, Chun-Peng; Chou, Li-Ping; Chan, Jaw-Wen

    2011-01-01

    Clopidogrel is approved for reduction of atherothrombotic events in patients with cardiovascular (CV) and cerebrovascular disease. Dual antiplatelet therapy with aspirin and clopidogrel decreases the risk of major adverse cardiac events after acute coronary syndrome or percutaneous coronary intervention, compared with aspirin alone. Due to concern about gastrointestinal bleeding in patients who are receiving clopidogrel and aspirin therapy, current guidelines recommend combined use of a proton pump inhibitor (PPI) to decrease the risk of bleeding. Data from previous pharmacological studies have shown that PPIs, which are extensively metabolized by the cytochrome system, may decrease the ADP-induced platelet aggregation of clopidogrel. Results from retrospective cohort studies have shown a higher incidence of major CV events in patients receiving both clopidogrel and PPIs than in those without PPIs. However, other retrospective analyses of randomized clinical trials have not shown that the concomitant PPI administration is associated with increased CV events among clopidogrel users. These controversial results suggest that large specific studies are needed. This article reviews the metabolism of clopidogrel and PPIs, existing clinical data regarding the interaction between clopidogrel and PPIs, and tries to provide recommendations for health care professionals. PMID:21666816

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

    PubMed Central

    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

    2016-01-01

    Objective 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. Design 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. Results 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. Conclusions 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. PMID:26719299

  16. Proton pump inhibitor-induced exfoliative dermatitis: A case report

    PubMed Central

    QIU, ZHIHONG; LIU, HONGTAO; HE, LIEN; MA, YINLING; SONG, HAOJING; BAI, WANJUN; YU, MEILING

    2016-01-01

    A 74-year-old female patient was admitted to hospital following a road accident with pains in the chest, abdomen, waist, back, nose, left wrist and lower limbs. After 1 week, the patient presented with gastrointestinal bleeding, and thus was treated with protein pump inhibitors (PPIs), including lansoprazole, esomeprazole and omeprazole enteric-coated tablets, in order to inhibit acid secretion and attenuate bleeding. However, the patient developed skin rashes on the chest and right lower limb and foot 28 days following treatment initiation. The skin rashes spread and ulcerated after 3 days, and were associated with tracheal mucosal injury and hemoptysis. Subsequently, treatment of the patient with PPIs was terminated, after which the tracheal hemoptysis and skin rashes markedly improved. In addition, no new skin rashes appeared following termination of the PPI treatment. In the present case, long-term treatment of an elderly patient with PPIs may have induced exfoliative dermatitis, due to hepatic ischemia, hypoxia and acute renal failure, which may have decreased the metabolism of PPIs, resulting in the accumulation of PPI metabolites. PMID:26893644

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

    PubMed

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

    2013-09-21

    We report the case of a 17-year-old male admitted to our academic hospital with massive rectal bleeding. Since childhood he had reported recurrent gastrointestinal bleeding and had two exploratory laparotomies 5 and 2 years previously. An emergency abdominal computed tomography scan, gastroscopy and colonoscopy, performed after hemodynamic stabilization, were considered normal. High-dose intravenous proton pump inhibitor (PPI) therapy was initiated and bleeding stopped spontaneously. Two other massive rectal bleeds occurred 8 h after each cessation of PPI which led to a hemostatic laparotomy after negative gastroscopy and small bowel capsule endoscopy. This showed long tubular duplication of the right colon, with fresh blood in the duplicated colon. Obscure lower gastrointestinal bleeding is a difficult medical situation and potentially life-threatening. The presence of ulcerated ectopic gastric mucosa in the colonic duplication explains the partial efficacy of PPI therapy. Obscure gastrointestinal bleeding responding to empiric anti-acid therapy should probably evoke the diagnosis of bleeding ectopic gastric mucosa such as Meckel's diverticulum or gastrointestinal duplication, and gastroenterologists should be aware of this potential medical situation. PMID:24124344

  18. Case report of proton pump inhibitor responsive esophageal eosinophilia: why 2 months of proton pump inhibitors is required.

    PubMed

    Lipka, S; Muhammad, A; Champeaux, A; Richter, J E

    2016-08-01

    Eosinophilic esophagitis (EoE) is a chronic inflammatory disease defined by the 2nd EoE consensus panel as: 'symptoms related to esophageal dysfunction, ≥15 eosinophils per high-power field, eosinophilia that persists after a trial of proton pump inhibitor (PPI) therapy, and exclusion of other secondary causes of esophageal eosinophilia'. After Ngo et al. first reported a case series of 3 patients initially diagnosed with eosinophilic esophagitis responding endoscopically and histologically to PPI therapy, the term PPI-responsive esophageal eosinophilia has evolved. Several studies have since confirmed the existence of this entity. Although recent ACG guidelines call for a 2-month course of PPI followed by endoscopy biopsies this recommendation is classified as a strong recommendation with 'low evidence', and has not been proven in the literature. We present a case of PPI-REE treated with rabeprazole 20 mg BID for 2 months, and describe simultaneous symptom resolution with histological and endoscopic remission of disease. This unique case with serial endoscopy and histology at baseline and monthly suggests the current recommendation of at least two months therapy with PPIs dosed twice daily is appropriate. Future studies will need to address duration of high dose therapy, whether patients can be stepped down to once a day PPI, and therapeutic strategy for transient responders. PMID:24842729

  19. 1-Arylsulfonyl-2-(pyridylmethylsulfinyl) benzimidazoles as new proton pump inhibitor prodrugs.

    PubMed

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

    2009-01-01

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

  20. 1-Arylsulfonyl-2-(Pyridylmethylsulfinyl) Benzimidazoles as New Proton Pump Inhibitor Prodrugs

    PubMed Central

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

    2010-01-01

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

  1. Multidrug Pump Inhibitors Uncover Remarkable Activity of Plant Antimicrobials

    PubMed Central

    Tegos, George; Stermitz, Frank R.; Lomovskaya, Olga; Lewis, Kim

    2002-01-01

    Plant antimicrobials are not used as systemic antibiotics at present. The main reason for this is their low level of activity, especially against gram-negative bacteria. The reported MIC is often in the range of 100 to 1,000 μg/ml, orders of magnitude higher than those of common broad-spectrum antibiotics from bacteria or fungi. Major plant pathogens belong to the gram-negative bacteria, which makes the low level of activity of plant antimicrobials against this group of microorganisms puzzling. Gram-negative bacteria have an effective permeability barrier, comprised of the outer membrane, which restricts the penetration of amphipathic compounds, and multidrug resistance pumps (MDRs), which extrude toxins across this barrier. It is possible that the apparent ineffectiveness of plant antimicrobials is largely due to the permeability barrier. We tested this hypothesis in the present study by applying a combination of MDR mutants and MDR inhibitors. A panel of plant antimicrobials was tested by using a set of bacteria representing the main groups of plant pathogens. The human pathogens Pseudomonas aeruginosa, Escherichia coli, and Salmonella enterica serovar Typhimurium were also tested. The results show that the activities of the majority of plant antimicrobials were considerably greater against the gram-positive bacteria Staphylococcus aureus and Bacillus megaterium and that disabling of the MDRs in gram-negative species leads to a striking increase in antimicrobial activity. Thus, the activity of rhein, the principal antimicrobial from rhubarb, was potentiated 100- to 2,000-fold (depending on the bacterial species) by disabling the MDRs. Comparable potentiation of activity was observed with plumbagin, resveratrol, gossypol, coumestrol, and berberine. Direct measurement of the uptake of berberine, a model plant antimicrobial, confirmed that disabling of the MDRs strongly increases the level of penetration of berberine into the cells of gram-negative bacteria. These

  2. Influence of proton pump inhibitor use in gastrointestinal polyps.

    PubMed

    Hsu, Wen-Hung; Wu, I-Chen; Kuo, Chao-Hung; Su, Yu-Chung; Lu, Chien-Yu; Kuo, Fu-Chen; Jan, Chang-Ming; Wang, Wen-Ming; Wu, Deng-Chyang; Yu, Fang-Jung

    2010-02-01

    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. PMID:20123595

  3. Proton pump inhibitor alone vs proton pump inhibitor plus mucosal protective agents for endoscopic submucosal dissection-induced ulcer: a systematic review and meta-analysis

    PubMed Central

    Nishizawa, Toshihiro; Suzuki, Hidekazu; Kanai, Takanori; Yahagi, Naohisa

    2015-01-01

    Mucosal protective agents may improve healing of patients with endoscopic submucosal dissection-induced ulcers. The present study systematically evaluated published clinical trials to determine whether combined therapeutic use of mucosal protective agents and proton pump inhibitors can improve the outcome of patients with endoscopic submucosal dissection-induced ulcers compared to treatment with proton pump inhibitors alone. PubMed, the Cochrane Library, and the Igaku-Chuo-Zasshi database were searched to identify eligible randomized trials for systematic review. We identified 11 randomized trials for inclusion in our study (1,160 patients). Pooled endoscopic submucosal dissection-induced ulcer healing rates were 45.8% and 34.4% for patients with or without mucosal protective agents, respectively. The odds ratio was 2.28 (95% confidence interval, 1.57–3.31) with no significant study heterogeneity. In conclusion, the systematic review and meta-analysis showed that the combined therapeutic use of proton pump inhibitors and mucosal protective agents improved healing rates of endoscopic submucosal dissection-induced ulcers compared to treatment with proton pump inhibitor monotherapy. PMID:25759512

  4. Natural and Synthetic Polymers as Inhibitors of Drug Efflux Pumps

    PubMed Central

    2007-01-01

    Inhibition of efflux pumps is an emerging approach in cancer therapy and drug delivery. Since it has been discovered that polymeric pharmaceutical excipients such as Tweens® or Pluronics® can inhibit efflux pumps, various other polymers have been investigated regarding their potential efflux pump inhibitory activity. Among them are polysaccharides, polyethylene glycols and derivatives, amphiphilic block copolymers, dendrimers and thiolated polymers. In the current review article, natural and synthetic polymers that are capable of inhibiting efflux pumps as well as their application in cancer therapy and drug delivery are discussed. PMID:17896100

  5. Outbreak of giardiasis: effect of a new antiflagellate drug, tinidazole.

    PubMed

    Andersson, T; Forssell, J; Sterner, G

    1972-05-20

    We describe here an intensive outbreak of mostly symptomatic (90%) Giardia lamblia infestation in a Swedish student group visiting the U.S.S.R. A new antiflagellate drug, ethyl (2-(2-methyl-5-nitro-1-imidazolyl)ethyl) sulphone, tinidazole, Pfizer, was given in a dosage of 150 mg twice daily for seven days to 10 healthy volunteers and to 24 students infested with G. lamblia. The drug was found to be effective in curing giardiasis and in eradicating G. lamblia from the intestinal tract. All the students with symptomatic giardia infestation became free from gastrointestinal disturbance, usually soon after treatment was started. None of the 24 students had G. lamblia in their stools after tinidazole treatment was discontinued or at follow-up. No side effects of the drug were seen and all of the subjects tolerated it very well. PMID:5031661

  6. Plasma membrane calcium pumps in smooth muscle: from fictional molecules to novel inhibitors.

    PubMed

    Pande, Jyoti; Grover, Ashok K

    2005-01-01

    Plasma membrane Ca2+ pumps (PMCA pumps) are Ca2+-Mg2+ ATPases that expel Ca2+ from the cytosol to extracellular space and are pivotal to cell survival and function. PMCA pumps are encoded by the genes PMCA1, -2, -3, and -4. Alternative splicing results in a large number of isoforms that differ in their kinetics and activation by calmodulin and protein kinases A and C. Expression by 4 genes and a multifactorial regulation provide redundancy to allow for animal survival despite genetic defects. Heterozygous mice with ablation of any of the PMCA genes survive and only the homozygous mice with PMCA1 ablation are embryolethal. Some PMCA isoforms may also be involved in other cell functions. Biochemical and biophysical studies of PMCA pumps have been limited by their low levels of expression. Delineation of the exact physiological roles of PMCA pumps has been difficult since most cells also express sarco/endoplasmic reticulum Ca2+ pumps and a Na+-Ca2+-exchanger, both of which can lower cytosolic Ca2+. A major limitation in the field has been the lack of specific inhibitors of PMCA pumps. More recently, a class of inhibitors named caloxins have emerged, and these may aid in delineating the roles of PMCA pumps. PMID:16333376

  7. Efflux pump inhibitors: targeting mycobacterial efflux systems to enhance TB therapy.

    PubMed

    Pule, Caroline M; Sampson, Samantha L; Warren, Robin M; Black, Philippa A; van Helden, Paul D; Victor, Tommie C; Louw, Gail E

    2016-01-01

    The emergence of drug resistance continues to plague TB control, with a global increase in the prevalence of MDR-TB. This acts as a gateway to XDR-TB and thus emphasizes the urgency for drug development and optimal treatment options. Bedaquiline is the first new anti-TB drug approved by the FDA in 40 years and has been shown to be an effective treatment option for MDR Mycobacterium tuberculosis infection. Bedaquiline has also recently been included in clinical trials for new regimens with the aim of improving and shortening treatment periods. Alarmingly, efflux-mediated bedaquiline resistance, as well as efflux-mediated cross-resistance to clofazimine, has been identified in treatment failures. This mechanism of resistance results in efflux of a variety of anti-TB drugs from the bacterial cell, thereby decreasing the intracellular drug concentration. In doing so, the bacillus is able to render the antibiotic treatment ineffective. Recent studies have explored strategies to reverse the resistance phenotype conferred by efflux pump activation. It was observed that the addition of efflux pump inhibitors partially restored drug susceptibility in vitro and in vivo. This has significant clinical implications, especially in MDR-TB management where treatment options are extremely limited. This review aims to highlight the current efflux pump inhibitors effective against M. tuberculosis, the effect of efflux pump inhibitors on mycobacterial growth and the clinical promise of treatment with efflux pump inhibitors and standard anti-TB therapy. PMID:26472768

  8. Use of Proton Pump Inhibitors and Subsequent Risk of Celiac Disease

    PubMed Central

    Lebwohl, Benjamin; Spechler, Stuart J.; Wang, Timothy C.; Green, Peter H.R.; Ludvigsson, Jonas F.

    2013-01-01

    Background The prevalence of celiac disease and the use of medications that inhibit acid secretion have both increased in recent decades. Aims To explore the association between antisecretory medication exposure and subsequent development of celiac disease. Methods In this population-based case control study, we identified patients with celiac disease diagnosed at all pathology departments in Sweden from July 2005 through February 2008. Patients were matched by age and gender with up to 5 controls. We identified prior prescriptions for proton pump inhibitors and histamine-2 receptor antagonists in all subjects. We used conditional logistic regression to measure the association between these prescriptions and the subsequent diagnosis of celiac disease. Results Prior proton pump inhibitor prescription was strongly associated with celiac disease (OR 4.79; 95% CI 4.17-5.51). Patients prescribed both proton pump inhibitors and histamine-2 receptor antagonists had a higher risk of celiac disease (OR 5.96; 95% CI 3.58-9.91) than those prescribed proton pump inhibitors alone (OR 4.91; 95% CI 4.26-5.66) or histamine-2 receptor antagonists alone (OR 4.16; 95% CI 2.89-5.99). Conclusions Exposure to antisecretory medications is associated with a subsequent diagnosis of celiac disease. The persistence of this association after excluding prescriptions in the year preceding the celiac disease diagnosis suggests a causal relationship. PMID:24035759

  9. Multidrug Efflux Pumps Attenuate the Effect of MGMT Inhibitors.

    PubMed

    Tomaszowski, Karl-Heinz; Schirrmacher, Ralf; Kaina, Bernd

    2015-11-01

    Various mechanisms of drug resistance attenuate the effectiveness of cancer therapeutics, including drug transport and DNA repair. The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is a key factor determining the resistance against alkylating anticancer drugs inducing the genotoxic DNA lesions O(6)-methylguanine and O(6)-chloroethylguanine, and MGMT inactivation or depletion renders cells more susceptible to treatment with methylating and chloroethylating agents. Highly specific and efficient inhibitors of the repair protein MGMT were designed, including O(6)-benzylguanine (O(6)BG) and O(6)-(4-bromothenyl)guanine (O(6)BTG) that are nontoxic on their own. Unfortunately, these inhibitors do not select between MGMT in normal and cancer cells, causing nontarget effects in the healthy tissue. Therefore, a targeting strategy for MGMT inhibitors is required. Here, we used O(6)BG and O(6)BTG conjugated to β-d-glucose (O(6)BG-Glu and O(6)BTG-Glu, respectively) in order to selectively inhibit MGMT in tumors, harnessing their high demand for glucose. Both glucose conjugates efficiently inhibited MGMT in several cancer cell lines, but with different extents of sensitization to DNA alkylating agents, with lomustine being more effective than temozolomide. We further show that the glucose conjugates are subject to ATP-binding cassette (ABC) transporter mediated efflux, involving P-glycoprotein, MRP1, and BCRP, which impacts the efficiency of MGMT inhibition. Surprisingly, also O(6)BG and O(6)BTG were subject to an active transport out of the cell. We also show that pharmacological inhibition of efflux transporters increases the induction of cell death following treatment with these MGMT inhibitors and temozolomide. We conclude that strategies of attenuating the efflux by ABC transporters are required for achieving successful MGMT targeting. PMID:26379107

  10. Flavonolignans As a Novel Class of Sodium Pump Inhibitors

    PubMed Central

    Kubala, Martin; Čechová, Petra; Geletičová, Jaroslava; Biler, Michal; Štenclová, Tereza; Trouillas, Patrick; Biedermann, David

    2016-01-01

    We examined the inhibitory effects of three flavonolignans and their dehydro- derivatives, taxifolin and quercetin on the activity of the Na+/K+-ATPase (NKA). The flavonolignans silychristin, dehydrosilychristin and dehydrosilydianin inhibited NKA with IC50 of 110 ± 40 μM, 38 ± 8 μM, and 36 ± 14 μM, respectively. Using the methods of molecular modeling, we identified several possible binding sites for these species on NKA and proposed the possible mechanisms of inhibition. The binding to the extracellular- or cytoplasmic C-terminal sites can block the transport of cations through the plasma membrane, while the binding on the interface of cytoplasmic domains can inhibit the enzyme allosterically. Fluorescence spectroscopy experiments confirmed the interaction of these three species with the large cytoplasmic segment connecting transmembrane helices 4 and 5 (C45). The flavonolignans are distinct from the cardiac glycosides that are currently used in NKA treatment. Because their binding sites are different, the mechanism of inhibition is different as well as the range of active concentrations, one can expect that these new NKA inhibitors would exhibit also a different biomedical actions than cardiac glycosides. PMID:27065883

  11. Evaluation of Secnidazole Gel and Tinidazole Suspension in the Treatment of Giardiasis in Children.

    PubMed

    Cimerman; Camilo Coura L; C Salle JM; Gurvitz; Rocha; Bandeira; Cimerman; Katz

    1997-10-01

    Giardiasis is a cosmopolitan parasitosis. Diarrhea, abdominal colic, and flatulence are the main clinical symptoms, however, malabsorption, and impairment of growth of children may occur. The 5-nitroimidazoles are the drugs of choice in the treatment of giardiasis. Methods: The efficacy and tolerability of secnidazole and tinidazole were evaluated in a randomized, open-label, clinical trial performed with 267 Giardia lamblia-positive children. Secnidazole, in a new gel formulation, and tinidazole suspension were prescribed as single oral doses of 30mg/kg and 50mg/kg, respectively. Clinical and parasitological follow-up was carried out before, and at 7, 14, and 21 days after treatment. Results: Clinical cure was observed in 77.3% and 75.7% of the patients in the secnidazole and tinidazole groups, respectively. Parasitological cure was obtained in the 91.3% and 89.6% in the secnidazole and tinidazole groups, respectively. A metallic taste after drug ingestion was more commonly reported in the tinidazole group than in the secnidazole group (p<0.05). Conclusions: The authors conclude that both secnidazole gel and tinidazole administered as a single oral dose are effective treatments for children with giardiasis since both high cure rates and good tolerability were observed. PMID:11105144

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

    PubMed

    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. PMID:18720145

  13. Left ventricular assist device pump thrombosis: is there a role for glycoprotein IIb/IIIa inhibitors?

    PubMed

    Bellumkonda, Lavanya; Subrahmanyan, Lakshman; Jacoby, Daniel; Bonde, Pramod

    2014-01-01

    Left ventricular assist devices (LVADs) fill a critical need by providing circulatory support to patients with end-stage heart failure who are either ineligible for heart transplant or too ill to stably wait for an eventual donor organ. Furthermore, they are critical to the arsenal of the heart failure cardiologist, given the supply/demand mismatch for donor organs. Unfortunately, these devices present their own complications. Despite antiplatelet agents and systemic anticoagulation, a number of patients present with pump thrombosis, a life-threatening event requiring either pump exchange or treatment with systemic thrombolytics. In an effort to avoid these morbid therapies, glycogen IIb/IIIa inhibitors, which have both antiplatelet and thrombolytic properties, have been proposed to treat pump thrombosis. We report here the largest case series using these agents and document a previously unreported high failure rate with this therapy. PMID:24335386

  14. Empiric treatment of children with gastroesophageal reflux-like symptoms: Effect of proton pump inhibitors.

    PubMed

    Gündüz, Mehmet; Yamaç, Pınar; Baysoy, Gökhan

    2015-01-01

    Gastroesophageal reflux disease is an important cause of morbidity in childhood. Although various diagnostic methods are available, short course of empiric treatment with a proton pump inhibitor is widely used in adults as a diagnostic test. Data about empiric treatment is scarce in children. The aim of this study is to evaluate the effectiveness of empiric treatment of reflux-like symptoms in children. Pediatric gastroenterology outpatient files were searched and patients with a diagnosis of gastroesophageal reflux were found. Patient complaints, history and the treatments provided were recorded. Treatment naive patients older than 2 years of age with symptoms suggestive of gastroesophageal reflux were selected and included if they were given empiric treatment with a proton pump inhibitor. Empiric treatment was found to be effective in 78% of patients. Treatment response tended to be better in children older than 5 years of age. Of the 22 non-responders 9 underwent endoscopy and pathological findings were discovered in 7 of them. Treatment of children with gastroesophageal reflux symptoms with a proton pump inhibitor might significantly decrease the need for extensive evaluations. However it is important to investigate non-responders to empiric therapy, as it seems there might be high probability of pathological findings. PMID:27411415

  15. Implications of over-the-counter proton pump inhibitors for patient counseling by pharmacists.

    PubMed

    Simonson, William

    2013-01-01

    The article reviews the literature on the role of the pharmacist in patient counseling and discusses how that role may apply to patients with frequent heartburn who are seeking an over-the-counter (OTC) treatment. Searches of the National Library of Medicine PubMed database were conducted using the terms "heartburn," "nonprescription," "therapy," "pharmacist," and "counseling," supplemented by additional searches on counseling for prescription products, and by the author's knowledge of pharmacy practice and the scientific literature. Accurate recognition of the signs of heartburn are an important first step in counseling a patient on the appropriate OTC medication; immediate referral to a health care provider is mandatory if cardiac pain or certain gastrointestinal symptoms are present. When counseling a patient about treatments for heartburn, the pharmacist should practice effective listening in an environment that is conducive to communication by the patient. Proton pump inhibitors are effective for the treatment of heartburn; the histamine2 receptor antagonists and antacids should also be considered for appropriate patients. Adverse events have been noted with proton pump inhibitors; however, overall the benefits significantly outweigh the risks and problems are unlikely to arise during the 2-week duration of OTC treatment of heartburn. Pharmacists can provide valuable services to patients with frequent heartburn, particularly with regard to counseling about the condition and appropriate OTC therapy. The availability of numerous OTC products, including antacids, histamine2 receptor antagonists, and proton pump inhibitors, enables pharmacists to fulfill an important clinical role and improve patient satisfaction. PMID:21642828

  16. Pharmacophore generation of 2-substituted benzothiazoles as AdeABC efflux pump inhibitors in A. baumannii.

    PubMed

    Yilmaz, S; Altinkanat-Gelmez, G; Bolelli, K; Guneser-Merdan, D; Over-Hasdemir, M U; Yildiz, I; Aki-Yalcin, E; Yalcin, I

    2014-01-01

    RND family efflux pumps are important for multidrug resistance in Gram-negative bacteria. To date no efflux pump inhibitors for clinical use have been found, so developing the specific inhibitors of this pump system will be beneficial for the treatment of infections caused by these multidrug-resistant pathogens. A set of BSN-coded 2-substituted benzothiazoles were tested alone and in combination with ciprofloxacin (CIP) against the RND family efflux pump AdeABC overexpressor Acinetobacter baumannii SbMox-2 strain. The results indicated that the BSN compounds did not have antimicrobial activity when tested alone. However, if they were applied in combination with CIP, it was observed that the antibiotic had antimicrobial activity against the tested pathogen, possessing a minimum inhibitory concentration value that could be utilized in clinical treatment. A 3D-common features pharmacophore model was applied by using the HipHop method and the generated pharmacophore hypothesis revealed that the hydrogen bond acceptor property of nitrogen in the thiazole ring and the oxygen of the amide substituted at the second position of the benzothiazole ring system were significant for binding to the target protein. Moreover, three hydrophobic aromatic features were found to be essential for inhibitory activity. PMID:24905472

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

    SciTech Connect

    Becker, Jan C. . E-mail: beckeja@uni-muenster.de; Grosser, Nina; Waltke, Christian; Schulz, Stephanie; Erdmann, Kati; Domschke, Wolfram; Schroeder, Henning; Pohle, Thorsten

    2006-07-07

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

  18. Efflux pump inhibitors (EPIs) as new antimicrobial agents against Pseudomonas aeruginosa

    PubMed Central

    Askoura, Momen; Mottawea, Walid; Abujamel, Turki; Taher, Ibrahim

    2011-01-01

    Pseudomonas aeruginosa is an opportunistic human pathogen and one of the leading causes of nosocomial infections worldwide. The difficulty in treatment of pseudomonas infections arises from being multidrug resistant (MDR) and exhibits resistance to most antimicrobial agents due to the expression of different mechanisms overcoming their effects. Of these resistance mechanisms, the active efflux pumps in Pseudomonas aeruginosa that belong to the resistance nodulation division (RND) plays a very important role in extruding the antibiotics outside the bacterial cells providing a protective means against their antibacterial activity. Beside its role against the antimicrobial agents, these pumps can extrude biocides, detergents, and other metabolic inhibitors. It is clear that efflux pumps can be targets for new antimicrobial agents. Peptidomimetic compounds such as phenylalanine arginyl β-naphthylamide (PAβN) have been introduced as efflux pump inhibitors (EPIs); their mechanism of action is through competitive inhibition with antibiotics on the efflux pump resulting in increased intracellular concentration of antibiotic, hence, restoring its antibacterial activity. The advantage of EPIs is the difficulty to develop bacterial resistance against them, but the disadvantage is their toxic property hindering their clinical application. The structure activity relationship of these compounds showed other derivatives from PAβN that are higher in their activity with higher solubility in biological fluids and decreased toxicity level. This raises further questions on how can we compact Pseudomonas infections. Of particular importance, the recent resurgence in the use of older antibiotics such as polymyxins and probably applying stricter control measures in order to prevent their spread in clinical sittings. PMID:21594004

  19. Pgp efflux pump decreases the cytostatic effect of CENP-E inhibitor GSK923295.

    PubMed

    Tcherniuk, Sergey O; Oleinikov, Andrew V

    2015-05-28

    Human kinesin CENP-E is an attractive target for cancer chemotherapy. The allosteric CENP-E inhibitor GSK923295 was proposed as a promising anticancer compound with potent cytostatic effect. In our work, we have analyzed the influence of the Pgp efflux pump on the cytostatic effect of GSK923295. We have demonstrated that multidrug resistant MESSA Dx5 cells overexpressing Pgp are 70-80 times more resistant to GSK923295 than their parental counterpart MESSA cells. Addition of 20 µM verapamil restored the drug sensibility of MESSA Dx5 cells. Combinations of GSK923295 with verapamil showed nearly additive effects in MESSA and synergistic effects in MESSA Dx5 cells. Our results demonstrate that tumors possessing Pgp could be more resistant to GSK923295, and that overexpression of Pgp can decrease the therapeutic effect of this drug. Development of structural analogs of GSK923295 which would not be a substrate of the Pgp efflux pump or addition of Pgp pump inhibitors can significantly improve the cytostatic effect of this drug. PMID:25725449

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

    PubMed Central

    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

    Objective: 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. Methods: 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. Results: 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 <0.001).The annual justified cost was estimated to be US$ 1,654,701 and the unjustified cost was estimated to be U.S. $2,202,590, as calculated using the minimum reference prices. Discussion: Each month, the Colombian health system is overloaded by unjustified costs that include payments for non-approved indications of proton pump inhibitors and for drugs outside the list of essential medications. This issue is contributing to rising costs of healthcare in Colombia. PMID:24892316

  1. Identification of Acinetobacter baumannii Serum-Associated Antibiotic Efflux Pump Inhibitors

    PubMed Central

    Blanchard, Catlyn; Barnett, Pamela; Perlmutter, Jessamyn

    2014-01-01

    Adaptive antibiotic resistance is a newly described phenomenon by which Acinetobacter baumannii induces efflux pump activity in response to host-associated environmental cues that may, in part, account for antibiotic treatment failures against clinically defined susceptible strains. To that end, during adaptation to growth in human serum, the organism induces approximately 22 putative efflux-associated genes and displays efflux-mediated minocycline tolerance at antibiotic concentrations corresponding to patient serum levels. Here, we show that in addition to minocycline, growth in human serum elicits A. baumannii efflux-mediated tolerance to the antibiotics ciprofloxacin, meropenem, tetracycline, and tigecycline. Moreover, using a whole-cell high-throughput screen and secondary assays, we identified novel serum-associated antibiotic efflux inhibitors that potentiated the activities of antibiotics toward serum-grown A. baumannii. Two compounds, Acinetobacter baumannii efflux pump inhibitor 1 (ABEPI1) [(E)-4-((4-chlorobenzylidene)amino)benezenesulfonamide] and ABEPI2 [N-tert-butyl-2-(1-tert-butyltetrazol-5-yl)sulfanylacetamide], were shown to lead to minocycline accumulation within A. baumannii during serum growth and inhibit the efflux potential of the organism. While both compounds also inhibited the antibiotic efflux properties of the bacterial pathogen Pseudomonas aeruginosa, they did not display significant cytotoxicity toward human cells or mammalian Ca2+ channel inhibitory effects, suggesting that ABEPI1 and ABEPI2 represent promising structural scaffolds for the development of new classes of bacterial antibiotic efflux pump inhibitors that can be used to potentiate the activities of current and future antibiotics for the therapeutic intervention of Gram-negative bacterial infections. PMID:25114126

  2. [Chronic use of proton pump inhibitors: is the risk of osteoporosis and fractures real?].

    PubMed

    Martí-Cabrera, Miguel; Martí-Masanet, Miguel; Esplugues, Juan V

    2011-04-01

    Proton pump inhibitors (PPI) are one of the most widely used groups of drugs and their potential toxicity is periodically reviewed, emphasizing aspects originally considered secondary. The present review analyzes the physiological and pharmacological bases and the scarce clinical evidence for a potential association between the continued administration of PPI and the development of osteoporosis and bone fractures. Both disorders are clearly related to calcium homeostasis and are highly important in elderly patients due to their poor general prognosis and disabling consequences. PMID:21419526

  3. Antagonism of Fluconazole and a Proton Pump Inhibitor against Candida albicans

    PubMed Central

    Liu, Ning-Ning

    2015-01-01

    Hospitalized ill patients, at risk for invasive candidiasis, often receive multiple medications, including proton pump inhibitors (PPIs). The antifungal fluconazole perturbs the vacuolar proton ATPase. The PPI omeprazole antagonized Candida albicans growth inhibition by fluconazole. A C. albicans codon-adapted pHluorin, Ca.pHluorin, was generated to measure cytosolic pH. The fungal cytosol was acidified by omeprazole and realkalinized by coexposure to fluconazole. Vacuolar pH was alkalinized by fluconazole. Off-target effects of any medication on fungal pathogens may occur. PMID:26596946

  4. Effects of Efflux Pump Inhibitors on Colistin Resistance in Multidrug-Resistant Gram-Negative Bacteria.

    PubMed

    Ni, Wentao; Li, Yanjun; Guan, Jie; Zhao, Jin; Cui, Junchang; Wang, Rui; Liu, Youning

    2016-05-01

    We tested the effects of various putative efflux pump inhibitors on colistin resistance in multidrug-resistant Gram-negative bacteria. Addition of 10 mg/liter cyanide 3-chlorophenylhydrazone (CCCP) to the test medium could significantly decrease the MICs of colistin-resistant strains. Time-kill assays showed CCCP could reverse colistin resistance and inhibit the regrowth of the resistant subpopulation, especially in Acinetobacter baumannii and Stenotrophomonas maltophilia These results suggest colistin resistance in Gram-negative bacteria can be suppressed and reversed by CCCP. PMID:26953203

  5. Hypomagnesaemia associated with long-term use of proton pump inhibitors

    PubMed Central

    Toh, James Wei Tatt; Ong, Evonne; Wilson, Robert

    2015-01-01

    Hypomagnesaemia and associated hypocalcaemia and hypoparathyroidism have been increasingly recognised as rare long-term side-effects of proton pump inhibitors (PPIs). The PPIs may inhibit active magnesium (Mg) absorption by interfering with transcellular transient receptor potential melastatin-6 and -7 (TRPM 6 and 7) channels. More recent cell culture studies have suggested concomitant inhibition of passive Mg absorption by omeprazole. After being treated with a range of PPIs, the four patients in our case series developed hypomagnesaemia, which responded to withdrawal of therapy and initiation of Mg replacement. Their clinical course and management demonstrate key aspects of hypomagnesaemia associated with long-term use of PPIs. PMID:25138239

  6. Evidence-based assessment of proton-pump inhibitors in Helicobacter pylori eradication: A systematic review

    PubMed Central

    Nagaraja, Vinayak; Eslick, Guy D

    2014-01-01

    Peptic ulcer disease continues to be issue especially due to its high prevalence in the developing world. Helicobacter pylori (H. pylori) infection associated duodenal ulcers should undergo eradication therapy. There are many regimens offered for H. pylori eradication which include triple, quadruple, or sequential therapy regimens. The central aim of this systematic review is to evaluate the evidence for H. pylori therapy from a meta-analytical outlook. The consequence of the dose, type of proton-pump inhibitor, and the length of the treatment will be debated. The most important risk factor for eradication failure is resistance to clarithromycin and metronidazole. PMID:25356018

  7. Allosteric inhibitors of plasma membrane Ca pumps: Invention and applications of caloxins.

    PubMed

    Pande, Jyoti; Szewczyk, Magdalena M; Grover, Ashok K

    2011-03-26

    Plasma membrane Ca(2+) pumps (PMCA) play a major role in Ca(2+) homeostasis and signaling by extruding cellular Ca(2+) with high affinity. PMCA isoforms are encoded by four genes which are expressed differentially in various cell types in normal and disease states. Therefore, PMCA isoform selective inhibitors would aid in delineating their role in physiology and pathophysiology. We are testing the hypothesis that extracellular domains of PMCA can be used as allosteric targets to obtain a novel class of PMCA-specific inhibitors termed caloxins. This review presents the concepts behind the invention of caloxins and our progress in this area. A section is also devoted to the applications of caloxins in literature. We anticipate that isoform-selective caloxins will aid in understanding PMCA physiology in health and disease. With strategies to develop therapeutics from bioactive peptides, caloxins may become clinically useful in cardiovascular diseases, neurological disorders, retinopathy, cancer and contraception. PMID:21537489

  8. Repeated Administration of Inhibitors for Ion Pumps Reduce Markedly Tumor Growth in Vivo

    PubMed Central

    Hrgovic, Igor; Glavic, Zeljko; Kovacic, Zeljko; Mulic, Smaila; Zunic, Lejla; Hrgovic, Zlatko

    2014-01-01

    ABSTRACT Introduction: Measurements of extracellular pH show that the micro environment of malignant tumors is more acidic than that of normal cells, whereas pH does not differ appreciable in normal and malignant cells. The acid micro environment of tumors is created by the secretion of tumor factors and ATP hydrolysis in hypoxic tumor tissue. In order to survive in a low pH-environment tumor cells develop regulatory mechanisms which keep their intracellular pH stable. Two of the most important systems are the Na+/H+ ion pump and the Na-dependent HCO3-/Cl- pump of stilbenian derivatives. Material and methods: Experiments were carried out on DBA mice of both sexes at the age of 4 month. Laboratory animals were grown in our institute and supplied with food and aqua ad libitum. Results: After termination of the experiments the mean tumor diameter in the control group was 12.4±0.8mm, in group A it was 6.9±0.6mm, and in group B we measured 6.6±3.1mm. At the final day the tumor size in treated animals was twice as small as in the control group. In addition we observed the rate of survival. In the control group only 18% of the animals were still alive at day 18. Considering the rate of survival a statistically significant difference between treated and untreated animals was observed. The survival of tumor cells is dependent on the function of these ion pumps which keep their intracellular pH values constant in the setting of an acid extracellular environment. Conclusion: The activity of the ion pump is especially important at the beginning of cell division and in cell proliferation. Our in vivo experiments demonstrate that prolonged administration of intratumoral ion pump inhibitors suppresses tumor growth as well as enhances survival of tumor-bearing animals. Research of inhibitors of ion pumps and their action in tumor growth opens new perspectives into pathophysiology of malignant tumors and may create new therapeutic options. PMID:24937925

  9. Virtual screening for novel Staphylococcus Aureus NorA efflux pump inhibitors from natural products.

    PubMed

    Thai, Khac-Minh; Ngo, Trieu-Du; Phan, Thien-Vy; Tran, Thanh-Dao; Nguyen, Ngoc-Vinh; Nguyen, Thien-Hai; Le, Minh-Tri

    2015-01-01

    NorA is a member of the Major Facilitator Superfamily (MFS) drug efflux pumps that have been shown to mediate antibiotic resistance in Staphylococcus aureus (SA). In this study, QSAR analysis, virtual screening and molecular docking were implemented in an effort to discover novel SA NorA efflux pump inhibitors. Originally, a set of 47 structurally diverse compounds compiled from the literature was used to develop linear QSAR models and another set of 15 different compounds were chosen for extra validation. The final model which was estimated by statistical values for the full data set (n = 45, Q(2) = 0.80, RMSE = 0.20) and for the external test set (n = 15, R(2) = 0.60, |res|max = 0.75, |res|min = 0.02) was applied on the collection of 182 flavonoides and the traditional Chinese medicine (TCM) database to screen for novel NorA inhibitors. Finally, 33 lead compounds that met the Lipinski's rules of five/three and had good predicted pIC50 values from in silico screening process were employed to analyze the binding ability by docking studies on NorA homology model in place of its unavailable crystal structures at two active sites, the central channel and the Walker B. PMID:25181985

  10. Proton-pump inhibitors in patients requiring antiplatelet therapy: new FDA labeling.

    PubMed

    Johnson, David A; Chilton, Robert; Liker, Harley R

    2014-05-01

    Proton-pump inhibitors (PPIs) are recommended for patients who require antiplatelet therapy and have a history of upper gastrointestinal bleeding. Proton-pump inhibitors should also be considered for patients receiving antiplatelet therapy who have other risk factors for gastrointestinal bleeding, including use of aspirin. Thus, evidence of pharmacokinetic and pharmacodynamic interactions between PPIs and consequent impaired effectiveness of the antiplatelet agent clopidogrel has caused concern. Here, we discuss comparative studies suggesting that the extent to which a PPI reduces exposure to the active metabolite of clopidogrel and attenuates its antithrombotic effect differs among PPIs. Although a clinically meaningful effect of the interaction between PPIs and clopidogrel on cardiovascular outcomes has not been established, these studies provided the basis for recent changes in US Food and Drug Administration (FDA) labeling for several PPIs and clopidogrel. New labeling suggests that PPI use among patients taking clopidogrel be limited to pantoprazole, rabeprazole, lansoprazole, or dexlansoprazole. Because comparative studies indicate that omeprazole and esomeprazole have a greater effect on the CYP2C19-mediated conversion of clopidogrel to its active metabolite and, consequently, clopidogrel's effect on platelet reactivity, FDA labeling recommends avoiding omeprazole and esomeprazole in patients taking clopidogrel. Even a 12-hour separation of dosing does not appear to prevent drug interactions between omeprazole and clopidogrel. PMID:24918808

  11. Pharmacodynamic effects of antibiotics and acid pump inhibitors on Helicobacter pylori.

    PubMed Central

    Sörberg, M; Hanberger, H; Nilsson, M; Nilsson, L E

    1997-01-01

    Pharmacodynamic studies of Helicobacter pylori exposed to amoxicillin, clarithromycin, metronidazole, omeprazole, and lansoprazole were performed with microscopy, viable count determination, and bioluminescence assay of intracellular ATP. The pharmacodynamic parameters determined were change in morphology, change in cell density, postantibiotic effect (PAE), and control-related effective regrowth time (CERT). The PAE is delayed regrowth after brief exposure to antibiotics or acid pump inhibitors. CERT was defined as the time required for the bacteria to resume logarithmic growth and return to the pre-exposure inoculum in the test culture minus the corresponding time for the control culture. CERT measures the combined effect of initial killing and PAE. There was a good concordance between the bioluminescence assay and viable counts for determining CERT, which makes this parameter useful for pharmacodynamic studies of the effects of antibiotics and acid pump inhibitors on H. pylori. Amoxicillin and metronidazole produced a strong, concentration-dependent initial decrease in CFU per milliliter, but there was a less prominent initial change in intracellular ATP in these cultures. Amoxicillin caused a long PAE when assayed by the bioluminescence assay but no PAE or a negative PAE when assayed by viable count determination. However, amoxicillin showed similar long CERTs with both methods. The pharmacodynamic effects of amoxicillin were concentration dependent up to a maximum response, indicating that concentrations above this level do not increase the antibiotic effect. The PAEs and CERTs of clarithromycin and metronidazole were concentration dependent with no maximum response. With omeprazole and lanzoprazole, there was no PAE or CERT. PMID:9333051

  12. Interdomain communication in calcium pump as revealed in the crystal structures with transmembrane inhibitors

    PubMed Central

    Takahashi, Mihoko; Kondou, Youhei; Toyoshima, Chikashi

    2007-01-01

    Ca2+-ATPase of skeletal muscle sarcoplasmic reticulum is an ATP-driven Ca2+ pump consisting of three cytoplasmic domains and 10 transmembrane helices. In the absence of Ca2+, the three cytoplasmic domains gather to form a compact headpiece, but the ATPase is unstable without an inhibitor. Here we describe the crystal structures of Ca2+-ATPase in the absence of Ca2+ stabilized with cyclopiazonic acid alone and in combination with other inhibitors. Cyclopiazonic acid is located in the transmembrane region of the protein near the cytoplasmic surface. The binding site partially overlaps with that of 2,5-di-tert-butyl-1,4-dihydroxybenzene but is separate from that of thapsigargin. The overall structure is significantly different from that stabilized with thapsigargin: The cytoplasmic headpiece is more upright, and the transmembrane helices M1–M4 are rearranged. Cyclopiazonic acid primarily alters the position of the M1′ helix and thereby M2 and M4 and then M5. Because M5 is integrated into the phosphorylation domain, the whole cytoplasmic headpiece moves. These structural changes show how an event in the transmembrane domain can be transmitted to the cytoplasmic domain despite flexible links between them. They also reveal that Ca2+-ATPase has considerable plasticity even when fixed by a transmembrane inhibitor, presumably to accommodate thermal fluctuations. PMID:17389383

  13. Liquid chromatographic assay for metronidazole and tinidazole: pharmacokinetic and metabolic studies in human subjects.

    PubMed Central

    Nilsson-Ehle, I; Ursing, B; Nilsson-Ehle, P

    1981-01-01

    We developed methods for measuring metronidazole, its two major metabolites, and tinidazole in serum and urine. After treatment of each sample with an equal volume of 5% perchloric acid, the drugs were separated by reverse-phase high-pressure liquid chromatography (retention times, 6 to 18 min). Quantitation was based on spectrometry at 320 nm. These assays were sensitive, rapid, and specific, and recoveries from biological samples were quantitative. Metronidazole and tinidazole were given as rapid intravenous infusions to four healthy human volunteers. The biological half-lives of these two compounds were 5.4 and 11.1 h, respectively. The hydroxy metabolite of metronidazole appeared quickly in serum and was eliminated at a slow rate. The acetic acid metabolite of metronidazole was detected in serum at very low levels and only for a limited time. No metabolic products of tinidazole were found in serum samples. In urine, 43.7% of the administered dose of metronidazole was recovered over a period of 24 h (24.1% of the dose as the hydroxy metabolite, 12.0% as the acetic acid metabolite, and 7.6% as unchanged drug). Only 18.4% of the infused dose of tinidazole was eliminated in urine over a period of 72 h, and no metabolic products were detected. PMID:7294765

  14. Molecular Mechanism of MBX2319 Inhibition of Escherichia coli AcrB Multidrug Efflux Pump and Comparison with Other Inhibitors

    PubMed Central

    Vargiu, Attilio V.; Ruggerone, Paolo; Opperman, Timothy J.; Nguyen, Son T.

    2014-01-01

    Efflux pumps of the resistance nodulation division (RND) superfamily, such as AcrB, make a major contribution to multidrug resistance in Gram-negative bacteria. The development of inhibitors of the RND pumps would improve the efficacy of current and next-generation antibiotics. To date, however, only one inhibitor has been cocrystallized with AcrB. Thus, in silico structure-based analysis is essential for elucidating the interaction between other inhibitors and the efflux pumps. In this work, we used computer docking and molecular dynamics simulations to study the interaction between AcrB and the compound MBX2319, a novel pyranopyridine efflux pump inhibitor with potent activity against RND efflux pumps of Enterobacteriaceae species, as well as other known inhibitors (D13-9001, 1-[1-naphthylmethyl]-piperazine, and phenylalanylarginine-β-naphthylamide) and the binding of doxorubicin to the efflux-defective F610A variant of AcrB. We also analyzed the binding of a substrate, minocycline, for comparison. Our results show that MBX2319 binds very tightly to the lower part of the distal pocket in the B protomer of AcrB, strongly interacting with the phenylalanines lining the hydrophobic trap, where the hydrophobic portion of D13-9001 was found to bind by X-ray crystallography. Additionally, MBX2319 binds to AcrB in a manner that is similar to the way in which doxorubicin binds to the F610A variant of AcrB. In contrast, 1-(1-naphthylmethyl)-piperazine and phenylalanylarginine-β-naphthylamide appear to bind to somewhat different areas of the distal pocket in the B protomer of AcrB than does MBX2319. However, all inhibitors (except D13-9001) appear to distort the structure of the distal pocket, impairing the proper binding of substrates. PMID:25114133

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

    PubMed

    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. PMID:26242498

  16. Magnesium Deficiency and Proton-Pump Inhibitor Use: A Clinical Review.

    PubMed

    William, Jeffrey H; Danziger, John

    2016-06-01

    The association of proton-pump inhibitor (PPI) use and hypomagnesemia has garnered much attention over the last 5 years. A large body of observational data has linked chronic PPI use with hypomagnesemia, presumably due to decreased intestinal absorption and consequent magnesium deficiency. However, despite the increasing prevalence of this highly popular class of medicine, and despite potential significant risks associated with magnesium depletion, including cardiac arrhythmias and seizures, there are no well-designed studies to delineate the nature of this observed association. Consequently, providers must use best judgment to inform clinical decision making. This review summarizes the current body of evidence linking PPI use with hypomagnesemia, acknowledges the possibility of significant residual confounding in the observational data, explains potential physiologic mechanisms, and offers clinical recommendations. PMID:26582556

  17. Proton-pump inhibitor-induced hypomagnesemia: Current research and proposed mechanisms

    PubMed Central

    William, Jeffrey H; Danziger, John

    2016-01-01

    Since the early reports nearly a decade ago, proton-pump inhibitor-induced hypomagnesemia (PPIH) has become a well-recognized phenomenon. While many observational studies in the inpatient and outpatient populations have confirmed the association of PPI exposure and serum magnesium concentrations, there are no prospective, controlled studies to support causation. Molecular mechanisms of magnesium transporters, including the pH-dependent regulation of transient receptor potential melastatin-6 transporters in the colonic enterocyte, have been proposed to explain the effect of PPIs on magnesium reabsorption, but may be a small part of a more complicated interplay of molecular biology, pharmacology, and genetic predisposition. This review explores the current state of research in the field of PPIH and the proposed mechanisms of this effect. PMID:26981439

  18. The role of proton pump inhibitor therapy in the management of eosinophilic esophagitis.

    PubMed

    Molina-Infante, Javier; Prados-Manzano, Raul; Gonzalez-Cordero, Pedro Luis

    2016-09-01

    Eosinophilic esophagitis (EoE) is a chronic esophageal disease characterized by a Th2 inflammatory response triggered by food/environmental allergens. Solid data confirm that up to half of patients with suspected EoE achieve complete remission on proton pump inhibitors (PPI) therapy. This disease phenotype is currently labelled as PPI-responsive esophageal eosinophilia (PPI-REE). Albeit initially believed to represent gastro-esophageal reflux disease (GERD), evolving evidence has underscored that PPI-REE and EoE show a significant overlap regarding clinic, endoscopic, histologic, Th2 immune-mediated inflammation and gene expression features. Moreover, PPI therapy can effectively reverse Th2 inflammation and the EoE transcriptome expression in PPI-REE patients. Therefore, EoE and PPI-REE likely represent a common allergic disorder, where PPI therapy should be considered a short- and long-term therapeutic asset, along with diet and topical steroids. PMID:27097787

  19. Deprescribing in a family health team: a study of chronic proton pump inhibitor use.

    PubMed

    Walsh, Kate; Kwan, Debbie; Marr, Patricia; Papoushek, Christine; Lyon, W Kirk

    2016-06-01

    BACKGROUND Proton pump inhibitors (PPIs) are often used inappropriately, without an indication, or for longer durations than recommended. Few tools exist to guide reassessment of their continued use and deprescribing if required. We aimed to reduce inappropriate drug use by developing and implementing a PPI deprescribing tool and process in a family medicine unit. ASSESSMENT OF PROBLEM Primary care providers of adults taking a PPI for 8 weeks with an upcoming periodic health examination were reminded to reassess therapy via electronic medical record (EMR) messaging. A PPI Deprescribing Tool was uploaded into the EMR as a second reminder and to guide reassessment and deprescribing where indicated. Ten weeks after the examination a chart review assessed changes to PPI use. A follow up survey of providers assessed the utility and barriers to implementing the Deprescribing Tool. RESULTS Forty-three of 46 patients on PPIs (93%) had their PPI reassessed, resulting in 11 patients (26%) having their PPI deprescribed. Strategies for Improvement Routine reassessment of long-term medications is often overlooked because of extensive demands on primary care providers' time. Deprescribing likely improved because potentially eligible patients were identified to the provider and a tool was provided at the time of the encounter to guide the deprescribing process. LESSONS Reassessment and deprescribing of PPIs can be supported by implementing a standardised process and use of guidance tools for clinicians. Providers found the timely and selective reminder message to deprescribe the most useful component of the intervention. KEYWORDS proton pump inhibitor; deprescribing; reassessment; primary care; medication therapy management; gastroesophageal reflux disease. PMID:27477559

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

    PubMed Central

    Drepper, Michael D; Spahr, Laurent; Frossard, Jean Louis

    2012-01-01

    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. PMID:22611308

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

    PubMed Central

    Otremba, Iwona; Wilczyński, Krzysztof; Szewieczek, Jan

    2016-01-01

    Background Delirium remains a major nosocomial complication of hospitalized elderly. Predictive models for delirium may be useful for identification of high-risk patients for implementation of preventive strategies. Objective Evaluate specific factors for development of delirium in a geriatric ward setting. Methods Prospective cross-sectional study comprised 675 consecutive patients aged 79.2±7.7 years (66% women and 34% men), admitted to the subacute geriatric ward of a multiprofile university hospital after exclusion of 113 patients treated with antipsychotic medication because of behavioral disorders before admission. Comprehensive geriatric assessments including a structured interview, physical examination, geriatric functional assessment, blood sampling, ECG, abdominal ultrasound, chest X-ray, Confusion Assessment Method for diagnosis of delirium, Delirium-O-Meter to assess delirium severity, Richmond Agitation-Sedation Scale to assess sedation or agitation, visual analog scale and Doloplus-2 scale to assess pain level were performed. Results Multivariate logistic regression analysis revealed five independent factors associated with development of delirium in geriatric inpatients: transfer between hospital wards (odds ratio [OR] =2.78; confidence interval [CI] =1.54–5.01; P=0.001), preexisting dementia (OR =2.29; CI =1.44–3.65; P<0.001), previous delirium incidents (OR =2.23; CI =1.47–3.38; P<0.001), previous fall incidents (OR =1.76; CI =1.17–2.64; P=0.006), and use of proton-pump inhibitors (OR =1.67; CI =1.11–2.53; P=0.014). Conclusion Transfer between hospital wards, preexisting dementia, previous delirium incidents, previous fall incidents, and use of proton-pump inhibitors are predictive of development of delirium in the geriatric inpatient setting. PMID:27103793

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

    PubMed Central

    Hess, Mark W.; de Baaij, Jeroen H. F.; Gommers, Lisanne M. M.; Hoenderop, Joost G. J.; Bindels, René 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 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. Methods 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. Results 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. Conclusions 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. PMID:26397986

  3. Characterization of a Novel Pyranopyridine Inhibitor of the AcrAB Efflux Pump of Escherichia coli

    PubMed Central

    Kwasny, Steven M.; Kim, Hong-Suk; Nguyen, Son T.; Houseweart, Chad; D'Souza, Sanjay; Walker, Graham C.; Peet, Norton P.; Nikaido, Hiroshi; Bowlin, Terry L.

    2014-01-01

    Members of the resistance-nodulation-division (RND) family of efflux pumps, such as AcrAB-TolC of Escherichia coli, play major roles in multidrug resistance (MDR) in Gram-negative bacteria. A strategy for combating MDR is to develop efflux pump inhibitors (EPIs) for use in combination with an antibacterial agent. Here, we describe MBX2319, a novel pyranopyridine EPI with potent activity against RND efflux pumps of the Enterobacteriaceae. MBX2319 decreased the MICs of ciprofloxacin (CIP), levofloxacin, and piperacillin versus E. coli AB1157 by 2-, 4-, and 8-fold, respectively, but did not exhibit antibacterial activity alone and was not active against AcrAB-TolC-deficient strains. MBX2319 (3.13 μM) in combination with 0.016 μg/ml CIP (minimally bactericidal) decreased the viability (CFU/ml) of E. coli AB1157 by 10,000-fold after 4 h of exposure, in comparison with 0.016 μg/ml CIP alone. In contrast, phenyl-arginine-β-naphthylamide (PAβN), a known EPI, did not increase the bactericidal activity of 0.016 μg/ml CIP at concentrations as high as 100 μM. MBX2319 increased intracellular accumulation of the fluorescent dye Hoechst 33342 in wild-type but not AcrAB-TolC-deficient strains and did not perturb the transmembrane proton gradient. MBX2319 was broadly active against Enterobacteriaceae species and Pseudomonas aeruginosa. MBX2319 is a potent EPI with possible utility as an adjunctive therapeutic agent for the treatment of infections caused by Gram-negative pathogens. PMID:24247144

  4. Identification of Inhibitors of V-ATPase Pumps in Yeast by HTS Flow Cytometry

    PubMed Central

    Johnson, Rebecca M.; Allen, Chris; Melman, Sandra D.; Waller, Anna; Young, Susan M.; Sklar, Larry A.; Parra, Karlett J.

    2010-01-01

    Fluorescence intensity of the pH-sensitive carboxyfluorescein derivative BCECF was monitored by high throughput flow cytometry in living yeast cells. We measured fluorescence intensity of BCECF trapped in yeast vacuoles, acidic compartments equivalent to lysosomes where V-ATPases are abundant. Because V-ATPases maintain a low pH in the vacuolar lumen, V-ATPase inhibition by concanamycin A alkalinized the vacuole and increased BCECF fluorescence. Likewise, V-ATPase deficient mutant cells had greater fluorescence intensity than wild-type cells. Thus, we detected an increase of fluorescence intensity after short-term and long-term inhibition of V-ATPase function. We used yeast cells loaded with BCECF to screen a small chemical library of structurally diverse compounds in order to identify V-ATPase inhibitors. One compound, disulfiram, enhanced BCECF fluorescence intensity (although to a degree beyond anticipated for pH changes alone in the mutant cells). Once confirmed by dose response assays (EC50=26 μM), we verified V-ATPase inhibition by disulfiram in secondary assays which measured ATP hydrolysis in vacuolar membranes. The inhibitory action of disulfiram against V-ATPase pumps revealed a novel effect previously unknown for this compound. Because V-ATPases are highly conserved, new inhibitors identified could be used as research and therapeutic tools in cancer, viral infections, and other diseases where V-ATPases are involved. PMID:20018164

  5. The efflux pump inhibitor timcodar improves the potency of antimycobacterial agents.

    PubMed

    Grossman, Trudy H; Shoen, Carolyn M; Jones, Steven M; Jones, Peter L; Cynamon, Michael H; Locher, Christopher P

    2015-03-01

    Previous studies indicated that inhibition of efflux pumps augments tuberculosis therapy. In this study, we used timcodar (formerly VX-853) to determine if this efflux pump inhibitor could increase the potency of antituberculosis (anti-TB) drugs against Mycobacterium tuberculosis in in vitro and in vivo combination studies. When used alone, timcodar weakly inhibited M. tuberculosis growth in broth culture (MIC, 19 μg/ml); however, it demonstrated synergism in drug combination studies with rifampin, bedaquiline, and clofazimine but not with other anti-TB agents. When M. tuberculosis was cultured in host macrophage cells, timcodar had about a 10-fold increase (50% inhibitory concentration, 1.9 μg/ml) in the growth inhibition of M. tuberculosis and demonstrated synergy with rifampin, moxifloxacin, and bedaquiline. In a mouse model of tuberculosis lung infection, timcodar potentiated the efficacies of rifampin and isoniazid, conferring 1.0 and 0.4 log10 reductions in bacterial burden in lung, respectively, compared to the efficacy of each drug alone. Furthermore, timcodar reduced the likelihood of a relapse infection when evaluated in a mouse model of long-term, chronic infection with treatment with a combination of rifampin, isoniazid, and timcodar. Although timcodar had no effect on the pharmacokinetics of rifampin in plasma and lung, it did increase the plasma exposure of bedaquiline. These data suggest that the antimycobacterial drug-potentiating activity of timcodar is complex and drug dependent and involves both bacterial and host-targeted mechanisms. Further study of the improvement of the potency of antimycobacterial drugs and drug candidates when used in combination with timcodar is warranted. PMID:25534740

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

    PubMed Central

    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 < 0.001) and individual HLMs (86% versus 76%; P < 0.001). The mean percent change in the 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

  7. In vitro study of the variable effects of proton pump inhibitors on voriconazole.

    PubMed

    Niece, Krista L; Boyd, Natalie K; Akers, Kevin S

    2015-09-01

    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 < 0.001) and individual HLMs (86% versus 76%; P < 0.001). The mean percent change in the 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

  8. Proton pump inhibitors and vascular function: A prospective cross-over pilot study

    PubMed Central

    Ghebremariam, Yohannes T.; Cooke, John P.; Khan, Fouzia; Thakker, Rahul N.; Chang, Peter; Shah, Nigam H.; Nead, Kevin T.; Leeper, Nicholas J.

    2015-01-01

    Background Proton pump inhibitors (PPIs) are commonly used drugs for the treatment of gastric reflux. Recent retrospective cohorts and large database studies have raised concern that the use of PPIs is associated with increased cardiovascular (CV) risk. However, there is no prospective clinical study evaluating whether the use of PPIs directly causes CV harm. Methods We conducted a controlled open-label cross-over pilot study among 21 adults aged 18 and older who are healthy (n = 11) or have established clinical cardiovascular disease (n = 10). Study subjects were assigned to receive a PPI (Prevacid; 30 mg) or a placebo pill once daily for 4 weeks. After a 2 week washout period, participants were crossed-over to receive the alternate treatment for the ensuing 4 weeks. Subjects underwent evaluation of vascular function (by the EndoPAT technique) and had plasma levels of asymmetric dimethylarginine (ADMA, an endogenous inhibitor of endothelial function previously implicated in PPI-mediated risk) measured prior to and after each treatment interval. Results We observed a marginal inverse correlation between the EndoPAT score and plasma levels of ADMA (r = −0.364). Subjects experienced a greater worsening in plasma ADMA levels while on PPI than on placebo, and this trend was more pronounced amongst those subjects with a history of vascular disease. However, these trends did not reach statistical significance, and PPI use was also not associated with an impairment in flow mediated vasodilation during the course of this study. Conclusions In this open-label, cross-over pilot study conducted among healthy subjects and coronary disease patients, PPI use did not significantly influence vascular endothelial function. Larger, long-term and blinded trials are needed to mechanistically explain the correlation between PPI use and adverse clinical outcomes, which has recently been reported in retrospective cohort studies. PMID:25835348

  9. Efflux pump inhibitor potentiates antimicrobial photodynamic inactivation of Enterococcus faecalis biofilm.

    PubMed

    Kishen, Anil; Upadya, Megha; Tegos, George P; Hamblin, Michael R

    2010-01-01

    Microbial biofilm architecture contains numerous protective features, including extracellular polymeric material that render biofilms impermeable to conventional antimicrobial agents. This study evaluated the efficacy of antimicrobial photodynamic inactivation (aPDI) of Enterococcus faecalis biofilms. The ability of a cationic, phenothiazinium photosensitizer, methylene blue (MB) and an anionic, xanthene photosensitizer, rose bengal (RB) to inactivate biofilms of E. faecalis (OG1RF and FA 2-2) and disrupt the biofilm structure was evaluated. Bacterial cells were tested as planktonic suspensions, intact biofilms and biofilm-derived suspensions obtained by the mechanical disruption of biofilms. The role of a specific microbial efflux pump inhibitor (EPI), verapamil hydrochloride in the MB-mediated aPDI of E. faecalis biofilms was also investigated. The results showed that E. faecalis biofilms exhibited significantly higher resistance to aPDI when compared with E. faecalis in suspension (P < 0.001). aPDI with cationic MB produced superior inactivation of E. faecalis strains in a biofilm along with significant destruction of biofilm structure when compared with anionic RB (P < 0.05). The ability to inactivate biofilm bacteria was further enhanced when the EPI was used with MB (P < 0.001). These experiments demonstrated the advantage of a cationic phenothiazinium photosensitizer combined with an EPI to inactivate biofilm bacteria and disrupt biofilm structure. PMID:20860692

  10. Interaction between clopidogrel and proton-pump inhibitors and management strategies in patients with cardiovascular diseases

    PubMed Central

    Gurbel, Paul A; Tantry, Udaya S; Kereiakes, Dean J

    2010-01-01

    Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin has been successful in reducing ischemic events in a wide range of patients with cardiovascular diseases. However, the anti-ischemic effects of DAPT may also be associated with gastrointestinal (GI) complications including ulceration and bleeding particularly in ‘high risk’ and elderly patients. Current guidelines recommend the use of proton-pump inhibitors (PPIs) to reduce the risk of GI bleeding in patients treated with DAPT. However, pharmacodynamic studies suggest an effect of PPIs on clopidogrel metabolism with a resultant reduction in platelet inhibitory effects. Similarly, several observational studies have demonstrated reduced clopidogrel benefit in patients who coadministered PPIs. Although recent US Food and Drug Administration and European Medicines Agency statements discourage PPI (particularly omeprazole) and clopidogrel coadministration, the 2009 AHA/ACC/SCAI PCI guidelines do not support a change in current practice in the absence of adequately powered prospective randomized clinical trial data. The data regarding pharmacologic and clinical interactions between PPI and clopidogrel therapies are herein examined and treatment strategies are provided. PMID:21701635

  11. Is the required therapeutic effect always achieved by racemic switch of proton-pump inhibitors?

    PubMed Central

    Zhou, Quan; Yan, Xiao-Feng; Pan, Wen-Sheng; Zeng, Su

    2008-01-01

    Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers by racemic switch. In a recent study by Pai et al, dexrabeprazole [R(+)-rabeprazole] (10 mg) was found to be more effective than rabeprazole (20 mg) in the treatment of gastroesophageal reflux disease. We read with great interest in this study and discussed whether such racemic switch would be applicable to other proton-pump inhibitors (PPIs). A literature review indicates that stereoselective pharmacokinetics, rather than stereoselective pharmacological activity, is the main cause of differences in clinical efficacy between pure enantiomer and racemic PPI. Racemic switches of PPI provide the therapeutic advantages such as reducing metabolic load on the body, simplifying pharmacokinetics, providing benefit to the non-responders to standard dose of racemate, more homogenous response to treatment and better efficacy with equal safety. Further studies in quantitative structure-activity relationships (QSARs) are needed to address the fact that the preferred enantiomer of PPI is not always in the same absolute configuration, i.e., S-form is for omeprazole, pantoprazole and tenatoprazole whereas R-form is for lansoprazole and rabeprazole. PMID:18442220

  12. Effect of the proton pump inhibitor omeprazole on the gastrointestinal bacterial microbiota of healthy dogs.

    PubMed

    Garcia-Mazcorro, Jose F; Suchodolski, Jan S; Jones, Katherine R; Clark-Price, Stuart C; Dowd, Scot E; Minamoto, Yasushi; Markel, Melissa; Steiner, Jörg M; Dossin, Olivier

    2012-06-01

    The effect of a proton pump inhibitor on gastrointestinal (GI) microbiota was evaluated. Eight healthy 9-month-old dogs (four males and four females) received omeprazole (1.1 mg kg(-1) ) orally twice a day for 15 days. Fecal samples and endoscopic biopsies from the stomach and duodenum were obtained on days 30 and 15 before omeprazole administration, on day 15 (last day of administration), and 15 days after administration. The microbiota was evaluated using 16S rRNA gene 454-pyrosequencing, fluorescence in situ hybridization, and qPCR. In the stomach, pyrosequencing revealed a decrease in Helicobacter spp. during omeprazole (median 92% of sequences during administration compared to > 98% before and after administration; P = 0.0336), which was accompanied by higher proportions of Firmicutes and Fusobacteria. FISH confirmed this decrease in gastric Helicobacter (P < 0.0001) and showed an increase in total bacteria in the duodenum (P = 0.0033) during omeprazole. However, Unifrac analysis showed that omeprazole administration did not significantly alter the overall phylogenetic composition of the gastric and duodenal microbiota. In feces, qPCR showed an increase in Lactobacillus spp. during omeprazole (P < 0.0001), which was accompanied by a lower abundance of Faecalibacterium spp. and Bacteroides-Prevotella-Porphyromonas in the male dogs. This study suggests that omeprazole administration leads to quantitative changes in GI microbiota of healthy dogs. PMID:22324305

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

    PubMed Central

    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

  14. Antisecretory and antiulcer effect of T-330, a novel reversible proton pump inhibitor, in rats.

    PubMed

    Kinoshita, M; Saito, N; Tamaki, H

    1997-03-01

    The antisecretory and antiulcer effects of T-330 (2-[(2-dimethylaminobenzyl)sulfinyl]-1-(3-methylpyridine-2-yl)imidazole) , a novel reversible proton pump inhibitor, were studied in rats. T-330 suppressed dibutyryl cyclic AMP-stimulated acid formation in isolated rat gastric mucosal cells with the IC50 value of 0.57 microM. In chronic fistula rats, intravenous, intraduodenal and oral administration of T-330 inhibited pentagastrin-stimulated gastric acid secretion; the ED50 values calculated from the peak inhibition were 0.36, 0.43 and 0.73 mg/kg, respectively. T-330 also reduced dimaprit-stimulated gastric acid secretion following its intraduodenal injection (ED50 0.85 mg/kg). The antisecretory activities of T-330 following its intraduodenal and oral administration were 3-6- and 4-10-times more potent than those of omeprazole and ranitidine, respectively, while the duration of action of T-330 was apparently shorter than that of omeprazole and was almost equal to that of ranitidine. Oral or duodenal administration of T-330 inhibited the development of acid-related damage (water-immersion- and aspirin-induced gastric lesions, cysteamine-induced duodenal ulcers and reflux esophagitis) with equal or higher potency than omeprazole or ranitidine. Furthermore, T-330 prevented ethanol-induced gastric lesions. These findings indicate that T-330 exerts its antiulcer effect mainly via its potent antisecretory action and partly via its gastroprotective action. PMID:9085044

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

    PubMed

    Fais, Stefano

    2015-01-01

    'We can only cure what we can understand first', said Otto H. Warburg, the 1931 Nobel laureate for his discovery on tumor metabolism. Unfortunately, we still don't know too much the mechanisms underlying of cancer development and progression. One of the unsolved mystery includes the strategies that cancer cells adopt to cope with an adverse microenvironment. However, we knew, from the Warburg's discovery, that through their metabolism based on sugar fermentation, cancer cells acidify their microenvironment and this progressive acidification induces a selective pressure, leading to development of very malignant cells entirely armed to survive in the hostile microenvironment generated by their own metabolism. One of the most mechanism to survive to the acidic tumor microenvironment are proton exchangers not allowing intracellular acidification through a continuous elimination of H(+) either outside the cells or within the internal vacuoles. This article wants to comment a translational process through which from the preclinical demonstration that a class of proton pump inhibitors (PPI) exploited worldwide for peptic ulcer treatment and gastroprotection are indeed chemosensitizers as well, we have got to the clinical proof of concept that PPI may well be included in new anti-cancer strategies, and with a solid background and rationale. PMID:26597250

  16. What are the effects of proton pump inhibitors on the small intestine?

    PubMed Central

    Fujimori, Shunji

    2015-01-01

    Generally, proton-pump inhibitors (PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestinal bacterial flora, exacerbating nonsteroidal anti-inflammatory drug-induced small intestinal injury. Several meta-analyses and systematic reviews have reported that patients treated with PPIs, as well as post-gastrectomy patients, have a higher frequency of small intestinal bacterial overgrowth (SIBO) compared to patients who lack the aforementioned conditions. Furthermore, there is insufficient evidence that these conditions induce Clostridium difficile infection. At this time, PPI-induced dysbiosis is considered a type of SIBO. It now seems likely that intestinal bacterial flora influence many diseases, such as inflammatory bowel disease, diabetes mellitus, obesity, non-alcoholic fatty liver disease, and autoimmune diseases. When attempting to control intestinal bacterial flora with probiotics, prebiotics, and fecal microbiota transplantation, etc., the influence of acid suppression therapy, especially PPIs, should not be overlooked. PMID:26078557

  17. What are the effects of proton pump inhibitors on the small intestine?

    PubMed

    Fujimori, Shunji

    2015-06-14

    Generally, proton-pump inhibitors (PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestinal bacterial flora, exacerbating nonsteroidal anti-inflammatory drug-induced small intestinal injury. Several meta-analyses and systematic reviews have reported that patients treated with PPIs, as well as post-gastrectomy patients, have a higher frequency of small intestinal bacterial overgrowth (SIBO) compared to patients who lack the aforementioned conditions. Furthermore, there is insufficient evidence that these conditions induce Clostridium difficile infection. At this time, PPI-induced dysbiosis is considered a type of SIBO. It now seems likely that intestinal bacterial flora influence many diseases, such as inflammatory bowel disease, diabetes mellitus, obesity, non-alcoholic fatty liver disease, and autoimmune diseases. When attempting to control intestinal bacterial flora with probiotics, prebiotics, and fecal microbiota transplantation, etc., the influence of acid suppression therapy, especially PPIs, should not be overlooked. PMID:26078557

  18. Effect of food or proton pump inhibitor treatment on the bioavailability of dacomitinib in healthy volunteers.

    PubMed

    Ruiz-Garcia, Ana; Masters, Joanna C; Mendes da Costa, Laure; LaBadie, Robert R; Liang, Yali; Ni, Grace; Ellery, Craig A; Boutros, Tanya; Goldberg, Zelanna; Bello, Carlo L

    2016-02-01

    This phase 1, open-label crossover study evaluated the relative bioavailability of dacomitinib in healthy volunteers under fed and fasted conditions and following coadministration with rabeprazole, a potent acid-reducing proton pump inhibitor (PPI). Twenty-four male subjects received a single dacomitinib 45-mg dose under 3 different conditions separated by washout periods of ≥ 16 days: coadministered with rabeprazole 40 mg under fasting conditions; alone under fasting conditions; and alone after a high-fat, high-calorie meal. Increased peak exposure of 23.7% (90% confidence interval [CI], 5.3%-45.2%) was detected with dacomitinib taken after food versus fasting. The adjusted geometric mean ratio (fed/fasted) for area under the plasma concentration-time curve from time zero to infinity (AUCinf ) was 114.2% (90%CI, 104.7%-124.5%) and not considered clinically meaningful. In the fasted state, a decrease in dacomitinib AUCinf was observed following rabeprazole versus dacomitinib alone (PPI+fasted/fasted alone): 71.1% (90%CI, 61.7%-81.8%). Dacomitinib was generally well tolerated. Dacomitinib may be taken with or without food. Use of long-acting acid-reducing agents, such as PPIs with dacomitinib should be avoided if possible. Shorter-acting agents such as antacids and H2-receptor antagonists may have lesser impact on dacomitinib exposure and may be preferable to PPIs if acid reduction is clinically required. PMID:26179237

  19. Effects of proton pump inhibitors on gastric emptying: a systematic review.

    PubMed

    Sanaka, Masaki; Yamamoto, Takatsugu; Kuyama, Yasushi

    2010-09-01

    The proton pump inhibitor (PPI) is widely used for the treatment of gastroesophageal reflux disease, peptic ulcer diseases, and functional dyspepsia. The pathogenesis of these acid-related and/or functional upper gastrointestinal disorders is potentially associated with abnormal gastric emptying. To date, variable effects of PPIs on gastric emptying have been reported. Therefore, it is relevant to gather and analyze published information on this topic. A systematic literature search has been performed, showing that the delaying effect of PPIs on gastric emptying of solid meals is consistent, whereas the effect of PPIs on the emptying of liquids is inconsistent. The underlying mechanisms whereby PPIs may affect gastric emptying have been discussed, most of which still remain hypothetic. Gastric emptying of solids involves a process of peptic hydrolysis. PPIs impair the hydrolytic digestion by inhibiting acid-dependent peptic activity, thereby delaying the solid emptying. Gastric emptying of liquids largely depends on volume and energy density of intragastric contents. PPIs variably modify the volume and the energy density by reducing gastric fluid secretion, thereby modifying the liquid emptying in an unpredictable manner. Hypergastrinemia has been considered to delay gastric emptying, but it seems of minor importance in the regulation of gastric emptying during PPI use. The delayed emptying of solids due to PPI therapy may have clinical implications in the management of gastroesophageal reflux disease, functional dyspepsia, as well as diabetes. PMID:20012198

  20. Are proton pump inhibitors a new antidiabetic drug? A cross sectional study

    PubMed Central

    Boj-Carceller, Diana; Bocos-Terraz, Pilar; Moreno-Vernis, Miguel; Sanz-Paris, Alejandro; Trincado-Aznar, Pablo; Albero-Gamboa, Ramón

    2011-01-01

    AIM: To investigate the effect of proton pump inhibitors (PPIs) on glycemic control (HbA1c) in type 2 diabetic patients. METHODS: A cross-sectional study of consecutive in-patients admitted to hospital in any department during the first semester of the year 2010 who had a recent HbA1c measurement. The study excluded those with a diagnosis of hyperglycemic decompensation, diabetic onset or pregnancy. It compared HbA1c levels of those taking PPIs and those not. RESULTS: A total of 97 patients were recruited. The average HbA1C level was 7.0% ± 1.2%. Overall PPI consumption was 55.7%. HbA1c was significantly lower in individuals who took PPIs: -0.6%, 95% CI: -0.12 to -0.83. People who used PPIs with some type of insulin therapy had a HbA1c reduction by -0.8%, 95% CI: -0.12 to -1.48. For the rest of subgroup analysis based on the antidiabetic drug used, PPI consumption always exhibited lower HbA1c levels. CONCLUSION: PPIs seems to be consistently associated with better glycemic control in type 2 diabetes. HbA1c reduction observed is similar to incretin-based therapies. PMID:22174957

  1. 16S community profiling identifies proton pump inhibitor related differences in gastric, lung and oropharyngeal microflora

    PubMed Central

    Rosen, Rachel; Hu, Lan; Amirault, Janine; Khatwa, Umakanth; Ward, Doyle V.; Onderdonk, Andrew

    2015-01-01

    Objectives To test the hypothesis that PPI use results in changes in gastric microflora which, through full column reflux, results in lung and oropharyngeal microflora changes. Study design We performed a prospective, cross sectional cohort study of 116 children (57 off and 59 on PPIs) undergoing simultaneous bronchoscopy and upper endoscopy for the evaluation of chronic cough. We performed 16S sequencing on gastric, bronchoalveolar lavage and oropharyngeal fluid. Fifty patients also underwent multichannel intraluminal impedance (pH-MII) testing. Results Streptococcus was more abundant in the gastric fluid of patients taking proton pump inhibitors (PPIs) and there was a significant correlation with PPI dose (mg/kg/day) and abundance of gastric Streptococcus (p=0.01). There was also a significant difference in the abundance of oropharyngeal Streptococcus in PPI treated patients. Eight unique bacterial genera were found in the gastric and lung fluid but not in the oropharyngeal suggesting exchange between the two sites and two of the seven (Lactococcus, Acinetobacter) were more abundant in patients with more full column reflux, suggesting direct aspiration. Principal component analysis revealed greater overlap between gastric and lung than oropharyngeal microflora. Conclusions PPI use was associated with differences in gastric, lung and oropharyngeal microflora. Although microflora exchange can occur between all three sites, gastric and lung microflora are more closely related and the mechanism of exchange between sites may be aspiration of full column reflux. PMID:25661411

  2. Attitude and Knowledge of Indian Emergency Care Residents towards Use of Proton Pump Inhibitors

    PubMed Central

    Padhy, Biswa Mohan; Bhadauria, Hemant Singh; Gupta, Yogendra Kumar

    2014-01-01

    Objective. Several studies carried out in developed countries have reported disproportionately high usage of acid suppressive drugs, especially proton pump inhibitors (PPIs). However, systematic assessment of attitude and practices of health care providers towards the use of these drugs in developing countries is lacking. In this study, we assessed the knowledge, attitude, and preferences of resident doctors posted in the emergency department of a tertiary care hospital in North India, towards the use of PPIs. Methods. A questionnaire based survey was carried out. Results. Fifty resident doctors responded to the questionnaire. Thirty-six percent reported prescribing acid suppressive drugs for majority of their patients, while 12% prescribed them to almost all patients they attended. Acute gastritis was the most common indication for prescribing PPI/H2 blockers (50%). The majority of respondents (92%) regarded PPIs as their first choice in acid suppressive agents and 58% administered it through intravenous route. Knowledge about PPI related adverse effects was low. Conclusions. Emergency care residents in India also tend to overuse PPIs in a manner similar to their counterparts in developed countries. Specific measures may be helpful in preventing such practices.

  3. The impact of proton pump inhibitors on the human gastrointestinal microbiome

    PubMed Central

    Freedberg, Daniel E.; Lebwohl, Benjamin; Abrams, Julian A.

    2014-01-01

    Potent gastric acid suppression using proton pump inhibitors (PPIs) is common in clinical practice yet may have important effects on human health that are mediated through changes in the gastrointestinal microbiome. Acting through pH-dependent or pH-independent mechanisms, PPIs have the potential to alter the normal microbiota throughout the human gastrointestinal lumen. In the esophagus, PPIs change the normal bacterial milieu to decrease distal esophageal exposure to inflammatory Gram-negative bacteria which may lower the risk of Barrett's esophagus. In the stomach, PPIs alter the abundance and location of gastric Helicobacter pylori and other bacteria, which has implications for peptic ulcer disease and gastric malignancy. In the small bowel, PPIs cause polymicrobial small bowel bacterial overgrowth and have been associated with the diagnosis of celiac disease. In the colon, PPIs associate with incident but not recurrent Clostridium difficile infection, putatively through alterations in commensal colonic anaerobes. Our understanding of the effect of gastric acid suppression on the human gastrointestinal microbiome is incomplete but is rapidly advancing. PMID:25439276

  4. Prenatal exposure to H2 blockers and to proton pump inhibitors and asthma development in offspring.

    PubMed

    Yitshak-Sade, Maayan; Gorodischer, Rafael; Aviram, Micha; Novack, Lena

    2016-01-01

    Fetal exposure to H2 blockers (H2 Bs) or proton pump inhibitors (PPIs) has been reported to be associated with asthma in children. We evaluated the risk of asthma in offspring following prenatal H2 Bs. We enrolled 91 428 children and their mothers who resided in southern Israel during 1998-2011. The computerized medications database was linked with records from the district hospital. Of the eligible children, 11 227 developed asthma, and overall 5.5% had been exposed to H2 Bs or PPIs prenatally. The risk of developing asthma was slightly higher in the group exposed to H2 Bs or PPIs (RR, 1.09; P = .023). At greater risk were children whose mothers purchased these medications more than 3 times (RR, 1.22; P = .038) or exposed to >20 defined daily doses or prenatally exposed to lansoprazole. The statistical association was significant and depended on magnitude of exposure and specific medication, but the absolute risk was low. The association between maternal consumption of H2 Bs or PPIs and asthma and childhood remained statistically significant 2 years after delivery, raising the possibility of confounding by the indication phenomenon. In view of the findings, a causal relationship could not be ascertained, and an unidentified etiological factor could be operative. PMID:26096778

  5. Use of proton-pump inhibitors among adults: a Danish nationwide drug utilization study

    PubMed Central

    Pottegård, Anton; Broe, Anne; Hallas, Jesper; de Muckadell, Ove B. Schaffalitzky; Lassen, Annmarie T.; Lødrup, Anders B.

    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 Danish Prescription Registry, we identified all Danish adults filling a PPI between 2002 and 2014. Using descriptive statistics, we reported (i) the distribution of use between single PPI entities, (ii) the development in incidence and prevalence of use over time, (iii) measures of duration and intensity of treatment, and (iv) the prevalence of use of ulcerogenic drugs among users of PPIs. Results: We identified 1,617,614 adults using PPIs during the study period. The prevalence of PPI use increased fourfold during the study period to 7.4% of all Danish adults in 2014. PPI use showed strong age dependency, reaching more than 20% among those aged at least 80 years. The proportion of users maintaining treatment over time increased with increasing age, with less than10% of those aged 18–39 years using PPIs 2 years after their first prescription, compared with about 40% among those aged at least 80 years. The overall use of ulcerogenic drugs among PPI users increased moderately, from 35% of users of PPI in 2002 to 45% in 2014. Conclusions: The use of PPIs is extensive and increasing rapidly, especially among the elderly. PMID:27582879

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

    PubMed Central

    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

  7. Proton Pump Inhibitors Alter Specific Taxa in the Human Gastrointestinal Microbiome: A Crossover Trial.

    PubMed

    Freedberg, Daniel E; Toussaint, Nora C; Chen, Sway P; Ratner, Adam J; Whittier, Susan; Wang, Timothy C; Wang, Harris H; Abrams, Julian A

    2015-10-01

    We conducted an open-label crossover trial to test whether proton pump inhibitors (PPIs) affect the gastrointestinal microbiome to facilitate Clostridium difficile infection (CDI). Twelve healthy volunteers each donated 2 baseline fecal samples, 4 weeks apart (at weeks 0 and 4). They then took PPIs for 4 weeks (40 mg omeprazole, twice daily) and fecal samples were collected at week 8. Six individuals took the PPIs for an additional 4 weeks (from week 8 to 12) and fecal samples were collected from all subjects at week 12. Samples were analyzed by 16S ribosomal RNA gene sequencing. We found no significant within-individual difference in microbiome diversity when we compared changes during baseline vs changes on PPIs. There were, however, significant changes during PPI use in taxa associated with CDI (increased Enterococcaceae and Streptococcaceae, decreased Clostridiales) and taxa associated with gastrointestinal bacterial overgrowth (increased Micrococcaceae and Staphylococcaceae). In a functional analysis, there were no changes in bile acids on PPIs, but there was an increase in genes involved in bacterial invasion. These alterations could provide a mechanism by which PPIs predispose to CDI. ClinicalTrials.gov ID NCT01901276. PMID:26164495

  8. Meta-analysis of the efficacy of proton pump inhibitors for the symptoms of laryngopharyngeal reflux.

    PubMed

    Liu, C; Wang, H; Liu, K

    2016-07-01

    The objective of this study was to perform a systematic review and meta-analysis to assess the effectiveness of proton pump inhibitors (PPI) for reflux disease in adult patients with laryngopharyngeal symptoms. A comprehensive search of Cochrane Library, EMBASE, Ovid EBM Reviews, and PubMed was performed for English-language literature about laryngopharyngeal reflux (LPR), in September 2014. The papers were filtered using pre-defined inclusion and exclusion criteria. Eight papers were identified and included in this meta-analysis. The sample comprised a pooled total of 370 patients, of which 210 and 160 patients took PPIs and placebo, respectively. The difference between PPIs and placebo groups in overall improvement of symptoms in adult patients with LPR was not statistically significant (RR=1.22; 95%CI=0.93-1.58; P=0.149). The difference in cough improvement was also not significant between PPIs and placebo groups (RR=0.65; 95%CI=0.30-1.41; P=0.279). PMID:27383119

  9. Meta-analysis of the efficacy of proton pump inhibitors for the symptoms of laryngopharyngeal reflux

    PubMed Central

    Liu, C.; Wang, H.; Liu, K.

    2016-01-01

    The objective of this study was to perform a systematic review and meta-analysis to assess the effectiveness of proton pump inhibitors (PPI) for reflux disease in adult patients with laryngopharyngeal symptoms. A comprehensive search of Cochrane Library, EMBASE, Ovid EBM Reviews, and PubMed was performed for English-language literature about laryngopharyngeal reflux (LPR), in September 2014. The papers were filtered using pre-defined inclusion and exclusion criteria. Eight papers were identified and included in this meta-analysis. The sample comprised a pooled total of 370 patients, of which 210 and 160 patients took PPIs and placebo, respectively. The difference between PPIs and placebo groups in overall improvement of symptoms in adult patients with LPR was not statistically significant (RR=1.22; 95%CI=0.93-1.58; P=0.149). The difference in cough improvement was also not significant between PPIs and placebo groups (RR=0.65; 95%CI=0.30-1.41; P=0.279). PMID:27383119

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

    PubMed

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

    2016-07-01

    Multiple Myeloma (MM) is the second most common hematological malignancy and is responsive to a limited number of drugs. Unfortunately, to date, despite the introduction of novel drugs, no relevant increase in survival rates has been obtained. Proton pump inhibitors (PPIs) have been shown to have significant antitumor action as single agents as well as in combination with chemotherapy. This study investigates the potential anti-tumor effectiveness of two PPIs, Lansoprazole and Omeprazole, against human MM cells. We found that Lansoprazole exerts straightforward efficacy against myeloma cells, even at suboptimal concentrations (50 µM), while Omeprazole has limited cytotoxic action. The Lansoprazole anti-MM effect was mostly mediated by a caspase-independent apoptotic-like cytotoxicity, with only a secondary anti-proliferative action. This study provides clear evidence supporting the use of Lansoprazole in the strive against MM with an efficacy proven much higher than current therapeutical approaches and without reported side effects. It is however conceivable that, consistent with the results obtained in other human tumors, Lansoprazole may well be combined with existing anti-myeloma therapies with the aim to improve the low level of efficacy of the current strategies. PMID:27084522

  11. Proton Pump Inhibitor Use and Magnesium Concentrations in Hemodialysis Patients: A Cross-Sectional Study

    PubMed Central

    Nakashima, Akio; Ohkido, Ichiro; Yokoyama, Keitaro; Mafune, Aki; Urashima, Mitsuyoshi; Yokoo, Takashi

    2015-01-01

    Magnesium concentration is a proven predictor of mortality in hemodialysis patients. Recent reports have indicated that proton pump inhibitor (PPI) use affects serum magnesium levels, however few studies have investigated the relationship between PPI use and magnesium levels in hemodialysis patients. This study aimed to clarify the association between PPI use and serum magnesium levels in hemodialysis patients. We designed this cross sectional study and included 1189 hemodialysis patients in stable condition. Associations between PPI and magnesium-related factors, as well as other possible confounders, were evaluated using a multiple regression model. We defined hypomagnesemia as a value < 2.0 mg/dL, and created comparable logistic regression models to assess the association between PPI use and hypomagnesemia. PPI use is associated with a significantly lower mean serum magnesium level than histamine 2 (H2) receptor antagonists or no acid-suppressive medications (mean [SD] PPI: 2.52 [0.45] mg/dL; H2 receptor antagonist: 2.68 [0.41] mg/dL; no acid suppressive medications: 2.68 [0.46] mg/dL; P = 0.001). Hypomagnesemia remained significantly associated with PPI (adjusted OR, OR: 2.05; 95% CI: 1.14–3.69; P = 0.017). PPI use is associated with an increased risk of hypomagnesemia in hemodialysis patients. Future prospective studies are needed to explore magnesium replacement in PPI users on hemodialysis. PMID:26618538

  12. Prophylactic proton pump inhibitors in femoral neck fracture patients - A life - and cost-saving intervention.

    PubMed

    Singh, R; Trickett, R; Meyer, Cer; Lewthwaite, S; Ford, D

    2016-07-01

    Introduction Acute gastrointestinal stress ulceration is a common and serious complication of trauma. Prophylactic proton pump inhibitors (PPIs) or histamine receptor antagonists have been used in poly-trauma, burns and head and spinal injuries, as well as on intensive care units, for the prevention of acute gastric stress ulcers. Methods We prospectively studied the use of prophylactic PPIs in with femoral neck fracture patients, gathering data on all acute gastric ulcer complications, including coffee-ground vomiting, malena and haematemesis. We then implemented a treatment protocol in which all patients were given prophylactic PPIs, again prospectively collecting all data. Results Five hundred and fifteen patients were included. Prior to prophylactic PPI, 15% of patients developed gastric stress ulcer complications, with 3% requiring acute intervention with oesophagogastroduodenoscopy (OGD), 5% requiring transfusions and 4% experiencing surgical delays. All patients had delayed discharges. Following PPI implementation, no patients developed gastric stress ulcer complications. Conclusions Femoral neck fracture patients create a substantial workload for orthopaedic units. The increasingly elderly population often have comorbidities, and concomitantly use medications with gastrointestinal side effects. This, combined with the stress of a fracture and preoperative starvation periods increases the risk of gastric ulcers. Here, the use of prophylactic PPIs statistically reduced the incidence of gastric stress ulcers in patients with femoral neck fractures, resulting in fewer surgical delays, reduced length of hospital stay and reduced stress ulcer-related mortality. PMID:27055405

  13. Proton Pump Inhibitor Use Is not Associated with Cardiac Arrhythmia in Critically Ill Patients

    PubMed Central

    Chen, Kenneth P.; Lee, Joon; Mark, Roger G.; Feng, Mornin; Celi, Leo A.; Danziger, John

    2016-01-01

    Hypomagnesemia can lead to cardiac arrhythmias. Recently, observational data has linked chronic proton pump inhibitor (PPI) exposure to hypomagnesemia. Whether PPI exposure increases the risk for arrhythmias has not been well studied. Using a large, single center inception cohort of critically ill patients, we examined whether PPI exposure was associated with admission electrocardiogram (ECG) readings of a cardiac arrhythmia in over 8000 patients. There were 24.5% PPI users while 6% were taking a histamine 2 antagonist. 14.3% had a cardiac arrhythmia. PPI use was associated with a 1.18 (95% CI=1.02–1.36, p=0.02) unadjusted and 0.96 (95% CI=0.83–1.12, p=0.62) adjusted risk of arrhythmia. Amongst diuretic users (n=2468), PPI use was similarly not associated with an increased risk of cardiac arrhythmia. In summary, in a large cohort of critically ill patients, PPI exposure is not associated with an increased risk of cardiac arrhythmia. PMID:25655574

  14. PUMPS

    DOEpatents

    Thornton, J.D.

    1959-03-24

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

  15. A comparative study of oral single dose of metronidazole, tinidazole, secnidazole and ornidazole in bacterial vaginosis

    PubMed Central

    Thulkar, Jyoti; Kriplani, Alka; Agarwal, Nutan

    2012-01-01

    Objective: To compare the cure rates of oral single dose of metronidazole (2 g), tinidazole (2 g), secnidazole (2 g), and ornidazole (1.5 g) in cases of bacterial vaginosis. Materials and Methods: This was a prospective, comparative, randomized clinical trial on 344 Indian women (86 women in each group) who attended a gynecology outpatient department with complaint of abnormal vaginal discharge or who had abnormal vaginal discharge on Gynecological examination but they did not complaint of it. For diagnosis and cure rate of bacterial vaginosis, Amsel's criteria were used. Statistical analysis was done by Chi-square test of proportions. The cure rate was compared considering metronidazole cure rate as gold standard. Results: At 1 week, the cure rate of tinidazole and ornidazole was 100% and at 4 weeks, it was 97.7% for both drugs (P<0.001). Secnidazole had cure rate of 80.2% at 4 weeks (P=NS). Metronidazole showed a cure rate of 77.9% at 4 weeks, which is the lowest of all four drugs. Conclusion: Tinidazole and ornidazole have better cure rate as compared to metronidazole in cases of bacterial vaginosis. PMID:22529484

  16. In vitro effect of tinidazole and furazolidone on metronidazole-resistant Trichomonas vaginalis.

    PubMed Central

    Narcisi, E M; Secor, W E

    1996-01-01

    Trichomonas vaginalis is a common sexually transmitted protozoan parasite. Although often considered simply a nuisance infection, T. vaginalis has been implicated in premature rupture of placental membranes and increases in the risk of acquiring human immunodeficiency virus. Metronidazole, a 5-nitroimidazole, is currently the drug of choice to treat T. vaginalis infection. Because some patients have severe reactions to metronidazole and others are infected with metronidazole-resistant T. vaginalis, we were prompted to investigate alternative therapies. Tinidazole, another 5-nitroimidazole used in other countries to treat T. vaginalis infections, and furazolidone, a nitrofuran presently used to treat giardiasis and infections with some anaerobic enteric bacteria, were investigated for effectiveness against 9 metronidazole-susceptible and 12 metronidazole-resistant T. vaginalis patient isolates. The in vitro aerobic and anaerobic minimum lethal concentrations (MLC) and the time for drug efficacy were determined. Tinidazole killed the metronidazole-susceptible isolates at a low MLC but was effective against only 4 of the 12 metronidazole-resistant isolates. In contrast, furazolidone was effective at a low MLC for all isolates. When tinidazole was effective, it required > 6 h to kill trichomonads. However, furazolidone killed both metronidazole-susceptible and resistant trichomonads within 2 to 3 h of exposure. These data suggest that furazolidone may be a good candidate for treating metronidazole-resistant trichomoniasis and that further investigation of this drug is warranted. PMID:8723451

  17. The interaction between clopidogrel and proton pump inhibitors (PPI): is there any clinical relevance?

    PubMed Central

    Sharma, Rakesh K; Reddy, Hanumanth K; Sharma, Rohit K; Moazazi, Mathilde; Elango, Lovett; Singh, Vibhuti N; Williams, D Keith; Voelker, Donald J

    2010-01-01

    The potential interaction between clopidogrel and proton pump inhibitors (PPI) in patients with acute coronary syndrome (ACS) raises serious concerns for cardiologists. However, in patients on this combination of drugs, there is no conclusive evidence of an increase in adverse cardiovascular events. From pharmacologic and pharmacodynamic perspectives, there is a real interaction between clopidogrel and PPIs because of the competitive inhibition of CYP2C19 isoenzyme which is required for biotransformation of clopidogrel to its active metabolite. The consequent decrease in the availability of this active metabolite leads to attenuation of antiplatelet efficacy of clopidogrel. In several observational trials, it was shown that decreased antiplatelet effect of clopidogrel due to PPIs may translate into poor cardiovascular outcomes. However, an incomplete RCT (COGENT) and a post hoc analysis of two large trials (PRINCIPLE-TIMI 44 and TRITON-TIMI 38 trial) showed no significant adverse cardiovascular events with this combination. Caution is however needed in patients who are hypometabolizers of clopidogrel putting them at a higher risk of adverse coronary events. Since 3% of patients are likely to be hypometabolizers of clopidogrel, routine combination of clopidogrel and PPIs should be avoided. There is a heightened awareness of this interaction following multiple advisory warnings. At the same time, one should not withhold PPIs in patients who are at a high risk of developing gastrointestinal (GI) bleeding. In these patients, selected choices of PPI such as pantoprazole may be helpful and for low risk patients, serious consideration should be given to H2 receptor antagonists or antacids. Therefore, while not compromising the cardioprotective effect of antiplatelet agents, the gastroprotective benefit of PPI should be strongly considered in patients who need both. Health care providers should remain alert to more outcome data. Future researchers will need to demonstrate

  18. Can proton pump inhibitors reduce rebleeding following Histoacryl sclerotherapy for gastric variceal hemorrhage?

    PubMed Central

    Kim, Ka Rham; Jun, Chung Hwan; Cho, Kyu Man; Wi, Jin Woo; Park, Seon Young; Cho, Sung Bum; Lee, Wan Sik; Park, Chang Hwan; Joo, Young Eun; Kim, Hyun Soo; Choi, Sung Kyu; Rew, Jong Sun

    2015-01-01

    Background/Aims: To evaluate the efficacy of proton pump inhibitors (PPIs) in reducing rebleeding and bleeding-related death rates after endoscopic gastric variceal obliteration (GVO) using N-butyl-2-cyanoacrylate (NBC). Methods: This study enrolled 341 patients who were consecutively diagnosed with and treated for bleeding gastric varices. The patients were divided into PPI and non-PPI groups, and their endoscopic findings, initial hemostasis outcomes, rebleeding and bleeding-related death rates, and treatment-related complications were analyzed. Results: The rate of initial hemostasis was 97.1%. rebleeding occurred in 2.2% of patients within 2 weeks, 3.9% of patients within 4 weeks, 18.9% of patients within 6 months, and 27.6% of patients within 12 months of the GVO procedure. A previous history of variceal bleeding (relative risk [RR], 1.955; 95% confidence interval [CI], 1.263 to 3.028; p = 0.003) and use of PPIs (RR, 0.554; 95% CI, 0.352 to 0.873; p = 0.011) were associated with rebleeding. Child-Pugh class C (RR, 10.914; 95% CI, 4.032 to 29.541; p < 0.001), failure of initial hemostasis (RR, 13.329; 95% CI, 2.795 to 63.556; p = 0.001), and the presence of red-colored concomitant esophageal varices (RR, 4.096; 95% CI, 1.320 to 12.713; p = 0.015) were associated with bleeding-related death. Conclusions: The prophylactic use of PPIs reduces rebleeding after GVO using NBC in patients with gastric variceal hemorrhage. However, prophylactic use of PPIs does not reduce bleeding-related death. PMID:26354053

  19. Trends in the coprescription of proton pump inhibitors with clopidogrel: an ecological analysis

    PubMed Central

    Juurlink, David N.; Gomes, Tara; Paterson, J. Michael; Hellings, Chelsea; Mamdani, Muhammad M.

    2015-01-01

    Background: In early 2009, 2 observational studies and a US Food and Drug Administration (FDA) advisory addressed the drug interaction between proton pump inhibitors (PPIs) and clopidogrel. One study suggested that pantoprazole could be used safely in this setting, whereas the other study and the FDA advisory did not distinguish among PPIs. We examined trends in PPI prescribing among clopidogrel recipients in the period following these events. Methods: We conducted a population-based time series analysis of Ontario residents aged 66 years or older for whom clopidogrel was prescribed between Apr. 1, 1999, and Sept. 30, 2013. We determined the proportion of clopidogrel recipients dispensed a PPI during each quarter and the proportions who received pantoprazole or other PPIs. The outcome of interest was change in the use of pantoprazole. Results: In the final quarter of 2008, pantoprazole represented 23.7% of all PPI prescriptions dispensed to patients receiving clopidogrel. Following the publications and FDA advisory in early 2009, pantoprazole use increased substantially. By the end of 2009, this medication accounted for 52.5% of all PPI prescriptions issued to patients receiving clopidogrel; by the end of the study period, it accounted for 71.0% of all PPI prescriptions dispensed to such patients (p < 0. 001). We also observed a modest drop in overall PPI use among clopidogrel recipients beginning in early 2009. Interpretation: In 2009, the prescribing of PPIs with clopidogrel changed substantially in Ontario, with pantoprazole rapidly becoming the most commonly prescribed agent in its class. However, a modest decline in overall PPI use also occurred that may reflect suboptimal translation of emerging drug safety information to clinical practice. PMID:26770965

  20. [Clopidogrel--proton pump inhibitors drug interaction: implications to clinical practice].

    PubMed

    Fontes-Carvalho, Ricardo; Albuquerque, Aníbal

    2010-10-01

    Recent studies have raised the concern that proton pump inhibitors (PPIs) could potentially interfere with clopidogrel antiplatelet effect. This association is frequent in clinical practice and is recommended by recent consensus guidelines in patients taking dual antiplatelet therapy to prevent gastrointestinal (GI) bleeding. Clopidogrel is a pro-drug which needs to be metabolized into its active metabolite, by cytochrome P450, especially by CYP2C19 isoenzyme. Various PPIs can inhibit CYP2C19, which could possibly decrease clopidogrel bioactivation process and, therefore, its antiplatelet effect. Various platelet function studies have shown that omeprazol can significantly decrease clopidogrel inhibitory effect on platelet P2Y12 receptor, leading to an increase in the number of patients who are "nonresponders" to clopidogrel. These pharmacokinetic studies also shown that this is not probably a class effect of PPIs, because they are metabolized to varying degrees by CYP2C19. The clinical impact of these observations remains uncertain, because various observational studies have shown conflicting results, and remains to demonstrate if PPIs can really increase the risk of cardiovascular events in patients taking clopidogrel. In this review we will discuss the pharmacokinetic basis underlying this drug interaction, the effect of different PPIs on platelet function tests and we will analyze in detail the potential clinical implications of using this association, both on cardiovascular and gastrointestinal events. Until further data is available, some clinical strategies can be recommended: (1) individual gastrointestinal risk assessment, with PPIs administration only to patients on dual anti-platelet therapy with additional GI risk factors; (2) preferential use of PPIs that have shown less interference with clopidogrel efficacy; (3) wide separation of PPI and clopidogrel dosing to minimize the risk of interaction (PPI may be given before breakfast and clopidogrel at

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

    PubMed Central

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

    2015-01-01

    AIM: To determine the preventive effect and safety of proton pump inhibitors (PPIs) in low-dose aspirin (LDA)-associated gastrointestinal (GI) ulcers and bleeding. METHODS: 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. RESULTS: 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). CONCLUSION: 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. PMID:25954113

  2. Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis.

    PubMed

    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 J; Wen, Ting; Straumann, Alex; Lucendo, Alfredo J

    2016-03-01

    Consensus diagnostic recommendations to distinguish GORD from eosinophilic oesophagitis (EoE) by response to a trial of proton pump inhibitors (PPIs) unexpectedly uncovered an entity called 'PPI-responsive oesophageal eosinophilia' (PPI-REE). PPI-REE refers to patients with clinical and histological features of EoE that remit with PPI treatment. Recent and evolving evidence, mostly from adults, shows that patients with PPI-REE and patients with EoE at baseline are clinically, endoscopically and histologically indistinguishable and have a 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 patients with PPI-REE, similar to the effects of topical steroids in patients with EoE. Additionally, recent series have reported that patients with EoE 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 immunological 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 histological 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 patients with EoE respond to PPI, while others do not, remain to be elucidated. PMID:26685124

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

    PubMed Central

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

    2015-01-01

    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. PMID:26212113

  4. Proton pump inhibitor administration delays rebleeding after endoscopic gastric variceal obturation

    PubMed Central

    Jang, Won Seok; Shin, Hyun Phil; Lee, Joung Il; Joo, Kwang Ro; Cha, Jae Myung; Jeon, Jung Won; Lim, Jun Uk

    2014-01-01

    AIM: To clarify the efficacy of proton pump inhibitors (PPIs) after endoscopic variceal obturation (EVO) with N-butyl-2-cyanoacrylate. METHODS: A retrospective study was performed on 16 liver cirrhosis patients with gastric variceal bleeding that received EVO with injections of N-butyl-2-cyanoacrylate at a single center (Kyung Hee University Hospital at Gangdong) from January 2008 to December 2012. Medical records including patient characteristics and endoscopic findings were reviewed. Treatment results, liver function, serum biochemistry and cirrhosis etiology were compared between patients receiving PPIs and those that did not. Furthermore, the rebleeding interval was compared between patients that received PPI treatment after EVO and those who did not. RESULTS: The patient group included nine males and seven females with a mean age of 61.8 ± 11.7 years. Following the EVO procedure, eight of the 12 patients that received PPIs and three of the four non-PPI patients experienced rebleeding. There were no differences between the groups in serum biochemistry or patient characteristics. The rebleeding rate was not significantly different between the groups, however, patients receiving PPIs had a significantly longer rebleeding interval compared to non-PPI patients (22.2 ± 11.2 mo vs 8.5 ± 5.5 mo; P = 0.008). The duration of PPI use was not related to the rebleeding interval. A total of six patients, who had ulcers at the injection site, exhibited a shorter rebleeding interval (16.8 ± 5.9 mo) than patients without ulcers (19.9 ± 3.2 mo), though this difference was not statistically significant. CONCLUSION: PPI therapy can extend the rebleeding interval, and should therefore be considered after EVO treatment for gastric varices. PMID:25493026

  5. Cost-Effectiveness of Chemoprevention with Proton Pump Inhibitors in Barrett’s Esophagus

    PubMed Central

    Freedberg, Daniel E.; Abrams, Julian A.; Wang, Y. Claire

    2015-01-01

    Background Proton pump inhibitors (PPIs) may reduce the risk of esophageal adenocarcinoma (EAC) in patients with Barrett’s esophagus. PPIs are prescribed for virtually all patients with Barrett’s esophagus, irrespective of the presence of reflux symptoms, and represent a de facto chemopreventive agent in this population. However, long-term PPI use has been associated with several adverse effects, and the cost-effectiveness of chemoprevention with PPIs has not been evaluated. Aim The purpose of this study was to assess the cost-effectiveness of PPIs for the prevention of EAC in Barrett’s esophagus without reflux. Methods We designed a state-transition Markov micro-simulation model of a hypothetical cohort of 50-year-old white men with Barrett’s esophagus. We modeled chemoprevention with PPIs or no chemoprevention, with endoscopic surveillance for all treatment arms. Outcome measures were life-years, quality-adjusted life years (QALYs), incident EAC cases and deaths, costs, and incremental cost-effectiveness ratios. Results Assuming 50 % reduction in EAC, chemoprevention with PPIs was a cost-effective strategy compared to no chemoprevention. In our model, administration of PPIs cost $23,000 per patient and resulted in a gain of 0.32 QALYs for an incremental cost-effectiveness ratio of $12,000/QALY. In sensitivity analyses, PPIs would be cost-effective at $50,000/QALY if they reduce EAC risk by at least 19 %. Conclusions Chemoprevention with PPIs in patients with Barrett’s esophagus without reflux is cost-effective if PPIs reduce EAC by a minimum of 19 %. The identification of subgroups of Barrett’s esophagus patients at increased risk for progression would lead to more cost-effective strategies for the prevention of esophageal adenocarcinoma. PMID:24795040

  6. Effect of a proton pump inhibitor on the pharmacokinetics of imatinib

    PubMed Central

    Egorin, Merrill J; Shah, Dhvani D; Christner, Susan M; Yerk, Mara A; Komazec, Kristin A; Appleman, Leonard R; Redner, Robert L; Miller, Brian M; Beumer, Jan H

    2009-01-01

    AIMS Imatinib mesylate (Gleevec®/Glivec®), which has revolutionized the treatment of chronic myeloid leukemias (CML) and gastrointestinal stromal tumours (GIST), has been reported to cause gastric upset. Consequently, proton pump inhibitors (PPI) are frequently co-administered with imatinib. Because PPI can elevate gastric pH and delay gastric emptying or antagonize ATP-binding-cassette transporters, they could influence imatinib absorption and pharmacokinetics. We aimed to evaluate whether use of omeprazole has a significant effect on imatinib pharmacokinetics. METHODS Twelve healthy subjects were enrolled in a two-period, open-label, single-institution, randomized cross-over, fixed-schedule study. In one period, each subject received 400 mg imatinib orally. In the other period, 40 mg omeprazole (Prilosec®) was administered orally for 5 days, and on day 5 it was administered 15 min before 400 mg imatinib. Plasma concentrations of imatinib and its active N-desmethyl metabolite CGP74588 were assayed by LC-MS, and data were analyzed non-compartmentally. RESULTS PPI administration did not significantly affect the imatinib area under the plasma concentration vs time curve (AUC) (34.1 µg ml−1 h alone vs 33.1 µg ml−1 h with omeprazole, P= 0.64; 80% power), maximum plasma concentration (Cmax) (2.04 µg ml−1 alone vs 2.02 µg ml−1 with omeprazole, P= 0.97), or half-life (13.4 h alone vs 14.1 h with omeprazole, P= 0.13). CONCLUSIONS Our results indicate that the use of omeprazole does not significantly affect the pharmacokinetics of imatinib, as opposed to, for example, dasatinib where PPI decreased AUC and Cmax two-fold. PMID:19740393

  7. Effect of proton pump inhibitors on glycemic control in patients with diabetes

    PubMed Central

    Takebayashi, Kohzo; Inukai, Toshihiko

    2015-01-01

    Gastrin is a linear peptide hormone which is secreted mostly in the stomach pyloric antrum G cells. Although the main role of this hormone is the promotion of the secretion of gastric acid from the stomach parietal cells, gastrin can also behave as a growth factor and stimulate gastric cell proliferation. It is also reported that gastrin promotes β cell neogenesis in the pancreatic ductal complex, modest pancreatic β cell replication, and improvement of glucose tolerance in animal models, in which the remodeling of pancreatic tissues is promoted. These findings suggest the possibility that gastrin has the potential to promote an increase of β cell mass in pancreas, and therefore that gastrin may improve glucose tolerance. Proton pump inhibitors (PPIs) are wildly used clinically for the therapy of gastro-esophageal reflex disease, gastritis due to excess stomach acid, and gastric ulcers. PPIs indirectly elevate serum gastrin levels via a negative feedback effect. Recent evidence has revealed the beneficial effect of PPIs on glycemic control especially in patients with type 2 diabetes mellitus (T2DM), probably via the elevation of the levels of serum gastrin, although the detailed mechanism remains unclear. In addition, the beneficial effects of a combination therapy of gastrin or a PPI with a glucagon-like peptide-1 receptor agonist on glycemic control in animal models have been demonstrated. Although PPIs may be possible candidates for a new approach in the therapy of diabetes, a prospective, long-term, randomized, double-blind, placebo-controlled study is needed to establish the effect of PPIs on glycemic control in a large number of patients with T2DM. PMID:26322158

  8. Idiopathic Pulmonary Fibrosis: Novel Concepts of Proton Pump Inhibitors as Antifibrotic Drugs.

    PubMed

    Ghebre, Yohannes T; Raghu, Ganesh

    2016-06-15

    The prevalence of abnormal acid gastroesophageal reflux (GER) is higher in patients with idiopathic pulmonary fibrosis (IPF) than in matched control subjects. Several studies demonstrated that more than one-third of patients with IPF have abnormal esophageal acid exposures. In addition, many of these studies indicate that the majority of patients with IPF have silent reflux with no symptoms of GER. Findings of abnormal reflux persist in a large proportion of patients with IPF placed on antacid therapy such as proton pump inhibitors (PPIs). This seemingly paradoxical observation suggests that either patients with IPF are somehow resistant to PPI-based intervention or PPIs are inherently unable to suppress acid GER. By contrast, patients with IPF who undergo Nissen fundoplication surgery are effectively relieved from the complications of GER, and retrospective studies suggest improved lung function. Retrospective, anecdotal data suggest a beneficial role of PPIs in IPF including stabilization of lung function, reduction in episodes of acute exacerbation, and enhanced longevity. The recent evidence-based guidelines for treatment of IPF approved conditional recommendation of PPIs for all patients with IPF regardless of their GER status. Recently, we have reported that PPIs possess antiinflammatory and antifibrotic activities by directly suppressing proinflammatory cytokines, profibrotic proteins, and proliferation of lung fibroblasts. Our study provides an alternative explanation for the beneficial effect of PPIs in IPF. In this Perspective, we reviewed emerging progress on antifibrotic effect of PPIs using IPF as a disease model. In addition, we summarized surgical and pharmacological interventions for GER and their downstream effect on lung physiology. PMID:27110898

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

    PubMed

    Niioka, Takenori

    2011-03-01

    Cytochrome P450 (CYP) 2C19 (CYP2C19) genotype is regarded as a useful tool to predict area under the blood concentration-time curve (AUC) of proton pump inhibitors (PPIs). In our results, however, CYP2C19 genotypes had no influence on AUC of all PPIs during fluvoxamine treatment. These findings suggest that CYP2C19 genotyping is not always a good indicator for estimating AUC of PPIs. Limited sampling strategies (LSS) were developed to estimate AUC simply and accurately. It is important to minimize the number of blood samples because of patient's acceptance. This article reviewed the usefulness of LSS for estimating AUC of three PPIs (omeprazole: OPZ, lansoprazole: LPZ and rabeprazole: RPZ). The best prediction formulas in each PPI were AUC(OPZ)=9.24 x C(6h)+2638.03, AUC(LPZ)=12.32 x C(6h)+3276.09 and AUC(RPZ)=1.39 x C(3h)+7.17 x C(6h)+344.14, respectively. In order to optimize the sampling strategy of LPZ, we tried to establish LSS for LPZ using a time point within 3 hours through the property of pharmacokinetics of its enantiomers. The best prediction formula using the fewest sampling points (one point) was AUC(racemic LPZ)=6.5 x C(3h) of (R)-LPZ+13.7 x C(3h) of (S)-LPZ-9917.3 x G1-14387.2×G2+7103.6 (G1: homozygous extensive metabolizer is 1 and the other genotypes are 0; G2: heterozygous extensive metabolizer is 1 and the other genotypes are 0). Those strategies, plasma concentration monitoring at one or two time-points, might be more suitable for AUC estimation than reference to CYP2C19 genotypes, particularly in the case of coadministration of CYP mediators. PMID:21372537

  10. Risk of drug-eluting stent thrombosis in patients receiving proton pump inhibitors.

    PubMed

    Sarafoff, Nikolaus; Sibbing, Dirk; Sonntag, Ulrich; Ellert, Julia; Schulz, Stefanie; Byrne, Robert A; Mehilli, Julinda; Schömig, Albert; Kastrati, Adnan

    2010-09-01

    Clopidogrel is a prodrug that is converted via the hepatic cytochrome P450 system into its active thiol metabolite. Evidence is accumulating that proton pump inhibitors (PPIs) inhibit this enzymatic pathway and may therefore attenuate the antiplatelet effect of clopidogrel. The objective of this study was to investigate whether patients on clopidogrel therapy after drug-eluting stent (DES) placement who also receive a PPI are at higher risk of stent thrombosis (ST). This is a retrospective analysis of patients who received dual antiplatelet treatment including clopidogrel after DES placement. Outcomes were compared according to PPI therapy. The primary endpoint was the incidence of definite ST at 30 days. Secondary endpoints were death, combined death or ST and myocardial infarction (MI). The study population included 3,338 patients and 698 patients (20.9%) received PPIs. Patients receiving a PPI had a higher risk profile at baseline. Multivariate analysis showed that PPI treatment was not independently associated with the occurrence of ST [adjusted HR 1.8 (95% CI: 0.7-4.7), p=0.23] or MI [adjusted HR 1.3 (0.8-2.3), p=0.11]. PPI treatment was significantly associated with death [adjusted HR 2.2 (1.1-4.3), p=0.02] and death or ST [adjusted HR 3.3(1.7-6.7), p=0.02]. Concomitant treatment with a PPI in patients receiving dual antiplatelet treatment after coronary stenting is not an independent predictor of ST. The higher mortality is probably due to confounding as patients on PPIs had a higher risk profile at baseline. PMID:20664905

  11. Proton pump inhibitors and risk of periampullary cancers--A nested case-control study.

    PubMed

    Chien, Li-Nien; Huang, Yan-Jiun; Shao, Yu-Hsuan Joni; Chang, Chen-Jung; Chuang, Ming-Tsang; Chiou, Hung-Yi; Yen, Yun

    2016-03-15

    Considerable attention has been focused on long-term use of proton pump inhibitor (PPI) medications in relation to increased risk of cancer via stimulation of DNA-damaged cells. The aim of this study is to examine the dose-dependent effect of PPI on periampullary cancers in a national population-based cohort. A nested case-control analysis was constructed based on Taiwan's National Health Insurance Research Database and the Taiwan Cancer Registry between the years 2000 and 2010. Cases involving patients diagnosed with periampullary cancers were selected and controls were matched to cases according to age, sex and observational period. A "PPI user" was defined as any patient receiving more than 28 cumulative defined daily doses as measured by prescription drug claims. Conditional logistic regression analysis was conducted to calculate odds ratios (ORs) and 95% confidence intervals (CIs) according to the level of PPI exposure. A total of 7,681 cases and 76,762 matched controls were included with a mean follow-up period of 6.6 years (SD: 2.0). The odds of PPI exposure in patients with periampullary cancers were higher than that of control patients with an adjusted OR of 1.35 (95% CIs: 1.16-1.57). Our results also showed that PPI exposure was slightly linked to periampullary cancers in dose-dependent manner. A similar association was observed in patients who solely took PPI but no eradication therapy for Helicobacter pylori infection. Long-term PPI use was associated with an increased risk of periampullary cancers in the current population-based study. Physicians must weigh potential risks of long-term maintenance against therapeutic benefit. PMID:26488896

  12. Proton pump inhibitors and risk of periampullary cancers—A nested case–control study

    PubMed Central

    Chien, Li‐Nien; Huang, Yan‐Jiun; Shao, Yu‐Hsuan Joni; Chang, Chen‐Jung; Chuang, Ming‐Tsang; Chiou, Hung‐Yi

    2015-01-01

    Considerable attention has been focused on long‐term use of proton pump inhibitor (PPI) medications in relation to increased risk of cancer via stimulation of DNA‐damaged cells. The aim of this study is to examine the dose‐dependent effect of PPI on periampullary cancers in a national population‐based cohort. A nested case–control analysis was constructed based on Taiwan's National Health Insurance Research Database and the Taiwan Cancer Registry between the years 2000 and 2010. Cases involving patients diagnosed with periampullary cancers were selected and controls were matched to cases according to age, sex and observational period. A “PPI user” was defined as any patient receiving more than 28 cumulative defined daily doses as measured by prescription drug claims. Conditional logistic regression analysis was conducted to calculate odds ratios (ORs) and 95% confidence intervals (CIs) according to the level of PPI exposure. A total of 7,681 cases and 76,762 matched controls were included with a mean follow‐up period of 6.6 years (SD: 2.0). The odds of PPI exposure in patients with periampullary cancers were higher than that of control patients with an adjusted OR of 1.35 (95% CIs: 1.16–1.57). Our results also showed that PPI exposure was slightly linked to periampullary cancers in dose‐dependent manner. A similar association was observed in patients who solely took PPI but no eradication therapy for Helicobacter pylori infection. Long‐term PPI use was associated with an increased risk of periampullary cancers in the current population‐based study. Physicians must weigh potential risks of long‐term maintenance against therapeutic benefit. PMID:26488896

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

    PubMed Central

    Bauer-Mehren, Anna; Ghebremariam, Yohannes T.; Iyer, Srinivasan V.; Marcus, Jake; Nead, Kevin T.; Cooke, John P.; Leeper, Nicholas J.

    2015-01-01

    Background and Aims Proton pump inhibitors (PPIs) have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome. Recent pre-clinical results suggest that this risk might extend to subjects without any prior history of cardiovascular disease. We explore this potential risk in the general population via data-mining approaches. Methods Using a novel approach for mining clinical data for pharmacovigilance, we queried over 16 million clinical documents on 2.9 million individuals to examine whether PPI usage was associated with cardiovascular risk in the general population. Results In multiple data sources, we found gastroesophageal reflux disease (GERD) patients exposed to PPIs to have a 1.16 fold increased association (95% CI 1.09–1.24) with myocardial infarction (MI). Survival analysis in a prospective cohort found a two-fold (HR = 2.00; 95% CI 1.07–3.78; P = 0.031) increase in association with cardiovascular mortality. We found that this association exists regardless of clopidogrel use. We also found that H2 blockers, an alternate treatment for GERD, were not associated with increased cardiovascular risk; had they been in place, such pharmacovigilance algorithms could have flagged this risk as early as the year 2000. Conclusions Consistent with our pre-clinical findings that PPIs may adversely impact vascular function, our data-mining study supports the association of PPI exposure with risk for MI in the general population. These data provide an example of how a combination of experimental studies and data-mining approaches can be applied to prioritize drug safety signals for further investigation. PMID:26061035

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

    PubMed Central

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

    2011-01-01

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

  15. Effect of inhibitors and uncouplers on the Na pump of the Maia muscle fibre

    PubMed Central

    Bittar, E. E.

    1966-01-01

    1. A study has been made of sodium efflux from single muscle fibres of the crab Maia squinado, and of the effect of inhibitors and uncouplers on this efflux, using the microsyringe technique. 2. (i) Externally applied ethacrynic acid or injected ethacrynic acid produces 50% inhibition. The inhibitory state due to externally applied ethacrynic acid is shown to be sensitive to 40 mM-K+ in the bathing medium. (ii) Internally applied chlorpromazine causes 40% inhibition. (iii) Internally applied ethyl alcohol causes a slight increase or a slight decrease in Na efflux or no effect. (iv) Internally applied antimycin A produces a net inhibitory effect of almost 50%. (v) Internally applied rotenone produces a 60% inhibitory effect while fibres that fail to contract initially show about a 90% fall in efflux. (vi) The response pattern to internally applied oligomycin is similar to that of antimycin but the net inhibitory effect is only 25%. (vii) Internally applied atractylate produces 45% inhibition. (viii) Internally applied gramicidin A produces about 40% inhibition. (ix) Internally applied valinomycin is without an effect, but in the presence of 40 mM-K+ in the external medium there is marked inhibition of Na efflux. 3. The evidence put forward suggests that the Na pump of the Maia fibre is divided into two parts, one the Na+-K+-ATPase, driven by ATP and arginine phosphate (ArP), and the other, an electrogenic mechanism, driven by respiration and possibly direct coupling of glycolytic energy. The process of reverse electron flow can be invoked as a reasonable explanation of some of the observations made. PMID:5972170

  16. Double-blind test of metronidazole and tinidazole in the treatment of asymptomatic Entamoeba histolytica and Entamoeba hartmanni carriers.

    PubMed

    Spillmann, R; Ayala, S C; Sanchez, C E

    1976-07-01

    One hundred and fifteen persons with asymptomatic Entamoeba histolytica or E. hartmanni infection, or both, were given metronidazole (750 mg three times daily for 5 days), tinidazole (1 g twice daily on 2 consecutive days), or a starch placebo. Three post-treatment stools were examined in the 2 weeks following initiation of treatment. Cysts of E. histolytica reappeared in the stools of 37% of 30 given metronidazole, 62% of 34 given tinidazole, and 70% of 31 given placebo. Cysts of E. hartmanni reappeared in the stools of 46% of 24 given metronidazole, 69% of 16 given tinidazole, and 90% of 10 given placebo. Rapid absorption and short duration of treatment make both drugs ineffective for the treatment of ameba carriers. PMID:183554

  17. Proton Pump Inhibitors and Hospitalization with Hypomagnesemia: A Population-Based Case-Control Study

    PubMed Central

    Zipursky, Jonathan; Macdonald, Erin M.; Hollands, Simon; Gomes, Tara; Mamdani, Muhammad M.; Paterson, J. Michael; Lathia, Nina; Juurlink, David N.

    2014-01-01

    Background Some evidence suggests that proton pump inhibitors (PPIs) are an under-appreciated risk factor for hypomagnesemia. Whether hospitalization with hypomagnesemia is associated with use of PPIs is unknown. Methods and Findings We conducted a population-based case-control study of multiple health care databases in Ontario, Canada, from April 2002 to March 2012. Patients who were enrolled as cases were Ontarians aged 66 years or older hospitalized with hypomagnesemia. For each individual enrolled as a case, we identified up to four individuals as controls matched on age, sex, kidney disease, and use of various diuretic classes. Exposure to PPIs was categorized according to the most proximate prescription prior to the index date as current (within 90 days), recent (within 91 to 180 days), or remote (within 181 to 365 days). We used conditional logistic regression to estimate the odds ratio for the association of outpatient PPI use and hospitalization with hypomagnesemia. To test the specificity of our findings we examined use of histamine H2 receptor antagonists, drugs with no causal link to hypomagnesemia. We studied 366 patients hospitalized with hypomagnesemia and 1,464 matched controls. Current PPI use was associated with a 43% increased risk of hypomagnesemia (adjusted odds ratio, 1.43; 95% CI 1.06–1.93). In a stratified analysis, the risk was particularly increased among patients receiving diuretics, (adjusted odds ratio, 1.73; 95% CI 1.11–2.70) and not significant among patients not receiving diuretics (adjusted odds ratio, 1.25; 95% CI 0.81–1.91). We estimate that one excess hospitalization with hypomagnesemia will occur among 76,591 outpatients treated with a PPI for 90 days. Hospitalization with hypomagnesemia was not associated with the use of histamine H2 receptor antagonists (adjusted odds ratio 1.06; 95% CI 0.54–2.06). Limitations of this study include a lack of access to serum magnesium levels, uncertainty regarding diagnostic coding of

  18. Proton Pump Inhibitors Decrease Eotaxin-3 Expression in the Proximal Esophagus of Children with Esophageal Eosinophilia

    PubMed Central

    Park, Jason Y.; Zhang, Xi; Nguyen, Nathalie; Souza, Rhonda F.; Spechler, Stuart J.; Cheng, Edaire

    2014-01-01

    Objective Besides reducing gastric acid secretion, proton pump inhibitors (PPIs) suppress Th2-cytokine-stimulated expression of an eosinophil chemoattractant (eotaxin-3) by esophageal epithelial cells through acid-independent, anti-inflammatory mechanisms. To explore acid-inhibitory and acid-independent, anti-inflammatory PPI effects in reducing esophageal eosinophilia, we studied eotaxin-3 expression by the proximal and distal esophagus of children with esophageal eosinophilia before and after PPI therapy. In vitro, we studied acid and bile salt effects on IL-13-stimulated eotaxin-3 expression by esophageal epithelial cells. Design Among 264 children with esophageal eosinophilia seen at a tertiary pediatric hospital from 2008 through 2012, we identified 10 with esophageal biopsies before and after PPI treatment alone. We correlated epithelial cell eotaxin-3 immunostaining with eosinophil numbers in those biopsies. In vitro, we measured eotaxin-3 protein secretion by esophageal squamous cells stimulated with IL-13 and exposed to acid and/or bile salt media, with or without omeprazole. Results There was strong correlation between peak eosinophil numbers and peak eotaxin-3-positive epithelial cell numbers in esophageal biopsies. Eotaxin-3 expression decreased significantly with PPIs only in the proximal esophagus. In esophageal cells, exposure to acid-bile salt medium significantly suppressed IL-13-induced eotaxin-3 secretion; omeprazole added to the acid-bile salt medium further suppressed that eotaxin-3 secretion, but not as profoundly as at pH-neutral conditions. Conclusion In children with esophageal eosinophilia, PPIs significantly decrease eotaxin-3 expression in the proximal but not the distal esophagus. In esophageal squamous cells, acid and bile salts decrease Th2 cytokine-stimulated eotaxin-3 secretion profoundly, possibly explaining the disparate PPI effects on the proximal and distal esophagus. In the distal esophagus, where acid reflux is greatest, a PPI

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

    PubMed Central

    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 < 0.001). Intestinal metaplasia was more likely to be detected in the latter patients (1.4% vs 6.5%, P = 0.023). Multivariate analysis has also demonstrated that in the presence of previous PPI exposure (OR = 0.217, 95%CI: 0.123-0.385), GERD (OR = 0.317, 95%CI: 0.132-0.763, P = 0.01), alcohol intake (OR = 0.396, 95%CI: 0.195-0.804, P = 0.01), the detection of H. pylori was less likely. Chronic use of PPIs may mask H. pylori infections promoting the diagnosis of non-H. pylori

  20. Prolonged use of a proton pump inhibitor reduces microbial diversity: implications for Clostridium difficile susceptibility

    PubMed Central

    2014-01-01

    Background The role of the gut microbiome in arresting pathogen colonization and growth is important for protection against Clostridium difficile infection (CDI). Observational studies associate proton pump inhibitor (PPI) use and CDI incidence. We hypothesized that PPI use affected the distal gut microbiome over time, an effect that would be best explored by time-longitudinal study of healthy subjects on PPI in comparison to treatment-naïve CDI subjects. This study enrolled nine healthy human subjects and five subjects with treatment-naïve CDI. After random assignment to a low (20 mg/day) or high (2× 20 mg/day) dose group, fecal samples were collected from the nine healthy subjects before, during, and after 28 days of PPI use. This was done in conjunction with pre-treatment fecal collection from CDI subjects. High-throughput sequencing (16S rRNA) was performed on time-longitudinal samples to assess changes to the healthy gut microbiome associated with prolonged PPI usage. The healthy samples were then compared to the CDI subjects to explore changes over time to the gut microbiome associated with PPI use and potentially related to CDI. Results We report that PPI usage at low and high dosages, administered for 28 days, resulted in decreases to observed operational taxonomic unit (OTU) counts after both 1 week and 1 month. This decrease resulted in observed OTU levels that were similar to those found in treatment-naïve CDI patients, which was partly reversible after a 1 month recovery period. We did not detect a dose-dependent difference in OTU levels nor did we detect significant changes in taxa previously reported to be affected by PPI treatment. Conclusion While our observation of diminishing observed OTU counts during PPI therapy is a preliminary finding in a small cohort, our hypothesis that PPIs disrupt the healthy human gut microbiome is supported in this group. We conclude that decreases in observed species counts were reversible after cessation of

  1. Proton pump inhibitor for non-erosive reflux disease: A meta-analysis

    PubMed Central

    Zhang, Ji-Xiang; Ji, Meng-Yao; Song, Jia; Lei, Hong-Bo; Qiu, Shi; Wang, Jing; Ai, Ming-Hua; Wang, Jun; Lv, Xiao-Guang; Yang, Zi-Rong; Dong, Wei-Guo

    2013-01-01

    AIM: To evaluate the efficacy, safety and influential factors of proton pump inhibitor (PPI) treatment for non-erosive reflux disease (NERD). METHODS: PubMed, MEDLINE, EMBASE and the Cochrane Library were searched up to April 2013 to identify eligible randomized controlled trials (RCTs) that probed into the efficacy, safety and influential factors of PPI treatment for NERD. The rates of symptomatic relief and adverse events were measured as the outcomes. After RCT selection, assessment and data collection, the pooled RRs and 95%CI were calculated. This meta-analysis was performed using the Stata 12.0 software (Stata Corporation, College Station, Texas, United States). The level of evidence was estimated by the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: Seventeen RCTs including 6072 patients met the inclusion criteria. The results of the meta-analysis showed that PPI treatment was significantly superior to H2 receptor antagonists (H2RA) treatment (RR = 1.629, 95%CI: 1.422-1.867, P = 0.000) and placebo (RR = 1.903, 95%CI: 1.573-2.302, P = 0.000) for the symptomatic relief of NERD. However, there were no obvious differences between PPI and H2RA (RR = 0.928, 95%CI: 0.776-1.110, P = 0.414) or PPI and the placebo (RR = 1.000, 95%CI: 0.896-1.116, P = 0.997) regarding the rate of adverse events. The overall rate of symptomatic relief of PPI against NERD was 51.4% (95%CI: 0.433-0.595, P = 0.000), and relief was influenced by hiatal hernia (P = 0.030). The adverse rate of PPI against NERD was 21.0% (95%CI: 0.152-0.208, P = 0.000), and was affected by hiatal hernia (P = 0.081) and drinking (P = 0.053). CONCLUSION: PPI overmatched H2RA on symptomatic relief rate but not on adverse rate for NERD. Its relief rate and adverse rate were influenced by hiatal hernia and drinking. PMID:24363534

  2. Current Diagnosis and Management of Suspected Reflux Symptoms Refractory to Proton Pump Inhibitor Therapy

    PubMed Central

    2014-01-01

    Suspected reflux symptoms that are refractory to proton pump inhibitors (PPIs) are rapidly becoming the most common presentation of gastroesophageal reflux disease (GERD) in patients seen in gastroenterology clinics. These patients are a heterogeneous group, differing in symptom frequency and severity, PPI dosing regimens, and responses to therapy (from partial to absent). Before testing, the physician needs to question the patient carefully about PPI compliance and the timing of drug intake in relation to meals. Switching PPIs or doubling the dose is the next step, but only 20% to 25% of the group refractory to PPIs will respond. The first diagnostic test should be upper gastrointestinal endoscopy. In more than 90% of cases, the results will be normal, but persistent esophagitis may suggest pill esophagitis, eosinophilic esophagitis, or rarer diseases, such as lichen planus, Zollinger-Ellison syndrome, or genotype variants of PPI metabolism. If the endoscopy results are normal, esophageal manometry and especially reflux testing should follow. Whether patients should be tested on or off PPI therapy is controversial. Most physicians prefer to test patients off PPIs to identify whether abnormal acid reflux is even present; if it is not, PPIs can be stopped and other diagnoses sought. Testing patients on PPI therapy allows nonacid reflux to be identified, but more than 50% of patients have a normal test result, leaving the clinician with a conundrum—whether to stop PPIs or continue them because the GERD is being treated adequately. Alternative diagnoses in patients with refractory GERD and normal reflux testing include achalasia, eosinophilic esophagitis, gastroparesis, rumination, and aerophagia. However, more than 50% will be given the diagnosis of functional heartburn, a visceral hypersensitivity syndrome. Treating patients with PPI-refractory GERD–like symptoms can be difficult and frustrating. Any of the following may help: a histamine-2 receptor antagonist

  3. Chalcone inhibitors of the NorA efflux pump in Staphylococcus aureus whole cells and enriched everted membrane vesicles.

    PubMed

    Holler, Jes Gitz; Slotved, Hans-Christian; Mølgaard, Per; Olsen, Carl Erik; Christensen, Søren Brøgger

    2012-07-15

    A library of 117 chalcones was screened for efflux pump inhibitory (EPI) activity against NorA mediated ethidium bromide efflux. Five of the chalcones (5-7, 9, and 10) were active and two chalcones (9 and 10) were equipotent to reserpine with IC(50)-values of 9.0 and 7.7 μM, respectively. Twenty chalcones were subsequently proved to be inhibitors of the NorA efflux pump in everted membrane vesicles. Compounds 5, 7, and 9 synergistically increased the effect of ciprofloxacin on Staphylococcus aureus. Our results suggest that chalcones might be developed into drugs for overcoming multidrug resistance based on efflux transporters of microorganisms. PMID:22682300

  4. Use of Osmotic Pumps to Establish the Pharmacokinetic-Pharmacodynamic Relationship and Define Desirable Human Performance Characteristics for Aggrecanase Inhibitors.

    PubMed

    Wiley, Michael R; Durham, Timothy B; Adams, Lisa A; Chambers, Mark G; Lin, Chaohua; Liu, Chin; Marimuthu, Jothirajah; Mitchell, Peter G; Mudra, Daniel R; Swearingen, Craig A; Toth, James L; Weller, Jennifer M; Thirunavukkarasu, Kannan

    2016-06-23

    The development of reliable relationships between in vivo target engagement, pharmacodynamic activity, and efficacy in chronic disease models is beneficial for enabling hypothesis-driven drug discovery and facilitating the development of patient-focused candidate selection criteria. Toward those ends, osmotic infusion pumps can be useful for overcoming limitations in the PK properties of proof-of-concept (POC) compounds to accelerate the development of such relationships. In this report, we describe the application of this strategy to the development of hydantoin-derived aggrecanase inhibitors (eg, 3) for the treatment of osteoarthiritis (OA). Potent, selective inhibitors were efficacious in both chemical and surgical models of OA when exposures were sustained in excess of 10 times the plasma IC50. The use of these data for establishing patient-focused candidate selection criteria is exemplified with the characterization of compound 8, which is projected to sustain the desired level of target engagement at a dose of 45 mg qd. PMID:27194201

  5. Expression of homologous RND efflux pump genes is dependent upon AcrB expression: implications for efflux and virulence inhibitor design

    PubMed Central

    Blair, Jessica M. A.; Smith, Helen E.; Ricci, Vito; Lawler, Amelia J.; Thompson, Louisa J.; Piddock, Laura J. V.

    2015-01-01

    Objectives Enterobacteriaceae have multiple efflux pumps that confer intrinsic resistance to antibiotics. AcrB mediates clinically relevant multidrug resistance and is required for virulence and biofilm formation, making it an attractive target for the design of inhibitors. The aim of this study was to assess the viability of single transporters as a target for efflux inhibition using Salmonella Typhimurium as the model pathogen. Methods The expression of resistance–nodulation–division (RND) efflux pump genes in response to the inactivation of single or multiple homologues was measured using real-time RT–PCR. Phenotypes of mutants were characterized by measuring antimicrobial susceptibility, dye accumulation and the ability to cause infection in vitro. Results The expression of all RND efflux pump genes was increased when single or multiple acr genes were inactivated, suggesting a feedback mechanism that activates the transcription of homologous efflux pump genes. When two or three acr genes were inactivated, the mutants had further reduced efflux, altered susceptibility to antimicrobials (including increased susceptibility to some, but conversely and counterintuitively, decreased susceptibility to some others) and were more attenuated in the tissue culture model than mutants lacking single pumps were. Conclusions These data indicate that it is critical to understand which pumps an inhibitor is active against and the effect of this on the expression of homologous systems. For some antimicrobials, an inhibitor with activity against multiple pumps will have a greater impact on susceptibility, but an unintended consequence of this may be decreased susceptibility to other drugs, such as aminoglycosides. PMID:25288678

  6. Structure-Activity Relationships of a Novel Pyranopyridine Series of Gram-negative Bacterial Efflux Pump Inhibitors

    PubMed Central

    Nguyen, Son T.; Kwasny, Steven M.; Ding, Xiaoyuan; Cardinale, Steven C.; McCarthy, Courtney T.; Kim, Hong-Suk; Nikaido, Hiroshi; Peet, Norton P.; Williams, John D.; Bowlin, Terry L.; Opperman, Timothy J.

    2015-01-01

    Recently we described a novel pyranopyridine inhibitor (MBX2319) of RND-type efflux pumps of the Enterobacteriaceae. MBX2319 (3,3-dimethyl-5-cyano-8-morpholino-6-(phenethylthio)-3,4-dihydro-1H-pyrano[3,4-c]pyridine) is structurally distinct from other known Gram-negative efflux pump inhibitors (EPIs), such as 1-(1-naphthylmethyl)-piperazine (NMP), phenylalanylarginine-β-naphthylamide (PAβN), D13-9001, and the pyridopyrimidine derivatives. Here, we report the synthesis and biological evaluation of 60 new analogs of MBX2319 that were designed to probe the structure activity relationships (SARs) of the pyranopyridine scaffold. The results of these studies produced a molecular activity map of the scaffold, which identifies regions that are critical to efflux inhibitory activities and those that can be modified to improve potency, metabolic stability and solubility. Several compounds, such as 22d–f, 22i and 22k, are significantly more effective than MBX2319 at potentiating the antibacterial activity of levofloxacin and piperacillin against Escherichia coli. PMID:25818767

  7. Synergy in a medicinal plant: antimicrobial action of berberine potentiated by 5'-methoxyhydnocarpin, a multidrug pump inhibitor.

    PubMed

    Stermitz, F R; Lorenz, P; Tawara, J N; Zenewicz, L A; Lewis, K

    2000-02-15

    Multidrug resistance pumps (MDRs) protect microbial cells from both synthetic and natural antimicrobials. Amphipathic cations are preferred substrates of MDRs. Berberine alkaloids, which are cationic antimicrobials produced by a variety of plants, are readily extruded by MDRs. Several Berberis medicinal plants producing berberine were found also to synthesize an inhibitor of the NorA MDR pump of a human pathogen Staphylococcus aureus. The inhibitor was identified as 5'-methoxyhydnocarpin (5'-MHC), previously reported as a minor component of chaulmoogra oil, a traditional therapy for leprosy. 5'-MHC is an amphipathic weak acid and is distinctly different from the cationic substrates of NorA. 5'-MHC had no antimicrobial activity alone but strongly potentiated the action of berberine and other NorA substrates against S. aureus. MDR-dependent efflux of ethidium bromide and berberine from S. aureus cells was completely inhibited by 5'-MHC. The level of accumulation of berberine in the cells was increased strongly in the presence of 5'-MHC, indicating that this plant compound effectively disabled the bacterial resistance mechanism against the berberine antimicrobial. PMID:10677479

  8. Proton Pump Inhibitors Inhibit Pancreatic Secretion: Role of Gastric and Non-Gastric H+/K+-ATPases

    PubMed Central

    Tozzi, Marco; Giannuzzo, Andrea; Sørensen, Christiane E.; Novak, Ivana

    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+-ATPases are expressed and functional in human pancreatic ducts and whether proton pump inhibitors (PPIs) have effect on those. Here we show that the gastric HKα1 and HKβ subunits (ATP4A; ATP4B) and non-gastric HKα2 subunits (ATP12A) of H+/K+-ATPases are expressed in human pancreatic cells. Pumps have similar localizations in duct cell monolayers (Capan-1) and human pancreas, and notably the gastric pumps are localized on the luminal membranes. In Capan-1 cells, PPIs inhibited recovery of intracellular pH from acidosis. Furthermore, in rats treated with PPIs, pancreatic secretion was inhibited but concentrations of major ions in secretion follow similar excretory curves in control and PPI treated animals. In addition to HCO3-, pancreas also secretes K+. In conclusion, this study calls for a revision of the basic model for HCO3- secretion. We propose that proton transport is driving secretion, and that in addition 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. PMID:25993003

  9. Proton pump inhibitor-induced Sweet’s syndrome: report of acute febrile neutrophilic dermatosis in a woman with recurrent breast cancer

    PubMed Central

    Cohen, Philip R.

    2015-01-01

    Background: Sweet’s syndrome, also referred to as acute febrile neutrophilic dermatosis, can either occur as an idiopathic disorder or associated with another condition, including cancer, or induced by exposure to a drug. Proton pump inhibitors selectively inhibit gastric parietal cell H+-K+-adenosine triphosphatase and are most commonly used for the treatment of gastroesophageal reflux disease. Purpose: Proton pump inhibitor-associated Sweet’s syndrome is described in a woman with recurrent breast cancer. Methods: PubMed was used to search the following terms, separately and in combination: acute febrile neutrophilic dermatosis, breast cancer, malignancy, paraneoplastic, proton pump inhibitor, and Sweet’s syndrome. All papers were reviewed and relevant manuscripts, along with their reference citations, were evaluated. Results: Proton pump inhibitors have previously been associated with cutaneous adverse reactions including maculopapular rash, subacute cutaneous lupus erythematosus and toxic epidermal necrolysis. However, drug-induced Sweet’s syndrome has not been observed in patients receiving proton pump inhibitors. The reported woman developed Sweet’s syndrome after initial exposure and subsequent repeat challenge to proton pump inhibitors; subsequent studies also observed recurrence of her breast cancer presenting as metastases to her stomach and bone. Conclusions: Drug-induced Sweet’s syndrome has most commonly been associated with granulocyte colony stimulating factor in oncology patients. Malignancy-associated Sweet’s syndrome has been observed in patients with solid tumors, including breast cancer. Confirmation of proton pump inhibitor-induced Sweet’s syndrome, by repeat challenge with another medication in the same class of drug, was observed in a woman with breast cancer; although the subsequent discovery of recurrent breast cancer presenting as gastric mucosa and vertebral metastases also raises the possibility of concurrent

  10. Changes in Practice Patterns of Clopidogrel in Combination with Proton Pump Inhibitors after an FDA Safety Communication

    PubMed Central

    Guérin, Annie; Mody, Reema; Carter, Valerie; Ayas, Charles; Patel, Haridarshan; Lasch, Karen; Wu, Eric

    2016-01-01

    Objectives In 2009, the FDA issued a warning that omeprazole–a proton pump inhibitor (PPI)–reduces the antithrombotic effect of clopidogrel by almost half when taken concomitantly. This study aims to analyze the impact of the FDA Safety Communications on prescribing clopidogrel together with PPIs. Methods This retrospective study identified clopidogrel users from the Truven Health Analytics MarketScan Databases (01/2006–12/2012). Rates of clopidogrel-PPI combination therapy were estimated in 6-month intervals for patients with ≥1 clopidogrel prescription fill, then were analyzed pre- and post-safety communication (11/17/2009). Analyses were also conducted by grouping PPIs into CYP2C19 inhibitors (omeprazole and esomeprazole) and CYP2C19 non-inhibitors (pantoprazole, lansoprazole, dexlansoprazole, and rabeprazole). Results Overall, 483,074 patients met the selection criteria; of these, 157,248 used a clopidogrel-PPI combination. On average, 30.5% of patients in the pre- and 19.9% in the post-communication period used a clopidogrel-PPI combination therapy. Among clopidogrel users, the probability of using clopidogrel-PPI combinations fell by over 40% in the post-communication period (OR = 0.57; p<0.001); the proportion of patients using esomeprazole fell from 12.9% to 5.3%, and the proportion using omeprazole fell from 10.1% to 6.3%. Among combination therapy users, the probability of patients using a combination with a CYP2C19 inhibitor decreased by 53% (OR = 0.47; p<0.001); however, 31.5% of patients were still prescribed a clopidogrel-PPI combination therapy. Trends were similar for all and newly treated patients, regardless of clopidogrel indication and physician specialty. Conclusions The FDA Safety Communication resulted in a reduction in the number of patients undergoing combination therapy; however approximately one-third of patients still used combination therapy post-communication. PMID:26727382

  11. Sarothrin from Alkanna orientalis is an antimicrobial agent and efflux pump inhibitor

    PubMed Central

    Bame, Jessica R.; Graf, Tyler N.; Junio, Hiyas A.; Bussey, R. Owen; Jarmusch, Scott A.; El-Elimat, Tamam; Falkinham, Joseph O.; Oberlies, Nicholas H.; Cech, Richard A.; Cech, Nadja B.

    2015-01-01

    An Alkanna orientalis leaf and flower extract inhibited the growth of Staphylococcus aureus, a pathogen that causes an estimated 478,000 hospitalizations in the US annually. Bioassay-guided fractionation of A. orientalis resulted in isolation of the flavonoid sarothrin (5,7,4′-trihydroxy-3,6,8-trimethoxyflavone), which inhibited the growth of Mycobacterium smegmatis (MIC 75 μM) and S. aureus (MIC >800 μM), and possessed efflux pump inhibitory activity. This is the first report of antimicrobial or efflux pump inhibitory activity of sarothrin, and of its presence in A. orientalis. Our findings suggest that the effectiveness of A. orientalis extracts is due to a combination of multiple constituents, including sarothrin. PMID:23468310

  12. Resolution of Fundic Gland Polyposis following Laparoscopic Magnetic Sphincter Augmentation and Subsequent Cessation of Proton Pump Inhibitors

    PubMed Central

    Brockmeyer, Joel R.; Connolly, Erin E.; Wittchow, Richard J.; Kothari, Shanu N.

    2015-01-01

    Gastric polyps occur from a variety of sources and are found commonly on upper endoscopy. We present the case of a 49-year-old female who presented for evaluation for antireflux surgery with a history of fundic gland polyposis who required twice-daily proton pump inhibitors (PPIs) for control of her gastric reflux. After verifying that she met criteria for surgery, she underwent an uncomplicated laparoscopic magnetic sphincter augmentation placement. With the cessation of PPIs following surgery, the fundic gland polyposis resolved. Fundic gland polyps may occur sporadically or within certain syndromes, such as familial adenomatous polyposis. Multiple possible inciting factors exist, including the use of PPIs. This is the first reported case of the resolution of numerous fundic gland polyps following the completion of laparoscopic magnetic sphincter augmentation. PMID:26600954

  13. Validated spectrophotometric methods for simultaneous determination of Omeprazole, Tinidazole and Doxycycline in their ternary mixture.

    PubMed

    Lotfy, Hayam M; Hegazy, Maha A; Mowaka, Shereen; Mohamed, Ekram Hany

    2016-01-15

    A comparative study of smart spectrophotometric techniques for the simultaneous determination of Omeprazole (OMP), Tinidazole (TIN) and Doxycycline (DOX) without prior separation steps is developed. These techniques consist of several consecutive steps utilizing zero/or ratio/or derivative spectra. The proposed techniques adopt nine simple different methods, namely direct spectrophotometry, dual wavelength, first derivative-zero crossing, amplitude factor, spectrum subtraction, ratio subtraction, derivative ratio-zero crossing, constant center, and successive derivative ratio method. The calibration graphs are linear over the concentration range of 1-20 μg/mL, 5-40 μg/mL and 2-30 μg/mL for OMP, TIN and DOX, respectively. These methods are tested by analyzing synthetic mixtures of the above drugs and successfully applied to commercial pharmaceutical preparation. The methods that are validated according to the ICH guidelines, accuracy, precision, and repeatability, were found to be within the acceptable limits. PMID:26322842

  14. Validated spectrophotometric methods for simultaneous determination of Omeprazole, Tinidazole and Doxycycline in their ternary mixture

    NASA Astrophysics Data System (ADS)

    Lotfy, Hayam M.; Hegazy, Maha A.; Mowaka, Shereen; Mohamed, Ekram Hany

    2016-01-01

    A comparative study of smart spectrophotometric techniques for the simultaneous determination of Omeprazole (OMP), Tinidazole (TIN) and Doxycycline (DOX) without prior separation steps is developed. These techniques consist of several consecutive steps utilizing zero/or ratio/or derivative spectra. The proposed techniques adopt nine simple different methods, namely direct spectrophotometry, dual wavelength, first derivative-zero crossing, amplitude factor, spectrum subtraction, ratio subtraction, derivative ratio-zero crossing, constant center, and successive derivative ratio method. The calibration graphs are linear over the concentration range of 1-20 μg/mL, 5-40 μg/mL and 2-30 μg/mL for OMP, TIN and DOX, respectively. These methods are tested by analyzing synthetic mixtures of the above drugs and successfully applied to commercial pharmaceutical preparation. The methods that are validated according to the ICH guidelines, accuracy, precision, and repeatability, were found to be within the acceptable limits.

  15. Na sup + pump in renal tubular cells is regulated by endogenous Na sup + -K sup + -ATPase inhibitor from hypothalamus

    SciTech Connect

    Cantiello, H.F.; Chen, E.; Ray, S.; Haupert, G.T. Jr. )

    1988-10-01

    Bovine hypothalamus contains a high affinity, specific, reversible inhibitor of mammalian Na{sup +}-K{sup +}-ATPase. Kinetic analysis using isolated membrane fractions showed binding and dissociation rates of the hypothalamic factor (HF) to be (like ouabain) relatively long (off rate = 60 min). To determine whether the kinetics of inhibition in intact cells might be more consistent with regulation of physiological processes in vivo, binding and dissociation reactions of HF in intact renal epithelial cells (LLC-PK{sup 1}) were studied using {sup 86}Rb{sup +} uptake and ({sup 3}H)ouabain binding. As with membranes, a 60-min incubation with HF inhibited Na{sup +}-K{sup +}-ATPase in LLC-PK{sub 1} cells. In contrast to membrane studies, no prolonged incubation with LLC-PK{sub 1} was needed to observe inhibition of Na{sup +}-K{sup +}-ATPase. HF caused a 33% inhibition of ouabain-sensitive {sup 86}Rb{sup +} influx within 10 min. Incubation of cells with HF followed by washout showed rapid reversal of pump inhibition and a doubling of pump activity. The dose-response curve for HF inhibition of LLC-PK{sub 1} {sup 86}Rb{sup +} uptake showed a sigmoidal shape consistent with an allosteric binding reaction. Thus HF is a potent regulator of Na{sup +}-K{sup +}-ATPase activity in intact renal cells, with binding and dissociation reactions consistent with relevant physiological processes.

  16. The Influence of Efflux Pump Inhibitors on the Activity of Non-Antibiotic NSAIDS against Gram-Negative Rods

    PubMed Central

    Laudy, Agnieszka E.; Mrowka, Agnieszka; Krajewska, Joanna; Tyski, Stefan

    2016-01-01

    Background Most patients with bacterial infections suffer from fever and various pains that require complex treatments with antibiotics, antipyretics, and analgaesics. The most common drugs used to relieve these symptoms are non-steroidal anti-inflammatory drugs (NSAIDs), which are not typically considered antibiotics. Here, we investigate the effects of NSAIDs on bacterial susceptibility to antibiotics and the modulation of bacterial efflux pumps. Methodology The activity of 12 NSAID active substances, paracetamol (acetaminophen), and eight relevant medicinal products was analyzed with or without pump inhibitors against 89 strains of Gram-negative rods by determining the MICs. Furthermore, the effects of NSAIDs on the susceptibility of clinical strains to antimicrobial agents with or without PAβN (Phe-Arg-β-naphtylamide) were measured. Results The MICs of diclofenac, mefenamic acid, ibuprofen, and naproxen, in the presence of PAβN, were significantly (≥4-fold) reduced, decreasing to 25–1600 mg/L, against the majority of the studied strains. In the case of acetylsalicylic acid only for 5 and 7 out of 12 strains of P. mirabilis and E. coli, respectively, a 4-fold increase in susceptibility in the presence of PAβN was observed. The presence of Aspirin resulted in a 4-fold increase in the MIC of ofloxacin against only two strains of E. coli among 48 tested clinical strains, which included species such as E. coli, K. pneumoniae, P. aeruginosa, and S. maltophilia. Besides, the medicinal products containing the following NSAIDs, diclofenac, mefenamic acid, ibuprofen, and naproxen, did not cause the decrease of clinical strains’ susceptibility to antibiotics. Conclusions The effects of PAβN on the susceptibility of bacteria to NSAIDs indicate that some NSAIDs are substrates for efflux pumps in Gram-negative rods. Morever, Aspirin probably induced efflux-mediated resistance to fluoroquinolones in a few E. coli strains. PMID:26771525

  17. CYP2C19 Phenoconversion by Routinely Prescribed Proton Pump Inhibitors Omeprazole and Esomeprazole: Clinical Implications for Personalized Medicine.

    PubMed

    Klieber, Martin; Oberacher, Herbert; Hofstaetter, Silvia; Beer, Beate; Neururer, Martin; Amann, Anton; Alber, Hannes; Modak, Anil

    2015-09-01

    The phenotype pantoprazole-(13)C breath test (Ptz-BT) was used to evaluate the extent of phenoconversion of CYP2C19 enzyme activity caused by commonly prescribed proton pump inhibitors (PPI) omeprazole and esomprazole. The Ptz-BT was administered to 26 healthy volunteers and 8 stable cardiovascular patients twice at baseline and after 28 days of PPI therapy to evaluate reproducibility of the Ptz-BT and changes in CYP2C19 enzyme activity (phenoconversion) after PPI therapy. The average intrapatient interday variability in CYP2C19 phenotype (n = 31) determined by Ptz-BT was considerably low (coefficient of variation, 17%). Phenotype conversion resulted in 25 of 26 (96%) nonpoor metabolizer (non-PM) volunteers/patients as measured by the Ptz-BT at baseline and after PPI therapy. The incidence of PM status by phenotype following administration of omeprazole/esomeprazole (known inhibitors of CYP2C19) was 10-fold higher than those who are genetically PMs in the general population, which could have critical clinical implications for personalizing medications primarily metabolized by CYP2C19, such as clopidogrel, PPI, cyclophosphamide, thalidomide, citalopram, clonazepam, diazepam, phenytoin, etc. The Ptz-BT can rapidly (30 minutes) evaluate CYP2C19 phenotype and, more importantly, can identify patients with phenoconversion in CYP2C19 enzyme activity caused by nongenetic factors such as concomitant drugs. PMID:26159874

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

    SciTech Connect

    Thanan, Raynoo; Ma, Ning; Iijima, Katsunori; Abe, Yasuhiko; Koike, Tomoyuki; Shimosegawa, Tooru; Pinlaor, Somchai; Hiraku, Yusuke; Oikawa, Shinji; Murata, Mariko; Kawanishi, Shosuke

    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 nuclear translocation

  19. [Study of serum concentrations and urinary excretion of secnidazole after oral administration in man. Comparison with tinidazole].

    PubMed

    Populaire, P; Decouvelaere, B; Renard, A; Pasquier, P

    1980-11-01

    Secnidazole, a derivative of 5-nitro imidazole exhibits trichomonacid, amoebicid and antimicrobial properties; it has been studied in view of its biological fate in healthy volunteers (man and woman) comparatively with tinidazole. Both products were administered orally to the same volunteers at the single dose level of 2 g. The seric concentrations and the pharmacokinetic profile were determined up to the 72nd hour after drug administration. The whole urinary excretion (unchanged product + metabolites) during the same period was determined in percent of the administered dose level. Secnidazole is particularly different from tinidazole owing to its slower blood clearance. The apparent average half-life in the ten volunteers (5 men and 5 women) is about 17 hours for secnidazole and 13 hours for tinidazole. However, for both drugs, a difference between men and women was demonstrated: in female volunteers, the decrease in blood concentrations occurs a little quicker than in male volunteers. Regarding urinary excretion, it is also a little greater in female volunteers than in male volunteers. PMID:7003510

  20. Inhibitors

    MedlinePlus

    ... Community Counts Blood Safety Inhibitors Articles & Key Findings Free Materials Videos Starting the Conversation Playing it Safe A Look at Hemophilia Joint Range of Motion My Story Links to Other Websites ...

  1. Proton pump inhibitors protect mice from acute systemic inflammation and induce long-term cross-tolerance

    PubMed Central

    Balza, E; Piccioli, P; Carta, S; Lavieri, R; Gattorno, M; Semino, C; Castellani, P; Rubartelli, A

    2016-01-01

    Incidence of sepsis is increasing, representing a tremendous burden for health-care systems. Death in acute sepsis is attributed to hyperinflammatory responses, but the underlying mechanisms are still unclear. We report here that proton pump inhibitors (PPIs), which block gastric acid secretion, selectively inhibited tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) secretion by Toll-like receptor (TLR)-activated human monocytes in vitro, in the absence of toxic effects. Remarkably, the oversecretion of IL-1β that represents a hallmark of monocytes from patients affected by cryopyrin-associated periodic syndrome is also blocked. Based on these propaedeutic experiments, we tested the effects of high doses of PPIs in vivo in the mouse model of endotoxic shock. Our data show that a single administration of PPI protected mice from death (60% survival versus 5% of untreated mice) and decreased TNF-α and IL-1β systemic production. PPIs were efficacious even when administered after lipopolysaccharide (LPS) injection. PPI-treated mice that survived developed a long-term cross-tolerance, becoming resistant to LPS- and zymosan-induced sepsis. In vitro, their macrophages displayed impaired TNF-α and IL-1β to different TLR ligands. PPIs also prevented sodium thioglycollate-induced peritoneal inflammation, indicating their efficacy also in a non-infectious setting independent of TLR stimulation. Lack of toxicity and therapeutic effectiveness make PPIs promising new drugs against sepsis and other severe inflammatory conditions. PMID:27441656

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

    PubMed

    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. PMID:27380396

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

    PubMed Central

    2010-01-01

    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. PMID:20562062

  4. Asymmetric Dimethylarginine versus Proton Pump Inhibitors Usage in Patients with Stable Coronary Artery Disease: A Cross-Sectional Study

    PubMed Central

    Kruszelnicka, Olga; Świerszcz, Jolanta; Bednarek, Jacek; Chyrchel, Bernadeta; Surdacki, Andrzej; Nessler, Jadwiga

    2016-01-01

    A recent experimental study suggested that proton pump inhibitors (PPI), widely used to prevent gastroduodenal complications of dual antiplatelet therapy, may increase the accumulation of the endogenous nitric oxide synthesis antagonist asymmetric dimethylarginine (ADMA), an adverse outcome predictor. Our aim was to assess the effect of PPI usage on circulating ADMA in coronary artery disease (CAD). Plasma ADMA levels were compared according to PPI use for ≥1 month prior to admission in 128 previously described non-diabetic men with stable CAD who were free of heart failure or other coexistent diseases. Patients on PPI tended to be older and with insignificantly lower estimated glomerular filtration rate (GFR). PPI use was not associated with any effect on plasma ADMA (0.51 ± 0.11 (SD) vs. 0.50 ± 0.10 µmol/L for those with PPI (n = 53) and without PPI (n = 75), respectively; p = 0.7). Additionally, plasma ADMA did not differ between PPI users and non-users stratified by a history of current smoking, CAD severity or extent. The adjustment for patients’ age and GFR did not substantially change the results. Thus, PPI usage does not appear to affect circulating ADMA in non-diabetic men with stable CAD. Whether novel mechanisms of adverse PPI effects on the vasculature can be translated into clinical conditions, requires further studies. PMID:27092494

  5. Asymmetric Dimethylarginine versus Proton Pump Inhibitors Usage in Patients with Stable Coronary Artery Disease: A Cross-Sectional Study.

    PubMed

    Kruszelnicka, Olga; Świerszcz, Jolanta; Bednarek, Jacek; Chyrchel, Bernadeta; Surdacki, Andrzej; Nessler, Jadwiga

    2016-01-01

    A recent experimental study suggested that proton pump inhibitors (PPI), widely used to prevent gastroduodenal complications of dual antiplatelet therapy, may increase the accumulation of the endogenous nitric oxide synthesis antagonist asymmetric dimethylarginine (ADMA), an adverse outcome predictor. Our aim was to assess the effect of PPI usage on circulating ADMA in coronary artery disease (CAD). Plasma ADMA levels were compared according to PPI use for ≥1 month prior to admission in 128 previously described non-diabetic men with stable CAD who were free of heart failure or other coexistent diseases. Patients on PPI tended to be older and with insignificantly lower estimated glomerular filtration rate (GFR). PPI use was not associated with any effect on plasma ADMA (0.51 ± 0.11 (SD) vs. 0.50 ± 0.10 µmol/L for those with PPI (n = 53) and without PPI (n = 75), respectively; p = 0.7). Additionally, plasma ADMA did not differ between PPI users and non-users stratified by a history of current smoking, CAD severity or extent. The adjustment for patients' age and GFR did not substantially change the results. Thus, PPI usage does not appear to affect circulating ADMA in non-diabetic men with stable CAD. Whether novel mechanisms of adverse PPI effects on the vasculature can be translated into clinical conditions, requires further studies. PMID:27092494

  6. Proton pump inhibitors protect mice from acute systemic inflammation and induce long-term cross-tolerance.

    PubMed

    Balza, E; Piccioli, P; Carta, S; Lavieri, R; Gattorno, M; Semino, C; Castellani, P; Rubartelli, A

    2016-01-01

    Incidence of sepsis is increasing, representing a tremendous burden for health-care systems. Death in acute sepsis is attributed to hyperinflammatory responses, but the underlying mechanisms are still unclear. We report here that proton pump inhibitors (PPIs), which block gastric acid secretion, selectively inhibited tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) secretion by Toll-like receptor (TLR)-activated human monocytes in vitro, in the absence of toxic effects. Remarkably, the oversecretion of IL-1β that represents a hallmark of monocytes from patients affected by cryopyrin-associated periodic syndrome is also blocked. Based on these propaedeutic experiments, we tested the effects of high doses of PPIs in vivo in the mouse model of endotoxic shock. Our data show that a single administration of PPI protected mice from death (60% survival versus 5% of untreated mice) and decreased TNF-α and IL-1β systemic production. PPIs were efficacious even when administered after lipopolysaccharide (LPS) injection. PPI-treated mice that survived developed a long-term cross-tolerance, becoming resistant to LPS- and zymosan-induced sepsis. In vitro, their macrophages displayed impaired TNF-α and IL-1β to different TLR ligands. PPIs also prevented sodium thioglycollate-induced peritoneal inflammation, indicating their efficacy also in a non-infectious setting independent of TLR stimulation. Lack of toxicity and therapeutic effectiveness make PPIs promising new drugs against sepsis and other severe inflammatory conditions. PMID:27441656

  7. Pyrazolo[4,3-c][1,2]benzothiazines 5,5-dioxide: a promising new class of Staphylococcus aureus NorA efflux pump inhibitors.

    PubMed

    Sabatini, Stefano; Gosetto, Francesca; Serritella, Serena; Manfroni, Giuseppe; Tabarrini, Oriana; Iraci, Nunzio; Brincat, Jean Pierre; Carosati, Emanuele; Villarini, Milena; Kaatz, Glenn W; Cecchetti, Violetta

    2012-04-12

    The increasing resistance to antibacterials commonly employed in the clinic and the growth of multidrug resistant strains suggest that the development of new therapeutic approaches should be of primary concern. In this context, EPIs may restore life to old drugs. In the present work, the EPI activity of the COX-2 inhibitor celecoxib was confirmed and a new class of pyrazolo[4,3-c][1,2]benzothiazine 5,5-dioxide analogues acting as inhibitors of the Staphylococcus aureus NorA multidrug efflux pump was identified. PMID:22432682

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

    PubMed Central

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

    2016-01-01

    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. PMID:27471402

  9. In Vitro Activities of Rabeprazole, a Novel Proton Pump Inhibitor, and Its Thioether Derivative Alone and in Combination with Other Antimicrobials against Recent Clinical Isolates of Helicobacter pylori

    PubMed Central

    Kawakami, Yoshiyuki; Akahane, Takayuki; Yamaguchi, Masaru; Oana, Kozue; Takahashi, Yuko; Okimura, Yukie; Okabe, Tadashi; Gotoh, Akira; Katsuyama, Tsutomu

    2000-01-01

    The MICs of rabeprazole sodium (RPZ), a newly developed benzimidazole proton pump inhibitor (PPI), against 133 clinical Helicobacter pylori strains revealed a higher degree of activity than the another two PPIs, lansoprazole and omeprazole. Time-kill curve assays of RPZ, when combined with amoxicillin, clarithromycin, or metronidazole, disclosed that synergistic effects were demonstrated in combination with each antibiotic examined. Moreover, no apparent antagonistic effect appeared among all of the strains tested. PMID:10639386

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

    PubMed

    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. PMID:25746736

  11. The use of proton pump inhibitors decreases the risk of diabetes mellitus in patients with upper gastrointestinal disease

    PubMed Central

    Lin, Hsiu-Chen; Hsiao, Yu-Ting; Lin, Hsiu-Li; Uang, Yow-Shieng; Cheng, Hui-Wen; Wang, Ying; Wang, Li-Hsuan

    2016-01-01

    Abstract Objectives: The aim of this study was to investigate the effects of proton pump inhibitors (PPIs) on the risk of diabetes mellitus (DM) among patients with upper gastrointestinal disease (UGID). Methods: This was a retrospective cohort study with a follow-up period of 5 years. We identified 388,098 patients who were diagnosed with UGID between 2000 and 2006 from the Longitudinal Health Insurance Database of the Taiwan National Health Insurance program. We used Cox proportional hazard ratio (HR) to compare the risk of DM between UGID patients received PPIs and those did not receive PPIs. HRs were adjusted for possible confounders, including age, sex, hypertension, gout and/or hyperuricemia, coronary artery disease, stroke, pancreatitis, hyperlipidemia, obesity, H2-blocker use, and clozapine or olanzapine use. The dose-related effects of PPIs on the risk of DM were evaluated according to the defined daily dose (DDD). Results: The adjusted HR was 0.80 (95% CI, 0.73–0.88) for the study group (UGID patients with PPIs) compared with comparison group I (UGID patients without PPIs). Among patients who used PPIs, those older than 60 years of age had a lower risk of DM (HR, 0.73; 95% CI, 0.63–0.83) than those younger than 40 years. Additionally, the effect of PPIs was significantly dose-dependent (P for trend <0.001). Patients with UGID who received >540 DDDs of PPIs exhibited the greatest reduction in the risk of DM. Conclusions: Our results demonstrated a decreased risk of DM in UGID patients who used PPIs; the risk appeared to be significantly dose-dependent. PMID:27428221

  12. Acute Coronary Syndromes, Gastrointestinal Protection, and Recommendations Regarding Concomitant Administration of Proton-Pump Inhibitors (Omeprazol/Esomeprazole) and Clopidogrel.

    PubMed

    Lozano, Iñigo; Sanchez-Insa, Esther; de Leiras, Sergio Rodríguez; Carrillo, Pilar; Ruiz-Quevedo, Valeriano; Pinar, Eduardo; Gopar-Gopar, Silvia; Bayon, Jeremías; Mañas, Pilar; Lasa, Garikoitz; CruzGonzalez, Ignacio; Hernandez, Felipe; Fernandez-Portales, Javier; Fernandez-Fernandez, Javier; Pérez-Serradilla, Ana; de la Torre Hernandez, José M; Gomez-Jaume, Alfredo

    2016-02-01

    The Food and Drug Administration and the European Medicines Agency sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. The purpose is to know the gastroprotective approach in patients with acute coronary syndrome (ACS) and the level of follow-up of the alert. In 17 hospitals with catheterization laboratory in Spain, 1 per region, we studied 25 consecutive patients per hospital whose diagnosis of discharge since October 1, 2013, had been any type of ACS. We analyzed their baseline clinical profile, the gatroprotective agents at admission and discharge and the antiplatelet therapy at discharge. The number of patients included was 425: age 67.2 ± 12.5 years, women 29.8%, diabetes 36.5%. The patients presented unstable angina in 21.6%, non-ST-elevation myocardial infarction in 35.3% and ST-elevation myocardial infarction in 43.1%. Conservative approach was chosen in 17.9%, bare-metal stents 32.2%, ≥ 1 drug-eluting stent 48.5%, and surgery 1.4%. Aspirin was indicated in 1.9%, aspirin + clopidogrel 73.6%, aspirin + prasugrel 17.6%, and aspririn + ticagrelor 6.8%. Gastroprotective agents were present in 40.2% patients at admission and this percentage increased to 93.7% at discharge. Of the 313 (73.6%) on clopidogrel in 96 (30.6%) was combined with omeprazole and 3 (0.95%) with esomeprazole, whereas the most commonly used was pantoprazole with 190 patients (44.7%). In conclusion, almost the totality of the patients with an ACS receive gastroprotective agents at the moment of discharge, most of them with proton-pump inhibitors. In one every 3 cases of the patients who are on clopidogrel, the recommendation of the Food and Drug Administration and the European Medicines Agency is not followed. PMID:26708640

  13. Transoral Incisionless Fundoplication Effective in Eliminating GERD Symptoms in Partial Responders to Proton Pump Inhibitor Therapy at 6 Months

    PubMed Central

    Barnes, William E.; Simoni, Gilbert; Shughoury, Ahmad B.; Mavrelis, Peter G.; Raza, Mamoon; Heise, Jeffrey A.; Turgeon, Daniel G.; Fox, Mark A.

    2015-01-01

    Background. Incomplete control of troublesome regurgitation and extraesophageal manifestations of chronic gastroesophageal reflux disease (GERD) is a known limitation of proton pump inhibitor (PPI) therapy. This multicenter randomized study compared the efficacy of transoral incisionless fundoplication (TIF) against PPIs in controlling these symptoms in patients with small hiatal hernias. Methods. Between June and August 2012, 63 patients were randomized at 7 US community hospitals. Patients in the PPI group were placed on maximum standard dose (MSD). Patients in the TIF group underwent esophagogastric fundoplication using the EsophyX2 device. Primary outcome was elimination of daily troublesome regurgitation or extraesophageal symptoms. Secondary outcomes were normalization of esophageal acid exposure (EAE), PPI usage and healing of esophagitis. Results. Of 63 randomized patients (40 TIF and 23 PPI), 3 were lost to follow-up leaving 39 TIF and 21 PPI patients for analysis. At 6-month follow-up, troublesome regurgitation was eliminated in 97% of TIF patients versus 50% of PPI patients, relative risk (RR) = 1.9, 95% confidence interval (CI) = 1.2-3.11 (P = .006). Globally, 62% of TIF patients experienced elimination of regurgitation and extraesophageal symptoms versus 5% of PPI patients, RR = 12.9, 95% CI = 1.9-88.9 (P = .009). EAE was normalized in 54% of TIF patients (off PPIs) versus 52% of PPI patients (on MSD), RR = 1.0, 95% CI = 0.6-1.7 (P = .914). Ninety percent of TIF patients were off PPIs. Conclusion. At 6-month follow-up, TIF was more effective than MSD PPI therapy in eliminating troublesome regurgitation and extraesophageal symptoms of GERD. PMID:24756976

  14. Bone Mineral Density Changes Among Women Initiating Proton Pump Inhibitors or H2 Receptor Antagonists: A SWAN Cohort Study

    PubMed Central

    Solomon, Daniel H; Diem, Susan J; Ruppert, Kristine; Juan Lian, Yin; Liu, Chih-Chin; Wohlfart, Alyssa; Greendale, Gail A; Finkelstein, Joel S

    2015-01-01

    Proton pump inhibitors (PPIs) have been associated with diminished bone mineral density (BMD) and an increased risk of fracture; however, prior studies have not yielded consistent results, and many have suboptimal ascertainment of both PPI use and BMD. We used data from the Study of Women’s Health Across the Nation (SWAN), a multicenter, multi-ethnic, community-based longitudinal cohort study of women across the menopause transition to examine the association between annualized BMD changes and new use of PPIs. We compared changes in BMD in new PPI users with changes in BMD in new users of histamine 2 receptor antagonists (H2RAs) and with changes in BMD in subjects who did not use either class of medications. Mixed linear regression models included recognized risk factors for osteoporosis, including demographics, menopausal transition stage, body mass index (BMI), lifestyle factors, as well as comorbidities and concomitant medications. To provide further evidence for the validity of our analytic approach, we also examined the effects of hormone-replacement therapy (HT), a class of medications that should reduce bone loss, on changes in BMD as an internal positive control group. We identified 207 new users of PPIs, 185 new users of H2RAs, and 1,676 non-users. Study subjects had a mean age of 50 years and were followed for a median of 9.9 years. Adjusted models found no difference in the annualized BMD change at the lumbar spine, femoral neck, or total hip in PPI users compared with H2RA users or non-users. These results were robust to sensitivity analyses. BMD increased as expected in HT users, supporting the validity of our study design. These longitudinal analyses plus similar prior studies argue against an association between PPI use and BMD loss. PMID:25156141

  15. Cardiovascular outcomes and mortality in patients using clopidogrel with proton pump inhibitors after percutaneous coronary intervention or acute coronary syndrome

    PubMed Central

    Rassen, Jeremy A.; Choudhry, Niteesh K.; Avorn, Jerry; Schneeweiss, Sebastian

    2010-01-01

    Background Recent studies have raised concerns about reduced efficacy of clopidogrel when used concurrently with proton pump inhibitors (PPIs), but those studies may have overestimated the risk. Methods and Results We studied the potential for increased risk of adverse cardiovascular events among users of clopidogrel with concurrent use of PPIs versus without, in three large cohorts of patients ≥ 65 years treated between 2001-2005. All patients had undergone percutaneous coronary intervention or been hospitalized for acute coronary syndrome in Pennsylvania, New Jersey, or British Columbia, and had subsequently initiated treatment with clopidogrel. We recorded myocardial infarction (MI) hospitalization, death, and revascularization among PPI users and non-users. We assessed our primary endpoint of MI or death using cohort-specific and pooled regression analyses. 18,565 clopidogrel users entered our analysis. On a pooled basis, 2.6% of those who also initiated a PPI versus 2.1% of PPI non-users had an MI hospitalization; 1.5% versus 0.9% died, and 3.4% versus 3.1% underwent revascularization. The propensity score-adjusted rate ratio for the primary endpoint of MI or death was 1.22 (95% confidence interval 0.99 to 1.51); for death 1.20 (0.84, 1.70); and for revascularization, 0.97 (0.79 to 1.21). Matched analyses generally yielded similar results. Conclusions Though point estimates indicated a slightly increased risk of MI or death in older patients initiating both clopidogrel and a PPI, we did not observe conclusive evidence of a clopidogrel/PPI interaction of major clinical relevance. Our data suggest that should this effect exist, is unlikely to exceed a 20% risk increase. PMID:19933932

  16. Non-Specific Gastric Inflammation in Children is Associated with Proton Pump Inhibitor Treatment for More than 6 Weeks

    PubMed Central

    Rosas-Blum, Eduardo; Tatevian, Nina; Hashmi, Syed Shahrukh; Rhoads, Jon Marc; Navarro, Fernando

    2014-01-01

    Background and Aims: Non-specific gastric inflammation (NSGI) is a commonly reported pathological finding. We investigated if it is associated with the use of proton pump inhibitors (PPIs) in children at a single tertiary center. Methods: We performed an IRB-approved chart review of all endoscopy and biopsy reports of patients who underwent esophagogastroduodenoscopy between July 2009 and July 2010 (n = 310). Demographic data, dose, duration of exposure to PPI, and biopsy results were collected and analyzed. All esophageal, gastric, and duodenal biopsies were independently reviewed by a pathologist. Patients with acute gastritis, moderate/severe chronic gastric inflammation, or Helicobacter pylori infection were excluded. The presence of NSGI was compared between patients exposed and not exposed to PPI as well as between patients with different doses and durations of PPI exposure to assess for potential associations. Results: A total of 193 patients were included: 88 (46%) had a history of PPI use and 48 (25%) were found to have NSGI. Compared to patients not exposed to PPI, the odds ratio of NSGI in patients exposed to PPIs was 2.81 (95% CI: 1.36–5.93). The odds ratio of NSGI in patients exposed to PPI for >3 months was 4.53 (95% CI: 1.69–11.97). Gender, ethnicity, and age were not associated with NSGI. No histological differences were found in the esophagus and duodenum between patients exposed and not exposed to PPI. Conclusion: This study found that PPI exposure is associated with NSGI with a higher risk for those exposed for >3 months. As the clinical implications of NSGI are not known, judicious use of PPIs is needed. Prospective studies are required to confirm and to determine the etiologic factors (i.e., alteration of the gastric pH, serum gastrin) that may be related with the presence of NGSI. PMID:24479108

  17. Proton Pump Inhibitor Therapy Is Associated With Reduction of Early Bleeding Risk After Prophylactic Endoscopic Variceal Band Ligation

    PubMed Central

    Kang, Seong Hee; Yim, Hyung Joon; Kim, Seung Young; Suh, Sang Jun; Hyun, Jong Jin; Jung, Sung Woo; Jung, Young Kul; Koo, Ja Seol; Lee, Sang Woo

    2016-01-01

    Abstract Endoscopic variceal band ligation (EVL) is an effective procedure to control and prevent variceal bleeding in patients with liver cirrhosis, but it can be complicated by bleeding from post-EVL ulcers. Several studies have reported that proton pump inhibitors (PPIs) decrease the size of post-EVL ulcers. However, evidence are limited as to whether PPIs actually reduce the risk of bleeding after EVL. This study aimed to analyze the factors associated with bleeding after prophylactic EVL and to assess the effect of PPI therapy. Five hundred and five cirrhotic patients with high risk esophageal varices who received primary prophylactic EVL were included for this retrospective cohort study. Post-EVL bleeding was defined as bleeding after prophylactic EVL within 8 weeks evidenced by the occurrence of melena or hematemesis, or by a decrease of hemoglobin by >2.0 g/dL. If evidence of bleeding from ulceration of the EVL sites was confirmed by endoscopy, we defined it as post-EVL ulcer bleeding. Fourteen patients developed bleeding after prophylactic EVL. Factors associated with post-EVL bleeding included alcohol as etiology, low albumin, high total bilirubin, high Child-Pugh score, high MELD score, coexistence of gastric varices, and not administrating PPI medication by univariate analysis. In multivariate logistic analysis, Co-existing gastric varix (odds ratio [OR] 5.680, P = 0.005] and not administrating PPIs (OR 8.217, P = 0.002) were associated with bleeding after prophylactic EVL. In the subgroup analysis excluding patients whose gastric varices were treated, not administering PPI medication (OR 8.827, P = 0.008) was the sole factor associated with post-EVL bleeding. We suggest that PPI therapy needs to be considered in patients receiving prophylactic EVL to reduce the risk of bleeding after prophylactic EVL. PMID:26937932

  18. Protective Effect of Proton Pump Inhibitor for Survival in Patients with Gastroesophageal Reflux Disease and Idiopathic Pulmonary Fibrosis

    PubMed Central

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

    2016-01-01

    Background/Aims The prevalence of gastroesophageal reflux disease (GERD) is high in patients with idiopathic pulmonary fibrosis (IPF). GERD may cause chronic microaspiration that leads to repeated subclinical lung injury, which leads to pulmonary fibrosis. Although some studies have suggested that proton pump inhibitors (PPI) were associated with a good prognosis in IPF, their effects remain unclear. Methods We retrospectively reviewed 786 consecutive adult patients with IPF at Seoul National University Bundang Hospital between April 2003 and March 2015. Results Mean duration of follow-up was 2.6 ± 2.8 years. Of the 786 patients with IPF, 107 (13.6%) were given diagnoses of GERD, and 103 (13.1%) died due to IPF-related pneumonia or respiratory failure. The prevalence of GERD and the cumulative incidence of de novo GERD increased depending on the period of follow-up in patients with IPF. Patients administered PPI for more than four months had a lower IPF-related mortality rate than patients on PPI less than 4 months (Log-rank P-value = 0.024 in Kaplan-Meier curve). In a univariate and multivariate Cox regression hazard model, younger age (hazard ratio [HR], 1.06; 95% CI, 1.03–1.10; P = 0.001), higher initial forced vital capacity (HR, 0.98; 95% CI, 0.96–0.99; P = 0.004), and longer duration of PPI use (HR, 0.97; 95% CI, 0.95–1.00; P = 0.022), but not a diagnosis of GERD, were significantly associated with lower IPF-related mortality. Conclusions In Korean patients with IPF, the prevalence of GERD was lower than in other countries. PPI use for at least 4 months may have a protective effect against IPF-related mortality. PMID:26932897

  19. Impact of concomitant treatment with proton pump inhibitors and clopidogrel on clinical outcome in patients after coronary stent implantation.

    PubMed

    Tentzeris, Ioannis; Jarai, Rudolf; Farhan, Serdar; Brozovic, Ivan; Smetana, Peter; Geppert, Alexander; Wojta, Johann; Siller-Matula, Jolanta; Huber, Kurt

    2010-12-01

    The aim of the study was to evaluate the effect of the concomitant treatment with proton-pump inhibitors (PPIs) and clopidogrel on the incidence of stent thrombosis, acute coronary syndrome (ACS) and death in patients who underwent percutaneous coronary intervention (PCI) and stent implantation. In total, 1,210 patients under dual antiplatelet therapy, who underwent PCI and stent implantation, were included in a prospective registry from January 2003 until December 2006. The patients were divided retrospectively into those with or without long-term PPI treatment (for the duration of dual antiplatelet therapy). All-cause mortality, cardiovascular death, re-hospitalisation for re-ACS, stent thrombosis, as well as the combined endpoint all-cause death, re-ACS or stent thrombosis were evaluated over a mean follow-up period of 7.8 (± 3.63) months (range 1-12 months). Propensity score analysis was performed to reduce potential selection bias and exhibited no significant difference between the two study groups with respect to all-cause mortality, cardiovascular death, re-ACS, stent thrombosis and the combined endpoint. In pre-specified subgroup analyses performed in patients presenting with ACS and referred for acute PCI or for stable patients referred for elective PCI, receiving drug-eluting stents or bare metal stents, in diabetics or non-diabetics, in males or females, and in patients older than 75 years or ≤75 years of age use of PPIs had no significant impact on clinical outcome. Our data suggest that a combined use of clopidogrel as part of dual antiplatelet therapy (DAPT) after coronary stenting and PPIs does not significantly influence the clinical outcome. PMID:20941464

  20. Association Between Recent Use of Proton Pump Inhibitors and Nontyphoid Salmonellosis: A Nested Case-Control Study

    PubMed Central

    Wu, Hau-Hsin; Chen, Yung-Tai; Shih, Chia-Jen; Lee, Yi-Tzu; Kuo, Shu-Chen; Chen, Te-Li

    2014-01-01

    Background. The association between proton pump inhibitors (PPIs) and nontyphoid salmonellosis (NTS) continues to be debated. The current study was designed to determine the association between use of oral PPIs and the diagnosis of NTS. Methods. The Taiwan National Health Insurance Research Database from 2000 to 2010 was searched for cases of NTS, defined by the International Classification of Disease, Ninth revision, Clinical Modification. A nested case-control study in hospitalized population was conducted using 4 controls for each case patient (14 736 case patients and 58 944 controls), matched for age, month and year of entry, Charlson comorbidity index score, and well-known predisposing factors for NTS, including autoimmune diseases, acquired immunodeficiency syndrome, diabetes, cirrhosis, transplantation, gastrointestinal operations or diseases, and malignancies. Results. Persons with NTS had a higher rate of using oral PPIs within the prior year (adjusted odds ratio [OR], 2.09; 95% confidence interval [CI], 1.95–2.24; P < .001). The association was greatest for current PPI use (adjusted OR, 5.39; 95% CI, 4.79–6.06; P < .001). Although use of H2-receptor antagonists (adjusted OR, 1.84; 95% CI, 1.71–1.98), antibiotics (5.21; 4.81–5.64), steroids (3.18; 2.99–3.39), and nonsteroidal anti-inflammatory drugs (2.37; 2.26–2.48) within the 30 days were also associated with NTS, the linkage between PPI use and NTS remained significant in the subgroup without these medications. Conclusions. The use of oral PPIs was associated with the occurrence of NTS. The risk waned with time after discontinuation. PMID:25091310

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

    PubMed Central

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

    2015-01-01

    AIM: To clarify the pathogenesis of gastroesophageal reflux disease symptoms in non-erosive reflux disease (NERD) patients. METHODS: Thirty-five NERD patients with persistent symptoms, despite taking rabeprazole 10 mg twice daily for at least 8 wk, were included in this study. All patients underwent 24 h combined impedance - pH on rabeprazole. The symptom index (SI) was considered to be positive if ≥ 50%, and proximal reflux episodes were determined when reflux reached 15 cm above the proximal margin of the lower esophageal sphincter. RESULTS: In 14 (40%) SI-positive patients, with liquid weakly acid reflux, the occurrence rate of reflux symptoms was significantly more frequent in proximal reflux episodes (46.7%) than in distal ones (5.7%) (P < 0.001). With liquid acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes (38.5%) and distal ones (20.5%) (NS). With mixed liquid-gas weakly acid reflux, the occurrence rate of reflux symptoms in proximal reflux episodes was significantly more frequent (31.0%) than in distal reflux ones (3.3%) (P < 0.001). With mixed liquid-gas acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes (29.4%) and distal ones (14.3%) (NS). CONCLUSION: The proximal extent of weakly acidic liquid and mixed liquid-gas reflux is a major factor associated with reflux perception in SI-positive patients on proton pump inhibitor therapy. PMID:26715820

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

    PubMed

    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. PMID:25947914

  3. Proton pump inhibitors

    MedlinePlus

    ... used to: Relieve symptoms of acid reflux, or gastroesophageal reflux disease (GERD). This is a condition in which food or ... MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol . 2013;108:308-28. ...

  4. Anti-cancer-prostaglandin-induced cell-cycle arrest and its modulation by an inhibitor of the ATP-dependent glutathione S-conjugate export pump (GS-X pump).

    PubMed Central

    Ishikawa, T; Akimaru, K; Nakanishi, M; Tomokiyo, K; Furuta, K; Suzuki, M; Noyori, R

    1998-01-01

    The A and J series of prostaglandins (PGs) accumulate in the nuclei to suppress the proliferation of cancer cells. Here we report that Delta7-PGA1 methyl ester, a synthetic anti-cancer PG, increased the level of mRNA for the cyclin-dependent kinase inhibitor p21 in human leukaemia HL-60 cells. The induction of p21 was associated with the accumulation of hypophosphorylated retinoblastoma protein (pRB) and the suppression of c-myc gene expression. Since the p53 gene is deleted in HL-60 cells, the anti-cancer PG is suggested to inhibit cancer cell growth by inducing p21 via a p53-independent pathway. Unlike HL-60 cells, cisplatin-resistant HL-60/R-CP cells were insensitive to Delta7-PGA1 methyl ester. While c-myc expression was transiently suppressed, neither G1 arrest nor hypophosphorylation of pRB was observed with the anti-cancer PG. Plasma membrane vesicles from HL-60/R-CP cells showed an enhanced level of GS-X pump (ATP-dependent glutathione S-conjugate export pump) activity towards the glutathione S-conjugate of Delta7-PGA1 methyl ester (Km 110 nM). GIF-0019 ¿N-carbomethoxy-S-[5-(4-benzoylphenyl)pentyl]glutathione dimethyl ester¿, a specific inhibitor of the GS-X pump, dose-dependently enhanced the cellular sensitivity of HL-60/R-CP cells to Delta7-PGA1 methyl ester and induced G1 arrest. The GS-X pump is suggested to play a pivotal role in modulating the biological action of the anti-cancer PG. PMID:9841867

  5. Mealtime-related dosing directions for proton-pump inhibitors in gastroesophageal reflux disease: physician knowledge, patient adherence.

    PubMed

    Solem, Caitlyn; Mody, Reema; Stephens, Jennifer; Macahilig, Cynthia; Gao, Xin

    2014-01-01

    OBJECTIVE To describe physicians' knowledge, patients' adherence, and perceptions of both regarding mealtime-related dosing directions for proton-pump inhibitors (PPIs). DESIGN Chart review and survey of patients and physicians. SETTING United States, with data collected between January and July 2011. PARTICIPANTS Patients being treated for gastroesophageal reflux disease (GERD) with PPIs and their prescribing physicians. MAIN OUTCOME MEASURES Patient- and physician-reported perception of PPI mealtime-related directions as important/inconvenient (seven-point Likert scale; 7 = very important/very inconvenient); physician-reported knowledge of PPI mealtime-related dosing directions based on whether the agent is labeled to be taken 30-60 minutes before eating (DIR-esomeprazole magnesium [Nexium-AstraZeneca], lansoprazole, and omeprazole) or labeled to be taken regardless of meals (NoDIR-dexlansoprazole [Dexilant-Takeda], rabeprazole, and pantoprazole); and patient-reported PPI mealtime-related directions received and adherence to directions. RESULTS Physicians (n = 262) recruited 501 patients who had been prescribed PPIs (262 DIR/239 NoDIR; mean age 51 years, 37% men, 56% nonerosive GERD [29% undocumented]). Across PPIs, physicians frequently reported incorrect directions or "did not know directions" (29% for esomeprazole to 69% for pantoprazole). While 98% of patients reported receiving directions from their physicians and 55% from their pharmacists, only 65% of DIR patients and 18% of NoDIR received directions consistent with product labeling. Physicians perceived greater inconvenience than patients (4.4 vs. 1.6, P < 0.001) and greater importance (5.2 vs. 4.5, P < 0.001) of mealtime-related directions. Overall, 81% of patients reported taking their PPI as directed. CONCLUSION While this patient cohort was adherent to directions given, physicians' directions were often inconsistent with product labeling. Understanding physician and patient knowledge gaps may be

  6. Efficacy of alfacalcidol and alendronate on lumbar bone mineral density in osteoporotic patients using proton pump inhibitors

    PubMed Central

    Asaoka, Daisuke; Nagahara, Akihito; Hojo, Mariko; Matsumoto, Kenshi; Ueyama, Hiroya; Matsumoto, Kohei; Izumi, Kentaro; Takeda, Tsutomu; Komori, Hiroyuki; Akazawa, Yoichi; Shimada, Yuji; Osada, Taro; Watanabe, Sumio

    2016-01-01

    It has been indicated that proton pump inhibitor (PPI) use is associated with a loss of the anti-fracture efficacy of alendronate (AD). However, there are few prospective studies that have investigated the efficacy of AD on lumbar bone mineral density (BMD) in osteoporotic patients who are using PPIs. Thus, the aim of the present study was to investigate the efficacy of alfacalcidol (AC) and AD on lumbar BMD in osteoporotic patients using PPIs. A prospective, randomized, active control study enrolled such osteoporotic patients (age, ≥50 years). The patients were randomly assigned to receive AC (1 µg/day) or AD (35 mg/week) and were followed up for one year. Patient profiles were maintained, and lumbar BMD, bone-specific alkaline-phosphatase (BAP) and collagen type-I cross-linked N-telopeptide (NTX), upper gastrointestinal endoscopy results, and the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) were evaluated. Percentage changes in lumbar BMD, NTX, BAP, and change in FSSG score from baseline to the end of one year of treatment were investigated. Sixteen patients were eligible for analysis (eight assigned to receive AC, eight assigned to receive AD). The percentage change in lumbar BMD from baseline to the end of treatment was −0.4±4.0% for the AC group vs. 6.8±6.3% for the AD group (P=0.015). No significant percentage change of BAP and NTX between the two groups was observed. Subsequent to one year of treatment, the FSSG score did not change from the baseline values for either study group, and no new bone fractures or esophagitis were observed in either group of patients. The findings demonstrated that in osteoporotic patients using concomitant PPIs, there was a greater increase in lumbar BMD after one year of treatment with AD compared with AC. However, the number of study subjects was small; thus, further, large prospective studies are required to determine the effect of AD in osteoporotic patients using concomitant PPIs. PMID

  7. Changes in serum magnesium concentration after use of a proton pump inhibitor in patients undergoing percutaneous coronary intervention

    PubMed Central

    Park, Sang-Ho; Lee, Sun-hyo; Lee, Ji-Sung; Shin, Won-Yong; Gil, Hyo-Wook; Yang, Jong-Oh; Lee, Eun-Young; Hong, Sae-Yong

    2015-01-01

    Background Although cross-sectional studies have suggested a relationship between proton pump inhibitor (PPI) use and hypomagnesemia, no large-scale cohort study has been conducted to date. Here, we examined the changes in serum magnesium levels in response to PPI use. We hypothesized that PPI use might change the serum magnesium concentration. Methods Of the 2,892 patients hospitalized for percutaneous coronary intervention between January 2007 and May 2012, 1,076 patients with normal baseline (1.6–2.5 mg/dL) and follow-up serum magnesium concentrations were enrolled. These patients were divided into two groups: the PPI group and the control group. Results The mean follow-up period was 9.51 ± 2.94 months. The incidence of hypomagnesemia (< 1.6 mg/dL) was 0.4% (3/834) in the PPI group and 0.4% (1/242) in the control group (P = 0.904). The change in magnesium levels did not differ between the two groups, and this result was maintained in the analysis of covariance after adjusting for confounding factors (P = 0.381). Moreover, magnesium levels did not significantly differ between the long-term (duration of use ≥ 12 months, n = 71) and short-term PPI groups (duration of use < 12 months, n = 763), and the control group (n = 242; P = 0.620). The effect of PPI use on change in serum magnesium concentration was affected by the use of multiple diuretics (−0.01 ± 0.25 mg/dL; P = 0.025), although a single diuretic use with PPI did not alter the change in magnesium level (0.12 ± 0.27 mg/dL). Conclusion Changes in magnesium levels might be subtle after PPI use in patients with normal baseline magnesium values. PMID:26484029

  8. Use of proton pump inhibitors and risk of hip/femur fracture: a population-based case-control study

    PubMed Central

    Pouwels, S.; Lalmohamed, A.; Souverein, P.; Cooper, C.; Veldt, B. J.; Leufkens, H. G.; de Boer, A.; van Staa, T.

    2010-01-01

    Summary Previous studies evaluated the association between proton pump inhibitor (PPI) use and subsequent fracture risk, but they showed ambiguous results. Therefore, the objective was to evaluate this association in a different study population. Our findings show that there is probably no causal relationship between PPI use and hip fracture risk. Introduction Previous studies evaluated the association between PPI use and subsequent fracture risk, but they showed ambiguous results. To further test these conflicting results, the objective of this study was to evaluate the association between the use of PPIs and the risk of hip/femur fracture in a different study population. Methods A case-control study was conducted using data from the Dutch PHARMO record linkage system. The study population included 6,763 cases aged 18 years and older with a first hip/femur fracture during enrolment and 26,341 age-, gender- and region-matched controls. Results Current users of PPIs had an increased risk of hip/femur fracture yielding an adjusted odds ratio (AOR) of 1.20 (95% CI 1.04–1.40). Fracture risk attenuated with increasing durations of use, resulting in AORs of 1.26 (95% CI 0.94–1.68) in the first 3 months, 1.31 (95% CI 0.97–1.75) between 3 and 12 months, 1.18 (95% CI 0.92–1.52) between 13 and 36 months and 1.09 (95% CI 0.81–1.47) for use longer than 36 months. Conclusion Our findings show that there is probably no causal relationship between PPI use and hip fracture risk. The observed association may be the result of unmeasured distortions: although current use of PPIs was associated with a 1.2-fold increased risk of hip/femur fracture, the positive association was attenuated with longer durations of continuous use. Our findings do not support that discontinuation of PPIs decreases risk of hip fracture in elderly patients. PMID:20585937

  9. Risk of Community-Acquired Pneumonia with Outpatient Proton-Pump Inhibitor Therapy: A Systematic Review and Meta-Analysis

    PubMed Central

    Lambert, Allison A.; Lam, Jennifer O.; Paik, Julie J.; Ugarte-Gil, Cesar; Drummond, M. Bradley; Crowell, Trevor A.

    2015-01-01

    Background Proton-pump inhibitors (PPIs) are among the most frequently prescribed medications. Community-acquired pneumonia (CAP) is a common cause of morbidity, mortality and healthcare spending. Some studies suggest an increased risk of CAP among PPI users. We conducted a systematic review and meta-analysis to determine the association between outpatient PPI therapy and risk of CAP in adults. Methods We conducted systematic searches of MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Scopus and Web of Science on February 3, 2014. Case-control studies, case-crossover, cohort studies and randomized controlled trials reporting outpatient PPI exposure and CAP diagnosis for patients ≥18 years old were eligible. Our primary outcome was the association between CAP and PPI therapy. A secondary outcome examined the risk of hospitalization for CAP and subgroup analyses evaluated the association between PPI use and CAP among patients of different age groups, by different PPI doses, and by different durations of PPI therapy. Results Systematic review of 33 studies was performed, of which 26 studies were included in the meta-analysis. These 26 studies included 226,769 cases of CAP among 6,351,656 participants. We observed a pooled risk of CAP with ambulatory PPI therapy of 1.49 (95% CI 1.16, 1.92; I2 99.2%). This risk was increased during the first month of therapy (OR 2.10; 95% CI 1.39, 3.16), regardless of PPI dose or patient age. PPI therapy also increased risk for hospitalization for CAP (OR 1.61; 95% CI: 1.12, 2.31). Discussion Outpatient PPI use is associated with a 1.5-fold increased risk of CAP, with the highest risk within the first 30 days after initiation of therapy. Providers should be aware of this risk when considering PPI use, especially in cases where alternative regimens may be available or the benefits of PPI use are uncertain. PMID:26042842

  10. Evolution from a natural flavones nucleus to obtain 2-(4-Propoxyphenyl)quinoline derivatives as potent inhibitors of the S. aureus NorA efflux pump.

    PubMed

    Sabatini, Stefano; Gosetto, Francesca; Manfroni, Giuseppe; Tabarrini, Oriana; Kaatz, Glenn W; Patel, Diixa; Cecchetti, Violetta

    2011-08-25

    Overexpression of efflux pumps is an important mechanism by which bacteria evade the effects of substrate antimicrobial agents. Inhibition of such pumps is a promising strategy to circumvent this resistance mechanism. NorA is a Staphylococcus aureus efflux pump that confers reduced susceptibility to many structurally unrelated agents, including fluoroquinolones, resulting in a multidrug resistant phenotype. In this work, a series of 2-phenyl-4(1H)-quinolone and 2-phenyl-4-hydroxyquinoline derivatives, obtained by modifying the flavone nucleus of known efflux pump inhibitors (EPIs), were synthesized in an effort to identify more potent S. aureus NorA EPIs. The 2-phenyl-4-hydroxyquinoline derivatives 28f and 29f display potent EPI activity against SA-1199B, a strain that overexpresses norA, in an ethidium bromide efflux inhibition assay. The same compounds, in combination with ciprofloxacin, were able to completely restore its antibacterial activity against both S. aureus SA-K2378 and SA-1199B, norA-overexpressing strains. PMID:21751791

  11. From phenothiazine to 3-phenyl-1,4-benzothiazine derivatives as inhibitors of the Staphylococcus aureus NorA multidrug efflux pump.

    PubMed

    Sabatini, Stefano; Kaatz, Glenn W; Rossolini, Gian Maria; Brandini, David; Fravolini, Arnaldo

    2008-07-24

    Overexpression of efflux pumps is an important mechanism by which bacteria evade effects of substrate antimicrobial agents and inhibition of such pumps is a promising strategy to circumvent this resistance mechanism. NorA is a Staphylococcus aureus multidrug efflux pump, the activity of which confers decreased susceptibility to many structurally unrelated agents, including fluoroquinolones, resulting in a multidrug resistant (MDR) phenotype. In this work, a series of 1,4-benzothiazine derivatives were designed and synthesized as a minimized structural template of phenothiazine MDR efflux pump inhibitors (EPIs) in an effort to identify more potent S. aureus NorA EPIs. Almost all derivatives evaluated showed good activity in combination with ciprofloxacin against S. aureus ATCC 25923; some were capable of completely restoring ciprofloxacin activity in a norA-overexpressing strain (SA-K2378). Compounds 6k and 7j displayed good activity against SA-1199B, a strain that also overexpresses norA, in an ethidium bromide (EtBr) efflux inhibition assay. PMID:18578473

  12. Amino acid amides of piperic acid (PA) and 4-ethylpiperic acid (EPA) as NorA efflux pump inhibitors of Staphylococcus aureus.

    PubMed

    Wani, Naiem Ahmad; Singh, Samsher; Farooq, Saleem; Shankar, Sudha; Koul, Surrinder; Khan, Inshad Ali; Rai, Rajkishor

    2016-09-01

    A total of eighteen piperic acid (PA) and 4-ethylpiperic acid (EPA) amides (C1-C18) with α-, β- and γ-amino acids were synthesized, characterized and evaluated for their efflux pump inhibitory activity against ciprofloxacin resistant Staphylococcus aureus. The amides were screened against NorA overexpressing S. aureus SA-1199B and wild type S. aureus SA-1199 using ethidium bromide as NorA efflux pump substrate. EPI C6 was found to be most potent and reduced the MIC of ciprofloxacin by 16 fold followed by C18 which showed 4 fold reduction of MIC. Ethidium bromide efflux inhibition and accumulation assay proved these compounds as NorA inhibitors. PMID:27503686

  13. Comparative Study of the Efficacy and Tolerability of Secnidazole Suspension (single dose) and Tinidazole Suspension (two days dosage) in the Treatment of Amebiasis in Children.

    PubMed

    Salles; Bechara; Tavares; Martins; Sobrinho; Dietrich-Neto; Costa

    1999-04-01

    Amebiasis caused by Entamoeba histolytica may be considered the most aggressive parasitic disease affecting human intestine, causing acute amoebic colitis and extra-intestinal diseases of high morbidity and mortality. 5-nitroimidazoles are the drugs of choice. In this multicenter, open and random clinical trial, the efficacy and tolerability of secnidazole suspension in a single oral dose of 1ml/kg was compared with 0.5ml/kg doses of tinidazole suspension given for 2 consecutive days to 303 Entamoeba histolytica-positive children aged 2 to 13. Patients with extra-intestinal complications were excluded from the study. Clinical and parasitological follow-up using the Faust and Kato-Katz method were carried out 7, 14, and 21 days after treatment. Clinical improvement/cure was observed in 93% of the patients in the secnidazole group and 91% in the tinidazole group. Parasitological success was reported for 77% and 63% of the secnidazole and tinidazole patients, respectively, showing a significant statistical difference between the two groups (p=0.007). Both drugs were well tolerated, and the adverse effects reported were mild, consisting mainly of digestive disturbances. This comparative study showed that a single oral dose of 1ml/kg of secnidazole produced a significantly higher parasitological cure rate than 2 doses of tinidazole. Secnidazole is a safe and effective drug for the treatment of uncomplicated intestinal amebiasis. PMID:11098194

  14. Development of microbial trigger based oral formulation of Tinidazole and its Gamma Scintigraphy Evaluation: A promising tool against anaerobic microbes associated GI problems.

    PubMed

    Sharma, Braj Gaurav; Kumar, Neeraj; Nishad, Dhruv Kumar; Khare, Naveen K; Bhatnagar, Aseem

    2016-06-30

    Tinidazole is a versatile anti-amoebic and anti-anaerobic drug used in treatment of intestinal infection. The aim of present study was to develop and evaluate a guar gum based novel target release Tinidazole matrix tablet in animal models and healthy human volunteer using Gamma Scintigraphy technique. Anti-anaerobic and anti-protozoal activity of the developed formulation was studied in vitro against Bacteroides fragilis and Dentamoeba fragilis. Tinidazole was successful radiolabelled with (99m)Tc-pertechnetate using stannous chloride as a reducing agent and stable up to 24h in normal saline and serum. Radiolabeled formulation was evaluated in 6 Newzealand white rabbits by gamma Scintigraphy in static manner up to 24h for its retention in gastrointestinal tract (GIT). Similar set of study was conducted in 12 healthy human volunteers for similar objective Scintigraphy images of healthy human volunteer showed retention of optimized formulations in stomach up to 60min, from where it moved to duodenum further and reached ileum in around 5h. However, initiation of drug release was observed from intestine at 7h. Complete dissociation and release of drug was observed at 24h in colon due to anaerobic microbial rich environment. Results drawn from Scintigraphy images indicate that radiolabeled (99m)Tc-Tinidazole tablet transit through upper part of GI without disintegration. Hence the developed matrix tablet may have a role in treatment of intestinal infection caused by anaerobic bacteria. PMID:27108116

  15. Efficacy of endoluminal gastroplication in Japanese patients with proton pump inhibitor-resistant, non-erosive esophagitis

    PubMed Central

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

    2012-01-01

    AIM: To evaluate the efficacy, safety, and long-term outcomes of endoluminal gastroplication (ELGP) in patients with proton pump inhibitor (PPI)-resistant, non-erosive reflux disease (NERD). METHODS: The subjects were NERD patients, diagnosed by upper endoscopy before PPI use, who had symptoms such as heartburn or reflux sensations two or more times a week even after 8 wk of full-dose PPI treatment. Prior to ELGP, while continuing full-dose PPI medication, patients’ symptoms and quality of life (QOL) were assessed using the questionnaire for the diagnosis of reflux disease, the frequency scale for symptoms of gastro-esophageal reflux disease (FSSG), gastrointestinal symptoms rating scale, a 36-item short-form. In addition, 24-h esophageal pH monitoring or 24-h intraesophageal pH/impedance (MII-pH) monitoring was performed. The Bard EndoCinchTM was used for ELGP, and 2 or 3 plications were made. After ELGP, all acid reducers were temporarily discontinued, and medication was resumed depending on the development and severity of symptoms. Three mo after ELGP, symptoms, QOL, pH or MII-pH monitoring, number of plications, and PPI medication were evaluated. Further, symptoms, number of plications, and PPI medication were evaluated 12 mo after ELGP to investigate long-term effects. RESULTS: The mean FSSG score decreased significantly from before ELGP to 3 and 12 mo after ELGP (19.1 ± 10.5 to 10.3 ± 7.4 and 9.3 ± 9.9, P < 0.05, respectively). The total number of plications decreased gradually at 3 and 12 mo after ELGP (2.4 ± 0.8 to 1.2 ± 0.8 and 0.8 ± 1.0, P < 0.05, respectively). The FSSG scores in cases with no remaining plications and in cases with one or more remaining plications were 4.4 and 2.7, respectively, after 3 mo, and 2.0 and 2.8, respectively, after 12 mo, showing no correlation to plication loss. On pH monitoring, there was no difference in the percent time pH < 4 from before ELGP to 3 mo after. Impedance monitoring revealed no changes in the number

  16. Effect of electrical stimulation of the lower esophageal sphincter in gastroesophageal reflux disease patients refractory to proton pump inhibitors

    PubMed Central

    Soffer, Edy; Rodríguez, Leonardo; Rodriguez, Patricia; Gómez, Beatriz; Neto, Manoel G; Crowell, Michael D

    2016-01-01

    AIM: To evaluate the efficacy of lower esophageal sphincter (LES)-electrical stimulation therapy (EST) in a subgroup of patients that reported only partial response to proton pump inhibitors (PPIs) therapy, compared to a group of patient with complete response. METHODS: Bipolar stitch electrodes were laparoscopically placed in the LES and connected to an implantable pulse generator (EndoStim BV, the Hague, the Netherlands), placed subcutaneously in the anterior abdominal wall. Stimulation at 20 Hz, 215 μsec, 3-8 mAmp in 30 min sessions was delivered starting on day 1 post-implant. Patients were evaluated using gastroesophageal reflux disease (GERD)-HRQL, symptom diaries; esophageal pH and esophageal manometry before and up to 24 mo after therapy and results were compared between partial and complete responders. RESULTS: Twenty-three patients with GERD on LES-EST were enrolled and received continuous per-protocol stimulation through 12 mo and 21 patients completed 24 mo of therapy. Of the 23 patients, 16 (8 male, mean age 52.1 ± 12 years) had incomplete response to PPIs prior to LES-EST, while 7 patients (5 male, mean age 52.7 ± 4.7) had complete response to PPIs. In the sub-group with incomplete response to PPIs, median (IQR) composite GERD-HRQL score improved significantly from 9.5 (9.0-10.0) at baseline on-PPI and 24.0 (20.8-26.3) at baseline off-PPI to 2.5 (0.0-4.0) at 12-mo and 0.0 (0.0-2.5) at 24-mo follow-up (P < 0.05 compared to on-and off-PPI at baseline). Median (IQR) % 24-h esophageal pH < 4.0 at baseline in this sub-group improved significantly from 9.8% (7.8-11.5) at baseline to 3.0% (1.9-6.3) at 12 mo (P < 0.001) and 4.6% (2.0-5.8) at 24 mo follow-up (P < 0.01). At their 24-mo follow-up, 9/11 patients in this sub-group were completely free of PPI use. These results were comparable to the sub-group that reported complete response to PPI therapy at baseline. No unanticipated implantation or stimulation-related adverse events, or any untoward sensation

  17. The in-vitro antimicrobial effect of non-antibiotics and putative inhibitors of efflux pumps on Pseudomonas aeruginosa and Staphylococcus aureus.

    PubMed

    Hendricks, O; Butterworth, T S; Kristiansen, J E

    2003-09-01

    The anti-microbial activity of six non-antibiotics (one amino-ethylchloride, three phenothiazines, two tricyclic antidepressives) were tested on 20 clinical isolates of Pseudomonas aeruginosa, one clinical isolate of Klebsiella pneumoniae, 2 ATTC strains and 14 clinical isolates of Staphylococccus aureus, using the plate dilution method. The effects on P. aeruginosa were independent of antibiotic resistance pattern and the species Stenotrophomonas maltophilia was found to be the most susceptible to the non-antibiotics, with MIC values as low as 20 mg/l for some of the substances. The 16 S. aureus strains tested were all particularly susceptible to the anti-microbial effects of the putative inhibitors of efflux pumps thioridazine and trifluoperazine with MIC values of < or =16 mg/l independently of the methicillin resistance profile of the strains. Because phenothiazines are well known to inhibit efflux pumps our results may indicate the existence of such pumps. Current works in progress are attempts at reversing the antibiotic resistance of selected bacterial strains using specific non-antibiotics and their stereo-chemical isomers. PMID:13678831

  18. Micro-osmotic pumps for continuous release of the tyrosine kinase inhibitor bosutinib in juvenile rats and its impact on bone growth

    PubMed Central

    Tauer, Josephine Tabea; Hofbauer, Lorenz C.; Jung, Roland; Erben, Reinhold G.; Suttorp, Meinolf

    2013-01-01

    Background Bosutinib is a third-generation dual tyrosine kinase inhibitor (TKI) inhibiting Abl and Src kinases. It was developed to act on up-regulated tyrosine kinases (TKs) like BCR-ABL in Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) when resistance to first- and second-generation TKIs developed. However, first- and second-generation TKIs show off-target effects on bone metabolism, whereas studies on skeletal adverse effects of bosutinib are still lacking. Therefore, it was the aim of this study to continuously expose juvenile rats to bosutinib and to analyze its influence on the growing bone. Material/Methods Starting after weaning, 4-week-old Wistar rats were chronically exposed over a 28-day period to varying concentrations of bosutinib, which were continuously administered subcutaneously via implanted Alzet® micro-osmotic pumps. After necropsy, the length of the femora and tibiae were analyzed. Results Continuous administration of bosutinib by micro-osmotic pumps led to serum drug levels in the lower therapeutic range, was well tolerated, and exhibited only minor adverse effects on the growing skeleton. Conclusions Micro-osmotic pumps represent a convenient system for continuous TKI release in young growing rats. Compared to first- and second-generation TKIs, bosutinib seems to exert fewer adverse effects on the growing bone. PMID:24185529

  19. Toward predicting drug-induced liver injury: parallel computational approaches to identify multidrug resistance protein 4 and bile salt export pump inhibitors.

    PubMed

    Welch, Matthew A; Köck, Kathleen; Urban, Thomas J; Brouwer, Kim L R; Swaan, Peter W

    2015-05-01

    Drug-induced liver injury (DILI) is an important cause of drug toxicity. Inhibition of multidrug resistance protein 4 (MRP4), in addition to bile salt export pump (BSEP), might be a risk factor for the development of cholestatic DILI. Recently, we demonstrated that inhibition of MRP4, in addition to BSEP, may be a risk factor for the development of cholestatic DILI. Here, we aimed to develop computational models to delineate molecular features underlying MRP4 and BSEP inhibition. Models were developed using 257 BSEP and 86 MRP4 inhibitors and noninhibitors in the training set. Models were externally validated and used to predict the affinity of compounds toward BSEP and MRP4 in the DrugBank database. Compounds with a score above the median fingerprint threshold were considered to have significant inhibitory effects on MRP4 and BSEP. Common feature pharmacophore models were developed for MRP4 and BSEP with LigandScout software using a training set of nine well characterized MRP4 inhibitors and nine potent BSEP inhibitors. Bayesian models for BSEP and MRP4 inhibition/noninhibition were developed with cross-validated receiver operator curve values greater than 0.8 for the test sets, indicating robust models with acceptable false positive and false negative prediction rates. Both MRP4 and BSEP inhibitor pharmacophore models were characterized by hydrophobic and hydrogen-bond acceptor features, albeit in distinct spatial arrangements. Similar molecular features between MRP4 and BSEP inhibitors may partially explain why various drugs have affinity for both transporters. The Bayesian (BSEP, MRP4) and pharmacophore (MRP4, BSEP) models demonstrated significant classification accuracy and predictability. PMID:25735837

  20. Toward Predicting Drug-Induced Liver Injury: Parallel Computational Approaches to Identify Multidrug Resistance Protein 4 and Bile Salt Export Pump Inhibitors

    PubMed Central

    Welch, Matthew A.; Köck, Kathleen; Urban, Thomas J.; Brouwer, Kim L. R.

    2015-01-01

    Drug-induced liver injury (DILI) is an important cause of drug toxicity. Inhibition of multidrug resistance protein 4 (MRP4), in addition to bile salt export pump (BSEP), might be a risk factor for the development of cholestatic DILI. Recently, we demonstrated that inhibition of MRP4, in addition to BSEP, may be a risk factor for the development of cholestatic DILI. Here, we aimed to develop computational models to delineate molecular features underlying MRP4 and BSEP inhibition. Models were developed using 257 BSEP and 86 MRP4 inhibitors and noninhibitors in the training set. Models were externally validated and used to predict the affinity of compounds toward BSEP and MRP4 in the DrugBank database. Compounds with a score above the median fingerprint threshold were considered to have significant inhibitory effects on MRP4 and BSEP. Common feature pharmacophore models were developed for MRP4 and BSEP with LigandScout software using a training set of nine well characterized MRP4 inhibitors and nine potent BSEP inhibitors. Bayesian models for BSEP and MRP4 inhibition/noninhibition were developed with cross-validated receiver operator curve values greater than 0.8 for the test sets, indicating robust models with acceptable false positive and false negative prediction rates. Both MRP4 and BSEP inhibitor pharmacophore models were characterized by hydrophobic and hydrogen-bond acceptor features, albeit in distinct spatial arrangements. Similar molecular features between MRP4 and BSEP inhibitors may partially explain why various drugs have affinity for both transporters. The Bayesian (BSEP, MRP4) and pharmacophore (MRP4, BSEP) models demonstrated significant classification accuracy and predictability. PMID:25735837

  1. [Investigation of the effect of efflux pump inhibitors to MIC values of ciprofloxacin in clinical isolates of Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii and Staphylococcus aureus].

    PubMed

    Cetinkaya, Ebru; Coban, Ahmet Yilmaz; Durupinar, Belma

    2008-10-01

    The aim of this study was to investigate the effects of efflux pump inhibitors on the minimal inhibitory concentration (MIC) values of ciprofloxacin (CIP) in fluoroquinolone-resistant 42 Pseudomonas aeruginosa (n= 42), Escherichia coil (n= 97), Acinetobacter baumannii (n= 58) and Staphylococcus aureus (n= 80) strains isolated from clinical specimens. For this purpose phenylalanyl-arginyl-beta-naphthylamide (PA beta N) was used for P. aeruginosa, E. coli, A. baumannii and reserpine for S. aureus isolates as pump inhibitors. Fluoroquinolone resistance of the clinical isolates were determined by VITEK2 Compact (BioMerieux, France) automated system and confirmed with standard broth microdilution method. For the investigation of the effects of inhibitor agents, the MIC values were also determined in the presence of 25 microg/ml and 100 microg/ml PA beta N and 20 microg/ml reserpine. In the presence of 25 mg/l PA beta N, 61.9% of CIP resistant P. aeruginosa strains converted to susceptible ones, while this rate was 73.8% in the presence of 100 mg/l PA beta N. In A. baumannii clinical isolates, 8.6% and 15.5% of CIP-resistant strains have become susceptible in the presence of 25 mg/l and 100 mg/l PA beta N, respectively. Similarly the MIC values for CIP have decreased > or = 4 folds in 42.2%, and > or = 2 folds in 30.9% of E. coli isolates, in the presence of 25 mg/l PA beta N, however, there was no change in MICs of 26.9% of E. coli strains. The MIC values have also been lowered for > or = 4 folds in 83.6%, and two folds in 13.4% of E. coli strains by the use of 100 mg/l PA beta N concentration, however, no decrease in MIC values was detected in 3% of the isolates. 20 mg/l of reserpine have caused a decrease of > or = 4 folds in 8.75%, and two folds in 33.75% of S. aureus isolates, while there was no change in MIC values of 57.5% of S. aureus strains. Our results showed that PA beta N causes significant reduction in MIC values for CIP in the clinical isolates of P

  2. Multiobjective optimization strategy based on desirability functions used for the microemulsion liquid chromatographic separation and quantification of norfloxacin and tinidazole in plasma and formulations.

    PubMed

    Abou-Taleb, Noura Hemdan; El-Wasseef, Dalia Rashad; El-Sherbiny, Dina Tawfik; El-Ashry, Saadia Mohamed

    2015-03-01

    The aim of the present study was to optimize a microemulsion liquid chromatography method for the simultaneous determination of norfloxacin and tinidazole binary mixture using a chemometric protocol. Optimization experiments were conducted through a process of screening and optimization. A 2(7-4) fractional factorial design was used as screening design. While the location of optimum conditions was established by applying Derringer's desirability function. The optimal mobile phase composition was predicted to be: 3.5% w/v SDS, 10.03% v/v 1-propanol, 0.5% v/v 1-octanol, and 0.3% triethylamine in 0.02 M phosphoric acid at pH 6.5. The mobile phase was delivered isocratically at a flow rate of 1 mL/min with UV detection at 290 nm. Tinidazole and norfloxacin were eluted with retention times of 1.8 and 5.8 min, respectively. The calibration plots displayed good linear relationships in the concentration ranges of 0.5-50 and 0.75-75 μg/mL for norfloxacin and tinidazole, respectively. The method was successfully applied for determination of both drugs in pharmaceutical dosage forms and real human plasma. Where the accuracy was proved by the low values of % error and high values of recovery, also the relative standard deviation for the results did not exceed 1.5%, proving the precision of the method. PMID:25565679

  3. Potent inhibitory action of the gastric proton pump inhibitor lansoprazole against urease activity of Helicobacter pylori: unique action selective for H. pylori cells.

    PubMed Central

    Nagata, K; Satoh, H; Iwahi, T; Shimoyama, T; Tamura, T

    1993-01-01

    The gastric proton pump inhibitor lansoprazole, its active analog AG-2000, and omeprazole dose dependently inhibited urease activity extracted with distilled water from Helicobacter pylori cells; the 50% inhibitory concentrations were between 3.6 and 9.5 microM, which were more potent than those of urease inhibitors, such as acetohydroxamic acid, hydroxyurea, and thiourea. These compounds also inhibited urease activity in intact cells of H. pylori and Helicobacter mustelae but did not inhibit ureases from other bacteria, such as Proteus vulgaris, Proteus mirabilis, and Providencia rettgeri. The mechanism of urease inhibition was considered to be blockage of the SH groups of H. pylori urease, since SH residues in the enzyme decreased after preincubation with lansoprazole and glutathione or dithiothreitol completely abolished the inhibitory action. The SH-blocking reagents N-ethylmaleimide and idoacetamide were also examined for their inhibition of the urease activity; their 50% inhibitory concentrations were 100- to 1,000-fold higher than those of lansoprazole. These results suggest that lansoprazole and omeprazole can potently and selectively inhibit H. pylori urease and that inhibition may be related to earlier findings indicating that these compounds have selective activity against HP growth. PMID:8494373

  4. Potent inhibitory action of the gastric proton pump inhibitor lansoprazole against urease activity of Helicobacter pylori: unique action selective for H. pylori cells.

    PubMed

    Nagata, K; Satoh, H; Iwahi, T; Shimoyama, T; Tamura, T

    1993-04-01

    The gastric proton pump inhibitor lansoprazole, its active analog AG-2000, and omeprazole dose dependently inhibited urease activity extracted with distilled water from Helicobacter pylori cells; the 50% inhibitory concentrations were between 3.6 and 9.5 microM, which were more potent than those of urease inhibitors, such as acetohydroxamic acid, hydroxyurea, and thiourea. These compounds also inhibited urease activity in intact cells of H. pylori and Helicobacter mustelae but did not inhibit ureases from other bacteria, such as Proteus vulgaris, Proteus mirabilis, and Providencia rettgeri. The mechanism of urease inhibition was considered to be blockage of the SH groups of H. pylori urease, since SH residues in the enzyme decreased after preincubation with lansoprazole and glutathione or dithiothreitol completely abolished the inhibitory action. The SH-blocking reagents N-ethylmaleimide and idoacetamide were also examined for their inhibition of the urease activity; their 50% inhibitory concentrations were 100- to 1,000-fold higher than those of lansoprazole. These results suggest that lansoprazole and omeprazole can potently and selectively inhibit H. pylori urease and that inhibition may be related to earlier findings indicating that these compounds have selective activity against HP growth. PMID:8494373

  5. Microbial light-activatable proton pumps as neuronal inhibitors to functionally dissect neuronal networks in C. elegans.

    PubMed

    Husson, Steven J; Liewald, Jana F; Schultheis, Christian; Stirman, Jeffrey N; Lu, Hang; Gottschalk, Alexander

    2012-01-01

    Essentially any behavior in simple and complex animals depends on neuronal network function. Currently, the best-defined system to study neuronal circuits is the nematode Caenorhabditis elegans, as the connectivity of its 302 neurons is exactly known. Individual neurons can be activated by photostimulation of Channelrhodopsin-2 (ChR2) using blue light, allowing to directly probe the importance of a particular neuron for the respective behavioral output of the network under study. In analogy, other excitable cells can be inhibited by expressing Halorhodopsin from Natronomonas pharaonis (NpHR) and subsequent illumination with yellow light. However, inhibiting C. elegans neurons using NpHR is difficult. Recently, proton pumps from various sources were established as valuable alternative hyperpolarizers. Here we show that archaerhodopsin-3 (Arch) from Halorubrum sodomense and a proton pump from the fungus Leptosphaeria maculans (Mac) can be utilized to effectively inhibit excitable cells in C. elegans. Arch is the most powerful hyperpolarizer when illuminated with yellow or green light while the action spectrum of Mac is more blue-shifted, as analyzed by light-evoked behaviors and electrophysiology. This allows these tools to be combined in various ways with ChR2 to analyze different subsets of neurons within a circuit. We exemplify this by means of the polymodal aversive sensory ASH neurons, and the downstream command interneurons to which ASH neurons signal to trigger a reversal followed by a directional turn. Photostimulating ASH and subsequently inhibiting command interneurons using two-color illumination of different body segments, allows investigating temporal aspects of signaling downstream of ASH. PMID:22815873

  6. SERCA Pump Inhibitors Do Not Correct Biosynthetic Arrest of ΔF508 CFTR in Cystic Fibrosis

    PubMed Central

    Grubb, Barbara R.; Gabriel, Sherif E.; Mengos, April; Gentzsch, Martina; Randell, Scott H.; Van Heeckeren, Anna M.; Knowles, Michael R.; Drumm, Mitchell L.; Riordan, John R.; Boucher, Richard C.

    2006-01-01

    Deletion of phenylalanine 508 (ΔF508) accounts for nearly 70% of all mutations that occur in the cystic fibrosis transmembrane conductance regulator (CFTR). The ΔF508 mutation is a class II processing mutation that results in very little or no mature CFTR protein reaching the apical membrane and thus no cAMP-mediated Cl− conductance. Therapeutic strategies have been developed to enhance processing of the defective ΔF508 CFTR molecule so that a functional cAMP-regulated Cl− channel targets to the apical membrane. Sarcoplasmic/endoplasmic reticulum calcium (SERCA) inhibitors, curcumin and thapsigargin, have been reported to effectively correct the CF ion transport defects observed in the ΔF508 CF mice. We investigated the effect of these compounds in human airway epithelial cells to determine if they could induce ΔF508 CFTR maturation, and Cl− secretion. We also used Baby Hamster Kidney cells, heterologously expressing ΔF508 CFTR, to determine if SERCA inhibitors could interfere with the interaction between calnexin and CFTR and thereby correct the ΔF508 CFTR misfolding defect. Finally, at the whole animal level, we tested the ability of curcumin and thapsigargin to (1) induce Cl− secretion and reduce hyperabsorption of Na+ in the nasal epithelia of the ΔF508 mouse in vivo, and (2) induce Cl− secretion in intestine (jejunum and distal colon) and the gallbladder of the ΔF508 CF mouse. We conclude that curcumin and thapsigargin failed to induce maturation of ΔF508 CFTR, or induce Cl− secretion, as measured by biochemical and electrophysiologic techniques in a variety of model systems ranging from cultured cells to in vivo studies. PMID:16284361

  7. SERCA pump inhibitors do not correct biosynthetic arrest of deltaF508 CFTR in cystic fibrosis.

    PubMed

    Grubb, Barbara R; Gabriel, Sherif E; Mengos, April; Gentzsch, Martina; Randell, Scott H; Van Heeckeren, Anna M; Knowles, Michael R; Drumm, Mitchell L; Riordan, John R; Boucher, Richard C

    2006-03-01

    Deletion of phenylalanine 508 (deltaF508) accounts for nearly 70% of all mutations that occur in the cystic fibrosis transmembrane conductance regulator (CFTR). The deltaF508 mutation is a class II processing mutation that results in very little or no mature CFTR protein reaching the apical membrane and thus no cAMP-mediated Cl- conductance. Therapeutic strategies have been developed to enhance processing of the defective deltaF508 CFTR molecule so that a functional cAMP-regulated Cl- channel targets to the apical membrane. Sarcoplasmic/endoplasmic reticulum calcium (SERCA) inhibitors, curcumin and thapsigargin, have been reported to effectively correct the CF ion transport defects observed in the deltaF508 CF mice. We investigated the effect of these compounds in human airway epithelial cells to determine if they could induce deltaF508 CFTR maturation, and Cl- secretion. We also used Baby Hamster Kidney cells, heterologously expressing deltaF508 CFTR, to determine if SERCA inhibitors could interfere with the interaction between calnexin and CFTR and thereby correct the deltaF508 CFTR misfolding defect. Finally, at the whole animal level, we tested the ability of curcumin and thapsigargin to (1) induce Cl- secretion and reduce hyperabsorption of Na+ in the nasal epithelia of the deltaF508 mouse in vivo, and (2) induce Cl- secretion in intestine (jejunum and distal colon) and the gallbladder of the deltaF508 CF mouse. We conclude that curcumin and thapsigargin failed to induce maturation of deltaF508 CFTR, or induce Cl- secretion, as measured by biochemical and electrophysiologic techniques in a variety of model systems ranging from cultured cells to in vivo studies. PMID:16284361

  8. Extractional spectrophotometric analysis of metronidazole, tinidazole, ornidazole and secnidazole bases through acid-dye complexation using bromothymol blue dye.

    PubMed

    Darwish, Khaled M; Salama, Ismail; Mostafa, Samia; El-Sadek, Mohamed

    2012-01-01

    An easy, precise and valid extractional-spectrophotometric technique is described for the assessment of metronidazole (MNZ), tinidazole (TNZ), ornidazole (ONZ) and secnidazole (SNZ) in pure state and in their pharmaceutical formulations. The technique includes first the reduction of above cited drugs using HCl and zinc powder, then the formation of intense yellow colored ion-association complex species (1:3 drug/dye) using bromothymol blue (BTB) in a buffered aqueous acidic medium at pH 3-3.50. The colored products are extracted into dichloromethane and quantitatively determined at 416-420 nm. The experimental operating factors influencing the ion-pairs development were studied and optimized to obtain the maximum color intensity. The Beer plots are obeyed in the concentration ranges 2.50-22.50, 2.50-30, 7.50-35 and 5-30 μgml-1 for MNZ, TNZ, ONZ and SNZ, respectively, with correlation coefficients not less than 0.9995. The proposed technique is recommended for the routine quality control analysis of the investigated drugs in commercial tablets with no observed interference from common pharmaceutical adjuvants. Results of such analysis were statistically validated and through recovery studies, showing excellent agreement with those achieved by the reported techniques. PMID:22186332

  9. Trends in Oral Antibiotic, Proton Pump Inhibitor, and Histamine 2 Receptor Blocker Prescription Patterns for Children Compared With Adults: Implications for Clostridium difficile Infection in the Community.

    PubMed

    Faden, Howard S; Ma, Chan-Xing

    2016-07-01

    The use of antibiotics, proton pump inhibitor (PPI), and histamine 2 receptor blocker (H2B) was compared between children and adults in the community from 2005 through 2011. Antibiotic prescription rates remained stable for children, but increased significantly for adults, P = .03. PPI prescription rates increased for children, P = .02 and for adults, P = .009. H2B prescription rates increased for children, P = .03, but not for adults. Antibiotic prescription rates were significantly higher in children than adults in all 7 years, P < .0001. In contrast, PPI prescription rates were significantly higher in adults than children in all 7 years, P < .0001. H2B prescription rates were significantly higher in adults than children 1 to 18 years old P < .0001; however, H2B prescription rates were highest in children <1 year old, P = .0001. The high use of oral antibiotics, PPI, and H2B among outpatients may be a contributing factor to the rise of Clostridium difficile infection in the community. PMID:26350427

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

    PubMed

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

    2016-07-30

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

  11. Impact of Dual Antiplatelet Therapy with Proton Pump Inhibitors on the Outcome of Patients with Acute Coronary Syndrome Undergoing Drug-Eluting Stent Implantation

    PubMed Central

    Macaione, Francesca; Montaina, Carla; Evola, Salvatore; Novo, Giuseppina; Novo, Salvatore

    2012-01-01

    This study aimed to assess if proton pump inhibitors (PPIs) may reduce the effectiveness of clopidogrel, than H2 antagonist (anti-H2) in order to determine rehospitalization for acute coronary syndrome (re-ACS), target vessel revascularization (TVR) and cardiac death. This case-control study included 176 patients with ACS undergoing angioplasty (PCI) with drug-eluting stent implantation. The population was divided into two groups: PPI group (n = 121) consisting of patients receiving at discharge dual antiplatelet therapy (DAT) plus PPI and anti-H2 group (n = 55), consisting of patients receiving at discharge DAT + H2 receptor antagonist (H2RA). In a followup of 36 months the prevalence of ACS event (P = 0.014), TVR (P = 0.031) was higher in the PPI group than in the anti-H2 group; instead there was no statistically significant difference between groups for death. The variables independently associated with ACS were the diabetes, omeprazole, and esomeprazole; instead the variables independently associated with TVR were only omeprazole. Our data shows that the use of omeprazole and esomeprazole, with clopidogrel, is associated with increased risk of adverse outcomes after PCI with drug-eluting stent implantation. PMID:22792485

  12. Rescue Therapy with a Proton Pump Inhibitor Plus Amoxicillin and Rifabutin for Helicobacter pylori Infection: A Systematic Review and Meta-Analysis

    PubMed Central

    Liu, Xiaoqun; Wang, Hui; Lv, Zhifa; Wang, Youhua; Wang, Ben; Xie, Yong; Zhou, Xiaojiang; Lv, Nonghua

    2015-01-01

    Background. To conduct a systematic review and meta-analysis of clinical trials for eradication of Helicobacter pylori (H. pylori) that included a treatment arm with a proton pump inhibitor, rifabutin, and amoxicillin. Materials and Methods. We selected clinical trials that examined the efficacy of H. pylori eradication therapies and included a study arm using the test regimen from major medical literature databases and abstracts from major gastroenterology meetings. We also did subgroup and sensitivity analyses. Results. Twenty-one studies were included in systematic review. The total eradication rates of the test regimen were 70.4% by intent-to-treat (ITT) and 72.0% by per-protocol (PP) analyses. The pooled odds ratio (OR) was 0.55 using fixed effects model (P = 0.283) for the test regimen versus other triple regimens. The total eradication rates were 68.4% for the test regimen and 81.9% in the control group by ITT, while the OR was 1.08 using random effects model (P = 0.019). The pooled eradication rate was 66.4% for the test regimen and 67.4% for the control group by ITT. The total adverse effects incidence were 25.1% for the test regimen. Conclusions. The test regimen for H. pylori rescue therapy may be not superior to control regimens in efficacy. PMID:26106411

  13. Association between use of proton pump inhibitors and non-typhoidal salmonellosis identified following investigation into an outbreak of Salmonella Mikawasima in the UK, 2013.

    PubMed

    Freeman, R; Dabrera, G; Lane, C; Adams, N; Browning, L; Fowler, T; Gorton, R; Peters, T; Mather, H; Ashton, P; Dallman, T; Godbole, G; Tubin-Delic, D; Charlett, A; Fisher, I; Adak, G K

    2016-04-01

    In November 2013, national public health agencies in England and Scotland identified an increase in laboratory-confirmed Salmonella Mikawasima. The role of proton pump inhibitors (PPIs) as a risk factor for salmonellosis is unclear; we therefore captured information on PPI usage as part of our outbreak investigation. We conducted a case-control study, comparing each case with two controls. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. Thirty-nine of 61 eligible cases were included in the study. The median age of cases was 45 years; 56% were female. Of these, 33% were admitted to hospital and 31% reported taking PPIs. We identified an association between PPIs and non-typhoidal salmonellosis (aOR 8·8, 95% CI 2·0-38·3). There is increasing evidence supporting the existence of an association between salmonellosis and PPIs; however, biological studies are needed to understand the effect of PPIs in the pathogenesis of Salmonella. We recommend future outbreak studies investigate PPI usage to strengthen evidence on the relevance of PPIs in Salmonella infection. These findings should be used to support the development of guidelines for patients and prescribers on the risk of gastrointestinal infection and PPI usage. PMID:26424497

  14. The efficacy and safety of proton-pump inhibitors in treating patients with non-erosive reflux disease: a network meta-analysis

    PubMed Central

    Chen, Lingxiao; Chen, Yujie; Li, Bo

    2016-01-01

    Proton-pump inhibitors (PPIs) have been proved as safe and effective ways to treat patients with non-erosive reflux disease (NERD). However, less is known about the comparisons among different PPIs and their best dosage. We aimed to synthesize the available evidence through network meta-analysis to investigate the efficacy and safety of different PPIs in treating patients with NERD. Fifteen studies with 6309 patients were included in the meta-analyses. For the rate of symptomatic relief, compared with control groups, all interventions except rabeprazole 5 mg significantly increased rate of symptomatic relief. Among the comparisons of different interventions, omeprazole 20 mg group was associated with a higher rate of symptomatic relief in contrast to omeprazole 10 mg group (odds ratio, OR: 1.89, 95% confidence interval, CI: 1.34, 2.67; p-value: 0.0005) or rabeprazole 5 mg group (OR: 2.51, 95%CI: 1.16, 5.42; p-value: 0.019); dexlansoprazole 30 mg therapy significantly improved the rate of symptomatic relief compared with rabeprazole 5 mg group (OR: 2.64, 95%CI: 1.08, 6.43; p-value: 0.03). For the rate of adverse events, there was no significant difference among all interventions. PMID:27581096

  15. Outcomes of a decision support prompt in community pharmacy-dispensing software to promote step-down of proton pump inhibitor therapy

    PubMed Central

    Curtain, Colin; Peterson, Gregory M; Tenni, Peter; Bindoff, Ivan K; Williams, Mackenzie

    2011-01-01

    AIM To evaluate the effect of a computerized decision support prompt regarding high-dose proton pump inhibitor (PPI) therapy on prescribing and medication costs. METHODS A prompt activated on dispensing high-dose esomeprazole or pantoprazole was implemented in 73 of 185 pharmacies. Anonymized prescription data and a patient survey were used to determine changes in prescribing and associated medication costs. RESULTS The pharmacist-recorded PPI intervention rate per 100 high-dose PPI prescriptions was 1.67 for the PPI prompt group and 0.17 for the control group (P < 0.001). During the first 28 days of the trial, 196 interventions resulted in 34 instances of PPI step-down, with 28 of these occurring in PPI prompt pharmacies. Cost savings attributable to the prompt were AUD 7.98 (£4.95) per month per PPI prompt pharmacy compared with AUD 1.05 (£0.65) per control pharmacy. CONCLUSION The use of electronic decision support prompts in community pharmacy practice can promote the quality use of medicines. PMID:21480953

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

    PubMed Central

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

    2016-01-01

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

  17. Can Helicobacter pylori be eradicated with high-dose proton pump inhibitor in extensive metabolizers with the CYP2C19 genotypic polymorphism?

    PubMed

    Ormeci, A; Emrence, Z; Baran, B; Soyer, O M; Gokturk, S; Evirgen, S; Akyuz, F; Karaca, C; Besisik, F; Kaymakoglu, S; Ustek, D; Demir, K

    2016-05-01

    Proton pump inhibitors (PPI) metabolism and pharmacokinetics are regulated by cytochrome P450 enzymes in the liver. Cytochrome P450 2C19 (CYP2C19) polymorphism plays an import role in the metabolism of PPIs. The three possible genotypes for CYP2C19 each has a distinct effect on the pharmacodynamics of PPIs. Homozygote extensive metabolizers (HomEM) are the most frequent genotype and have two wild-types (non-mutant) (*1/*1) alleles. HomEM is associated with increased enzyme activity, which increases the rate of PPI metabolism. Intragastric pH, which is required for eradication, is lowest in HomEM. In HomEMs, an insufficient increase in intragastric pH results in decreased anti-Helicobacter pylori (HP) efficacy of the antibiotics and, therefore, lower eradication rates. We determined whether the HP eradication rate would increase after high-dose PPI treatment of extensive PPI metabolizers who had been treated unsuccessfully with a standard PPI dose. In our report, increasing the PPI dosage in patients with genotype polymorphisms may be effective on eradication rates. Eradication rates are directly affected by CYP2C19 polymorphisms, and eradication treatments should be planned considering such genotypic polymorphisms. Hence, CYP2C19 genotyping prior to treatment may facilitate determination of the optimum PPI dose to improve the therapeutic outcome. However, further researches are required to confirm this hypothesis. PMID:27212172

  18. Patient-reported adherence to coprescribed proton pump inhibitor gastroprotection in osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis patients using nonsteroidal anti-inflammatory drugs

    PubMed Central

    Henriksson, Kenneth; From, Jesper; Stratelis, Georgios

    2014-01-01

    Background Patients with osteoarthritis (OA), rheumatoid arthritis (RA), or ankylosing spondylitis (AS) are commonly treated with nonsteroidal anti-inflammatory drugs (NSAIDs), sometimes with a concomitant gastroprotective proton pump inhibitor (PPI). The present study examines real-life patient adherence to PPIs when coprescribed with NSAIDs. Methods This retrospective medical record survey identified patients diagnosed with OA, RA, or AS who had PPIs coprescribed with NSAIDs for prevention of NSAID-associated gastrointestinal ulcers. Actual NSAID and PPI intake was retrospectively recorded using a self-reported questionnaire. Adherence to PPI treatment was assessed using descriptive statistics. Results In total, 96 patients (69% female, mean age 67 years, 72% OA, 16% RA, 12% AS) were included. The mean patient-reported adherence to coprescribed PPIs was 73%–81%. The percentage of patients with a self-reported adherence of ≤80% was 26%. No predictive factors for low adherence could be identified. Conclusion Despite doctors’ instructions to use PPIs concomitantly with NSAIDs, the mean patient-reported adherence to coprescribed PPIs in this population indicates a risk of a “gastroprotective treatment gap”. The patients’ adherence to gastroprotective PPIs for the prevention of NSAID-associated upper gastrointestinal ulcers can be improved. PMID:25429206

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

    PubMed Central

    Gerson, Lauren B; Triadafilopoulos, George; Sahbaie, Peyman; Young, Winston; Sloan, Sheldon; Robinson, Malcolm; Miner, Philip B; Gardner, Jerry D

    2008-01-01

    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 < 4. Methods We calculated integrated acidity and time pH < 4 from the 49 recordings of 24-hour gastric and esophageal pH from the Stanford study as well as from another study of 57 GERD subjects, 26 of whom were treated for 8 days with 20 mg omeprazole or 20 mg rabeprazole in a 2-way crossover fashion. Results The prevalence of pathologic 24-hour esophageal reflux in both studies was significantly higher when measured as time pH < 4 than when measured as integrated acidity. This difference was entirely attributable to a difference between the two measures during the nocturnal period. Nocturnal gastric acid breakthrough was not a useful predictor of pathologic nocturnal esophageal reflux. Conclusion In GERD subjects treated with a PPI, measuring time esophageal pH < 4 will significantly overestimate the prevalence of pathologic esophageal acid exposure over 24 hours and during the nocturnal period. PMID:18498663

  20. Addition of clidinium-C to the 14-day proton-pump inhibitor-based triple therapy for Helicobacter pylori eradication

    PubMed Central

    Seyyedmajidi, Mohammadreza; Homapoor, Saba; Zanganeh, Elahe; Dadjou, Mohammad; Eskandari Nejad, Shahab; Tajik Galayeri, Mohammad Hadi; Vafaeimanesh, Jamshid

    2016-01-01

    Background: Triple therapy with a proton pump inhibitor and two antibiotics in Helicobacter pylori (HP) eradication is widely accepted, but this combination fails in a considerable number of cases. The aim of this study was to assess the effect of clidinium-C addition on HP eradication and to investigate the efficacy and safety of clidinium-C in prevention of drugs' side effects. Methods: A total of 200 histopathologically confirmed HP positive peptic ulcer enrolled in this study which were randomly assigned to two treatment groups: OAC (20 mg omeprazole bid, 1000 mg amoxicillin bid and 500 mg clarithromycin bid) and OAC + clidinium-C. The effect of treatment and adverse effects were compared 6 weeks after completion of treatment. A13C-urea breath test was performed to confirm HP eradication. Results: A total of 184 patients (90 in group A and 94 in group B) completed the treatment protocols. HP eradication was achieved in 71.1% in OAC versus 72.3% in OCA+clidinium-C, (P=0.73). The frequencies of abdominal pain and stool abnormality, among the side effects recorded during the therapy period, were significantly lower in group B (OCA+clidinium-C) (P=0.01 and P=0.001, respectively). Conclusion: Addition of clidinium-C to OCA triple therapy decreases abdominal pain and frequency of stool abnormalities without affecting HP eradication rate. Based on these findings addition of clidinium-C may increase patient's compliance. PMID:27386057

  1. Suspicion of drug-drug interaction between high-dose methotrexate and proton pump inhibitors: a case report - should the practice be changed?

    PubMed

    Ranchon, F; Vantard, N; Gouraud, A; Schwiertz, V; Franchon, E; Pham, B N; Vial, T; You, B; Bouafia, F; Salles, G; Rioufol, C

    2011-01-01

    We report a case of a potential drug-drug interaction in a woman treated by a first injection of high-dose methotrexate for a T-lymphoblastic lymphoma. Valaciclovir, fluoxetine and pantoprazole were given concomitantly. A methotrexate overdosage was shown at 36 h after infusion associated with a severe renal failure. Alkaline hyperhydration, folinic acid and carboxypeptidase G2 were given. Prescription analyses by pharmacists and literature research have permitted us to suggest that a drug-drug interaction between methotrexate and proton pump inhibitors (PPI) was responsible for this renal failure. Several mechanisms of interaction were suggested and might be related to the inhibition of renal methotrexate transporters by PPI, an increase in the methotrexate efflux to the blood by an upregulation of multidrug resistance protein 3 by PPI or genetic polymorphisms. This case shows that pharmacists can help physicians to optimize patient treatment: they consensually decided on the systematic discontinuation of PPI or a switch to ranitidine when patients were treated by high-dose methotrexate. PMID:21597286

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

    PubMed Central

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

    2015-01-01

    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. PMID:26039946

  3. The widely utilized brominated flame retardant tetrabromobisphenol A (TBBPA) is a potent inhibitor of the SERCA Ca2+ pump

    PubMed Central

    Ogunbayo, Oluseye A.; Michelangeli, Francesco

    2007-01-01

    TBBPA (tetrabromobisphenol A) is currently the most widely used type of BFR (brominated flame retardant) employed to reduce the combustibility of a large variety of electronic and other manufactured products. Recent studies have indicated that BFRs, including TBBPA, are bio-accumulating within animal and humans. BFRs including TBBPA have also been shown to be cytotoxic and potentially endocrine-disrupting to a variety of cells in culture. Furthermore, TBBPA has specifically been shown to cause disruption of Ca2+ homoeostasis within cells, which may be the underlying cause of its cytotoxicity. In this study, we have demonstrated that TBBPA is a potent non-isoform-specific inhibitor of the SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) (apparent Ki 0.46–2.3 μM), thus we propose that TBBPA inhibition of SERCA contributes in some degree to Ca2+ signalling disruption. TBBPA binds directly to the SERCA without the need to partition into the phospholipid bilayer. From activity results and Ca2+-induced conformational results, it appears that the major effect of TBBPA is to decrease the SERCA affinity for Ca2+ (increasing the Kd from approx. 1 μM to 30 μM in the presence of 10 μM TBBPA). Low concentrations of TBBPA can quench the tryptophan fluorescence of the SERCA and this quenching can be reversed by BHQ [2,5-di-(t-butyl)-1,4-hydroquinone] and 4-n-nonylphenol, but not thapsigargin, indicating that TBBPA and BHQ may be binding to similar regions in the SERCA. PMID:17784851

  4. A meta-analysis of the efficacy of albendazole compared with tinidazole as treatments for Giardia infections in children.

    PubMed

    Escobedo, Angel A; Ballesteros, Javier; González-Fraile, Eduardo; Almirall, Pedro

    2016-01-01

    Metronidazole is frequently used against Giardia infection; however, it has been associated with significant failure rates in clearing parasites from the gut; additionally, as it should be taken for 5 to 10 days, it is associated with poor compliance, probably due to side effects. Other drugs, including tinidazole (TNZ) and albendazole (ABZ) have been included in the antigiardial armamentarium. Our aim was to assess the efficacy of ABZ compared with TNZ in Giardia infections in children. A systematic review and a meta-analysis were carried out. PubMed, Medline, EMBASE, CENTRAL, and LILACS were searched electronically until February 2015. Also relevant journals and references of studies included therein were hand-searched for randomised controlled trials (RCTs). The meta-analysis was limited to RCTs evaluating the use of ABZ compared with TNZ in children with Giardia infection. The assessed outcome was parasitological efficacy. Prediction intervals (PI) were computed to better express uncertainties in the effect estimates. Five RCTs including 403 children were included. Overall, TNZ significantly outperformed ABZ without differences between subgroups defined by ABZ dosages [relative risk, (RR) 1.61 (95% CI): (1.40-1.85); P<0.0001]. The 95% prediction interval range is 1.28-2.02. There was no significant heterogeneity (I(2)=0%; Q-test of heterogeneity P=0.4507. The number-needed-to-treat, the average number of patients who need to be treated with TNZ to gain one additional good outcome as compared with ABZ was 4, 95% CI: 3-5. Our results show that TNZ outperforms ABZ in the treatment of Giardia infections in children from developing countries. PMID:26476393

  5. Efflux Pump Inhibitor Phenylalanine-Arginine Β-Naphthylamide Effect on the Minimum Inhibitory Concentration of Imipenem in Acinetobacter baumannii Strains Isolated From Hospitalized Patients in Shahid Motahari Burn Hospital, Tehran, Iran

    PubMed Central

    Gholami, Mehrdad; Hashemi, Ali; Hakemi-Vala, Mojdeh; Goudarzi, Hossein; Hallajzadeh, Masoumeh

    2015-01-01

    Background: Acinetobacter baumannii has emerged as a highly troublesome pathogen and a leading cause of mortality and morbidity among hospitalized burn patients. Objectives: The aims of this study were to determine the frequency of the AdeABC genes and the role of the efflux pump (s) in the imipenem resistance of A. baumannii strains isolated from burn patients. Materials and Methods: This study was conducted on 60 A. baumannii isolates collected from 240 wound samples of burn patients admitted to the Burn Unit of Shahid Motahari Burn hospital, Tehran, Iran. Antibiotic susceptibility tests were performed using the Kirby-Bauer disc diffusion and broth microdilution according to the clinical and laboratory standards institute (CLSI) guidelines. The activity of the efflux pump was evaluated using the efflux pump inhibitor, the phenylalanine-arginine Β-naphthylamide (PAΒN). The AdeABC genes were detected by polymerase chain reaction (PCR) and sequencing. Results: In this study, 100% of the isolates were resistant to cefotaxime, ceftazidime, ceftriaxone, ciprofloxacin, cefepime, piperacillin, meropenem, co-trimoxazole, and piperacillin/tazobactam; 56 (94%) to gentamicin; 50 (81%) to amikacin; 58 (97%) to imipenem; and 45 (76%) to tetracycline. Additionally,all the isolates were susceptible to colistin. The susceptibility of the strains to imipenem was highly increased in the presence of the efflux pump inhibitor such that for 58 (96.6%) of the isolates, the PAΒN reduced the minimum inhibitory concentrations (MIC) by 4- to 64-fold. The adeA and adeB genes were detected in 60 (100%) of the isolates, and the adeC gene was present in 51 (85%). Conclusions: The efflux pump may play a role in antibiotic resistance in A. baumannii isolates. The ability of A. baumannii isolates to acquire drug resistance by the efflux pump mechanism is a concern. Thus, new strategies are required in order to eliminate the efflux transport activity from resistant A. baumannii isolates causing

  6. Population-based cohort study on the risk of pneumonia in patients with non-traumatic intracranial haemorrhage who use proton pump inhibitors

    PubMed Central

    Ho, Sai-Wai; Tsai, Ming-Che; Teng, Ying-Hock; Yeh, Ying-Tung; Wang, Yu-Hsun; Yang, Shun-Fa; Yeh, Chao-Bin

    2014-01-01

    Objectives This nationwide cohort study investigated the association between proton pump inhibitor (PPI) usage and the risk of pneumonia in patients with non-traumatic intracranial haemorrhage (ICH). Design Nationwide population-based cohort study. Setting Longitudinal Health Insurance Database 2010 (LHID2010) sampled from the Taiwan National Health Insurance Research Database. Participants 4644 patients with non-traumatic ICH from 2010 to 2011 were identified. Patients aged <18 years and newly diagnosed with non-traumatic ICH complicated with pneumonia during the same admission period were excluded. A total of 2170 participants were eligible for the final analysis. Main outcome measure Patients using PPIs or not during the study period were tracked to identify the occurrence of any type of pneumonia. Results The adjusted HR of the risk of pneumonia for ICH patients who used PPIs was 1.61 (95% CI 1.32 to 1.97, p<0.001). The risk of pneumonia was positively associated with the administration of PPIs. We observed a greater risk of pneumonia in patients who used PPIs than in those who did not. Moreover, we observed that the risk of pneumonia in patients who used PPIs was 2.60 and 2.04 (95% CI 2.01 to 3.38, p<0.001; 95% CI 1.34 to 3.10, p<0.001) greater than that in patients who did not use PPIs when the defined daily dose was <30 and 30−60, respectively. Conclusions The results of this study indicate that the use of PPIs in patients with non-traumatic ICH is associated with an increased risk of pneumonia, and the severity of this risk depends on the defined daily dose. Physicians should exercise caution when prescribing PPIs for patients with non-traumatic ICH. PMID:25384687

  7. Voluntary and controlled weight loss can reduce symptoms and proton pump inhibitor use and dosage in patients with gastroesophageal reflux disease: a comparative study.

    PubMed

    de Bortoli, N; Guidi, G; Martinucci, I; Savarino, E; Imam, H; Bertani, L; Russo, S; Franchi, R; Macchia, L; Furnari, M; Ceccarelli, L; Savarino, V; Marchi, S

    2016-02-01

    A wide variety of pieces of evidence has suggested that obesity is associated with a significant increase in the risk for gastroesophageal reflux disease (GERD) symptoms and its complications. The aim of this study was to evaluate the effect of weight loss on reflux symptoms in overweight/obese patients with proven GERD. We enrolled overweight/obese patients with typical GERD symptoms and erosive esophagitis. At baseline, patients underwent detailed reflux symptoms evaluation and anthropometric assessment, and were divided into two treatment groups: group A received proton pump inhibitor (PPI) and a personalized hypocaloric diet and aerobic exercise; and group B received PPI and a 'standard of care diet'. The dietetic treatment was considered effective if at least 10% of weight loss was achieved within 6 months. All patients were evaluated in terms of anthropometric data, GERD symptoms, and PPI use. In group A, mean body mass index (BMI) decreased from 30.3 ± 4.1 to 25.7 ± 3.1 (P < 0.05), and mean weight decreased from 82.1 ± 16.9 kg to 69.9 ± 14.4 kg (P < 0.05). In group B, there was no change in BMI and weight. Symptom perception decreased (P < 0.05) in both groups during PPI therapy, but a higher improvement was recorded in group A. In group A, PPI therapy was completely discontinued in 27/50 of the patients, and halved in 16/50. Only 7/50 continued the same PPI dosage. In group B, 22/51 halved the therapy and 29/51 maintained full dosage of therapy, but none was able to discontinue PPI due to a symptom recurrence. Overall, weight loss of at least 10% is recommended in all patients with GERD in order to boost the effect of PPI on reflux symptom relief and to reduce chronic medication use. PMID:25516110

  8. Different effects of proton pump inhibitors and famotidine on the clopidogrel metabolic activation by recombinant CYP2B6, CYP2C19 and CYP3A4.

    PubMed

    Ohbuchi, Masato; Noguchi, Kiyoshi; Kawamura, Akio; Usui, Takashi

    2012-07-01

    Inhibitory potential of proton pump inhibitors (PPIs) and famotidine, an H(2) receptor antagonist, on the metabolic activation of clopidogrel was evaluated using recombinant CYP2B6, CYP2C19 and CYP3A4. Formation of the active metabolite from an intermediate metabolite, 2-oxo-clopidogrel, was investigated by liquid chromatography-tandem mass spectrometry and three peaks corresponding to the pharmacologically active metabolite and its stereoisomers were detected. Omeprazole potently inhibited clopidogrel activation by CYP2C19 with an IC(50) of 12.8 μmol/L and more weakly inhibited that by CYP2B6 and CYP3A4. IC(50) of omeprazole for CYP2C19 and CYP3A4 was decreased about two- and three-fold, respectively, by 30-min preincubation with NADPH. Lansoprazole, esomeprazole, pantoprazole, rabeprazole and rabeprazole thioether, a major metabolite, also inhibited metabolic activation by CYP2C19, with an IC(50) of 4.3, 8.9, 48.3, 36.2 and 30.5 μmol/L, respectively. In contrast, famotidine showed no more than 20% inhibition of clopidogrel activation by CYP2B6, CYP2C19 and CYP3A4 at up to 100 μmol/L and had no time-dependent CYP2C19 and CYP3A4 inhibition. These results provide direct evidence that PPIs inhibit clopidogrel metabolic activation and suggest that CYP2C19 inhibition is the main cause of drug-drug interaction between clopidogrel and omeprazole. Famotidine is considered as a safe anti-acid agent for patients taking clopidogrel. PMID:22313038

  9. Correlation between virulence gene expression and proton pump inhibitors and ambient pH in Clostridium difficile: results of an in vitro study.

    PubMed

    Stewart, David B; Hegarty, John P

    2013-10-01

    Proton pump inhibitors (PPIs) are associated with the development of Clostridium difficile infection in humans. Though it is assumed that PPIs mediate this effect through gastric acid suppression, there has been little investigation into whether PPIs, or ambient pH, might directly affect the expression of C. difficile toxin genes. In the present study, C. difficile ribotypes 001, 027 and 078 obtained from human subjects were grown under anaerobic conditions prepared at pHs of 5, 7.3 and 9. Matched trios were exposed to 100 µM and 200 µM of omeprazole along with PPI untreated controls. Custom designed reverse transcription quantitative PCR hydrolysis probes were used to assess C. difficile gene expression for toxins A (tcdA), B (tcdB) and binary toxin (cdtB), as well as their positive regulators (tcdR and cdtR), using rrsA, which encodes 16S rRNA, as a constitutively expressed reference gene. tcdC and codY, negative regulators of toxin expression, were also assessed. Basic pH resulted in greater expression of tcdA, and with PPI exposure a 120-fold higher expression was noted with ribotype 001. tcdB and cdtB expressions were much less responsive to pH or PPIs, though a clear response to acidic pH and PPI exposure was observed in ribotype 027. tcdC and codY expressions were largely unaffected, except with ribotype 027; low pH and PPIs resulted in their greater expression, though to a lesser degree than with toxin genes and their positive regulators. Non-neutral pH and PPI exposure appear to have an effect on C. difficile, one that has a net effect towards toxin gene expression. PMID:23800596

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

    PubMed Central

    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 clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods We retrospectively analyzed data from a “real world”, international, multi-center registry between 2003 and 2014 (n = 15,401) and assessed the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year composite primary endpoint (all-cause death, re-infarction, or severe bleeding) in patients with ACS after PCI. Results Of 9429 patients in the final cohort, 54.8% (n = 5165) was prescribed a PPI at discharge. Patients receiving a PPI were older, more often female, and were more likely to have comorbidities. No association was observed between PPI use and the primary endpoint for patients receiving clopidogrel (adjusted HR: 1.036; 95% CI: 0.903–1.189) or ticagrelor (adjusted HR: 2.320; 95% CI: 0.875–6.151) (Pinteraction = 0.2004). Similarly, use of a PPI was not associated with increased risk of all-cause death, re-infarction, or a decreased risk of severe bleeding for patients treated with either clopidogrel or ticagrelor. Conclusions In patients with ACS following PCI, concomitant use of PPIs was not associated with increased risk of adverse outcomes in patients receiving either clopidogrel or ticagrelor. Our findings indicate it is reasonable to use a PPI in combination with clopidogrel or ticagrelor, especially in patients with a higher risk of gastrointestinal bleeding. PMID:27103915

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

    PubMed Central

    Di Pierro, Francesco; Gatti, Mario; Rapacioli, Giuliana; Ivaldi, Leandro

    2013-01-01

    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 two groups. Conclusion Use of low doses of pure glycyrrhetinic acid + bilberry anthocyanosides, together with alginic acid as addon therapy, substantially improves symptoms in patients with nonerosive reflux disease without increasing side effects or worsening

  12. Meta-analysis of the effect of proton pump inhibitors on obstructive sleep apnea symptoms and indices in patients with gastroesophageal reflux disease.

    PubMed

    Rassameehiran, Supannee; Klomjit, Saranapoom; Hosiriluck, Nattamol; Nugent, Kenneth

    2016-01-01

    This study was designed to assess evidence for an association between the treatment of gastroesophageal reflux disease (GERD) with proton pump inhibitors (PPIs) and improvement in obstructive sleep apnea (OSA). We conducted a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies to evaluate the treatment effect of PPIs on OSA symptoms and indices in patients with GERD. EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov were reviewed up to October 2014. From 238 articles, two randomized trials and four prospective cohort studies were selected. In four cohort studies there were no differences in the apnea-hypopnea indices before and after treatment with PPIs (standard mean difference, 0.21; 95% confidence interval, -0.11 to 0.54). There was moderate heterogeneity among these studies. Two cohort studies revealed significantly decreased apnea indices after treatment (percent change, 31% and 35%), but one showed no significant difference. A significant improvement in the Epworth Sleepiness Scale was observed in three cohort studies and one trial. The frequency of apnea attacks recorded in diaries was decreased by 73% in one trial. In conclusion, available studies do not provide enough evidence to make firm conclusions about the effects of PPI treatment on OSA symptoms and indices in patients with concomitant GERD. Controlled clinical trials with larger sample sizes are needed to evaluate these associations. We recommend PPIs in OSA patients with concomitant GERD to treat reflux symptoms. This treatment may improve the quality of sleep without any effect on apnea-hypopnea indices. PMID:26722154

  13. Meta-analysis of the effect of proton pump inhibitors on obstructive sleep apnea symptoms and indices in patients with gastroesophageal reflux disease

    PubMed Central

    Klomjit, Saranapoom; Hosiriluck, Nattamol; Nugent, Kenneth

    2016-01-01

    This study was designed to assess evidence for an association between the treatment of gastroesophageal reflux disease (GERD) with proton pump inhibitors (PPIs) and improvement in obstructive sleep apnea (OSA). We conducted a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies to evaluate the treatment effect of PPIs on OSA symptoms and indices in patients with GERD. EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov were reviewed up to October 2014. From 238 articles, two randomized trials and four prospective cohort studies were selected. In four cohort studies there were no differences in the apnea-hypopnea indices before and after treatment with PPIs (standard mean difference, 0.21; 95% confidence interval, −0.11 to 0.54). There was moderate heterogeneity among these studies. Two cohort studies revealed significantly decreased apnea indices after treatment (percent change, 31% and 35%), but one showed no significant difference. A significant improvement in the Epworth Sleepiness Scale was observed in three cohort studies and one trial. The frequency of apnea attacks recorded in diaries was decreased by 73% in one trial. In conclusion, available studies do not provide enough evidence to make firm conclusions about the effects of PPI treatment on OSA symptoms and indices in patients with concomitant GERD. Controlled clinical trials with larger sample sizes are needed to evaluate these associations. We recommend PPIs in OSA patients with concomitant GERD to treat reflux symptoms. This treatment may improve the quality of sleep without any effect on apnea-hypopnea indices. PMID:26722154

  14. ATP4a is required for development and function of the Xenopus mucociliary epidermis - a potential model to study proton pump inhibitor-associated pneumonia.

    PubMed

    Walentek, Peter; Beyer, Tina; Hagenlocher, Cathrin; Müller, Christina; Feistel, Kerstin; Schweickert, Axel; Harland, Richard M; Blum, Martin

    2015-12-15

    Proton pump inhibitors (PPIs), which target gastric H(+)/K(+)ATPase (ATP4), are among the most commonly prescribed drugs. PPIs are used to treat ulcers and as a preventative measure against gastroesophageal reflux disease in hospitalized patients. PPI treatment correlates with an increased risk for airway infections, i.e. community- and hospital-acquired pneumonia. The cause for this correlation, however, remains elusive. The Xenopus embryonic epidermis is increasingly being used as a model to study airway-like mucociliary epithelia. Here we use this model to address how ATP4 inhibition may affect epithelial function in human airways. We demonstrate that atp4a knockdown interfered with the generation of cilia-driven extracellular fluid flow. ATP4a and canonical Wnt signaling were required in the epidermis for expression of foxj1, a transcriptional regulator of motile ciliogenesis. The ATP4/Wnt module activated foxj1 downstream of ciliated cell fate specification. In multiciliated cells (MCCs) of the epidermis, ATP4a was also necessary for normal myb expression, apical actin formation, basal body docking and alignment of basal bodies. Furthermore, ATP4-dependent Wnt/β-catenin signaling in the epidermis was a prerequisite for foxa1-mediated specification of small secretory cells (SSCs). SSCs release serotonin and other substances into the medium, and thereby regulate ciliary beating in MCCs and protect the epithelium against infection. Pharmacological inhibition of ATP4 in the mature mucociliary epithelium also caused a loss of MCCs and led to impaired mucociliary clearance. These data strongly suggest that PPI-associated pneumonia in human patients might, at least in part, be linked to dysfunction of mucociliary epithelia of the airways. PMID:25848696

  15. Association Between the Use of Proton Pump Inhibitors and the Risk of ESRD in Renal Diseases: A Population-Based, Case-Control Study

    PubMed Central

    Peng, Yen-Chun; Lin, Cheng-Li; Yeh, Hong-Zen; Chang, Chi-Sen; Wu, Yu-Lin; Kao, Chia-Hung

    2016-01-01

    Abstract Proton pump inhibitors (PPIs) use may be associated with nephritis and acute renal injury. The risk of PPIs and deterioration of renal function, in patients with renal diseases, needs to be investigated. A case-control study was conducted in a nation-wide data setting from the Taiwan National Health Insurance Research Database (NHIRD). This case-control study used data extracted from NHIRD between the years 2006 and 2011. We used propensity scores to match 3808 patients suffering from renal diseases (ICD-9-CM codes 580–589), with patients (aged ≥20 years) who had had a recent diagnosis of end-stage renal diseases (ESRDs) and had undertaken renal replacement therapy during the period of 2006 to 2011. The 3808 control subjects were selected from people who had a history of renal diseases, but no ESRD. The risk of ESRD in patients with renal diseases and PPIs use was estimated by using odds ratios (ORs) and 95% confidence intervals (CI). The use of a PPIs was associated with a significantly higher risk of ESRD (adjusted OR = 1.88, 95% CI = 1.71–2.06) in renal disease patients. Of all the types of PPI combined, the adjusted OR was 1.92 (95% CI = 1.74–2.13) for those on <100 cumulative DDD and was 1.74-fold (95% CI = 1.52–2.00) for those on ≥100 cumulative DDD. PPIs use is associated with the risk of ESRD in patients with renal diseases. It is necessary that appropriate prescription of PPIs coordinated with the close monitoring renal function of patients diagnosed with renal disease. PMID:27082596

  16. Risk of Clostridium difficile Infection with the Use of a Proton Pump Inhibitor for Stress Ulcer Prophylaxis in Critically Ill Patients

    PubMed Central

    Ro, Youngouk; Eun, Chang Soo; Kim, Hyun Soo; Kim, Ji Yeoun; Byun, Young Jae; Yoo, Kyo-Sang; Han, Dong Soo

    2016-01-01

    Background/Aims Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are commonly prescribed for stress ulcer prophylaxis (SUP) in critically ill patients. Several studies have suggested that the use of PPIs is a potential risk factor for Clostridium difficile infection (CDI). We compared the incidences of CDI in the PPI group and H2RA group for SUP in critically ill patients. Methods From August 2005 to July 2012, the incidences of CDI were retrospectively analyzed in patients who were admitted directly to intensive care units and stayed for more than 3 days. SUP-related CDI was defined as a CDI diagnosed during the SUP period. Patient clinical data were analyzed to identify potential risk factors for SUP-related CDI. Results Of the 1,005 patients enrolled (444 patients received PPI and 561 received H2RA), 38 (3.8%) were diagnosed with SUP-related CDI. The incidence of SUP-related CDI was considerably higher in patients who received PPI than in those who received H2RA (6.7% vs 1.8%). PPI use for SUP (odds ratio [OR], 3.3; confidence interval [CI], 1.5 to 7.1; p=0.003) and diabetes mellitus (OR, 2.3; CI, 1.2 to 4.7; p=0.019) were independent risk factors for SUP-related CDI. Conclusions PPI therapy is associated with a higher risk of SUP-related CDI than H2RA therapy in critically ill patients. PMID:27021503

  17. Proton Pump Inhibitor Therapy Is Associated With Reduction of Early Bleeding Risk After Prophylactic Endoscopic Variceal Band Ligation: A Retrospective Cohort Study.

    PubMed

    Kang, Seong Hee; Yim, Hyung Joon; Kim, Seung Young; Suh, Sang Jun; Hyun, Jong Jin; Jung, Sung Woo; Jung, Young Kul; Koo, Ja Seol; Lee, Sang Woo

    2016-02-01

    Endoscopic variceal band ligation (EVL) is an effective procedure to control and prevent variceal bleeding in patients with liver cirrhosis, but it can be complicated by bleeding from post-EVL ulcers. Several studies have reported that proton pump inhibitors (PPIs) decrease the size of post-EVL ulcers. However, evidence are limited as to whether PPIs actually reduce the risk of bleeding after EVL. This study aimed to analyze the factors associated with bleeding after prophylactic EVL and to assess the effect of PPI therapy.Five hundred and five cirrhotic patients with high risk esophageal varices who received primary prophylactic EVL were included for this retrospective cohort study. Post-EVL bleeding was defined as bleeding after prophylactic EVL within 8 weeks evidenced by the occurrence of melena or hematemesis, or by a decrease of hemoglobin by >2.0 g/dL. If evidence of bleeding from ulceration of the EVL sites was confirmed by endoscopy, we defined it as post-EVL ulcer bleeding.Fourteen patients developed bleeding after prophylactic EVL. Factors associated with post-EVL bleeding included alcohol as etiology, low albumin, high total bilirubin, high Child-Pugh score, high MELD score, coexistence of gastric varices, and not administrating PPI medication by univariate analysis. In multivariate logistic analysis, Co-existing gastric varix (odds ratio [OR] 5.680, P = 0.005] and not administrating PPIs (OR 8.217, P = 0.002) were associated with bleeding after prophylactic EVL. In the subgroup analysis excluding patients whose gastric varices were treated, not administering PPI medication (OR 8.827, P = 0.008) was the sole factor associated with post-EVL bleeding.We suggest that PPI therapy needs to be considered in patients receiving prophylactic EVL to reduce the risk of bleeding after prophylactic EVL. PMID:26937932

  18. Effect of baseline gastrointestinal risk and use of proton pump inhibitors on frequency of discontinuation of aspirin for secondary cardiovascular prevention in United kingdom primary care.

    PubMed

    Martín Merino, Elisa; Johansson, Saga; Nagy, Péter; García Rodríguez, Luis A

    2013-10-15

    For patients at high cardiovascular and high gastrointestinal (GI) risk, coprescription of a proton pump inhibitor (PPI) with low-dose aspirin is recommended. We aimed to quantify the extent to which low-dose aspirin discontinuation in patients at high cardiovascular risk is affected by PPI use and baseline GI risk. Patients aged 50 to 84 years who had evidence of ischemic heart disease or cardiovascular disease and who were new users of low-dose aspirin in 2000 to 2007 were identified using The Health Improvement Network (n = 35,604). Aspirin discontinuation was defined as a period of at least 90 days after completion of the last prescribed course during which no repeat prescription was issued. The incidence of low-dose aspirin discontinuation was 26.8 per 100 person-years (95% confidence interval [CI] 26.2 to 27.4). The age-, gender-, and indication-adjusted risk of aspirin discontinuation was 15% less among continuous PPI users than among PPI nonusers (hazard ratio [HR] 0.85, 95% CI 0.78 to 0.92); after further adjusting for number of coprescribed medications, the HR was 0.95 (95% CI 0.87 to 1.03). Continuous PPI use was associated with a reduced risk of aspirin discontinuation among patients at high GI risk (HR 0.83; 95% CI 0.74 to 0.93) but not among those at low GI risk (HR 1.08; 95% CI 0.96 to 1.21). In conclusion, among patients at high GI risk, concomitant users of aspirin and PPI showed a greater aspirin adherence than aspirin users not on PPI. Further studies need to confirm factors with the potential to increase adherence to long-term aspirin. PMID:23831164

  19. Effects of Clopidogrel and Proton Pump Inhibitors on Cardiovascular Events in Patients with Type 2 Diabetes Mellitus after Drug-Eluting Stent Implantation: A Nationwide Cohort Study

    PubMed Central

    Hsieh, Chi-Feng; Huang, Weng-Foung; Chiang, Yi-Ting; Chen, Chun-Yen

    2015-01-01

    Objective To investigate whether there is an increased risk of cardiac events in diabetic patients with a combined therapy of clopidogrel (CLO) and proton pump inhibitors (PPIs) after drug-eluting stent (DES) deployment. Methods By using National Health Insurance Research Database, all patients who received CLO with or without PPI therapy within 90 days after undergoing DES (limus-eluting or paclitaxel-eluting stents) deployment were enrolled. Endpoints were acute coronary syndrome (ACS) and readmission for revascularization (percutaneous coronary intervention or coronary artery bypass graft surgery) after 3, 6, and 12 months. Results A total of 6,603 diabetic patients received LESs (5,933 in the CLO subgroup and 670 in the CLO plus PPIs subgroup), and 3,202 patients received PESs (2,923 in the CLO subgroup and 279 in the CLO plus PPIs subgroup). The patients who received CLO plus PPIs were at higher risk of ACS than those receiving CLO within 1 year after DES deployment (LESs: 6-month hazard ratio [HR] = 1.63, and 1-year HR = 1.37; PESs: 3-month HR = 1.72). Patients with a history of ACS who received CLO plus PPIs were at higher risk of ACS after LES implantation (HR = 1.55) than those in the CLO group. Conclusion In “real-world” diabetic patients with LES deployment, the combination of PPIs and CLO is associated with higher rates of ACS after 6 months and 1 year. Even after correction for confounding factors, concomitant PPI use remained an independent predictor of cardiac events, emphasizing the clinical importance of this drug—drug interaction. PMID:26313000

  20. Risk factors determining the need for second-look endoscopy for peptic ulcer bleeding after endoscopic hemostasis and proton pump inhibitor infusion

    PubMed Central

    Cheng, Hsiu-Chi; Wu, Chung-Tai; Chen, Wei-Ying; Yang, Er-Hsiang; Chen, Po-Jun; Sheu, Bor-Shyang

    2016-01-01

    Background and study aims: The need for routine second-look endoscopy in cases of peptic ulcer bleeding remains uncertain. We investigated risk factors related to the need for second-look endoscopy after endoscopic hemostasis and proton pump inhibitor (PPI) infusion. Patients and methods: We prospectively enrolled 316 patients with peptic ulcer bleeding after endoscopic hemostasis. Second-look endoscopy was scheduled after 72-hour PPI infusion (Day-3 subgroup) or one day early (Day-2 subgroup). If early rebleeding developed within 3 days, emergent second-look endoscopy was conducted. Risk factors for early rebleeding (use of E2nd score to predict the need for early second-look endoscopy) and persistent major stigmata in the Day-3 subgroup (use of R2nd score to predict the need for routine second-look endoscopy) were analyzed using univariable and multivariable regression. Results: Excluding 10 of 316 patients with early rebleeding, the rate of persistent major stigmata was lower in the Day-3 subgroup than in the Day-2 subgroup (4.8 % vs. 15.4 %, P  = 0.002). Endoscopic epinephrine-injection monotherapy and hypoalbuminemia < 3.0 g/dL were two independent risk factors for early rebleeding (P  ≤ 0.05). The Forrest Ia-Ib type and hypoalbuminemia < 3.5 g/dL were two independent risk factors for persistent major stigmata on the day-3 second-look endoscopy (P  < 0.05). The E2nd score was highly accurate for prediction of early rebleeding (AUROC 0.86; 95 % CI, 0.73~0.99), and the R2nd score could predict persistent major stigmata at second-look endoscopy (AUROC 0.84; 95 % CI, 0.69~0.99). Conclusions: For patients with peptic ulcer bleeding, E2nd and R2nd scores can indicate the need for early and routine second-look endoscopy, respectively (Trial registration identifier: NCT02197039). PMID:27004241

  1. The Effect of Helicobacter pylori Infection, Aging, and Consumption of Proton Pump Inhibitor on Fungal Colonization in the Stomach of Dyspeptic Patients

    PubMed Central

    Massarrat, Sadegh; Saniee, Parastoo; Siavoshi, Farideh; Mokhtari, Reyhane; Mansour-Ghanaei, Fariborz; Khalili-Samani, Saman

    2016-01-01

    Background: The importance of coinfection of Helicobacter pylori (H.pylori) and Candida albicans (C. albicans) in the development of gastric diseases is not known. In this study, the frequency of concurrent infection of H. pylori and C. albicans in dyspeptic patients was assessed while considering age, gender, and PPI consumption of patients. Methods: Gastric biopsies were taken from 74 yeast-positive dyspeptic patients and gastric disease, age, gender, and proton pump inhibitor (PPI) consumption of subjects were recorded. One antral biopsy was used for rapid urease test (RUT) and one for H. pylori and yeast cultivation and smear preparation. Bacterial isolates were identified according to spiral morphology and the biochemical characteristics. Yeast isolates were identified on Chromagar and by the Nested-PCR amplification of C. albicans-specific topoisomerase II gene. Twenty-seven biopsy smears were Gram-stained and examined by the light microscope for observing H. pylori and yeast cells. Results: Fifty-four (73%) of patients were >40 year. Of 68 patients with PPI consumption record, 46 (67.6%) consumed PPI (p = 0). Comparison of patients in peptic ulcer group (12, 16.2%) with (6, 8.1%) or without (6, 8.1%) H. pylori or in gastritis group (62, 83.8%) with (25, 33.8%) or without (37, 50%) H. pylori showed no significant difference (p > 0.05). Of the 46 patients who consumed PPI, 13 (17.5%) were H. pylori-positive and 33 (44.6%) H. pylori-negative (p = 0). Ten out of twenty-seven smears showed the occurrence of H. pylori cells, including three with yeast cells. Of the 17 H. pylori-negative smears, three showed the occurrence of yeast cells only. Yeasts stained Gram-positive or Gram-negative and appeared as single or budding cells. Conclusion: The older age and PPI consumption could favor fungal colonization in the human stomach. The occurrence of a considerable number of H. pylori-positive or H. pylori-negative patients with gastritis or peptic ulcer shows that co

  2. Crystal structure and bonding analysis of the first dinuclear calcium(II)-proton-pump inhibitor (PPI) `butterfly molecule': a combined microcrystal synchrotron and DFT study.

    PubMed

    Cong, Hengjiang

    2016-04-01

    Proton-pump inhibitors (PPI) are prodrugs used widely to treat acid-related diseases since the late 1980s. After an extensive research effort it has become clear that the fundamental interactions between metal atoms and PPIs are of paramount importance for both drug release and long-term therapeutic safety. Unfortunately, until now, very little information has been available on this topic. In this paper, we report the crystal structure analysis of a novel calcium-PPI compound incorporating bridging and terminal deprotonated (R)-rabeprazole tricyclic ligands (L), namely bis[μ-(R)-2-({[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methyl}sulfinyl)-6,7-dihydro-3H-benzofuro[5,6-d]imidazol-1-ido]bis{dimethanol[(R)-2-({[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methyl}sulfinyl)-6,7-dihydro-3H-benzofuro[5,6-d]imidazol-1-ido]calcium(II)} methanol hexasolvate, [Ca2(C20H22N3O4S)4(CH3OH)4]·6CH3OH or [Ca2(L)4(CH3OH)4]·6CH3OH, which crystallizes from methanol in the polar C2 space group. Using low-temperature microcrystal synchrotron radiation, we demonstrate that this compound is in the form of a beautiful `butterfly molecule', consisting of a C2-symmetric dinuclear (CH3OH)2LCa(II)(μ2-L)2Ca(II)L(HOCH3)2 framework. A large amount of disorder is found within the bridging L ligand and the conformation of the fused tetrahydrofuran ring exhibits great variety. All the sulfinyl groups remain intact and the nonbonded Ca...Ca distance is significantly longer than in other calcium dimers, indicating steric hindrance in the bridging ligands. Considerable hydrogen bonding and aromatic C-H...π interactions co-operate to stabilize the whole complex, as well as to facilitate supramolecular assembly. Additional investigations into the bond nature were made using density functional theory (DFT) methods at the B3LYP/6-31G(d) level; geometry optimization, Mulliken atomic charges, MEP (molecular electrostatic potential), HOMO-LUMO (highest occupied molecular orbital-lowest unoccupied molecular

  3. Re-evolution of the 2-phenylquinolines: ligand-based design, synthesis, and biological evaluation of a potent new class of Staphylococcus aureus NorA efflux pump inhibitors to combat antimicrobial resistance.

    PubMed

    Sabatini, Stefano; Gosetto, Francesca; Iraci, Nunzio; Barreca, Maria Letizia; Massari, Serena; Sancineto, Luca; Manfroni, Giuseppe; Tabarrini, Oriana; Dimovska, Mirjana; Kaatz, Glenn W; Cecchetti, Violetta

    2013-06-27

    Overexpression of efflux pumps is an important mechanism by which bacteria evade the effects of antimicrobial agents that are substrates. NorA is a Staphylococcus aureus efflux pump that confers reduced susceptibility to many structurally unrelated agents, including fluoroquinolones, biocides, and dyes, resulting in a multidrug resistant (MDR) phenotype. In this work, a series of 2-phenylquinoline derivatives was designed by means of ligand-based pharmacophore modeling in an attempt to identify improved S. aureus NorA efflux pump inhibitors (EPIs). Most of the 2-phenylquinoline derivatives displayed potent EPI activity against the norA overexpressing strain SA-1199B. The antibacterial activity of ciprofloxacin, when used in combination with some of the synthesized compounds, was completely restored in SA-1199B and SA-K2378, a strain overexpressing norA from a multicopy plasmid. Compounds 3m and 3q also showed potent synergistic activity with the ethidium bromide dye in a strain overexpressing the MepA MDR efflux pump. PMID:23710549

  4. Effects of chlorophyll-derived efflux pump inhibitor pheophorbide a and pyropheophorbide a on erythromycin resistance of Staphylococcus aureus, Enterococcus faecalis, Salmonella Typhimurium and Escherichia coli

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to validate the hypothesis that pheophorbide a and pyropheophorbide a reduce erythromycin resistance of reference strains of facultative anaerobic bacteria with multidrug or macrolide efflux pumps, as indicative of their effect on bacteria indigenous to anaerobic swine ...

  5. Effects of chlorophyll-derived efflux pump inhibitor pheophorbide a and pyropheophorbide a on growth and macrolide antibiotic resistance of indicator and anaerobic swine manure bacteria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Natural plant compounds, such as the chlorophyll a catabolites pheophorbide a (php) and pyropheophorbide a (pyp), are potentially active in the gastrointestinal tracts and wastes of livestock as antimicrobial resistance-modifying agents through inhibition of bacterial efflux pumps. To investigate w...

  6. 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

    PubMed Central

    2012-01-01

    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 < 0.05) and angiogenic factors including VEGF, bFGF, and HIF-1α. Indomethacin markedly increased the expressions of TNF-α, IL-1ß, IL-8, NOX-1, ICAM-1 and VCAM, whereas pantoprazole significantly decreased the expressions of indomethacin-induced these inflammatory mediators in accord with pantoprazole-induced HO-1 (P < 0.05) as documented with HO-1 inhibitor. 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

  7. PUMP CONSTRUCTION

    DOEpatents

    Strickland, G.; Horn, F.L.; White, H.T.

    1960-09-27

    A pump which utilizes the fluid being pumped through it as its lubricating fluid is described. This is achieved by means of an improved bearing construction in a pump of the enclosed or canned rotor type. At the outlet end of the pump, adjacent to an impeller mechanism, there is a bypass which conveys some of the pumped fluid to a chamber at the inlet end of the pump. After this chamber becomes full, the pumped fluid passes through fixed orifices in the top of the chamber and exerts a thrust on the inlet end of the pump rotor. Lubrication of the rotor shaft is accomplished by passing the pumped fluid through a bypass at the outlet end of the rotor shaft. This bypass conveys Pumped fluid to a cooling means and then to grooves on the surface of the rotor shait, thus lubricating the shaft.

  8. Industrial Pumps

    NASA Technical Reports Server (NTRS)

    1986-01-01

    A flow inducer is a device that increases the pump intake capacity of a Worthington Centrifugal pump. It lifts the suction pressure sufficiently for the rotating main impeller of the centrifugal pump to operate efficiently at higher fluid intake levels. The concept derives from 1960's NASA technology which was advanced by Worthington Pump Division. The pumps are used to recirculate wood molasses, a highly viscous substance.

  9. Oxygen pumps

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Special considerations to be given to the design, fabrication, and use of centrifugal pumps for liquid O2 to avoid conditions that lead to system failure are given. Emphasis was placed on turbine pumps for flight applications.

  10. Casing pump

    SciTech Connect

    Bass, H.E.; Bass, R.E.

    1987-09-29

    A natural gas operated pump is described for use in the casing of an oil well, comprising: a tubular pump body having an open lower end for admitting well fluids to the interior of the pump body and an open upper end, wherein a downwardly facing seating surface is formed on the inner periphery of the pump body adjacent the upper end thereof; means for forming a seal between the pump body and the casing of the well; a rod extending longitudinally through the seating surface formed in the pump body and protruding from the upper end of the pump body; a valve member mounted on the rod below the seating surface and shaped to mate with the seating surface; and means for vertically positioning the rod in proportion to fluid pressure within the pump body.

  11. Magnetocaloric pump

    NASA Technical Reports Server (NTRS)

    Brown, G. V.

    1973-01-01

    Very cold liquids and gases such as helium, neon, and nitrogen can be pumped by using magnetocaloric effect. Adiabatic magnetization and demagnetization are used to alternately heat and cool slug of pumped fluid contained in closed chamber.

  12. ELECTROMAGNETIC PUMP

    DOEpatents

    Pulley, O.O.

    1954-08-17

    This patent reiates to electromagnetic pumps for electricity-conducting fluids and, in particular, describes several modifications for a linear conduction type electromagnetic interaction pump. The invention resides in passing the return conductor for the current traversing the fiuid in the duct back through the gap in the iron circuit of the pump. Both the maximum allowable pressure and the efficiency of a linear conduction electromagnetic pump are increased by incorporation of the present invention.

  13. Pantoprazole, an FDA-approved proton-pump inhibitor, suppresses colorectal cancer growth by targeting T-cell-originated protein kinase.

    PubMed

    Zeng, Xiaoyu; Liu, Lin; Zheng, Mengzhu; Sun, Huimin; Xiao, Juanjuan; Lu, Tao; Huang, Guangqian; Chen, Pianpian; Zhang, Jianmin; Zhu, Feng; Li, Hua; Duan, Qiuhong

    2016-04-19

    T-cell-originated protein kinase (TOPK) is highly expressed in several cancer cells and promotes tumorigenesis and progression, and therefore, it is an important target for drug treatment of tumor. Pantoprazole (PPZ) was identified to be a TOPK inhibitor from FDA-approved drug database by structure based virtual ligand screening. Herein, the data indicated that pantoprazole inhibited TOPK activities by directly binding with TOPK in vitro and in vivo. Ex vivo studies showed that pantoprazole inhibited TOPK activities in JB6 Cl41 cells and HCT 116 colorectal cancer cells. Moreover, knockdown of TOPK in HCT 116 cells decreased their sensitivities to pantoprazole. Results of an in vivo study demonstrated that i.p. injection of pantoprazole in HCT 116 colon tumor-bearing mice effectively suppressed cancer growth. The TOPK downstream signaling molecule phospho-histone H3 in tumor tissues was also decreased after pantoprazole treatment. In short, pantoprazole can suppress growth of colorectal cancer cells as a TOPK inhibitor both in vitro and in vivo. PMID:26967058

  14. Pantoprazole, an FDA-approved proton-pump inhibitor, suppresses colorectal cancer growth by targeting T-cell-originated protein kinase

    PubMed Central

    Sun, Huimin; Xiao, Juanjuan; Lu, Tao; Huang, Guangqian; Chen, Pianpian; Zhang, Jianmin; Zhu, Feng; Li, Hua; Duan, Qiuhong

    2016-01-01

    T-cell-originated protein kinase (TOPK) is highly expressed in several cancer cells and promotes tumorigenesis and progression, and therefore, it is an important target for drug treatment of tumor. Pantoprazole (PPZ) was identified to be a TOPK inhibitor from FDA-approved drug database by structure based virtual ligand screening. Herein, the data indicated that pantoprazole inhibited TOPK activities by directly binding with TOPK in vitro and in vivo. Ex vivo studies showed that pantoprazole inhibited TOPK activities in JB6 Cl41 cells and HCT 116 colorectal cancer cells. Moreover, knockdown of TOPK in HCT 116 cells decreased their sensitivities to pantoprazole. Results of an in vivo study demonstrated that i.p. injection of pantoprazole in HCT 116 colon tumor-bearing mice effectively suppressed cancer growth. The TOPK downstream signaling molecule phospho-histone H3 in tumor tissues was also decreased after pantoprazole treatment. In short, pantoprazole can suppress growth of colorectal cancer cells as a TOPK inhibitor both in vitro and in vivo. PMID:26967058

  15. OSCILLATORY PUMP

    DOEpatents

    Underwood, N.

    1958-09-23

    This patent relates to a pump suitable fur pumping highly corrosive gases wherein no lubricant is needed in the pumping chamber thus eliminating possible contamination sources. The chamber contains a gas inlet and outlet in each side, with a paddle like piston suspended by a sylphon seal between these pcrts. An external arrangement causes the paddle to oscillate rapidly between the ports, alternately compressing and exhausting the gas trapped on each side of the paddle. Since the paddle does nnt touch the chamber sides at any point, no lubricant is required. This pump is useful for pumping large quantities of uranium hexafluorine.

  16. Changes in CYP2C19 enzyme activity evaluated by the [(13)C]-pantoprazole breath test after co-administration of clopidogrel and proton pump inhibitors following percutaneous coronary intervention and correlation to platelet reactivity.

    PubMed

    Harvey, Adrien; Modak, Anil; Déry, Ugo; Roy, Mélanie; Rinfret, Stéphane; Bertrand, Olivier F; Larose, Éric; Rodés-Cabau, Josep; Barbeau, Gérald; Gleeton, Onil; Nguyen, Can Manh; Proulx, Guy; Noël, Bernard; Roy, Louis; Paradis, Jean-Michel; De Larochellière, Robert; Déry, Jean-Pierre

    2016-03-01

    Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is used for the prevention of cardiovascular events following percutaneous coronary intervention (PCI). These agents increase the risk of gastrointestinal bleeding. To prevent these events, proton pump inhibitors (PPI) are routinely prescribed. It has been reported that with the exception of pantoprazole and dexlanzoprazole, PPIs can impede conversion of clopidogrel by cytochrome P450 2C19 (CYP2C19) to its active metabolite, a critical step required for clopidogrel efficacy. Changes in CYP2C19 enzyme activity (phenotype) and its correlation with platelet reactivity following PPI therapy has not yet been fully described. In this study we attempted to determine if the [ (13)C]-pantoprazole breath test (Ptz-BT) can evaluate changes in CYP2C19 enzyme activity (phenoconversion) following the administration of PPI in coronary artery disease (CAD) patients treated with DAPT after PCI. Thirty (30) days after successful PCI with stent placement, 59 patients enrolled in the Evaluation of the Influence of Statins and Proton Pump Inhibitors on Clopidogrel Antiplatelet Effects (SPICE) trial (ClinicalTrials.gov Identifier: NCT00930670) were recruited to participate in this sub study. Patients were randomized to one of 4 antacid therapies (omeprazole, esomeprazole. pantoprazole or ranitidine). Subjects were administered the Ptz-BT and platelet function was evaluated by vasodilator-stimulated phosphoprotein (VASP) phosphorylation and light transmittance aggregometry before and 30 d after treatment with antacid therapy. Patients randomized to esomeprazole and omeprazole had greater high on-treatment platelet reactivity and lowering of CYP2C19 enzyme activity at Day 60 after 30 d of PPI therapy. Patients randomized to ranitidine and pantoprazole did not show any changes in platelet activity or CYP 2C19 enzyme activity. In patients treated with esomeprazole and omeprazole, changes in CYP2C19 enzyme activity

  17. 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

    PubMed Central

    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

    2015-01-01

    Background Refractory gastroesophageal reflux disease (GERD) may deteriorate patient quality of life (QOL) despite proton pump inhibitor (PPI) therapy. Material/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. PMID:26719012

  18. Axial Pump

    NASA Technical Reports Server (NTRS)

    Bozeman, Richard J., Jr. (Inventor); Akkerman, James W. (Inventor); Aber, Gregory S. (Inventor); VanDamm, George Arthur (Inventor); Bacak, James W. (Inventor); Svejkovsky, Paul A. (Inventor); Benkowski, Robert J. (Inventor)

    1997-01-01

    A rotary blood pump includes a pump housing for receiving a flow straightener, a rotor mounted on rotor bearings and having an inducer portion and an impeller portion, and a diffuser. The entrance angle, outlet angle, axial and radial clearances of blades associated with the flow straightener, inducer portion, impeller portion and diffuser are optimized to minimize hemolysis while maintaining pump efficiency. The rotor bearing includes a bearing chamber that is filled with cross-linked blood or other bio-compatible material. A back emf integrated circuit regulates rotor operation and a microcomputer may be used to control one or more back emf integrated circuits. A plurality of magnets are disposed in each of a plurality of impeller blades with a small air gap. A stator may be axially adjusted on the pump housing to absorb bearing load and maximize pump efficiency.

  19. Ferroelectric Pump

    NASA Technical Reports Server (NTRS)

    Jalink, Antony, Jr. (Inventor); Hellbaum, Richard F. (Inventor); Rohrbach, Wayne W. (Inventor)

    2000-01-01

    A ferroelectric pump has one or more variable volume pumping chambers internal to a housing. Each chamber has at least one wall comprising a dome shaped internally prestressed ferroelectric actuator having a curvature and a dome height that varies with an electric voltage applied between an inside and outside surface of the actuator. A pumped medium flows into and out of each pumping chamber in response to displacement of the ferroelectric actuator. The ferroelectric actuator is mounted within each wall and isolates each ferroelectric actuator from the pumped medium, supplies a path for voltage to be applied to each ferroelectric actuator, and provides for positive containment of each ferroelectric actuator while allowing displacement of the entirety of each ferroelectric actuator in response to the applied voltage.

  20. Submersible pump

    SciTech Connect

    Todd, D. B.

    1985-08-27

    A method and apparatus for using a submersible pump to lift reservoir fluids in a well while having the tubing/casing annulus isolated from the produced fluids. The apparatus allows the submersible pump to be positioned above the annular packoff device. The apparatus comprises an outer shield that encloses the pump and can be attached to the production tubing. The lower end of the shield attaches to a short tubing section that seals with the annular packoff device or a receptacle above the annular packoff device.

  1. Non-Carriers of Reduced-Function CYP2C19 Alleles are Most Susceptible to Impairment of the Anti-Platelet Effect of Clopidogrel by Proton-Pump Inhibitors: A Pilot Study

    PubMed Central

    Lee, Jen-Kuang; Wu, Cho-Kai; Juang, Jyh-Ming; Tsai, Chia-Ti; Hwang, Juey-Jen; Lin, Jiuun-Lee; Chiang, Fu-Tien

    2016-01-01

    Background The phenomenon of CYP2C19 polymorphism affects the metabolism of both clopidogrel and proton-pump inhibitors (PPI). However, concomitant use of both drugs may reduce the desired therapeutic effects. In this study, we evaluated whether individuals with different numbers of reduced-function CYP2C19 alleles were equally affected and whether PPIs with different dependencies on CYP2C19 metabolism were equally involved. Methods Thirty healthy volunteers were recruited to a six-week regimen of clopidogrel. Three PPIs with different metabolic dependencies on CYP2C19 were included and separately administered in this order. Each PPI was given for a week, followed by a one-week washout period before the intervention of the next PPI. The anti-platelet effect was examined by Thromboelastography Platelet MappingTM (TEG®) and vasodilator-stimulated phosphoprotein (VASP) assays. Results Both TEG® and VASP tests showed the same general qualitative trend, but TEG® detected a statistically significant fluctuation of platelet aggregation in response to different drug interventions. The TEG® results also demonstrated that non-carriers experienced the most significant impairment of anti-platelet effect of clopidogrel after concomitant use of PPIs. This impairment was closely related to the metabolic dependence on CYP2C19 of PPI. Conclusions Our study indicated that non-carriers of reduced-function CYP2C19 alleles are most susceptible to impairment of the anti-platelet effect of clopidogrel after concomitant PPI use. Individual subjects are not equally affected, and PPIs are not equally involved. However, large-scale randomized clinical trials are needed to evaluate the clinical outcome. PMID:27122952

  2. ION PUMP

    DOEpatents

    Milleron, N.

    1961-01-01

    An ion pump and pumping method are given for low vacuum pressures in which gases introduced into a pumping cavity are ionized and thereafter directed and accelerated into a quantity of liquid gettering metal where they are absorbed. In the preferred embodiment the metal is disposed as a liquid pool upon one electrode of a Phillips ion gauge type pump. Means are provided for continuously and remotely withdrawing and degassing the gettering metal. The liquid gettering metal may be heated if desired, although various combinations of gallium, indium, tin, bismuth, and lead, the preferred metals, have very low melting points. A background pressure of evaporated gettering metal may be provided by means of a resistance heated refractory metal wick protruding from the surface of the pcol of gettering metal.

  3. Electrokinetic pump

    DOEpatents

    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.

  4. Insulin pumps.

    PubMed

    Pickup, J

    2011-02-01

    The last year has seen a continued uptake of insulin pump therapy in most countries. The USA is still a leader in pump use, with probably some 40% of type 1 diabetic patients on continuous subcutaneous insulin infusion (CSII), but the large variation in usage within Europe remains, with relatively high use (> 15%) in, for example, Norway, Austria, Germany and Sweden and low use (< 5%) in Spain, the UK, Finland and Portugal. There is much speculation on the factors responsible for this variation, and the possibilities include physician attitudes to CSII and knowledge about its benefits and indications for its use (and inappropriate beliefs about dangers), the availability of reimbursement from insurance companies or funding from national health services, the availability of sufficient diabetes nurse educators and dietitians trained in pump procedures, and clear referral pathways for the pump candidate from general practitioner or general hospital to specialist pump centre. There are now several comprehensive national guidelines on CSII use (see ATTD Yearbook 2009) but more work needs to be done in unifying uptake and ensuring all those who can benefit do so. Technology developments recently include increasing use of pumps with continuous glucose monitoring (CGM) connectivity (see elsewhere in this volume) and the emergence of numerous manufacturers developing so-called 'patch pumps', often for the type 2 diabetes market. Interestingly, the evidence base for CSII in this group is not well established, and for this reason the selected papers on CSII in this section include several in this area. The use of CSII in diabetic pregnancy is a long-established practice, in spite of the lack of evidence that it is superior to multiple daily injections (MDI), and few randomised controlled trials have been done in recent years. Several papers in this field this year continue the debate about the usefulness of CSII in diabetic pregnancy and are reviewed here. It is pleasing

  5. Electrokinetic pump

    DOEpatents

    Hencken, Kenneth R.; Sartor, George B.

    2004-08-03

    An electrokinetic pump in which the porous dielectric medium of conventional electrokinetic pumps is replaced by a patterned microstructure. The patterned microstructure is fabricated by lithographic patterning and etching of a substrate and is formed by features arranged so as to create an array of microchannels. The microchannels have dimensions on the order of the pore spacing in a conventional porous dielectric medium. Embedded unitary electrodes are vapor deposited on either end of the channel structure to provide the electric field necessary for electroosmotic flow.

  6. DIFFUSION PUMP

    DOEpatents

    Levenson, L.

    1963-09-01

    A high-vacuum diffusion pump is described, featuring a novel housing geometry for enhancing pumping speed. An upright, cylindrical lower housing portion is surmounted by a concentric, upright, cylindrical upper housing portion of substantially larger diameter; an uppermost nozzle, disposed concentrically within the upper portion, is adapted to eject downwardly a conical sheet of liquid outwardly to impinge upon the uppermost extremity of the interior wall of the lower portion. Preferably this nozzle is mounted upon a pedestal rising coaxially from within the lower portion and projecting up into said upper portion. (AEC)

  7. 18. Electrically driven pumps in Armory Street Pump House. Pumps ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. Electrically driven pumps in Armory Street Pump House. Pumps in background formerly drew water from the clear well. They went out of service when use of the beds was discontinued. Pumps in the foreground provide high pressure water to Hamden. - Lake Whitney Water Filtration Plant, Armory Street Pumphouse, North side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

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

    PubMed

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

    2016-05-01

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

  9. Well pump

    DOEpatents

    Ames, Kenneth R.; Doesburg, James M.

    1987-01-01

    A well pump includes a piston and an inlet and/or outlet valve assembly of special structure. Each is formed of a body of organic polymer, preferably PTFE. Each includes a cavity in its upper portion and at least one passage leading from the cavity to the bottom of the block. A screen covers each cavity and a valve disk covers each screen. Flexible sealing flanges extend upwardly and downwardly from the periphery of the piston block. The outlet valve block has a sliding block and sealing fit with the piston rod.

  10. Proteasome inhibitors.

    PubMed

    Teicher, Beverly A; Tomaszewski, Joseph E

    2015-07-01

    Proteasome inhibitors have a 20 year history in cancer therapy. The first proteasome inhibitor, bortezomib (Velcade, PS-341), a break-through multiple myeloma treatment, moved rapidly through development from bench in 1994 to first approval in 2003. Bortezomib is a reversible boronic acid inhibitor of the chymotrypsin-like activity of the proteasome. Next generation proteasome inhibitors include carfilzomib and oprozomib which are irreversible epoxyketone proteasome inhibitors; and ixazomib and delanzomib which are reversible boronic acid proteasome inhibitors. Two proteasome inhibitors, bortezomib and carfilzomib are FDA approved drugs and ixazomib and oprozomib are in late stage clinical trials. All of the agents are potent cytotoxics. The disease focus for all the proteasome inhibitors is multiple myeloma. This focus arose from clinical observations made in bortezomib early clinical trials. Later preclinical studies confirmed that multiple myeloma cells were indeed more sensitive to proteasome inhibitors than other tumor cell types. The discovery and development of the proteasome inhibitor class of anticancer agents has progressed through a classic route of serendipity and scientific investigation. These agents are continuing to have a major impact in their treatment of hematologic malignancies and are beginning to be explored as potential treatment agent for non-cancer indications. PMID:25935605

  11. LMFBR with booster pump in pumping loop

    DOEpatents

    Rubinstein, H.J.

    1975-10-14

    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.

  12. Winding for linear pump

    DOEpatents

    Kliman, Gerald B.; Brynsvold, Glen V.; Jahns, Thomas M.

    1989-01-01

    A winding and method of winding for a submersible linear pump for pumping liquid sodium is disclosed. The pump includes a stator having a central cylindrical duct preferably vertically aligned. The central vertical duct is surrounded by a system of coils in slots. These slots are interleaved with magnetic flux conducting elements, these magnetic flux conducting elements forming a continuous magnetic field conduction path along the stator. The central duct has placed therein a cylindrical magnetic conducting core, this core having a cylindrical diameter less than the diameter of the cylindrical duct. The core once placed to the duct defines a cylindrical interstitial pumping volume of the pump. This cylindrical interstitial pumping volume preferably defines an inlet at the bottom of the pump, and an outlet at the top of the pump. Pump operation occurs by static windings in the outer stator sequentially conveying toroidal fields from the pump inlet at the bottom of the pump to the pump outlet at the top of the pump. The winding apparatus and method of winding disclosed uses multiple slots per pole per phase with parallel winding legs on each phase equal to or less than the number of slots per pole per phase. The slot sequence per pole per phase is chosen to equalize the variations in flux density of the pump sodium as it passes into the pump at the pump inlet with little or no flux and acquires magnetic flux in passage through the pump to the pump outlet.

  13. Winding for linear pump

    DOEpatents

    Kliman, G.B.; Brynsvold, G.V.; Jahns, T.M.

    1989-08-22

    A winding and method of winding for a submersible linear pump for pumping liquid sodium are disclosed. The pump includes a stator having a central cylindrical duct preferably vertically aligned. The central vertical duct is surrounded by a system of coils in slots. These slots are interleaved with magnetic flux conducting elements, these magnetic flux conducting elements forming a continuous magnetic field conduction path along the stator. The central duct has placed therein a cylindrical magnetic conducting core, this core having a cylindrical diameter less than the diameter of the cylindrical duct. The core once placed to the duct defines a cylindrical interstitial pumping volume of the pump. This cylindrical interstitial pumping volume preferably defines an inlet at the bottom of the pump, and an outlet at the top of the pump. Pump operation occurs by static windings in the outer stator sequentially conveying toroidal fields from the pump inlet at the bottom of the pump to the pump outlet at the top of the pump. The winding apparatus and method of winding disclosed uses multiple slots per pole per phase with parallel winding legs on each phase equal to or less than the number of slots per pole per phase. The slot sequence per pole per phase is chosen to equalize the variations in flux density of the pump sodium as it passes into the pump at the pump inlet with little or no flux and acquires magnetic flux in passage through the pump to the pump outlet. 4 figs.

  14. Liquid metal pump

    DOEpatents

    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.

  15. Discovery of 4-acetyl-3-(4-fluorophenyl)-1-(p-tolyl)-5-methylpyrrole as a dual inhibitor of human P-glycoprotein and Staphylococcus aureus Nor A efflux pump.

    PubMed

    Bharate, Jaideep B; Singh, Samsher; Wani, Abubakar; Sharma, Sadhana; Joshi, Prashant; Khan, Inshad A; Kumar, Ajay; Vishwakarma, Ram A; Bharate, Sandip B

    2015-05-21

    Polysubstituted pyrrole natural products, lamellarins, are known to overcome multi-drug resistance in cancer via the inhibition of p-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) efflux pumps. Herein, a series of simplified polysubstituted pyrroles, prepared via a one-pot domino protocol, were screened for P-gp inhibition in P-gp overexpressing human adenocarcinoma LS-180 cells using a rhodamine 123 efflux assay. Several compounds showed the significant inhibition of P-gp at 50 μM, as indicated by increase in the intracellular accumulation of Rh123 in LS-180 cells. Furthermore, pyrrole 5i decreased the efflux of digoxin, a FDA approved P-gp substrate in MDCK-MDR1 cells with an IC50 of 11.2 μM. In in vivo studies, following the oral administration of a P-gp substrate drug, rifampicin, along with compound , the Cmax and AUC0-∞ of rifampicin was enhanced by 31% and 46%, respectively. All the compounds were then screened for their ability to potentiate ciprofloxacin activity via the inhibition of Staphylococcus aureus Nor A efflux pump. Pyrrole showed the significant inhibition of S. aureus Nor A efflux pump with 8- and 4-fold reductions in the MIC of ciprofloxacin at 50 and 6.25 μM, respectively. The molecular docking studies of compound with the human P-gp and S. aureus Nor A efflux pump identified its plausible binding site and key interactions. Thus, the results presented herein strongly indicate the potential of this scaffold for its use as multi-drug resistance reversal agent or bioavailability enhancer. PMID:25865846

  16. Multiple pump housing

    DOEpatents

    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.

  17. CFTR Inhibitors

    PubMed Central

    Verkman, Alan S.; Synder, David; Tradtrantip, Lukmanee; Thiagarajah, Jay R.; Anderson, Marc O.

    2014-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a cAMP-regulated Cl− channel whose major function is to facilitate epithelial fluid secretion. Loss-of-function mutations in CFTR cause the genetic disease cystic fibrosis. CFTR is required for transepithelial fluid transport in certain secretory diarrheas, such as cholera, and for cyst expansion in autosomal dominant polycystic kidney disease. High-throughput screening has yielded CFTR inhibitors of the thiazolidinone, glycine hydrazide and quinoxalinedione chemical classes. The glycine hydrazides target the extracellular CFTR pore, whereas the thiazolidinones and quinoxalinediones act at the cytoplasmic surface. These inhibitors have been widely used in cystic fibrosis research to study CFTR function at the cell and organ levels. The most potent CFTR inhibitor has IC50 of approximately 4 nM. Studies in animal models support the development of CFTR inhibitors for antisecretory therapy of enterotoxin-mediated diarrheas and polycystic kidney disease. PMID:23331030

  18. Continuously pumping and reactivating gas pump

    DOEpatents

    Batzer, T.H.; Call, W.R.

    Apparatus for continuous pumping using cycling cryopumping panels. A plurality of liquid helium cooled panels are surrounded by movable nitrogen cooled panels that alternatively expose or shield the helium cooled panels from the space being pumped. Gases condense on exposed helium cooled panels until the nitrogen cooled panels are positioned to isolate the helium cooled panels. The helium cooled panels are incrementally warmed, causing captured gases to accumulate at the base of the panels, where an independant pump removes the gases. After the helium cooled panels are substantially cleaned of condensate, the nitrogen cooled panels are positioned to expose the helium cooled panels to the space being pumped.

  19. Continuously pumping and reactivating gas pump

    DOEpatents

    Batzer, Thomas H.; Call, Wayne R.

    1984-01-01

    Apparatus for continuous pumping using cycling cyropumping panels. A plurality of liquid helium cooled panels are surrounded by movable nitrogen cooled panels the alternatively expose or shield the helium cooled panels from the space being pumped. Gases condense on exposed helium cooled panels until the nitrogen cooled panels are positioned to isolate the helium cooled panels. The helium cooled panels are incrementally warmed, causing captured gases to accumulate at the base of the panels, where an independent pump removes the gases. After the helium cooled panels are substantially cleaned of condensate, the nitrogen cooled panels are positioned to expose the helium cooled panels to the space being pumped.

  20. Alternative backing up pump for turbomolecular pumps

    DOEpatents

    Myneni, Ganapati Rao

    2003-04-22

    As an alternative to the use of a mechanical backing pump in the application of wide range turbomolecular pumps in ultra-high and extra high vacuum applications, palladium oxide is used to convert hydrogen present in the evacuation stream and related volumes to water with the water then being cryo-pumped to a low pressure of below about 1.e.sup.-3 Torr at 150.degree. K. Cryo-pumping is achieved using a low cost Kleemenco cycle cryocooler, a somewhat more expensive thermoelectric cooler, a Venturi cooler or a similar device to achieve the required minimization of hydrogen partial pressure.

  1. Gastrostomy feeding tube - pump - child

    MedlinePlus

    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 set that matches the feeding pump (includes a feeding bag, drip chamber, roller clamp, ...

  2. Gas pump with movable gas pumping panels

    DOEpatents

    Osher, J.L.

    Apparatus for pumping gas continuously a plurality of articulated panels of getter material, each of which absorbs gases on one side while another of its sides is simultaneously reactivated in a zone isolated by the panels themselves from a working space being pumped.

  3. Gas pump with movable gas pumping panels

    DOEpatents

    Osher, John E.

    1984-01-01

    Apparatus for pumping gas continuously a plurality of articulated panels of getter material, each of which absorbs gases on one side while another of its sides is simultaneously reactivated in a zone isolated by the panels themselves from a working space being pumped.

  4. Liquid metal enabled pump

    PubMed Central

    Tang, Shi-Yang; Khoshmanesh, Khashayar; Sivan, Vijay; Petersen, Phred; O’Mullane, Anthony P.; Abbott, Derek; Mitchell, Arnan; Kalantar-zadeh, Kourosh

    2014-01-01

    Small-scale pumps will be the heartbeat of many future micro/nanoscale platforms. However, the integration of small-scale pumps is presently hampered by limited flow rate with respect to the input power, and their rather complicated fabrication processes. These issues arise as many conventional pumping effects require intricate moving elements. Here, we demonstrate a system that we call the liquid metal enabled pump, for driving a range of liquids without mechanical moving parts, upon the application of modest electric field. This pump incorporates a droplet of liquid metal, which induces liquid flow at high flow rates, yet with exceptionally low power consumption by electrowetting/deelectrowetting at the metal surface. We present theory explaining this pumping mechanism and show that the operation is fundamentally different from other existing pumps. The presented liquid metal enabled pump is both efficient and simple, and thus has the potential to fundamentally advance the field of microfluidics. PMID:24550485

  5. Insulin pump (image)

    MedlinePlus

    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 ...

  6. Sizing pumps for slurries

    SciTech Connect

    Akhtar, S.Z.

    1996-11-01

    Slurry characteristics have a significant impact on centrifugal pump performance. For instance, as particle size increases or the percent solids concentration increases, pump head and efficiency decrease. Therefore, before a slurry pump is selected, it is important to define the slurry characteristics as accurately as possible. The effect of the slurry characteristics on the head and efficiency of the centrifugal pump will be emphasized (the effect on flowrate is less significant). The effect of slurry characteristics is more predominant in smaller pumps (with smaller diameter impellers) than in larger pumps. The data and relationship between the various slurry parameters have been developed from correlations and nomographs published by pump vendors from their field data and test results. The information helps to avoid specifying an undersized pump/motor assembly for slurry service.

  7. Pancreatic Bicarbonate Secretion Involves Two Proton Pumps*

    PubMed Central

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

    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+/HCO3− transporters, which depend on gradients created by the Na+/K+-ATPase. However, the model cannot fully account for high-bicarbonate concentrations, and other active transporters, i.e. pumps, have not been explored. Here we show that pancreatic ducts express functional gastric and non-gastric H+-K+-ATPases. We measured intracellular pH and secretion in small ducts isolated from rat pancreas and showed their sensitivity to H+-K+ pump inhibitors and ion substitutions. Gastric and non-gastric H+-K+ pumps were demonstrated on RNA and protein levels, and pumps were localized to the plasma membranes of pancreatic ducts. Quantitative analysis of H+/HCO3− and fluid transport shows that the H+-K+ pumps can contribute to pancreatic secretion in several species. Our results call for revision of the bicarbonate transport physiology in pancreas, and most likely other epithelia. Furthermore, because pancreatic ducts play a central role in several pancreatic diseases, it is of high relevance to understand the role of H+-K+ pumps in pathophysiology. PMID:20978133

  8. Photovoltaic pump systems

    NASA Astrophysics Data System (ADS)

    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.

  9. Intravenous smart pumps.

    PubMed

    Harding, Andrew D

    2013-01-01

    Intravenous (IV) smart pumps provide substantial safety features during infusion. However, nurses need to understand the requisite education necessary to fully benefit from and improve IV smart pump use and clinical integration. Failure to use IV smart pumps places the nurse and patient at increased risk. PMID:23558918

  10. Multiwell pumping device

    SciTech Connect

    Dysarz, E.D.

    1987-06-30

    This patent describes a balanced pumping apparatus for pumping two laterally spaced wells comprising: a left conductor on a left well; a right conductor on a right the well; a left pump casing inside the well conductor; a right pump casing inside the right well conductor; a left sucker rod inside the left pump casing; a right sucker rod inside the right pump casing; flexible linkage means for attachment to the top ends of the right sucker rod and left sucker rod; a drive motor with a rotating shaft; a drive sprocket rotatably engaging the flexible linkage means; a separate pump casing flange attached to the upper section of each well conductors; a separate upper flange attached to the upper section of each pump casing and positioned at an axial location above the point attached to the pump casing; a separate transition piece attached to the top of each pump casing flange; a separate pump support attached to the top of each transition piece; a plate-like structural support means placed in a vertical plane above the well conductors and supporting the drive motor, the drive sprocket, the flexible linkage means, and the sucker rods; a structural load transfer means connecting the plate-like structural support means to the well conductors; a motor control unit for supporting itself and controlling the drive motor; and a separate shaft extending across each pump support.

  11. Rotary magnetic heat pump

    DOEpatents

    Kirol, Lance D.

    1988-01-01

    A rotary magnetic heat pump constructed without flow seals or segmented rotor accomplishes recuperation and regeneration by using split flow paths. Heat exchange fluid pumped through heat exchangers and returned to the heat pump splits into two flow components: one flowing counter to the rotor rotation and one flowing with the rotation.

  12. Green pumped Alexandrite lasers

    NASA Astrophysics Data System (ADS)

    Kuper, Jerry W.; Brown, David C.

    2005-04-01

    Initial experiments with pulsed and CW pumping an alexandrite laser rod at 532 nm are presented. This pumping architecture holds promise for the production of scalable diode-pumped, tunable alexandrite laser systems operating in the near infrared (750 nm), and the ultraviolet (375 and 250 nm) spectral regions.

  13. Pump for Saturated Liquids

    NASA Technical Reports Server (NTRS)

    Elliott, D. G.

    1986-01-01

    Boiling liquids pumped by device based on proven components. Expanding saturated liquid in nozzle and diverting its phases along separate paths in liquid/vapor separator raises pressure of liquid. Liquid cooled in process. Pump makes it unnecessary to pressurize cryogenic liquids in order to pump them. Problems of introducing noncondensable pressurizing gas avoided.

  14. Types of Breast Pumps

    MedlinePlus

    ... uses batteries or a cord plugged into an electrical outlet to power a small motorized pump that creates suction to ... pumping. Because these breast pumps rely on a power source, women who use ... situations when electricity or extra batteries may not be available. If ...

  15. Rotary magnetic heat pump

    DOEpatents

    Kirol, L.D.

    1987-02-11

    A rotary magnetic heat pump constructed without flow seals or segmented rotor accomplishes recuperation and regeneration by using split flow paths. Heat exchange fluid pumped through heat exchangers and returned to the heat pump splits into two flow components: one flowing counter to the rotor rotation and one flowing with the rotation. 5 figs.

  16. Jet pump assisted artery

    NASA Technical Reports Server (NTRS)

    1975-01-01

    A procedure for priming an arterial heat pump is reported; the procedure also has a means for maintaining the pump in a primed state. This concept utilizes a capillary driven jet pump to create the necessary suction to fill the artery. Basically, the jet pump consists of a venturi or nozzle-diffuser type constriction in the vapor passage. The throat of this venturi is connected to the artery. Thus vapor, gas, liquid, or a combination of the above is pumped continuously out of the artery. As a result, the artery is always filled with liquid and an adequate supply of working fluid is provided to the evaporator of the heat pipe.

  17. Liquid metal electric pump

    DOEpatents

    Abbin, Joseph P.; Andraka, Charles E.; Lukens, Laurance L.; Moreno, James B.

    1992-01-01

    An electrical pump for pumping liquid metals to high pressures in high temperature environments without the use of magnets or moving mechanical parts. The pump employs a non-porous solid electrolyte membrane, typically ceramic, specific to the liquid metal to be pumped. A DC voltage is applied across the thickness of the membrane causing ions to form and enter the membrane on the electrically positive surface, with the ions being neutralized on the opposite surface. This action provides pumping of the liquid metal from one side of the non-porous solid electrolyte membrane to the other.

  18. [Proteasome inhibitor].

    PubMed

    Yagi, Hideo

    2014-06-01

    The ubiquitin-proteasome system plays an essential role in degradation of eukaryotic intracellular protein, including cell cycle regulation, cell growth and proliferation, and survival. Cancer cells generally have higher level of proteasome activity compared with normal cells, suggesting proteasome inhibition could be therapeutic target in oncology. Bortezomib, the first proteasome inhibitor introduced into the clinic, is approved for the treatment of patients with multiple myeloma (MM). Although it was approved as single agent in the relapsed setting, bortezomib is now predominantly used in combination with conventional and novel targeted agents because bortezomib has demonstrated additive and synergistic activity in preclinical studies. Recently, several second-generation proteasome inhibitors, such as carfilzomib and MLN9708, have been developed and entered into clinical trials. These agents were investigated in frontline MM in combination with lenalidomide and low-dose dexamethasone. These studies demonstrated positive efficacy and safety, and it is expected that they will be approved in near future. PMID:25016815

  19. Effect of 16.16 dimethyl prostaglandin E2, N-acetyl-cysteine and the proton pump inhibitor BY 831-78 on hydrogen peroxide-induced mucosal damage in the rat stomach.

    PubMed

    Schürer-Maly, C C; Haussner, V; Halter, F

    1990-01-01

    Reactive oxygen species are noxious to gastrointestinal mucosa and contribute to a variety of gastrointestinal diseases. We examined whether 16.16 dimethyl prostaglandin E2 (PG) is protective against the oxidizing action of 6% H2O2 causing gross hemorrhagic lesions in rat gastric mucosa. Male Wistar rats were treated with PG, 0.005-5 micrograms/kg, either intragastrically (i.g.) or subcutaneously, 30 min prior to i.g. administration of 6% H2O2, 0.5 ml/100 g. Further animals received 25 mg of the mucus dissolvent N-acetyl-cystein (NAC) following oral PG treatment or 30 mumol/kg of the H+K(+)-ATPase inhibitor BY 831-78 (BY), 4 h before onset of the experiments. Volume, pH and beta-N-acetyl-glucosaminidase and lactate dehydrogenase as parameters of cell damage were determined in the gastric juice. i.g. PG treatment achieved 60 and 55% reduction of the mucosal lesions in doses between 5 and 0.05 micrograms/kg, respectively. i.p. PG administration was effective in all doses tested. Gastric juice volume was only slightly and enzymes were not significantly affected by PG treatment. NAC did not diminish PG efficacy or aggravate mucosal lesions. Gastric acid suppression did not increase PG-induced protection but was strongly protective by itself, reducing damage by 75%. Low-dose PG treatment achieves an effective protection against oxidative damage in gastric mucosa, which is not the result of dilution or enhanced mucus production. PMID:2147665

  20. Rotary blood pump

    NASA Technical Reports Server (NTRS)

    Bozeman, Richard J. (Inventor); Akkerman, James W. (Inventor); Aber, Greg S. (Inventor); Vandamm, George A. (Inventor); Bacak, James W. (Inventor); Svejkovsky, Paul A. (Inventor); Benkowski, Robert J. (Inventor)

    1993-01-01

    A rotary blood pump is presented. The pump includes a pump housing for receiving a flow straightener, a rotor mounted on rotor bearings and having an inducer portion and an impeller portion, and a diffuser. The entrance angle, outlet angle, axial, and radial clearances of the blades associated with the flow straightener, inducer portion, impeller portion, and diffuser are optimized to minimize hemolysis while maintaining pump efficiency. The rotor bearing includes a bearing chamber that is filled with crosslinked blood or other bio-compatible material. A back emf integrated circuit regulates rotor operation and a microcomputer may be used to control one or more back emf integrated circuits. A plurality of magnets are disposed in each of a plurality of impeller blades with a small air gap. A stator may be axially adjusted on the pump housing to absorb bearing load and maximize pump efficiency.

  1. DIRECT CURRENT ELECTROMAGNETIC PUMP

    DOEpatents

    Barnes, A.H.

    1957-11-01

    An improved d-c electromagnetic pump is presented in which the poles, and consequently the magetic gap at the poles, are tapered to be wider at the upstream end. In addition, the cross section of the tube carryiQ the liquid metal is tapered so that the velocity of the pumped liquid increases in the downstream direction at a rate such that the counter-induced voltage in the liquid metal remains constant as it traverses the region between the poles. This configuration compensates for the distortion of the magnetic field caused by the induced voltage that would otherwise result in the lowering of the pumping capacity. This improved electromagnetic pump as practical application in the pumping of liquid metal coolants for nuclear reactors where conventional positive displacement pumps have proved unsatisfactory due to the high temperatures and the corrosive properties of the liquid metals involved.

  2. Electrokinetic pumps and actuators

    SciTech Connect

    Phillip M. Paul

    2000-03-01

    Flow and ionic transport in porous media are central to electrokinetic pumping as well as to a host of other microfluidic devices. Electrokinetic pumping provides the ability to create high pressures (to over 10,000 psi) and high flow rates (over 1 mL/min) with a device having no moving parts and all liquid seals. The electrokinetic pump (EKP) is ideally suited for applications ranging from a high pressure integrated pump for chip-scale HPLC to a high flow rate integrated pump for forced liquid convection cooling of high-power electronics. Relations for flow rate and current fluxes in porous media are derived that provide a basis for analysis of complex microfluidic systems as well as for optimization of electrokinetic pumps.

  3. Pump isolation valve

    DOEpatents

    Kinney, Calvin L.; Wetherill, Todd M.

    1983-08-02

    The pump isolation valve provides a means by which the pump may be selectively isolated from the remainder of the coolant system while being compatible with the internal hydraulic arrangement of the pump during normal operation of the pump. The valve comprises a valve cylinder disposed around the pump and adjacent to the last pump diffuser with a turning vane attached to the lower end of the valve cylinder in a manner so as to hydraulically match with the discharge diffuser. The valve cylinder is connected to a drive means for sliding the valve cylinder relative to the diffuser support cylinder so as to block flow in either direction through the discharge diffuser when the valve is in the closed position and to aid in the flow of the coolant from the discharge diffuser by means of the turning vane when the valve is in the open position.

  4. A compact cryogenic pump

    NASA Astrophysics Data System (ADS)

    Li, Gang; Caldwell, Shane; Clark, Jason A.; Gulick, Sidney; Hecht, Adam; Lascar, Daniel D.; Levand, Tony; Morgan, Graeme; Orford, Rodney; Savard, Guy; Sharma, Kumar S.; Van Schelt, Jonathon

    2016-04-01

    A centrifugal cryogenic pump has been designed at Argonne National Laboratory to circulate liquid nitrogen (LN2) in a closed circuit allowing the recovery of excess fluid. The pump can circulate LN2 at rates of 2-10 L/min, into a head of 0.5-3 m. Over four years of laboratory use the pump has proven capable of operating continuously for 50-100 days without maintenance.

  5. Detection of pump degradation

    SciTech Connect

    Greene, R.H.; Casada, D.A.; Ayers, C.W.

    1995-08-01

    This Phase II Nuclear Plant Aging Research study examines the methods of detecting pump degradation that are currently employed in domestic and overseas nuclear facilities. This report evaluates the criteria mandated by required pump testing at U.S. nuclear power plants and compares them to those features characteristic of state-of-the-art diagnostic programs and practices currently implemented by other major industries. Since the working condition of the pump driver is crucial to pump operability, a brief review of new applications of motor diagnostics is provided that highlights recent developments in this technology. The routine collection and analysis of spectral data is superior to all other technologies in its ability to accurately detect numerous types and causes of pump degradation. Existing ASME Code testing criteria do not require the evaluation of pump vibration spectra but instead overall vibration amplitude. The mechanical information discernible from vibration amplitude analysis is limited, and several cases of pump failure were not detected in their early stages by vibration monitoring. Since spectral analysis can provide a wealth of pertinent information concerning the mechanical condition of rotating machinery, its incorporation into ASME testing criteria could merit a relaxation in the monthly-to-quarterly testing schedules that seek to verify and assure pump operability. Pump drivers are not included in the current battery of testing. Operational problems thought to be caused by pump degradation were found to be the result of motor degradation. Recent advances in nonintrusive monitoring techniques have made motor diagnostics a viable technology for assessing motor operability. Motor current/power analysis can detect rotor bar degradation and ascertain ranges of hydraulically unstable operation for a particular pump and motor set. The concept of using motor current or power fluctuations as an indicator of pump hydraulic load stability is presented.

  6. Fakir fuel pump

    NASA Technical Reports Server (NTRS)

    1922-01-01

    In designing the Fakir fuel pump, the fundamental idea was to obtain a simple and reliable method of conveying the fuel from a low tank to the carburetor, with the avoidance of the faults of all former methods and the simultaneous warming of the fuel by means of the heat of compression generated. The principle of the Fakir fuel pump rests on the well-known principle of the diaphragm pump, which must be suitably adapted to the present purpose.

  7. Detection of pump degradation

    SciTech Connect

    Casada, D.

    1995-04-01

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

  8. Champagne Heat Pump

    NASA Technical Reports Server (NTRS)

    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.

  9. Submersible sodium pump

    DOEpatents

    Brynsvold, Glen V.; Lopez, John T.; Olich, Eugene E.; West, Calvin W.

    1989-01-01

    An electromagnetic submerged pump has an outer cylindrical stator with an inner cylindrical conductive core for the submerged pumping of sodium in the cylindrical interstitial volume defined between the stator and core. The cylindrical interstitial volume is typically vertically oriented, and defines an inlet at the bottom and an outlet at the top. The outer stator generates upwardly conveyed toroidal magnetic fields, which fields convey preferably from the bottom of the pump to the top of the pump liquid sodium in the cold leg of a sodium cooled nuclear reactor. The outer cylindrical stator has a vertically disposed duct surrounded by alternately stacked layers of coil units and laminates.

  10. Submersible sodium pump

    DOEpatents

    Brynsvold, G.V.; Lopez, J.T.; Olich, E.E.; West, C.W.

    1989-11-21

    An electromagnetic submerged pump has an outer cylindrical stator with an inner cylindrical conductive core for the submerged pumping of sodium in the cylindrical interstitial volume defined between the stator and core. The cylindrical interstitial volume is typically vertically oriented, and defines an inlet at the bottom and an outlet at the top. The outer stator generates upwardly conveyed toroidal magnetic fields, which fields convey preferably from the bottom of the pump to the top of the pump liquid sodium in the cold leg of a sodium cooled nuclear reactor. The outer cylindrical stator has a vertically disposed duct surrounded by alternately stacked layers of coil units and laminates. 14 figs.

  11. Liquid pump for astronaut cooling

    NASA Technical Reports Server (NTRS)

    Carson, M. A.

    1972-01-01

    The Apollo portable life support system water-recirculation pump used for astronaut cooling is described. The problems associated with an early centrifugal pump and how these problems were overcome by the use of a new diaphragm pump are discussed. Performance comparisons of the two pump designs are given. Developmental problems and flight results with the diaphragm pump are discussed.

  12. Well-pump alignment system

    DOEpatents

    Drumheller, Douglas S.

    1998-01-01

    An improved well-pump for geothermal wells, an alignment system for a well-pump, and to a method for aligning a rotor and stator within a well-pump, wherein the well-pump has a whistle assembly formed at a bottom portion thereof, such that variations in the frequency of the whistle, indicating misalignment, may be monitored during pumping.

  13. 98. VIEW OF PUMPS FROM NORTH. MILL SOLUTION PUMP No. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    98. VIEW OF PUMPS FROM NORTH. MILL SOLUTION PUMP No. 2 IN FOREGROUND, ABANDONED BARREN SOLUTION PUMP BEYOND. AGITATOR No. 1 IN BACKGROUND. - Bald Mountain Gold Mill, Nevada Gulch at head of False Bottom Creek, Lead, Lawrence County, SD

  14. 32. PLAN OF DEER ISLAND PUMPING STATION SHOWING EXISTING PUMPING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    32. PLAN OF DEER ISLAND PUMPING STATION SHOWING EXISTING PUMPING PLANT AND LOCATION OF PROPOSED ADDITIONS, JULY 1898 SHEET NO. 1. Aperture card 4966-1 - Deer Island Pumping Station, Boston, Suffolk County, MA

  15. Looking south at boiler feedwater pumps (steam turbine pump on ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Looking south at boiler feedwater pumps (steam turbine pump on left, electric motor pump on right). - Wheeling-Pittsburgh Steel Corporation, Allenport Works, Boiler House, Route 88 on West bank of Monongahela River, Allenport, Washington County, PA

  16. 33. PLAN OF DEER ISLAND PUMPING STATION SHOWING EXISTING PUMPING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    33. PLAN OF DEER ISLAND PUMPING STATION SHOWING EXISTING PUMPING PLAN AND LOCATION OF PROPOSED ADDITIONS, METROPOLITAN WATER AND SEWERAGE BOARD, METROPOLITAN SEWERAGE WORKS, JULY 1908. Aperture card 6417. - Deer Island Pumping Station, Boston, Suffolk County, MA

  17. Micromachined peristaltic pumps

    NASA Technical Reports Server (NTRS)

    Hartley, Frank T. (Inventor)

    1999-01-01

    Micromachined pumps including a channel formed between a first membrane and a substrate or between first and second flexible membranes. A series of electrically conductive strips is applied to a surface of the substrate or one of the membranes. Application of a sequential voltage to the series of strips causes a region of closure to progress down the channel to achieve a pumping action.

  18. Detection of pump degradation

    SciTech Connect

    Casada, D.

    1994-12-31

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

  19. A Shocking New Pump

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Hydro Dynamics, Inc. received a technical helping hand from NASA that made their Hydrosonic Pump (HPump) a reality. Marshall engineers resolved a bearing problem in the rotor of the pump and recommended new bearings, housings and mounting hardware as a solution. The resulting HPump is able to heat liquids with greater energy efficiency using shock waves to generate heat.

  20. NEUTRONIC REACTOR FUEL PUMP

    DOEpatents

    Cobb, W.G.

    1959-06-01

    A reactor fuel pump is described which offers long life, low susceptibility to radiation damage, and gaseous fission product removal. An inert-gas lubricated bearing supports a journal on one end of the drive shsft. The other end has an impeller and expansion chamber which effect pumping and gas- liquid separation. (T.R.H.)

  1. Water Treatment Technology - Pumps.

    ERIC Educational Resources Information Center

    Ross-Harrington, Melinda; Kincaid, G. David

    One of twelve water treatment technology units, this student manual on pumps provides instructional materials for three competencies. (The twelve units are designed for a continuing education training course for public water supply operators.) The competencies focus on the following areas: types of pumps in plant and distribution systems, pump…

  2. Pump apparatus including deconsolidator

    DOEpatents

    Sonwane, Chandrashekhar; Saunders, Timothy; Fitzsimmons, Mark Andrew

    2014-10-07

    A pump apparatus includes a particulate pump that defines a passage that extends from an inlet to an outlet. A duct is in flow communication with the outlet. The duct includes a deconsolidator configured to fragment particle agglomerates received from the passage.

  3. Normetex Pump Alternatives Study

    SciTech Connect

    Clark, Elliot A.

    2013-04-25

    A mainstay pump for tritium systems, the Normetex scroll pump, is currently unavailable because the Normetex company went out of business. This pump was an all-metal scroll pump that served tritium processing facilities very well. Current tritium system operators are evaluating replacement pumps for the Normetex pump and for general used in tritium service. An all-metal equivalent alternative to the Normetex pump has not yet been identified. 1. The ideal replacement tritium pump would be hermetically sealed and contain no polymer components or oils. Polymers and oils degrade over time when they contact ionizing radiation. 2. Halogenated polymers (containing fluorine, chlorine, or both) and oils are commonly found in pumps. These materials have many properties that surpass those of hydrocarbon-based polymers and oils, including thermal stability (higher operating temperature) and better chemical resistance. Unfortunately, they are less resistant to degradation from ionizing radiation than hydrocarbon-based materials (in general). 3. Polymers and oils can form gaseous, condensable (HF, TF), liquid, and solid species when exposed to ionizing radiation. For example, halogenated polymers form HF and HCl, which are extremely corrosive upon reaction with water. If a pump containing polymers or oils must be used in a tritium system, the system must be designed to be able to process the unwanted by-products. Design features to mitigate degradation products include filters and chemical or physical traps (eg. cold traps, oil traps). 4. Polymer components can work in tritium systems, but must be replaced regularly. Polymer components performance should be monitored or be regularly tested, and regular replacement of components should be viewed as an expected normal event. A radioactive waste stream must be established to dispose of used polymer components and oil with an approved disposal plan developed based on the facility location and its regulators. Polymers have varying

  4. Rotary Blood Pump

    NASA Technical Reports Server (NTRS)

    Bozeman, Richard J., Jr. (Inventor); Akkerman, James W. (Inventor); Aber, Gregory S. (Inventor); VanDamm, George A. (Inventor); Bacak, James W. (Inventor); Svejkovsky, Paul A. (Inventor); Benkowski, Robert J. (Inventor)

    1996-01-01

    A rotary blood pump includes a pump housing for receiving a flow straightener, a rotor mounted on rotor bearings and having an inducer portion and an impeller portion, and a diffuser. The entrance angle, outlet angle, axial and radial clearances of blades associated with the flow straightener, inducer portion, impeller portion and diffuser are optimized to minimize hemolysis while maintaining pump efficiency. The rotor bearing includes a bearing chamber that is filled with cross-linked blood or other bio-compatible material. A back emf integrated circuit regulates rotor operation and a microcomputer may be used to control one or more back emf integrated circuits. A plurality of magnets are disposed in each of a plurality of impeller blades with a small air gap. A stator may be axially adjusted on the pump housing to absorb bearing load and maximize pump efficiency.

  5. Deep well solar pump

    SciTech Connect

    Vanek, J.

    1990-02-06

    This patent describes, in a pump having a source of gas under pressure, and a gas operated pump, a mechanism periodically injecting gas from the source of gas into the gas operated pump. It comprises: a long period pendulum turning towards a first position by gravity, an injection valve connected between the source of gas under pressure and the gas operated pump, a linkage between the pendulum and the injection valve. The linkage opening the injection valve when the pendulum is in the first position, an impulse tube connected between the injection valve and the gas operated pump, a member having a surface adjacent to the first position of the pendulum, and an elastic impulse bladder connected to the impulse tube adjacent to the surface so that inflation of the impulse bladder on the opening of the injection valve forces the impulse bladder against the pendulum urging the pendulum against the force of gravity toward a second position.

  6. Apparatus for Pumping a Fluid

    NASA Technical Reports Server (NTRS)

    Boeyen, Robert Van; Reeh, Jonathan

    2013-01-01

    A fluid pump has been developed for mechanically pumped fluid loops for spacecraft thermal control. Lynntech's technology utilizes a proprietary electrochemically driven pumping mechanism. Conventional rotodynamic and displacement pumps typically do not meet the stringent power and operational reliability requirements of space applications. Lynntech's developmental pump is a highly efficient solid-state pump with essentially no rotating or moving components (apart from metal bellows).

  7. Identification of a multidrug efflux pump in Mycobacterium smegmatis.

    PubMed

    Bansal, Ankita; Mallik, Dhriti; Kar, Debasish; Ghosh, Anindya S

    2016-07-01

    Cell wall impermeability and active efflux of drugs are among the primary reasons for drug resistance in mycobacteria. Efflux pumps are tripartite membrane localized transport proteins that expel drug molecules outside the cells. Several of such efflux pumps are annotated in mycobacteria, but few have been characterized, like MSMEG_2991, a putative efflux pump permease of Mycobacterium smegmatis To substantiate this, we overexpressed MSMEG_2991 protein in Escherichia coli 2443. Expression of MSMEG_2991 elevated the resistance towards structurally unrelated groups of antibiotics. An active antibiotic efflux pump nature of MSMEG_2991 was revealed by assessing the acquisition of ciprofloxacin in the absence and presence of the efflux pump inhibitor, carbonyl cyanide m-chlorophenyl hydrazone, indicating the involvement of proton-motive force (pmf) during the efflux activity. MSMEG_2991 expression elevated biofilm formation in E. coli by 4-fold, keeping parity to some of the earlier reported efflux pumps. In silico analysis suggested the presence of 12 transmembrane helices in MSMEG_2991 resembling EmrD efflux pump of E. coli Based on in vivo and in silico analyses, MSMEG_2991 may be designated as a pmf-mediated multidrug efflux pump protein that expels diverse groups of antibiotics and might as well be involved in the biofilm enhancement. PMID:27190152

  8. Recent advances toward a molecular mechanism of efflux pump inhibition

    PubMed Central

    Opperman, Timothy J.; Nguyen, Son T.

    2015-01-01

    Multidrug resistance (MDR) in Gram-negative pathogens, such as the Enterobacteriaceae and Pseudomonas aeruginosa, poses a significant threat to our ability to effectively treat infections caused by these organisms. A major component in the development of the MDR phenotype in Gram-negative bacteria is overexpression of Resistance-Nodulation-Division (RND)-type efflux pumps, which actively pump antibacterial agents and biocides from the periplasm to the outside of the cell. Consequently, bacterial efflux pumps are an important target for developing novel antibacterial treatments. Potent efflux pump inhibitors (EPIs) could be used as adjunctive therapies that would increase the potency of existing antibiotics and decrease the emergence of MDR bacteria. Several potent inhibitors of RND-type efflux pump have been reported in the literature, and at least three of these EPI series were optimized in a pre-clinical development program. However, none of these compounds have been tested in the clinic. One of the major hurdles to the development of EPIs has been the lack of biochemical, computational, and structural methods that could be used to guide rational drug design. Here, we review recent reports that have advanced our understanding of the mechanism of action of several potent EPIs against RND-type pumps. PMID:25999939

  9. Autophagy inhibitors.

    PubMed

    Pasquier, Benoit

    2016-03-01

    Autophagy is a lysosome-dependent mechanism of intracellular degradation. The cellular and molecular mechanisms underlying this process are highly complex and involve multiple proteins, including the kinases ULK1 and Vps34. The main function of autophagy is the maintenance of cell survival when modifications occur in the cellular environment. During the past decade, extensive studies have greatly improved our knowledge and autophagy has exploded as a research field. This process is now widely implicated in pathophysiological processes such as cancer, metabolic, and neurodegenerative disorders, making it an attractive target for drug discovery. In this review, we will summarize the different types of inhibitors that affect the autophagy machinery and provide some potential therapeutic perspectives. PMID:26658914

  10. Microfluidic reflow pumps.

    PubMed

    Haslam, Bryan; Tsai, Long-Fang; Anderson, Ryan R; Kim, Seunghyun; Hu, Weisheng; Nordin, Gregory P

    2015-07-01

    A new microfluidic pump, termed a reflow pump, is designed to operate with a sub-μl sample volume and transport it back and forth between two pneumatically actuated reservoirs through a flow channel typically containing one or more sensor surfaces. The ultimate motivation is to efficiently use the small sample volume in conjunction with convection to maximize analyte flux to the sensor surface(s) in order to minimize sensor response time. In this paper, we focus on the operational properties of the pumps themselves (rather than the sensor surfaces), and demonstrate both two-layer and three-layer polydimethylsiloxane reflow pumps. For the three-layer pump, we examine the effects of reservoir actuation pressure and actuation period, and demonstrate average volumetric flow rates as high as 500 μl/min. We also show that the two-layer design can pump up to 93% of the sample volume during each half period and demonstrate integration of a reflow pump with a single-chip microcantilever array to measure maximum flow rate. PMID:26221199

  11. Pressure charged airlift pump

    DOEpatents

    Campbell, Gene K.

    1983-01-01

    A pumping system is described for pumping fluids, such as water with entrained mud and small rocks, out of underground cavities such as drilled wells, which can effectively remove fluids down to a level very close to the bottom of the cavity and which can operate solely by compressed air pumped down through the cavity. The system utilizes a subassembly having a pair of parallel conduit sections (44, 46) adapted to be connected onto the bottom of a drill string utilized for drilling the cavity, the drill string also having a pair of coaxially extending conduits. The subassembly includes an upper portion which has means for connection onto the drill string and terminates the first conduit of the drill string in a plenum (55). A compressed air-driven pump (62) is suspended from the upper portion. The pump sucks fluids from the bottom of the cavity and discharges them into the second conduit. Compressed air pumped down through the first conduit (46) to the plenum powers the compressed air-driven pump and aerates the fluid in the second conduit to lift it to the earth's surface.

  12. Pressure charged airlift pump

    SciTech Connect

    Campbell, G.K.

    1980-08-15

    A pumping system is described for pumping fluids, such as water with entrained mud and small rocks, out of underground cavities such as drilled wells, which can effectively remove fluids down to a level very close to the bottom of the cavity and which can operate solely by compressed air pumped down through the cavity. The system utilizes a subassembly having a pair of parallel conduit sections adapted to be connected onto the bottom of a drill string utilized for drilling the cavity, the drill string also having a pair of coaxially extending conduits. The subassembly includes an upper portion which has means for connection onto the drill string and terminates the first conduit of the drill string in a plenum. A compressed air-driven pump is suspended from the upper portion. The pump sucks fluids from the bottom of the cavity and discharges them into the second conduit. Compressed air pumped down through the first conduit to the plenum powers the compressed air-driven pump and aerates the fluid in the second conduit to lift it to the earth's surface.

  13. Pressure charged airlift pump

    SciTech Connect

    Campbell, G.K.

    1983-02-15

    A pumping system is described for pumping fluids, such as water with entrained mud and small rocks, out of underground cavities such as drilled wells, which can effectively remove fluids down to a level very close to the bottom of the cavity and which can operate solely by compressed air pumped down through the cavity. The system utilizes a subassembly having a pair of parallel conduit sections adapted to be connected onto the bottom of a drill string utilized for drilling the cavity, the drill string also having a pair of coaxially extending conduits. The subassembly includes an upper portion which has means for connection onto the drill string and terminates the first conduit of the drill string in a plenum. A compressed air-driven pump is suspended from the upper portion. The pump sucks fluids from the bottom of the cavity and discharges them into the second conduit. Compressed air pumped down through the first conduit to the plenum powers the compressed air-driven pump and aerates the fluid in the second conduit to lift it to the earth's surface.

  14. Performance of mosquito's pump

    NASA Astrophysics Data System (ADS)

    Kikuchi, Kenji

    2005-11-01

    The flow of human blood in Mosquito's proboscis on Hagen-Poiseuille flow is investigated by using micro PIV system to apply mosquito's sucking system for micro-TAS devises. We want to know how high the power of Mosquito's pump is and how small the resistance in a proboscis is, a structure of Mosquito's sucking pump, and its characteristics as mechanical pump. We made the mosquito suck blood of our arm to obtain the average value, made many slices of a mosquito with 2μm thickness after fixed by wax. We anatomized the mosquito's head and picked up the sucking pump under the microscope to know its volume. Mosquito's pump shows high performance compared with the artificial pumps. The surfaces of proboscis were taken by using SEM, AFM because it is important factor for interaction between flow and its wall. Visualization of the blood flows near the tip of and inside proboscis are taken by micro PIV system to know the flow rate. We estimate the power of pump and the friction drag of proboscis by using these data.

  15. Microfluidic reflow pumps

    PubMed Central

    Haslam, Bryan; Tsai, Long-Fang; Anderson, Ryan R.; Kim, Seunghyun; Hu, Weisheng; Nordin, Gregory P.

    2015-01-01

    A new microfluidic pump, termed a reflow pump, is designed to operate with a sub-μl sample volume and transport it back and forth between two pneumatically actuated reservoirs through a flow channel typically containing one or more sensor surfaces. The ultimate motivation is to efficiently use the small sample volume in conjunction with convection to maximize analyte flux to the sensor surface(s) in order to minimize sensor response time. In this paper, we focus on the operational properties of the pumps themselves (rather than the sensor surfaces), and demonstrate both two-layer and three-layer polydimethylsiloxane reflow pumps. For the three-layer pump, we examine the effects of reservoir actuation pressure and actuation period, and demonstrate average volumetric flow rates as high as 500 μl/min. We also show that the two-layer design can pump up to 93% of the sample volume during each half period and demonstrate integration of a reflow pump with a single-chip microcantilever array to measure maximum flow rate. PMID:26221199

  16. Motion of the Ca2+-pump captured.

    PubMed

    Yokokawa, Masatoshi; Takeyasu, Kunio

    2011-09-01

    Studies of ion pumps, such as ATP synthetase and Ca(2+)-ATPase, have a long history. The crystal structures of several kinds of ion pump have been resolved, and provide static pictures of mechanisms of ion transport. In this study, using fast-scanning atomic force microscopy, we have visualized conformational changes in the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) in real time at the single-molecule level. The analyses of individual SERCA molecules in the presence of both ATP and free Ca(2+) revealed up-down structural changes corresponding to the Albers-Post scheme. This fluctuation was strongly affected by the ATP and Ca(2+) concentrations, and was prevented by an inhibitor, thapsigargin. Interestingly, at a physiological ATP concentrations, the up-down motion disappeared completely. These results indicate that SERCA does not transit through the shortest structure, and has a catalytic pathway different from the ordinary Albers-Post scheme under physiological conditions. PMID:21707923

  17. RENEWABLE LIQUID GETTERING PUMP

    DOEpatents

    Batzer, T.H.

    1962-08-21

    A method and structure were developed for pumping gases by simple absorption into a liquid gettering material. The invention comprises means ror continuously pumping a liquid getterrng material from a reservoir to the top of a generally vertical surface disposed in a vacuum pumping chamber to receive gaseous and other particles in the liquid gettering material which continuously flows downward over the vertical suiface. Means are provided for continuous removal, degassing, and return of a portion of the liquid gettering material from the reservoir connected with collectrng means at the base of the generally vertical plate. (AEC)

  18. A mass spectrometry-based assay for improved quantitative measurements of efflux pump inhibition.

    PubMed

    Brown, Adam R; Ettefagh, Keivan A; Todd, Daniel; Cole, Patrick S; Egan, Joseph M; Foil, Daniel H; Graf, Tyler N; Schindler, Bryan D; Kaatz, Glenn W; Cech, Nadja B

    2015-01-01

    Bacterial efflux pumps are active transport proteins responsible for resistance to selected biocides and antibiotics. It has been shown that production of efflux pumps is up-regulated in a number of highly pathogenic bacteria, including methicillin resistant Staphylococcus aureus. Thus, the identification of new bacterial efflux pump inhibitors is a topic of great interest. Existing assays to evaluate efflux pump inhibitory activity rely on fluorescence by an efflux pump substrate. When employing these assays to evaluate efflux pump inhibitory activity of plant extracts and some purified compounds, we observed severe optical interference that gave rise to false negative results. To circumvent this problem, a new mass spectrometry-based method was developed for the quantitative measurement of bacterial efflux pump inhibition. The assay was employed to evaluate efflux pump inhibitory activity of a crude extract of the botanical Hydrastis Canadensis, and to compare the efflux pump inhibitory activity of several pure flavonoids. The flavonoid quercetin, which appeared to be completely inactive with a fluorescence-based method, showed an IC50 value of 75 μg/mL with the new method. The other flavonoids evaluated (apigenin, kaempferol, rhamnetin, luteolin, myricetin), were also active, with IC50 values ranging from 19 μg/mL to 75 μg/mL. The assay described herein could be useful in future screening efforts to identify efflux pump inhibitors, particularly in situations where optical interference precludes the application of methods that rely on fluorescence. PMID:25961825

  19. A Mass Spectrometry-Based Assay for Improved Quantitative Measurements of Efflux Pump Inhibition

    PubMed Central

    Brown, Adam R.; Ettefagh, Keivan A.; Todd, Daniel; Cole, Patrick S.; Egan, Joseph M.; Foil, Daniel H.; Graf, Tyler N.; Schindler, Bryan D.; Kaatz, Glenn W.; Cech, Nadja B.

    2015-01-01

    Bacterial efflux pumps are active transport proteins responsible for resistance to selected biocides and antibiotics. It has been shown that production of efflux pumps is up-regulated in a number of highly pathogenic bacteria, including methicillin resistant Staphylococcus aureus. Thus, the identification of new bacterial efflux pump inhibitors is a topic of great interest. Existing assays to evaluate efflux pump inhibitory activity rely on fluorescence by an efflux pump substrate. When employing these assays to evaluate efflux pump inhibitory activity of plant extracts and some purified compounds, we observed severe optical interference that gave rise to false negative results. To circumvent this problem, a new mass spectrometry-based method was developed for the quantitative measurement of bacterial efflux pump inhibition. The assay was employed to evaluate efflux pump inhibitory activity of a crude extract of the botanical Hydrastis Canadensis, and to compare the efflux pump inhibitory activity of several pure flavonoids. The flavonoid quercetin, which appeared to be completely inactive with a fluorescence-based method, showed an IC50 value of 75 μg/mL with the new method. The other flavonoids evaluated (apigenin, kaempferol, rhamnetin, luteolin, myricetin), were also active, with IC50 values ranging from 19 μg/mL to 75 μg/mL. The assay described herein could be useful in future screening efforts to identify efflux pump inhibitors, particularly in situations where optical interference precludes the application of methods that rely on fluorescence. PMID:25961825

  20. Involvement of Na,K-pump in SEPYLRFamide-mediated reduction of cholinosensitivity in Helix neurons

    PubMed Central

    Pivovarov, Arkady S.; Foreman, Richard C.; Walker, Robert J.

    2007-01-01

    SEPYLRFamide acts as an inhibitory modulator of acetylcholine (ACh) receptors in Helix lucorum neurones. Ouabain, a specific inhibitor of Na,K-pump, (0.1 mM, bath application) decreased the ACh-induced inward current (ACh-current) and increased the leak current. Ouabain decreased the modulatory SEPYLRFamide effect on the ACh-current. There was a correlation between the effects of ouabain on the amplitude of the ACh-current and on the modulatory peptide effect. Ouabain and SEPYLRFamide inhibited the activity of Helix aspersa brain Na,K-ATPase. Activation of Na,K-pump by intracellular injection of 3 M Na acetate or 3 M NaCl reduced the modulatory peptide effect on the ACh-current. An inhibitor of Na/Ca-exchange, benzamil (25 μM, bath application), and an inhibitor of Ca2+-pump in the endoplasmic reticulum, thapsigargin (TG, applied intracellularly), both prevented the effect of ouabain on SEPYLRFamide-mediated modulatory effect. Another inhibitor of Ca2+-pump in the endoplasmic reticulum, cyclopiazonic acid (applied intracellularly), did not prevent the effect of ouabain on SEPYLRFamide-mediated modulatory effect. These results indicate that Na,K-pump is responsible for the SEPYLRFamide-mediated inhibition of ACh receptors in Helix neurons. Na/Ca-exchange and intracellular Ca2+ released from internal pools containing TG-sensitive Ca2+-pump are involved in the Na,K-pump pathway for the SEPYLRFamide-mediated inhibition of ACh receptors. PMID:17049630

  1. Involvement of Na,K-pump in SEPYLRFamide-mediated reduction of cholinosensitivity in Helix neurons.

    PubMed

    Pivovarov, Arkady S; Foreman, Richard C; Walker, Robert J

    2007-02-01

    SEPYLRFamide acts as an inhibitory modulator of acetylcholine (ACh) receptors in Helix lucorum neurones. Ouabain, a specific inhibitor of Na,K-pump, (0.1 mM, bath application) decreased the ACh-induced inward current (ACh-current) and increased the leak current. Ouabain decreased the modulatory SEPYLRFamide effect on the ACh-current. There was a correlation between the effects of ouabain on the amplitude of the ACh-current and on the modulatory peptide effect. Ouabain and SEPYLRFamide inhibited the activity of Helix aspersa brain Na,K-ATPase. Activation of Na,K-pump by intracellular injection of 3 M Na acetate or 3 M NaCl reduced the modulatory peptide effect on the ACh-current. An inhibitor of Na/Ca-exchange, benzamil (25 muM, bath application), and an inhibitor of Ca(2+)-pump in the endoplasmic reticulum, thapsigargin (TG, applied intracellularly), both prevented the effect of ouabain on SEPYLRFamide-mediated modulatory effect. Another inhibitor of Ca(2+)-pump in the endoplasmic reticulum, cyclopiazonic acid (applied intracellularly), did not prevent the effect of ouabain on SEPYLRFamide-mediated modulatory effect. These results indicate that Na,K-pump is responsible for the SEPYLRFamide-mediated inhibition of ACh receptors in Helix neurons. Na/Ca-exchange and intracellular Ca(2+) released from internal pools containing TG-sensitive Ca(2+)-pump are involved in the Na,K-pump pathway for the SEPYLRFamide-mediated inhibition of ACh receptors. PMID:17049630

  2. Keeping Hearts Pumping

    NASA Technical Reports Server (NTRS)

    2002-01-01

    A collaboration between NASA, Dr. Michael DeBakey, Dr. George Noon, and MicroMed Technology, Inc., resulted in a life-saving heart pump for patients awaiting heart transplants. The MicroMed DeBakey VAD functions as a "bridge to heart transplant" by pumping blood throughout the body to keep critically ill patients alive until a donor heart is available. Weighing less than 4 ounces and measuring 1 inch by 3 inches, the pump is approximately one-tenth the size of other currently marketed pulsatile VADs. This makes it less invasive and ideal for smaller adults and children. Because of the pump's small size, less than 5 percent of the patients implanted developed device-related infections. It can operate up to 8 hours on batteries, giving patients the mobility to do normal, everyday activities.The MicroMed DeBakey VAD is a registered trademark of MicroMed Technology, Inc.

  3. Pressurized Vessel Slurry Pumping

    SciTech Connect

    Pound, C.R.

    2001-09-17

    This report summarizes testing of an alternate ''pressurized vessel slurry pumping'' apparatus. The principle is similar to rural domestic water systems and ''acid eggs'' used in chemical laboratories in that material is extruded by displacement with compressed air.

  4. GAS METERING PUMP

    DOEpatents

    George, C.M.

    1957-12-31

    A liquid piston gas pump is described, capable of pumping minute amounts of gas in accurately measurable quantities. The pump consists of a flanged cylindrical regulating chamber and a mercury filled bellows. Sealed to the ABSTRACTS regulating chamber is a value and having a gas inlet and outlet, the inlet being connected by a helical channel to the bellows. A gravity check valve is in the gas outlet, so the gas passes through the inlet and the helical channel to the bellows where the pumping action as well as the metering is accomplished by the actuation of the mercury filled bellows. The gas then flows through the check valve and outlet to any associated apparatus.

  5. Direct nuclear pumped laser

    DOEpatents

    Miley, George H.; Wells, William E.; DeYoung, Russell J.

    1978-01-01

    There is provided a direct nuclear pumped gas laser in which the lasing mechanism is collisional radiated recombination of ions. The gas laser active medium is a mixture of the gases, with one example being neon and nitrogen.

  6. Tribology of hydraulic pumps

    SciTech Connect

    Yamaguchi, A.

    1997-12-31

    To obtain much higher performance than that of alternative power transmission systems, hydraulic systems have been continuously evolving to use high-pressure. Adoption of positive displacement pumps and motors is based on this reason. Therefore, tribology is a key terminology for hydraulic pumps and motors to obtain excellent performance and durability. In this paper the following topics are investigated: (1) the special feature of tribology of hydraulic pumps and motors; (2) indication of the important bearing/sealing parts in piston pumps and effects of the frictional force and leakage flow to performance; (3) the methods to break through the tribological limitation of hydraulic equipment; and (4) optimum design of the bearing/sealing parts used in the fluid to mixed lubrication regions.

  7. An artificial molecular pump.

    PubMed

    Cheng, Chuyang; McGonigal, Paul R; Schneebeli, Severin T; Li, Hao; Vermeulen, Nicolaas A; Ke, Chenfeng; Stoddart, J Fraser

    2015-06-01

    Carrier proteins consume fuel in order to pump ions or molecules across cell membranes, creating concentration gradients. Their control over diffusion pathways, effected entirely through noncovalent bonding interactions, has inspired chemists to devise artificial systems that mimic their function. Here, we report a wholly artificial compound that acts on small molecules to create a gradient in their local concentration. It does so by using redox energy and precisely organized noncovalent bonding interactions to pump positively charged rings from solution and ensnare them around an oligomethylene chain, as part of a kinetically trapped entanglement. A redox-active viologen unit at the heart of a dumbbell-shaped molecular pump plays a dual role, first attracting and then repelling the rings during redox cycling, thereby enacting a flashing energy ratchet mechanism with a minimalistic design. Our artificial molecular pump performs work repetitively for two cycles of operation and drives rings away from equilibrium toward a higher local concentration. PMID:25984834

  8. Absorption heat pump system

    DOEpatents

    Grossman, Gershon

    1984-01-01

    The efficiency of an absorption heat pump system is improved by conducting liquid from a second stage evaporator thereof to an auxiliary heat exchanger positioned downstream of a primary heat exchanger in the desorber of the system.

  9. Underground pumped hydroelectric storage

    NASA Astrophysics Data System (ADS)

    Allen, R. D.; Doherty, T. J.; Kannberg, L. D.

    1984-07-01

    Underground pumped hydroelectric energy storage was conceived as a modification of surface pumped storage to eliminate dependence upon fortuitous topography, provide higher hydraulic heads, and reduce environmental concerns. A UPHS plant offers substantial savings in investment cost over coal-fired cycling plants and savings in system production costs over gas turbines. Potential location near load centers lowers transmission costs and line losses. Environmental impact is less than that for a coal-fired cycling plant. The inherent benefits include those of all pumped storage (i.e., rapid load response, emergency capacity, improvement in efficiency as pumps improve, and capacity for voltage regulation). A UPHS plant would be powered by either a coal-fired or nuclear baseload plant. The economic capacity of a UPHS plant would be in the range of 1000 to 3000 MW. This storage level is compatible with the load-velocity requirements of a greater metropolitan area with population of 1 million or more.

  10. An artificial molecular pump

    NASA Astrophysics Data System (ADS)

    Cheng, Chuyang; McGonigal, Paul R.; Schneebeli, Severin T.; Li, Hao; Vermeulen, Nicolaas A.; Ke, Chenfeng; Stoddart, J. Fraser

    2015-06-01

    Carrier proteins consume fuel in order to pump ions or molecules across cell membranes, creating concentration gradients. Their control over diffusion pathways, effected entirely through noncovalent bonding interactions, has inspired chemists to devise artificial systems that mimic their function. Here, we report a wholly artificial compound that acts on small molecules to create a gradient in their local concentration. It does so by using redox energy and precisely organized noncovalent bonding interactions to pump positively charged rings from solution and ensnare them around an oligomethylene chain, as part of a kinetically trapped entanglement. A redox-active viologen unit at the heart of a dumbbell-shaped molecular pump plays a dual role, first attracting and then repelling the rings during redox cycling, thereby enacting a flashing energy ratchet mechanism with a minimalistic design. Our artificial molecular pump performs work repetitively for two cycles of operation and drives rings away from equilibrium toward a higher local concentration.

  11. Advanced heat pump

    NASA Astrophysics Data System (ADS)

    Ashley, Joseph L.; Matthews, John D.

    1989-09-01

    This patent application discloses a heat pump which includes a first packed bed of liquid desiccant for removing moisture from outside air in the heating mode of operation, and a pump for transferring the moisture laden desiccant to a second packed bed which humidifies condenser heated inside air by adding water vapor to the air. The first packed bed, by removing moisture from the outside air before it passes through the heat pump's evaporator coils, prevents frost from forming on the coils. In the cooling mode of operation the second packed bed of liquid desiccant removes water vapor from the air inside of the building. The moisture laden desiccant is then transferred to the first packed bed by a second pump where condenser heat transfers the moisture from the desiccant to outside air.

  12. Using a Breast Pump

    MedlinePlus

    ... check the outside of the box for a customer service line you can call to request a ... your pump continues to leak, call the manufacturer’s customer service line for help. When you have finished ...

  13. Adiabatically driven Brownian pumps.

    PubMed

    Rozenbaum, Viktor M; Makhnovskii, Yurii A; Shapochkina, Irina V; Sheu, Sheh-Yi; Yang, Dah-Yen; Lin, Sheng Hsien

    2013-07-01

    We investigate a Brownian pump which, being powered by a flashing ratchet mechanism, produces net particle transport through a membrane. The extension of the Parrondo's approach developed for reversible Brownian motors [Parrondo, Phys. Rev. E 57, 7297 (1998)] to adiabatically driven pumps is given. We demonstrate that the pumping mechanism becomes especially efficient when the time variation of the potential occurs adiabatically fast or adiabatically slow, in perfect analogy with adiabatically driven Brownian motors which exhibit high efficiency [Rozenbaum et al., Phys. Rev. E 85, 041116 (2012)]. At the same time, the efficiency of the pumping mechanism is shown to be less than that of Brownian motors due to fluctuations of the number of particles in the membrane. PMID:23944411

  14. Absorption heat pump system

    DOEpatents

    Grossman, G.

    1982-06-16

    The efficiency of an absorption heat pump system is improved by conducting liquid from a second stage evaporator thereof to an auxiliary heat exchanger positioned downstream of a primary heat exchanger in the desorber of the system.

  15. Lunar Base Heat Pump

    NASA Technical Reports Server (NTRS)

    Walker, D.; Fischbach, D.; Tetreault, R.

    1996-01-01

    The objective of this project was to investigate the feasibility of constructing a heat pump suitable for use as a heat rejection device in applications such as a lunar base. In this situation, direct heat rejection through the use of radiators is not possible at a temperature suitable for lde support systems. Initial analysis of a heat pump of this type called for a temperature lift of approximately 378 deg. K, which is considerably higher than is commonly called for in HVAC and refrigeration applications where heat pumps are most often employed. Also because of the variation of the rejection temperature (from 100 to 381 deg. K), extreme flexibility in the configuration and operation of the heat pump is required. A three-stage compression cycle using a refrigerant such as CFC-11 or HCFC-123 was formulated with operation possible with one, two or three stages of compression. Also, to meet the redundancy requirements, compression was divided up over multiple compressors in each stage. A control scheme was devised that allowed these multiple compressors to be operated as required so that the heat pump could perform with variable heat loads and rejection conditions. A prototype heat pump was designed and constructed to investigate the key elements of the high-lift heat pump concept. Control software was written and implemented in the prototype to allow fully automatic operation. The heat pump was capable of operation over a wide range of rejection temperatures and cooling loads, while maintaining cooling water temperature well within the required specification of 40 deg. C +/- 1.7 deg. C. This performance was verified through testing.

  16. Remotely Adjustable Hydraulic Pump

    NASA Technical Reports Server (NTRS)

    Kouns, H. H.; Gardner, L. D.

    1987-01-01

    Outlet pressure adjusted to match varying loads. Electrohydraulic servo has positioned sleeve in leftmost position, adjusting outlet pressure to maximum value. Sleeve in equilibrium position, with control land covering control port. For lowest pressure setting, sleeve shifted toward right by increased pressure on sleeve shoulder from servovalve. Pump used in aircraft and robots, where hydraulic actuators repeatedly turned on and off, changing pump load frequently and over wide range.

  17. Rotary blood pump

    NASA Technical Reports Server (NTRS)

    Benkowski, Robert J. (Inventor); Kiris, Cetin (Inventor); Kwak, Dochan (Inventor); Rosenbaum, Bernard J. (Inventor); Bacak, James W. (Inventor); DeBakey, Michael E. (Inventor)

    1999-01-01

    A blood pump that comprises a pump housing having a blood flow path therethrough, a blood inlet, and a blood outlet; a stator mounted to the pump housing, the stator having a stator field winding for producing a stator magnetic field; a flow straightener located within the pump housing, and comprising a flow straightener hub and at least one flow straightener blade attached to the flow straightener hub; a rotor mounted within the pump housing for rotation in response to the stator magnetic field, the rotor comprising an inducer and an impeller; the inducer being located downstream of the flow straightener, and comprising an inducer hub and at least one inducer blade attached to the inducer hub; the impeller being located downstream of the inducer, and comprising an impeller hub and at least one impeller blade attached to the impeller hub; and preferably also comprising a diffuser downstream of the impeller, the diffuser comprising a diffuser hub and at least one diffuser blade. Blood flow stagnation and clot formation within the pump are minimized by, among other things, providing the inducer hub with a diameter greater than the diameter of the flow straightener hub; by optimizing the axial spacing between the flow straightener hub and the inducer hub, and between the impeller hub and the diffuser hub; by optimizing the inlet angle of the diffuser blades; and by providing fillets or curved transitions between the upstream end of the inducer hub and the shaft mounted therein, and between the impeller hub and the shaft mounted therein.

  18. Lunar base heat pump

    NASA Technical Reports Server (NTRS)

    Goldman, Jeffrey H.; Tetreault, R.; Fischbach, D.; Walker, D.

    1994-01-01

    A heat pump is a device which elevates the temperature of a heat flow by a means of an energy input. By doing this, the heat pump can cause heat to transfer faster from a warm region to a cool region, or it can cause heat to flow from a cool region to a warmer region. The second case is the one which finds vast commercial applications such as air conditioning, heating, and refrigeration. Aerospace applications of heat pumps include both cases. The NASA Johnson Space Center is currently developing a Life Support Systems Integration Facility (LSSIF, previously SIRF) to provide system-level integration, operational test experience, and performance data that will enable NASA to develop flight-certified hardware for future planetary missions. A high lift heat pump is a significant part of the TCS hardware development associated with the LSSIF. The high lift heat pump program discussed here is being performed in three phases. In Phase 1, the objective is to develop heat pump concepts for a lunar base, a lunar lander, and for a ground development unit for the SIRF. In Phase 2, the design of the SIRF ground test unit is being performed, including identification and evaluation of safety and reliability issues. In Phase 3, the SIRF unit will be manufactured, tested, and delivered to the NASA Johnson Space Center.

  19. Lunar base heat pump

    NASA Astrophysics Data System (ADS)

    Goldman, Jeffrey H.; Tetreault, R.; Fischbach, D.; Walker, D.

    1994-10-01

    A heat pump is a device which elevates the temperature of a heat flow by a means of an energy input. By doing this, the heat pump can cause heat to transfer faster from a warm region to a cool region, or it can cause heat to flow from a cool region to a warmer region. The second case is the one which finds vast commercial applications such as air conditioning, heating, and refrigeration. Aerospace applications of heat pumps include both cases. The NASA Johnson Space Center is currently developing a Life Support Systems Integration Facility (LSSIF, previously SIRF) to provide system-level integration, operational test experience, and performance data that will enable NASA to develop flight-certified hardware for future planetary missions. A high lift heat pump is a significant part of the TCS hardware development associated with the LSSIF. The high lift heat pump program discussed here is being performed in three phases. In Phase 1, the objective is to develop heat pump concepts for a lunar base, a lunar lander, and for a ground development unit for the SIRF. In Phase 2, the design of the SIRF ground test unit is being performed, including identification and evaluation of safety and reliability issues. In Phase 3, the SIRF unit will be manufactured, tested, and delivered to the NASA Johnson Space Center.

  20. Satellite Propellant Pump Research

    NASA Technical Reports Server (NTRS)

    Schneider, Steven J.; Veres, Joseph P.; Hah, Chunill; Nerone, Anthony L.; Cunningham, Cameron C.; Kraft, Thomas G.; Tavernelli, Paul F.; Fraser, Bryan

    2005-01-01

    NASA Glenn initiated a satellite propellant pump technology demonstration program. The goal was to demonstrate the technologies for a 60 percent efficient pump at 1 gpm flow rate and 500 psia pressure rise. The pump design and analysis used the in-house developed computer codes named PUMPA and HPUMP3D. The requirements lead to a 4-stage impeller type pump design with a tip diameter of 0.54 inches and a rotational speed of 57,000 rpm. Analyses indicated that flow cavitation was not a problem in the design. Since the flow was incompressible, the stages were identical. Only the 2-stage pump was designed, fabricated, assembled, and tested for demonstration. Water was selected as the surrogate fluid for hydrazine in this program. Complete mechanical design including stress and dynamic analyses were conducted. The pump was driven by an electric motor directly coupled to the impellers. Runs up to 57,000 rpm were conducted, where a pressure rise of 200 psia at a flow rate of 0.8 gpm was measured to validate the design effort.

  1. The Evolution of Ion Pumps.

    ERIC Educational Resources Information Center

    Maloney, Peter C.; Wilson, T. Hastings

    1985-01-01

    Constructs an evolutionary sequence to account for the diversity of ion pumps found today. Explanations include primary ion pumps in bacteria, features and distribution of ATP-driven pumps, preference for cation transport, and proton pump reversal. The integrated evolutionary hypothesis should encourage new experimental approaches. (DH)

  2. Axial pumps for propulsion systems

    NASA Technical Reports Server (NTRS)

    Huppert, M. C.; Rothe, K.

    1974-01-01

    The development of axial flow hydrogen pumps is examined. The design features and the performance data obtained during the course of the development programs are discussed. The problems created by the pump characteristics are analyzed. Graphs of four stage pump performance for various turbine blade configurations are developed. The characteristics and performance of a variety of pumps are included.

  3. Remote mud pump control apparatus

    SciTech Connect

    Thompson, S.R.; Harbour, W.D. Jr.

    1986-06-17

    An apparatus is described for controlling the circulation of fluid in a subterranean well consisting of: a pump; a choke communicable with the pump; pump monitoring means for regulating the pump speed to vary the flow rate of the circulating fluid; choke monitoring means located at the surface of the well remote from the pump monitoring means and including choke regulating means for varying the fluid flow area through the choke to control the pressure of the circulating fluid as the flow rate is changed by variations in the pump speed; the improvement comprising: a second pump control means incorporated in the choke monitoring means and communicable with the pump through the pump monitoring means for regulating the pump speed.

  4. Thermally Actuated Hydraulic Pumps

    NASA Technical Reports Server (NTRS)

    Jones, Jack; Ross, Ronald; Chao, Yi

    2008-01-01

    Thermally actuated hydraulic pumps have been proposed for diverse applications in which direct electrical or mechanical actuation is undesirable and the relative slowness of thermal actuation can be tolerated. The proposed pumps would not contain any sliding (wearing) parts in their compressors and, hence, could have long operational lifetimes. The basic principle of a pump according to the proposal is to utilize the thermal expansion and contraction of a wax or other phase-change material in contact with a hydraulic fluid in a rigid chamber. Heating the chamber and its contents from below to above the melting temperature of the phase-change material would cause the material to expand significantly, thus causing a substantial increase in hydraulic pressure and/or a substantial displacement of hydraulic fluid out of the chamber. Similarly, cooling the chamber and its contents from above to below the melting temperature of the phase-change material would cause the material to contract significantly, thus causing a substantial decrease in hydraulic pressure and/or a substantial displacement of hydraulic fluid into the chamber. The displacement of the hydraulic fluid could be used to drive a piston. The figure illustrates a simple example of a hydraulic jack driven by a thermally actuated hydraulic pump. The pump chamber would be a cylinder containing encapsulated wax pellets and containing radial fins to facilitate transfer of heat to and from the wax. The plastic encapsulation would serve as an oil/wax barrier and the remaining interior space could be filled with hydraulic oil. A filter would retain the encapsulated wax particles in the pump chamber while allowing the hydraulic oil to flow into and out of the chamber. In one important class of potential applications, thermally actuated hydraulic pumps, exploiting vertical ocean temperature gradients for heating and cooling as needed, would be used to vary hydraulic pressures to control buoyancy in undersea research

  5. Clinically Relevant Chromosomally Encoded Multidrug Resistance Efflux Pumps in Bacteria

    PubMed Central

    Piddock, Laura J. V.

    2006-01-01

    Efflux pump genes and proteins are present in both antibiotic-susceptible and antibiotic-resistant bacteria. Pumps may be specific for one substrate or may transport a range of structurally dissimilar compounds (including antibiotics of multiple classes); such pumps can be associated with multiple drug (antibiotic) resistance (MDR). However, the clinical relevance of efflux-mediated resistance is species, drug, and infection dependent. This review focuses on chromosomally encoded pumps in bacteria that cause infections in humans. Recent structural data provide valuable insights into the mechanisms of drug transport. MDR efflux pumps contribute to antibiotic resistance in bacteria in several ways: (i) inherent resistance to an entire class of agents, (ii) inherent resistance to specific agents, and (iii) resistance conferred by overexpression of an efflux pump. Enhanced efflux can be mediated by mutations in (i) the local repressor gene, (ii) a global regulatory gene, (iii) the promoter region of the transporter gene, or (iv) insertion elements upstream of the transporter gene. Some data suggest that resistance nodulation division systems are important in pathogenicity and/or survival in a particular ecological niche. Inhibitors of various efflux pump systems have been described; typically these are plant alkaloids, but as yet no product has been marketed. PMID:16614254

  6. Well-pump alignment system

    DOEpatents

    Drumheller, D.S.

    1998-10-20

    An improved well-pump for geothermal wells, an alignment system for a well-pump, and to a method for aligning a rotor and stator within a well-pump are disclosed, wherein the well-pump has a whistle assembly formed at a bottom portion thereof, such that variations in the frequency of the whistle, indicating misalignment, may be monitored during pumping. 6 figs.

  7. New slurry pumps in China

    SciTech Connect

    Li, Z.; Wang, W.; Shi, Z.

    1998-07-01

    Wet parts of centrifugal slurry pumps are naturally subjected to wear, but local wear in pumps could be avoided, at least partly. Through studying the wear phenomenon of slurry pumps in industrial applications, a series of much more advanced slurry pumps was developed in China. Laboratory tests and industrial applications show that the new pumps are high in efficiency when transporting slurries, and uniform wear can be expected from them.

  8. New slurry pumps in China

    SciTech Connect

    Zhengwang Li; Wenlie Wang; Zhongyin Shi

    1998-04-01

    Wet parts of centrifugal slurry pumps are naturally subjected to wear, but local wear in pumps could be avoided, at least partly. Through studying the wear phenomenon of slurry pumps in industrial applications, a series of much more advanced slurry pumps was developed in China. Laboratory tests and industrial applications show that the new pumps are high in efficiency when transporting slurries, and uniform wear can be expected from them.

  9. Underground pumped hydroelectric storage

    SciTech Connect

    Allen, R.D.; Doherty, T.J.; Kannberg, L.D.

    1984-07-01

    Underground pumped hydroelectric energy storage was conceived as a modification of surface pumped storage to eliminate dependence upon fortuitous topography, provide higher hydraulic heads, and reduce environmental concerns. A UPHS plant offers substantial savings in investment cost over coal-fired cycling plants and savings in system production costs over gas turbines. Potential location near load centers lowers transmission costs and line losses. Environmental impact is less than that for a coal-fired cycling plant. The inherent benefits include those of all pumped storage (i.e., rapid load response, emergency capacity, improvement in efficiency as pumps improve, and capacity for voltage regulation). A UPHS plant would be powered by either a coal-fired or nuclear baseload plant. The economic capacity of a UPHS plant would be in the range of 1000 to 3000 MW. This storage level is compatible with the load-leveling requirements of a greater metropolitan area with population of 1 million or more. The technical feasibility of UPHS depends upon excavation of a subterranean powerhouse cavern and reservoir caverns within a competent, impervious rock formation, and upon selection of reliable and efficient turbomachinery - pump-turbines and motor-generators - all remotely operable.

  10. Heat driven pulse pump

    NASA Technical Reports Server (NTRS)

    Benner, Steve M (Inventor); Martins, Mario S. (Inventor)

    2000-01-01

    A heat driven pulse pump includes a chamber having an inlet port, an outlet port, two check valves, a wick, and a heater. The chamber may include a plurality of grooves inside wall of the chamber. When heated within the chamber, a liquid to be pumped vaporizes and creates pressure head that expels the liquid through the outlet port. As liquid separating means, the wick, disposed within the chamber, is to allow, when saturated with the liquid, the passage of only liquid being forced by the pressure head in the chamber, preventing the vapor from exiting from the chamber through the outlet port. A plurality of grooves along the inside surface wall of the chamber can sustain the liquid, which is amount enough to produce vapor for the pressure head in the chamber. With only two simple moving parts, two check valves, the heat driven pulse pump can effectively function over the long lifetimes without maintenance or replacement. For continuous flow of the liquid to be pumped a plurality of pumps may be connected in parallel.

  11. 20. Station Unwatering Pumps and Sump Pump, view to the ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Station Unwatering Pumps and Sump Pump, view to the north. The station unwatering pumps are the two large units in the center and right foreground of photograph and are marked with the numbers 1 and 2. The sump pump is the smaller unit in left foreground of photograph. These pumps are used for unwatering the draft chests for maintenance. Note the draft tube unwatering valve visible in background between the two unwatering pumps. - Washington Water Power Clark Fork River Noxon Rapids Hydroelectric Development, Powerhouse, South bank of Clark Fork River at Noxon Rapids, Noxon, Sanders County, MT

  12. Pump tank divider plate for sump suction sodium pumps

    DOEpatents

    George, John A.; Nixon, Donald R.

    1977-01-01

    A circular plate extends across the diameter of "sump suction" pump, with a close clearance between the edge of the plate and the wall of the pump tank. The plate is located above the pump impeller, inlet and outlet flow nozzles but below the sodium free surface and effectively divides the pump tank into two separate chambers. On change of pump speed, the close fitting flow restriction plate limits the rate of flow into or out of the upper chamber, thereby minimizing the rate of level change in the tank and permitting time for the pump cover gas pressure to be varied to maintain an essentially constant level.

  13. Pumping of helium and hydrogen by sputter-ion pumps. II. Hydrogen pumping

    SciTech Connect

    Welch, K.M.; Pate, D.J.; Todd, R.J. )

    1994-05-01

    The pumping of helium by various forms of sputter-ion pumps (i.e., SIPs) is given in part I [K. M. Welch, D. J. Pate, and R. J. Todd, J. Vac. Sci. Technol. A [bold 11], 1607 (1993)]. The pumping of hydrogen in diode and triode SIPs is herein discussed. The type of cathode material used in these pumps is shown to have a significant impact on the effectiveness with which hydrogen is pumped. Examples of this include data for pumps with aluminum, titanium, and titanium-alloy cathodes. Diode pumps with aluminum cathodes are shown to be no more effective in the pumping of hydrogen than in the pumping of helium. The use of titanium anodes and titanium [ital shielding] of a pump body is also shown to impact measurably the speed of a pump at very low pressures. This stems from the fact that hydrogen is [times]10[sup 6] more soluble in titanium than in stainless steel. Hydrogen becomes resident in the anodes because of fast neutral burial. Ions and fast neutrals of hydrogen are also buried in the walls of pump bodies. Outgassing of this hydrogen from the anodes and pump bodies results in a gradual increase in pump base pressure and consequential decrease in hydrogen pump speed at very low base pressures.

  14. Miniature Lightweight Ion Pump

    NASA Technical Reports Server (NTRS)

    Sinha, Mahadeva P.

    2010-01-01

    This design offers a larger surface area for pumping of active gases and reduces the mass of the pump by eliminating the additional vacuum enclosure. There are three main components to this ion pump: the cathode and anode pumping elements assembly, the vacuum enclosure (made completely of titanium and used as the cathode and maintained at ground potential) containing the assembly, and the external magnet. These components are generally put in a noble diode (or differential) configuration of the ion pump technology. In the present state of the art, there are two cathodes, one made of titanium and the other of tantalum. The anodes are made up of an array of stainless steel cylinders positioned between the two cathodes. All the elements of the pump are in a vacuum enclosure. After the reduction of pressure in this enclosure to a few microns, a voltage is applied between the cathode and the anode elements. Electrons generated by the ionization are accelerated toward the anodes that are confined in the anode space by the axial magnetic field. For the generation of the axial field along the anode elements, the magnet is designed in a C-configuration and is fabricated from rare earth magnetic materials (Nd-B-Fe or Sm-Co) possessing high energy product values, and the yoke is fabricated from the high permeability material (Hiperco-50A composed of Fe-Co-V). The electrons in this region collide with the gas molecules and generate their positive ions. These ions are accelerated into the cathode and eject cathode material (Ti). The neutral atoms deposit on the anode surfaces. Because of the chemical activity of Ti, the atoms combine with chemically active gas molecules (e.g. N2, O2, etc.) and remove them. New layers of Ti are continually deposited, and the pumping of active gases is thus accomplished. Pumping of the inert gases is accomplished by their burial several atomic layers deep into the cathode. However, they tend to re-emit if the entrapping lattice atoms are

  15. Fluid pumping apparatus

    DOEpatents

    West, Phillip B.

    2006-01-17

    A method and apparatus suitable for coupling seismic or other downhole sensors to a borehole wall in high temperature and pressure environments. In one embodiment, one or more metal bellows mounted to a sensor module are inflated to clamp the sensor module within the borehole and couple an associated seismic sensor to a borehole wall. Once the sensing operation is complete, the bellows are deflated and the sensor module is unclamped by deflation of the metal bellows. In a further embodiment, a magnetic drive pump in a pump module is used to supply fluid pressure for inflating the metal bellows using borehole fluid or fluid from a reservoir. The pump includes a magnetic drive motor configured with a rotor assembly to be exposed to borehole fluid pressure including a rotatable armature for driving an impeller and an associated coil under control of electronics isolated from borehole pressure.

  16. Regenerative adsorbent heat pump

    NASA Technical Reports Server (NTRS)

    Jones, Jack A. (Inventor)

    1991-01-01

    A regenerative adsorbent heat pump process and system is provided which can regenerate a high percentage of the sensible heat of the system and at least a portion of the heat of adsorption. A series of at least four compressors containing an adsorbent is provided. A large amount of heat is transferred from compressor to compressor so that heat is regenerated. The process and system are useful for air conditioning rooms, providing room heat in the winter or for hot water heating throughout the year, and, in general, for pumping heat from a lower temperature to a higher temperature.

  17. Measuring axial pump thrust

    DOEpatents

    Suchoza, B.P.; Becse, I.

    1988-11-08

    An apparatus for measuring the hydraulic axial thrust of a pump under operation conditions is disclosed. The axial thrust is determined by forcing the rotating impeller off of an associated thrust bearing by use of an elongate rod extending coaxially with the pump shaft. The elongate rod contacts an impeller retainer bolt where a bearing is provided. Suitable measuring devices measure when the rod moves to force the impeller off of the associated thrust bearing and the axial force exerted on the rod at that time. The elongate rod is preferably provided in a housing with a heat dissipation mechanism whereby the hot fluid does not affect the measuring devices. 1 fig.

  18. Measuring axial pump thrust

    DOEpatents

    Suchoza, Bernard P.; Becse, Imre

    1988-01-01

    An apparatus for measuring the hydraulic axial thrust of a pump under operation conditions is disclosed. The axial thrust is determined by forcing the rotating impeller off of an associated thrust bearing by use of an elongate rod extending coaxially with the pump shaft. The elongate rod contacts an impeller retainer bolt where a bearing is provided. Suitable measuring devices measure when the rod moves to force the impeller off of the associated thrust bearing and the axial force exerted on the rod at that time. The elongate rod is preferably provided in a housing with a heat dissipation mechanism whereby the hot fluid does not affect the measuring devices.

  19. Fusion reactor pumped laser

    DOEpatents

    Jassby, Daniel L.

    1988-01-01

    A nuclear pumped laser capable of producing long pulses of very high power laser radiation is provided. A toroidal fusion reactor provides energetic neutrons which are slowed down by a moderator. The moderated neutrons are converted to energetic particles capable of pumping a lasing medium. The lasing medium is housed in an annular cell surrounding the reactor. The cell includes an annular reflecting mirror at the bottom and an annular output window at the top. A neutron reflector is disposed around the cell to reflect escaping neutrons back into the cell. The laser radiation from the annular window is focused onto a beam compactor which generates a single coherent output laser beam.

  20. High pressure reciprocating pump

    SciTech Connect

    Besic, D.

    1990-05-01

    This patent describes an improvement in a reciprocating pump having a plunger and a pumping chamber. It comprises: the plunger having a bore communicating with an intersection opening and wherein the plunger incudes a central axis; a suction valve and a discharge valve, each having an axis of actuation parallel to a central axis of the plunger; the suction valve comprising a cylindrical core having a central passageway, and the core is slidably received by a seating member and resiliently biased to the seating member.

  1. Reactor coolant pump flywheel

    SciTech Connect

    Finegan, John Raymond; Kreke, Francis Joseph; Casamassa, John Joseph

    2013-11-26

    A flywheel for a pump, and in particular a flywheel having a number of high density segments for use in a nuclear reactor coolant pump. The flywheel includes an inner member and an outer member. A number of high density segments are provided between the inner and outer members. The high density segments may be formed from a tungsten based alloy. A preselected gap is provided between each of the number of high density segments. The gap accommodates thermal expansion of each of the number of segments and resists the hoop stress effect/keystoning of the segments.

  2. Acoustical heat pumping engine

    DOEpatents

    Wheatley, John C.; Swift, Gregory W.; Migliori, Albert

    1983-08-16

    The disclosure is directed to an acoustical heat pumping engine without moving seals. A tubular housing holds a compressible fluid capable of supporting an acoustical standing wave. An acoustical driver is disposed at one end of the housing and the other end is capped. A second thermodynamic medium is disposed in the housing near to but spaced from the capped end. Heat is pumped along the second thermodynamic medium toward the capped end as a consequence both of the pressure oscillation due to the driver and imperfect thermal contact between the fluid and the second thermodynamic medium.

  3. Acoustical heat pumping engine

    DOEpatents

    Wheatley, J.C.; Swift, G.W.; Migliori, A.

    1983-08-16

    The disclosure is directed to an acoustical heat pumping engine without moving seals. A tubular housing holds a compressible fluid capable of supporting an acoustical standing wave. An acoustical driver is disposed at one end of the housing and the other end is capped. A second thermodynamic medium is disposed in the housing near to but spaced from the capped end. Heat is pumped along the second thermodynamic medium toward the capped end as a consequence both of the pressure oscillation due to the driver and imperfect thermal contact between the fluid and the second thermodynamic medium. 2 figs.

  4. Paramagnetic spin pumping.

    PubMed

    Shiomi, Y; Saitoh, E

    2014-12-31

    We have demonstrated spin pumping from a paramagnetic state of an insulator La2NiMnO6 into a Pt film. Single-crystalline films of La2NiMnO6 which exhibit a ferromagnetic order at TC≈270  K were grown by pulsed laser deposition. The inverse spin Hall voltage induced by spin-current injection has been observed in the Pt layer not only in the ferromagnetic phase of La2NiMnO6, but also in a wide temperature range above TC. The efficient spin pumping in the paramagnetic phase is ascribable to ferromagnetic correlation, not to ferromagnetic order. PMID:25615367

  5. Pulsed differential pumping system

    SciTech Connect

    Antipov, G.N.; Bagautdinov, F.A.; Rybalov, S.V.

    1985-06-01

    A pulsed differential pumping system is described for extracting an electron beam from a shaping region at a pressure of 10/sup -5/ torr into a volume with a pressure of 10-100 torr. A fast valve is used with appropriate geometrical parameters to reduce the length of the outlet channel considerable while increasing its diameter. Test results are given. The pumping system has two sections which communicate one with the other and with the volume at the elevated pressure which is produced by gasdynamic nozzles.

  6. Plant proton pumps.

    PubMed

    Gaxiola, Roberto A; Palmgren, Michael G; Schumacher, Karin

    2007-05-25

    Chemiosmotic circuits of plant cells are driven by proton (H(+)) gradients that mediate secondary active transport of compounds across plasma and endosomal membranes. Furthermore, regulation of endosomal acidification is critical for endocytic and secretory pathways. For plants to react 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. PMID:17412324

  7. Velocity pump reaction turbine

    DOEpatents

    House, P.A.

    An expanding hydraulic/two-phase velocity pump reaction turbine including a dual concentric rotor configuration with an inter-rotor annular flow channel in which the inner rotor is mechanically driven by the outer rotor. In another embodiment, the inner rotor is immobilized and provided with gas recovery ports on its outer surface by means of which gas in solution may be recovered. This velocity pump reaction turbine configuration is capable of potential energy conversion efficiencies of up to 70%, and is particularly suited for geothermal applications.

  8. Velocity pump reaction turbine

    DOEpatents

    House, Palmer A.

    1984-01-01

    An expanding hydraulic/two-phase velocity pump reaction turbine including a dual concentric rotor configuration with an inter-rotor annular flow channel in which the inner rotor is mechanically driven by the outer rotor. In another embodiment, the inner rotor is immobilized and provided with gas recovery ports on its outer surface by means of which gas in solution may be recovered. This velocity pump reaction turbine configuration is capable of potential energy conversion efficiencies of up to 70%, and is particularly suited for geothermal applications.

  9. Velocity pump reaction turbine

    DOEpatents

    House, Palmer A.

    1982-01-01

    An expanding hydraulic/two-phase velocity pump reaction turbine including a dual concentric rotor configuration with an inter-rotor annular flow channel in which the inner rotor is mechanically driven by the outer rotor. In another embodiment, the inner rotor is immobilized and provided with gas recovery ports on its outer surface by means of which gas in solution may be recovered. This velocity pump reaction turbine configuration is capable of potential energy conversion efficiencies of up to 70%, and is particularly suited for geothermal applications.

  10. Air-Operated Sump Pump

    NASA Technical Reports Server (NTRS)

    Nolt, Gary D.

    1988-01-01

    Pump removes liquid seepage from small, restricted area and against large pressure head. Developed for moving small amounts of water and oil from sump pit 85 ft (25.91 m) deep. Fits in space only 6 1/2 in. (16.5 cm) in diameter and 18 in. (45.7 cm) long. In discharge part of pumping cycle, air forces liquid out of pump chamber through pipe. During filling part of pumping cycle, water enters pump chamber from sump pit. Float in chamber next to pump chamber controls pressurization through timer and solenoid valve.

  11. 12. Sewage Ejector Pumps, view to the southwest. These pumps ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. Sewage Ejector Pumps, view to the southwest. These pumps are connected to sewage treatment tanks. - Washington Water Power Clark Fork River Cabinet Gorge Hydroelectric Development, Powerhouse, North Bank of Clark Fork River at Cabinet Gorge, Cabinet, Bonner County, ID

  12. 3. Interior view of centrifugal pump house showing pumps and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. Interior view of centrifugal pump house showing pumps and engines, looking W. - Laurel Valley Sugar Plantation, Drainage Plant, 2 Miles South of Thibodaux on State Route 308, Thibodaux, Lafourche Parish, LA

  13. Portable engine-pump assembly

    SciTech Connect

    Eberhardt, H.A.

    1987-02-17

    This patent describes a portable engine-pump assembly that is compact and light in weight comprising: an internal combustion engine mounted with its crankshaft extending vertically, a centrifugal pump having an impeller mounted for rotation on a pump shaft within a volute chamber, means mounting the pump on and immediately beneath the engine with the pump shaft extending vertically in accurate alignment and concentricity with the engine crankshaft, means coupling the engine crankshaft and the pump shaft together so that the engine crankshaft drives the pump shaft, the pump comprising a pump body defining the volute chamber and providing a pump inlet passage and a pump discharge passage oriented in generally horizontal directions, the pump body defining an inlet chamber providing passages for the flow of liquid from the pump inlet passage into the impeller from both above and below same and including an upper body portion and a lower body portion, and an exhaust system for the engine including an exhaust passage contained in the upper body portion, a muffler having an inlet, and means providing flow communication between the exhaust passage and the inlet of the muffler.

  14. 39. THREECYLINDER HYDRAULIC OIL PUMP (MANUFACTURED BY WORTHINGTON: PUMP AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    39. THREE-CYLINDER HYDRAULIC OIL PUMP (MANUFACTURED BY WORTHINGTON: PUMP AND MACHINERY COMPANY, HOLYOKE MASSACHUSETTS) IN MACHINERY CHAMBER FOR SLUICE GATE WORKS ON GALLERY 1. NOTE OIL TANK ABOVE PUMP MOTOR. VIEW TO NORTHWEST. - Owyhee Dam, Across Owyhee River, Nyssa, Malheur County, OR

  15. 24. Pump Room interiordewatering pump motor on upper level. Note ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    24. Pump Room interior-dewatering pump motor on upper level. Note the removable roof hatch (steel frame) directly above motor. Dewatering pumps motor control center at left - Hunters Point Naval Shipyard, Drydock No. 4, East terminus of Palou Avenue, San Francisco, San Francisco County, CA

  16. PUMP SETS NO. 5 AND NO. 4. Each pump set ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    PUMP SETS NO. 5 AND NO. 4. Each pump set consists of a Worthington Pump and a General Electric motor - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Flame Deflector Water System, Test Area 1-120, north end of Jupiter Boulevard, Boron, Kern County, CA

  17. 29. WORTHINGTON FIRE PUMP WITH TURBINE HIDDEN BEHIND. PUMP HOUSE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    29. WORTHINGTON FIRE PUMP WITH TURBINE HIDDEN BEHIND. PUMP HOUSE IS LOCATED AT HEAD OF OLD TRASH GATES. PUMP ENTERS WATER ON EXTERIOR OF WALL IN FAR SIDE OF PHOTO. - Prattville Manufacturing Company, Number One, 242 South Court Street, Prattville, Autauga County, AL

  18. Overview of Pump Room, showing pumps at right and power ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Overview of Pump Room, showing pumps at right and power distribution cabinets for valve motors along north wall at left. View to east - Wellton-Mohawk Irrigation System, Pumping Plant No. 1, Bounded by Gila River & Union Pacific Railroad, Wellton, Yuma County, AZ

  19. Indexes of pumps for oil field pumping units

    SciTech Connect

    Ibragimov, E.S.

    1995-07-01

    As reported previously, a series of oil field pumping units has been developed with power outputs of 125, 250, 500, and 1000 kW, designed for injecting working fluids in cementing operations in oil and gas wells, hydraulic fracturing of formations, washing out sand plugs, and other production operations. The units are designed for the use of three-plunger pumps with individual power outputs of 125 or 500 kW. In the 250- and 1000-kW units, two such pumps are used. The 1000-kW pumping unit serves mainly for deep-penetration hydraulic fracturing of formations, and also for fracturing deep formations. The hydraulic fracturing process does not require the use of units with two pumps; this has been demonstrated by experience, both here and in other countries. All units intended for use in hydraulic fracturing are built with a single pump, transmission, and drive. Pumping units for well cementing must have two pumps that will give a high delivery rate. At the start of the operation, a single pump can be used to feed water into the cement mixer, with the second pump used to transfer the cement slurry to the well. Then both pumps are connected to the slurry injection line. The operation of these pumps is described.

  20. Piezohydraulic Pump Development

    NASA Technical Reports Server (NTRS)

    Lynch, Christopher S.

    2005-01-01

    Reciprocating piston piezohydraulic pumps were developed originally under the Smart Wing Phase II program (Lynch) and later under the CHAP program (CSA, Kinetic Ceramics). These pumps focused on 10 cm scale stack actuators operating below resonance and, more recently, at resonance. A survey of commercially available linear actuators indicates that obtaining power density and specific power greater than electromagnetic linear actuators requires driving the stacks at frequencies greater than 1 KHz at high fields. In the case of 10 cm scale actuators the power supply signal conditioning becomes large and heavy and the soft PZT stack actuators generate a lot of heat due to internal losses. Reciprocation frequencies can be increased and material losses significantly decreased through use of millimeter scale single crystal stack actuators. We are presently targeting the design of pumps that utilize stacks at the 1-10 mm length scale and run at reciprocating frequencies of 20kHz or greater. This offers significant advantages over current approaches including eliminating audible noise and significantly increasing the power density and specific power of the system (including electronics). The pump currently under development will comprise an LC resonant drive of a resonant crystal and head mass operating against a resonant fluid column. Each of these resonant systems are high Q and together should produce a single high Q second order system.

  1. Pump Flow Analysis

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Ingersoll-Rand Research, Inc.'s use of COSMIC's computer program MERIDL permits designers to evaluate performance and efficiency characteristics to be expected from the pump's impeller. It also provides information that enables a trained hydraulic engineer to make design improvements. Company was able to avoid the cost of developing new software and to improve some product design features.

  2. Magnetic-flux pump

    NASA Technical Reports Server (NTRS)

    Hildebrandt, A. F.; Elleman, D. D.; Whitmore, F. C. (Inventor)

    1966-01-01

    A magnetic flux pump is described for increasing the intensity of a magnetic field by transferring flux from one location to the magnetic field. The device includes a pair of communicating cavities formed in a block of superconducting material, and a piston for displacing the trapped magnetic flux into the secondary cavity producing a field having an intense flux density.

  3. Explosively pumped laser light

    DOEpatents

    Piltch, Martin S.; Michelotti, Roy A.

    1991-01-01

    A single shot laser pumped by detonation of an explosive in a shell casing. The shock wave from detonation of the explosive causes a rare gas to luminesce. The high intensity light from the gas enters a lasing medium, which thereafter outputs a pulse of laser light to disable optical sensors and personnel.

  4. Linear induction pump

    DOEpatents

    Meisner, John W.; Moore, Robert M.; Bienvenue, Louis L.

    1985-03-19

    Electromagnetic linear induction pump for liquid metal which includes a unitary pump duct. The duct comprises two substantially flat parallel spaced-apart wall members, one being located above the other and two parallel opposing side members interconnecting the wall members. Located within the duct are a plurality of web members interconnecting the wall members and extending parallel to the side members whereby the wall members, side members and web members define a plurality of fluid passageways, each of the fluid passageways having substantially the same cross-sectional flow area. Attached to an outer surface of each side member is an electrically conductive end bar for the passage of an induced current therethrough. A multi-phase, electrical stator is located adjacent each of the wall members. The duct, stators, and end bars are enclosed in a housing which is provided with an inlet and outlet in fluid communication with opposite ends of the fluid passageways in the pump duct. In accordance with a preferred embodiment, the inlet and outlet includes a transition means which provides for a transition from a round cross-sectional flow path to a substantially rectangular cross-sectional flow path defined by the pump duct.

  5. Progressive cavity pump

    SciTech Connect

    Mueller, J.W.

    1989-04-04

    A progressive cavity pump is described, comprising: a first housing portion defining an inlet; a second housing portion attachable to the first housing portion and defining an outlet; a substantially elastomeric stator comprising an outer portion removably attached to the first and second housing portions, having a first end and a second end spaced from the first end, an inner portion defining a pumping chamber and spaced an annular end portion interconnecting the first ends of the outer and inner portions; a rotor disposed in the inner portion of the stator and extending through the pumping chamber for pumping fluid from the inlet to the outlet in response to rotation of the rotor; and an elongated member disposed in the housing portions and generally annularly between the inner and outer portions of the stator and longitudinally between the annular end portion of the stator and a portion of the second housing portion, the member being removable from the housing portions and separable from the stator.

  6. Shrouded inducer pump

    DOEpatents

    Meng, Sen Y.

    1989-01-01

    An improvement in a pump including a shrouded inducer, the improvement comprising first and second sealing means 32,36 which cooperate with a first vortex cell 38 and a series of secondary vortex cells 40 to remove any tangential velocity components from the recirculation flow.

  7. Solar pumped laser

    NASA Technical Reports Server (NTRS)

    Lee, J. H.; Hohl, F.; Weaver, W. R. (Inventor)

    1984-01-01

    A solar pumped laser is described in which the lasant is a gas that will photodissociate and lase when subjected to sunrays. Sunrays are collected and directed onto the gas lasant to cause it to lase. Applications to laser propulsion and laser power transmission are discussed.

  8. Explosively pumped laser light

    SciTech Connect

    Piltch, M.S.; Michelott, R.A.

    1991-09-24

    This patent describes a single shot laser pumped by detonation of an explosive in a shell casing. The shock wave from detonation of the explosive causes a rare gas to luminesce. The high intensity light from the gas enters a lasing medium, which thereafter outputs a pulse of laser light to disable optical sensors and personnel.

  9. The Osmotic Pump

    ERIC Educational Resources Information Center

    Levenspiel, Octave; de Nevers, Noel

    1974-01-01

    Describes the principle involved in an osmotic pump used to extract fresh water from the oceans and in an osmotic power plant used to generate electricity. Although shown to be thermodynamically feasible, the osmotic principle is not likely to be used commerically for these purposes in the near future. (JR)

  10. Gastrostomy feeding tube - pump - child

    MedlinePlus

    ... supplies: Feeding pump (electronic or battery powered) Feeding set that matches the feeding pump (includes a feeding ... drip chamber, roller clamp, and long tube) Extension set, for a Bard Button or MIC-KEY (this ...

  11. Fuel pumping system and method

    DOEpatents

    Shafer, Scott F.; Wang, Lifeng ,

    2006-12-19

    A fuel pumping system that includes a pump drive is provided. A first pumping element is operatively connected to the pump drive and is operable to generate a first flow of pressurized fuel. A second pumping element is operatively connected to the pump drive and is operable to generate a second flow of pressurized fuel. A first solenoid is operatively connected to the first pumping element and is operable to vary at least one of a fuel pressure and a fuel flow rate of the first flow of pressurized fuel. A second solenoid is operatively connected to the second pumping element and is operable to vary at least one of a fuel pressure and a fuel flow rate of the second flow of pressurized fuel.

  12. Fuel Pumping System And Method

    DOEpatents

    Shafer, Scott F.; Wang, Lifeng

    2005-12-13

    A fuel pumping system that includes a pump drive is provided. A first pumping element is operatively connected to the pump drive and is operable to generate a first flow of pressurized fuel. A second pumping element is operatively connected to the pump drive and is operable to generate a second flow of pressurized fuel. A first solenoid is operatively connected to the first pumping element and is operable to vary at least one of a fuel pressure and a fuel flow rate of the first flow of pressurized fuel. A second solenoid is operatively connected to the second pumping element and is operable to vary at least one of a fuel pressure and a fuel flow rate of the second flow of pressurized fuel.

  13. Vacuum system pump down analysis

    SciTech Connect

    Rohrdanz, D.R.

    1990-08-01

    My assignment on the SP-100 Vacuum Vessel Vacuum System Team was to perform a transient pump down analysis for the vacuum vessel that will house the SP-100 reactor during testing. Pump down time was calculated for air and helium. For all cases the proposed vacuum system will be able to pump down the vessel within the required time. The use of a larger rotary piston pump (DUO250) improves the pump down time by 35 minutes and therefore should be considered. The 6-inch duct for the roughing line is optimal, however, because all cases are well below the 24 hour time frame, the 4-inch duct is sufficient. The use of the single turbomolecular pump during pump down is sufficient. A pump down with helium in the vessel and a helium inleakage delays the time to achieve the base pressure marginally and is acceptable.

  14. Installing and maintaining gear pumps

    SciTech Connect

    Whitmire, K.

    1996-03-01

    While not as common as centrifugal pumps in the CPI, gear pumps play important roles in handling many of today`s more difficult-to-pump fluids. Because they operate at lower speeds -- generally, 900 rpm or less -- their seals and bearings tend to last longer than those of centrifugal models. In addition, unlike centrifugal pumps, gear pumps` flows are independent of their systems` pressure curves, and they can handle a wider range of viscosities. Although high-flow, low-head applications remain the domain of centrifugal pumps, the use of gear pumps is increasing in the chemical process industries (CPI). While some application boundaries between gears and centrifugals are blurring, there are some crucial differences between the way the two are operated and maintained -- for example, where pressure relief is concerned. This article provides a general summary of gear pump characteristics and applications, highlighting critical aspects of installation, operation and maintenance.

  15. Blood Pump Bearing System

    NASA Technical Reports Server (NTRS)

    Aber, Gregory S. (Inventor)

    2000-01-01

    An apparatus is provided for a blood pump bearing system within a pump housing to support long-term highspeed rotation of a rotor with an impeller blade having a plurality of individual magnets disposed thereon to provide a small radial air gap between the magnets and a stator of less than 0.025 inches. The bearing system may be mounted within a flow straightener, diffuser, or other pump element to support the shaft of a pump rotor. The bearing system includes a zirconia shaft having a radiused end. The radiused end has a first radius selected to be about three times greater than the radius of the zirconia shaft. The radiused end of the zirconia shaft engages a flat sapphire endstone. Due to the relative hardness of these materials a flat is quickly produced during break-in on the zirconia radiused end of precisely the size necessary to support thrust loads whereupon wear substantially ceases. Due to the selection of the first radius, the change in shaft end-play during pump break-in is limited to a total desired end-play of less than about 0.010 inches. Radial loads are supported by an olive hole ring jewel that makes near line contact around the circumference of the Ir shaft to support big speed rotation with little friction. The width of olive hole ring jewel is small to allow heat to conduct through to thereby prevent heat build-up in the bearing. A void defined by the bearing elements may fill with blood that then coagulates within the void. The coagulated blood is then conformed to the shape of the bearing surfaces.

  16. Blood Pump Bearing System

    NASA Technical Reports Server (NTRS)

    Aber, Gregory S. (Inventor)

    1999-01-01

    Methods and apparatus are provided for a blood pump bearing system within a pump housing to support long-term high-speed rotation of a rotor with an impeller blade having a plurality of individual magnets disposed thereon to provide a small radial air gap between the magnets and a stator of less than 0.025 inches. The bearing system may be mounted within a flow straightener, diffuser, or other pump element to support the shaft of a pump rotor. The bearing system includes a zirconia shaft having a radiused end. The radiused end has a first radius selected to be about three times greater than the radius of the zirconia shaft. The radiused end of the zirconia shaft engages a flat sapphire endstone. Due to the relative hardness of these materials a flat is quickly produced during break-in on the zirconia radiused end of precisely the size necessary to support thrust loads whereupon wear substantially ceases. Due to the selection of the first radius, the change in shaft end-play during pump break-in is limited to a total desired end-play of less than about 0.010 inches. Radial loads are supported by an olive hole ring jewel that makes near line contact around the circumference of the shaft to support high speed rotation with little friction. The width of olive hole ring jewel is small to allow heat to conduct through to thereby prevent heat build-up in the bearing. A void defined by the bearing elements may fill with blood that then coagulates within the void. The coagulated blood is then conformed to the shape of the bearing surfaces.

  17. Shoring pumping station excavation

    SciTech Connect

    Glover, J.B.; Reardon, D.J. )

    1991-11-01

    The city of San Mateo, Calif., operates three 12- to 50-year old wastewater pumping stations on a 24-m (80-ft) wide lot located in a residential area near San Francisco Bay. Because the aging stations have difficulty pumping peak 2.19-m{sup 3}/s (50-mgd) wet-weather flows and have structural and maintenance problems, a new 2.62-m{sup 3}/s (60-mgd) station was proposed - the Dale Avenue Pumping Station - to replace the existing ones. To prevent potential damage to adjacent homes, the new station was originally conceived as a circular caisson type; however, a geotechnical investigation recommended against this type of structure because the stiff soils could make sinking the structure difficult. This prompted an investigation of possible shoring methods for the proposed structure. Several shoring systems were investigated, including steel sheeting, soldier beams and lagging, tieback systems, open excavation, and others; however, each had disadvantages that prevented its use. Because these conventional techniques were unacceptable, attention was turned to using deep soil mixing (DSM) to create a diaphragm wall around the area to be excavated before constructing the pumping station. Although this method has been used extensively in Japan since 1983, the Dale Avenue Pumping Station would be the technology's first US application. The technology's anticipated advantages were its impermeability, its fast and efficient installation that did not require tiebacks under existing homes, its adaptability to subsurface conditions ranging from soft ground to stiff clay to gravels, and its lack of pile-driving requirements that would cause high vibration levels during installation.

  18. Absorption heat pumps

    NASA Astrophysics Data System (ADS)

    Huhtinen, M.; Heikkilae, M.; Andersson, R.

    1987-03-01

    The aim of the study was to analyze the technical and economic feasibility of absorption heat pumps in Finland. The work was done as a case study: the technical and economic analyses have been carried out for six different cases, where in each the suitable size and type of the heat pump plant and the auxiliary components and connections were specified. The study also detailed the costs concerning the procurement, installation and test runs of the machinery, as well as the savings in energy costs incurred by the introduction of the plant. Conclusions were drawn of the economic viability of the applications studied. The following cases were analyzed: heat recovery from flue gases and productin of district heat in plants using peat, natural gas, and municipal wastes as a fuel. Heat recovery in the pulp and paper industry for the upgrading of pressure of secondary steam and for the heating of white liquor and combustion and drying the air. Heat recovery in a peat-fulled heat and power plant from flue gases that have been used for the drying of peat. According to the study, the absorption heat pump suits best to the production of district heat, when the heat source is the primary energy is steam produced by the boiler. Included in the flue as condensing is the purification of flue gases. Accordingly, benefit is gained on two levels in thick applications. In heat and power plants the use of absorption heat pumps is less economical, due to the fact that the steam used by the pump reduces the production of electricity, which is rated clearly higher than heat.

  19. Noncavitating Pump For Liquid Helium

    NASA Technical Reports Server (NTRS)

    Hasenbein, Robert; Izenson, Michael; Swift, Walter; Sixsmith, Herbert

    1996-01-01

    Immersion pump features high efficiency in cryogenic service. Simple and reliable centrifugal pump transfers liquid helium with mass-transfer efficiency of 99 percent. Liquid helium drawn into pump by helical inducer, which pressurizes helium slightly to prevent cavitation when liquid enters impeller. Impeller then pressurizes liquid. Purpose of pump to transfer liquid helium from supply to receiver vessel, or to provide liquid helium flow for testing and experimentation.

  20. Gas-heat-pump development

    NASA Astrophysics Data System (ADS)

    Creswick, F. A.

    Incentives for the development of gas heat pumps are discussed. Technical progress made on several promising technologies was reviewed. The status of development of gas-engine-driven heat pumps, the absorption cycle for the near- and long-term gas heat pump systems, the Stirling engine, the small Rankine-cycle engines, and gas-turbine-driven heat pump systems were briefly reviewed. Progress in the US, Japan, and Europe is noted.

  1. 5. Station Unwatering Pumps and Sump Pump for Units 1 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Station Unwatering Pumps and Sump Pump for Units 1 and 2, view to the west. The unwatering pumps are the two larger items toward the right side of the photograph (one in foreground and one in background. The smaller item toward the left of the photograph is the sump pump. These pumps are used for draining water from the draft chest for maintenance. - Washington Water Power Clark Fork River Cabinet Gorge Hydroelectric Development, Powerhouse, North Bank of Clark Fork River at Cabinet Gorge, Cabinet, Bonner County, ID

  2. Guide to Geothermal Heat Pumps

    SciTech Connect

    2011-02-01

    Geothermal heat pumps, also known as ground source heat pumps, geoexchange, water-source, earth-coupled, and earth energy heat pumps, take advantage of this resource and represent one of the most efficient and durable options on the market to heat and cool your home.

  3. Advanced high-temperature electromagnetic pump

    NASA Technical Reports Server (NTRS)

    Gahan, J. W.; Powell, A. H.

    1972-01-01

    Three phase helical, electromagnetic induction pump for use as boiler feed pump in potassium Rankine-cycle power system is described. Techniques for fabricating components of pump are discussed. Specifications of pump are analyzed.

  4. Improving pumping system efficiency at coal plants

    SciTech Connect

    Livoti, W.C.; McCandless, S.; Poltorak, R.

    2009-03-15

    The industry must employ ultramodern technologies when building or upgrading power plant pumping systems thereby using fuels more efficiently. The article discusses the uses and efficiencies of positive displacement pumps, centrifugal pumps and multiple screw pumps. 1 ref., 4 figs.

  5. SHINE Vacuum Pump Test Verification

    SciTech Connect

    Morgan, Gregg A; Peters, Brent

    2013-09-30

    Normetex pumps used world-wide for tritium service are no longer available. DOE and other researchers worldwide have spent significant funds characterizing this pump. Identification of alternate pumps is required for performance and compatibility with tritium gas. Many of the pumps that could be used to meet the functional performance requirements (e.g. pressure and flow conditions) of the Normetex pump have features that include the use of polymers or oils and greases that are not directly compatible with tritium service. This study assembles a test system to determine the flow characteristics for candidate alternate pumps. These tests are critical to the movement of tritium through the SHINE Tritium Purification System (TPS). The purpose of the pump testing is two-fold: (1) obtain baseline vacuum pump characteristics for an alternate (i.e. ''Normetex replacement'') pump intended for use in tritium service; and (2) verify that low pressure hydrogen gas can be transported over distances up to 300 feet by the candidate pumps. Flow rates and nominal system pressures have been identified for the SHINE Mo-99 production process Tritium Purification System (TPS). To minimize the line sizes for the transfer of low pressure tritium from the Neutron Driver Accelerator System (NDAS) to the primary processing systems in the TPS, a ''booster'' pump has been located near the accelerator in the design. A series of pump tests were performed at various configurations using hydrogen gas (no tritium) to ensure that this concept is practical and maintains adequate flow rates and required pressures. This report summarizes the results of the tests that have been performed using various pump configurations. The current design of the Tritium Purification System requires the ''booster'' pump to discharge to or to be backed by another vacuum pump. Since Normetex pumps are no longer manufactured, a commercially available Edwards scroll pump will be used to back the booster pump. In this

  6. Save by absorption heat pumping

    SciTech Connect

    Davidson, W.F.; Campagne, W.V.L.

    1987-12-01

    The author compares absorption heat pumping (AHP) to mechanical vapor compressor (MVC) heat pumping. The moving part of the AHP is a pump easy to maintain and inexpensive to spare. The mechanical component of the MVC is a vapor compressor which requires more maintenance and is cost-prohibitive to spare. Also, in the MVC system, a purified product stream is heat pumped in an open compressor, thus risking product contamination. In the AHP system, the cold and hot utilities are heat pumped. Therefore, product integrity with an AHP system is well protected as in a conventional fractionation column.

  7. Bearing for liquid metal pump

    DOEpatents

    Dickinson, Robert J.; Wasko, John; Pennell, William E.

    1984-01-01

    A liquid metal pump bearing support comprises a series of tangentially oriented spokes that connect the bearing cylinder to the pump internals structure. The spokes may be arranged in a plurality of planes extending from the bearing cylinder to the pump internals with the spokes in one plane being arranged alternately with those in the next plane. The bearing support structure provides the pump with sufficient lateral support for the bearing structure together with the capability of accommodating differential thermal expansion without adversely affecting pump performance.

  8. 46 CFR 182.520 - Bilge pumps.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... (incorporated by reference; see 46 CFR 175.600); (2) The pump is used to dewater not more than one watertight... passengers Length of vessel Bilge pumps required Min. capacity required per pump ltrs/min (gal/min) Any... capacity, a power bilge pump may also serve as a fire pump. (d) Where two fixed power bilge pumps...

  9. 21 CFR 880.5725 - Infusion pump.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Infusion pump. 880.5725 Section 880.5725 Food and... Infusion pump. (a) Identification. An infusion pump is a device used in a health care facility to pump fluids into a patient in a controlled manner. The device may use a piston pump, a roller pump, or...

  10. Vacuum pump aids ejectors

    SciTech Connect

    Nelson, R.E.

    1982-12-01

    The steam ejector/vacuum pump hybrid system has been operating satisfactorily since the summer of 1981. This system has essentially been as troublefree as the all-ejector system and, of course, has provided a substantial cost savings. Construction is currently under way to convert the vacuum system of another crude still which is equipped with steam ejectors and barometric condensers to the hybrid system of steam ejectors, surface condensers, and vacuum pumps. This current project is even more financially attractive because it allows a dirty water cooling tower which serves the barometric condensers to be shut down. Providing a vacuum for crude distillation vacuum towers with this hybrid system is by no means the only application of this technique. Any vacuum system consisting of all steam ejectors would be a candidate for this hybrid system and the resulting savings in energy.

  11. Multiple source heat pump

    DOEpatents

    Ecker, Amir L.

    1983-01-01

    A heat pump apparatus for conditioning a fluid characterized by a fluid handler and path for circulating a fluid in heat exchange relationship with a refrigerant fluid, at least three refrigerant heat exchangers, one for effecting heat exchange with the fluid, a second for effecting heat exchange with a heat exchange fluid, and a third for effecting heat exchange with ambient air; a compressor for compressing the refrigerant; at least one throttling valve connected at the inlet side of a heat exchanger in which liquid refrigerant is vaporized; a refrigerant circuit; refrigerant; a source of heat exchange fluid; heat exchange fluid circuit and pump for circulating the heat exchange fluid in heat exchange relationship with the refrigerant; and valves or switches for selecting the heat exchangers and directional flow of refrigerant therethrough for selecting a particular mode of operation. Also disclosed are a variety of embodiments, modes of operation, and schematics therefor.

  12. Water displacement mercury pump

    DOEpatents

    Nielsen, M.G.

    1984-04-20

    A water displacement mercury pump has a fluid inlet conduit and diffuser, a valve, a pressure cannister, and a fluid outlet conduit. The valve has a valve head which seats in an opening in the cannister. The entire assembly is readily insertable into a process vessel which produces mercury as a product. As the mercury settles, it flows into the opening in the cannister displacing lighter material. When the valve is in a closed position, the pressure cannister is sealed except for the fluid inlet conduit and the fluid outlet conduit. Introduction of a lighter fluid into the cannister will act to displace a heavier fluid from the cannister via the fluid outlet conduit. The entire pump assembly penetrates only a top wall of the process vessel, and not the sides or the bottom wall of the process vessel. This insures a leak-proof environment and is especially suitable for processing of hazardous materials.

  13. Fusion reactor pumped laser

    DOEpatents

    Jassby, D.L.

    1987-09-04

    A nuclear pumped laser capable of producing long pulses of very high power laser radiation is provided. A toroidal fusion reactor provides energetic neutrons which are slowed down by a moderator. The moderated neutrons are converted to energetic particles capable of pumping a lasing medium. The lasing medium is housed in an annular cell surrounding the reactor. The cell includes an annular reflecting mirror at the bottom and an annular output window at the top. A neutron reflector is disposed around the cell to reflect escaping neutrons back into the cell. The laser radiation from the annular window is focused onto a beam compactor which generates a single coherent output laser beam. 10 figs.

  14. Micromachined peristaltic pump

    NASA Technical Reports Server (NTRS)

    Hartley, Frank T. (Inventor)

    1998-01-01

    A micromachined pump including a channel formed in a semiconductor substrate by conventional processes such as chemical etching. A number of insulating barriers are established in the substrate parallel to one another and transverse to the channel. The barriers separate a series of electrically conductive strips. An overlying flexible conductive membrane is applied over the channel and conductive strips with an insulating layer separating the conductive strips from the conductive membrane. Application of a sequential voltage to the series of strips pulls the membrane into the channel portion of each successive strip to achieve a pumping action. A particularly desirable arrangement employs a micromachined push-pull dual channel cavity employing two substrates with a single membrane sandwiched between them.

  15. Water displacement mercury pump

    DOEpatents

    Nielsen, Marshall G.

    1985-01-01

    A water displacement mercury pump has a fluid inlet conduit and diffuser, a valve, a pressure cannister, and a fluid outlet conduit. The valve has a valve head which seats in an opening in the cannister. The entire assembly is readily insertable into a process vessel which produces mercury as a product. As the mercury settles, it flows into the opening in the cannister displacing lighter material. When the valve is in a closed position, the pressure cannister is sealed except for the fluid inlet conduit and the fluid outlet conduit. Introduction of a lighter fluid into the cannister will act to displace a heavier fluid from the cannister via the fluid outlet conduit. The entire pump assembly penetrates only a top wall of the process vessel, and not the sides or the bottom wall of the process vessel. This insures a leak-proof environment and is especially suitable for processing of hazardous materials.

  16. Solar-powered pump

    NASA Technical Reports Server (NTRS)

    Kirsten, C. C. (Inventor)

    1976-01-01

    A solar powered pump particularly suited for intermittently delivering a stream of water is reported. The pump is characterized by a housing adapted to be seated in a source of water having a water discharge port disposed above the water line of the source, a sump including a valved inlet port through which water is introduced to the sump, disposed beneath the water line, a displacer supported for vertical reciprocation in said housing, an air passageway extended between the vertically spaced faces of the displacer, and a tipple disposed adjacent to the water discharge port adapted to be filled in response to a discharge of water from the housing. Air above a displacer is expanded in response to solar energy impinging on the housing and transferred into pressurizing relation with the sump for forcing water from the sump.

  17. Molecular water pumps.

    PubMed

    Zeuthen, T

    2000-01-01

    There is good evidence that cotransporters of the symport type behave as molecular water pumps, in which a water flux is coupled to the substrate fluxes. The free energy stored in the substrate gradients is utilized, by a mechanism within the protein, for the transport of water. Accordingly, the water flux is secondary active and can proceed uphill against the water chemical potential difference. The effect has been recognized in all symports studied so far (Table 1). It has been studied in details for the K+/Cl- cotransporter in the choroid plexus epithelium, the H+/lactate cotransporter in the retinal pigment epithelium, the intestinal Na+/glucose cotransporter (SGLT1) and the renal Na+/dicarboxylate cotransporter both expressed in Xenopus oocytes. The generality of the phenomenon among symports with widely different primary structures suggests that the property of molecular water pumps derives from a pattern of conformational changes common for this type of membrane proteins. Most of the data on molecular water pumps are derived from fluxes initiated by rapid changes in the composition of the external solution. There was no experimental evidence for unstirred layers in such experiments, in accordance with theoretical evaluations. Even the experimental introduction of unstirred layers did not lead to any measurable water fluxes. The majority of the experimental data supports a molecular model where water is cotransported: A well defined number of water molecules act as a substrate on equal footing with the non-aqueous substrates. The ratio of any two of the fluxes is constant, given by the properties of the protein, and is independent of the driving forces or other external parameters. The detailed mechanism behind the molecular water pumps is as yet unknown. It is, however, possible to combine well established phenomena for enzymes into a working model. For example, uptake and release of water is associated with conformational changes during enzymatic action; a

  18. Magnetic heat pumps

    SciTech Connect

    Hull, J.R.; Uherka, K.L.

    1988-01-01

    Magnetic heat pumps and refrigerators are potential replacements for vapor-compression devices that use chlorofluorocarbon refrigerants. Several room-temperature designs, using low-temperature superconducting magnets, have reached the experimental device stage. High-temperature superconducting materials may significantly increase the viability of the technology, both by enhancing existing design concepts and by enabling new major design types such as field switching of the superconducting magnets.

  19. Nonazeotropic Heat Pump

    NASA Technical Reports Server (NTRS)

    Ealker, David H.; Deming, Glenn

    1991-01-01

    Heat pump collects heat from water circulating in heat-rejection loop, raises temperature of collected heat, and transfers collected heat to water in separate pipe. Includes sealed motor/compressor with cooling coils, evaporator, and condenser, all mounted in outer housing. Gradients of temperature in evaporator and condenser increase heat-transfer efficiency of vapor-compression cycle. Intended to recover relatively-low-temperature waste heat and use it to make hot water.

  20. Air circuit with heating pump

    NASA Astrophysics Data System (ADS)

    Holik, H.; Bauder, H. J.; Brugger, H.; Reinhart, A.; Spott, K. H.

    1980-12-01

    A pump which draws energy from exhaust air from a paper drying process to heat up the blow air was studied. The use of a heat pump instead of a steam heated exchanger can reduce primary energy consumption for blown air heating by more than half and the costs for air heating up to half. The amortization times for the heat pump extend from 5 to 10 years. Since in the pulp and paper industry, amortization times of less than two years are required for such relatively small investments, the heat pump so far is only used to heat blown air under highly favorable conditions. The rising energy prices shorten the heat pump amortization time. The 100% fuel price increase brought the heat pump with diesel engine drive already to very favorable amortization times of 2 to 5 years. A 20% increase will make the heat pump economically advantageous with an amortization time between 1 and 2 years.

  1. Nuclear-pumped flashlamp sources

    NASA Astrophysics Data System (ADS)

    Miley, George H.; Prelas, Mark A.

    2000-08-01

    Due to pump source restrictions, Nuclear-Pumped Lasers (NPLs) typically have relatively long (micro- to milli-second) pulse lengths with only modest peak powers but with very high total energy. These pump power restraints seriously limit the choice of laser media. One way to avoid this problem is to employ a Nuclear Driven Flashlamp (NDF) for the primary pumped element in the system. The fluorescence from this NDF can then be used for pumping a laser or for other high intensity light applications. The first experimental example of this approach was a 3He-XeBr2 NDF employed by Williams and Miley (1993) to pump a small iodine laser. The present paper discusses issues involved in scaling such an NDF up to high power levels. Possible optimum configurations include use of microsphere or fiber pump elements dispersed in the NPF media. Analysis of such possibilities is presented along with consideration of special reflecting surface designs.

  2. Stirling Engine Heat Pump

    NASA Astrophysics Data System (ADS)

    Kagawa, Noboru

    Recent advances in the feasibility studies related to the Stirling engines and Stirling engine heat pumps which have been considered attractive due to their promising role in helping to solve the global environmental and energy problems,are reviewed. This article begins to describe the brief history of the Stirling engines and theoretical thermodynamic analysis of the Stirling cycle in order to understand several advantages on the Stirling engine. Furthermore,they could throw light on our question why the dream engines had not been promoted to practical applications during two hundred years. The present review shows that the Stirling engines with several unique advantages including 30 to 40% thermal efficiency and preferable exhaust characteristics,had been designed and constructed by recent tackling for the development of the advanced automobile and other applications using them. Based on the current state of art,it is being provided to push the Stirling engines combined with heat pumps based on the reversed Rankine cycle to the market. At present,however, many problems, especially for the durability, cost, and delicate engine parts must be enforced to solve. In addition,there are some possibilities which can increase the attractiveness of the Stirling engines and heat pumps. The review closes with suggestions for further research.

  3. Pumping potential wells

    NASA Technical Reports Server (NTRS)

    Hershkowitz, N.; Forest, C.; Wang, E. Y.; Intrator, T.

    1987-01-01

    Nonmonotonic plasma potential structures are a common feature of many double layers and sheaths. Steady state plasma potential wells separating regions having different plasma potentials are often found in laboratory experiments. In order to exist, all such structures must find a solution to a common problem. Ions created by charge exchange or ionization in the region of the potential well are electrostatically confined and tend to accumulate and fill up the potential well. The increase in positive charge should eliminate the well. Nevertheless, steady state structures are found in which the wells do not fill up. This means that it is important to take into account processes which pump ions from the well. As examples of ion pumping of plasma wells, potential dips in front of a positively biased electron collecting anode in a relatively cold, low density, multidipole plasma are considered. Pumping is provided by ion leaks from the edges of the potential dip or by oscillating the applied potential. In the former case the two-dimensional character of the problem is shown to be important.

  4. Pumping potential wells

    NASA Technical Reports Server (NTRS)

    Hershkowitz, N.; Forest, C.; Wang, E. Y.; Intrator, T.

    1987-01-01

    Nonmonotonic plasma potential structures are a common feature of many double layers and sheaths. Steady state plasma potential wells separating regions having different plasma potentials are often found in laboratory experiments. In order to exist, such structures all must find a solution to a common problem. Ions created by charge exchange or ionization in the region of the potential well are electrostatically confined and tend to accumulate and fill up the potential well. The increase in positive charge should eliminate the well. Nevertheless, steady state structures are found in which the wells do not fill up. This means that it is important to take into account processes which 'pump' ions from the well. As examples of ion pumping of plasma wells, potential dips in front of a positively biased electro collecting anode in a relatively cold, low density multidipole plasma is considered. Pumping is provided by ion leaks from the edges of the potential dip or by oscillating the applied potential. In the former case the two dimensional character of the problem is shown to be important.

  5. MOLECULAR VACUUM PUMP

    DOEpatents

    Eckberg, E.E.

    1960-09-27

    A multiple molecular vacuum pump capable of producing a vacuum of the order of 10/sup -9/ mm Hg is described. The pump comprises a casing of an aggregate of paired and matched cylindrical plates, a recessed portion on one face of each plate concentrically positioned formed by a radially extending wall and matching the similarly recessed portion of its twin plate of that pair of plates and for all paired and matched plates; a plurality of grooves formed in the radially extending walls of each and all recesses progressing in a spiral manner from their respective starting points out at the periphery of the recess inwardly to the central area; a plurality of rotors rotatably mounted to closely occupy the spaces as presented by the paired and matched recesses between all paired plates; a hollowed drive-shaft perforated at points adjacent to the termini of all spiral grooves; inlet ports at the starting points of all grooves and through all plates at common points to each respectively; and a common outlet passage presented by the hollow portion of the perforated hollowed drive-shaft of the molecular pump. (AEC)

  6. A Magnetically Coupled Cryogenic Pump

    NASA Technical Reports Server (NTRS)

    Hatfield, Walter; Jumper, Kevin

    2011-01-01

    Historically, cryogenic pumps used for propellant loading at Kennedy Space Center (KSC) and other NASA Centers have a bellows mechanical seal and oil bath ball bearings, both of which can be problematic and require high maintenance. Because of the extremely low temperatures, the mechanical seals are made of special materials and design, have wearing surfaces, are subject to improper installation, and commonly are a potential leak path. The ball bearings are non-precision bearings [ABEC-1 (Annular Bearing Engineering Council)] and are lubricated using LOX compatible oil. This oil is compatible with the propellant to prevent explosions, but does not have good lubricating properties. Due to the poor lubricity, it has been a goal of the KSC cryogenics community for the last 15 years to develop a magnetically coupled pump, which would eliminate these two potential issues. A number of projects have been attempted, but none of the pumps was a success. An off-the-shelf magnetically coupled pump (typically used with corrosive fluids) was procured that has been used for hypergolic service at KSC. The KSC Cryogenics Test Lab (CTL) operated the pump in cryogenic LN2 as received to determine a baseline for modifications required. The pump bushing, bearings, and thrust rings failed, and the pump would not flow liquid (this is a typical failure mode that was experienced in the previous attempts). Using the knowledge gained over the years designing and building cryogenic pumps, the CTL determined alternative materials that would be suitable for use under the pump design conditions. The CTL procured alternative materials for the bearings (bronze, aluminum bronze, and glass filled PTFE) and machined new bearing bushings, sleeves, and thrust rings. The designed clearances among the bushings, sleeves, thrust rings, case, and case cover were altered once again using experience gained from previous cryogenic pump rebuilds and designs. The alternative material parts were assembled into

  7. Flagging Drugs That Inhibit the Bile Salt Export Pump.

    PubMed

    Montanari, Floriane; Pinto, Marta; Khunweeraphong, Narakorn; Wlcek, Katrin; Sohail, M Imran; Noeske, Tobias; Boyer, Scott; Chiba, Peter; Stieger, Bruno; Kuchler, Karl; Ecker, Gerhard F

    2016-01-01

    The bile salt export pump (BSEP) is an ABC-transporter expressed at the canalicular membrane of hepatocytes. Its physiological role is to expel bile salts into the canaliculi from where they drain into the bile duct. Inhibition of this transporter may lead to intrahepatic cholestasis. Predictive computational models of BSEP inhibition may allow for fast identification of potentially harmful compounds in large databases. This article presents a predictive in silico model based on physicochemical descriptors that is able to flag compounds as potential BSEP inhibitors. This model was built using a training set of 670 compounds with available BSEP inhibition potencies. It successfully predicted BSEP inhibition for two independent test sets and was in a further step used for a virtual screening experiment. After in vitro testing of selected candidates, a marketed drug, bromocriptin, was identified for the first time as BSEP inhibitor. This demonstrates the usefulness of the model to identify new BSEP inhibitors and therefore potential cholestasis perpetrators. PMID:26642869

  8. Rotating-Pump Design Code

    NASA Technical Reports Server (NTRS)

    Walker, James F.; Chen, Shu-Cheng; Scheer, Dean D.

    2006-01-01

    Pump Design (PUMPDES) is a computer program for designing a rotating pump for liquid hydrogen, liquid oxygen, liquid nitrogen, water, methane, or ethane. Using realistic properties of these fluids provided by another program called GASPAK, this code performs a station-by-station, mean-line analysis along the pump flow path, obtaining thermodynamic properties of the pumped fluid at each station and evaluating hydraulic losses along the flow path. The variables at each station are obtained under constraints that are consistent with the underlying physical principles. The code evaluates the performance of each stage and the overall pump. In addition, by judiciously choosing the givens and the unknowns, the code can perform a geometric inverse design function: that is, it can compute a pump geometry that yields a closest approximation of given design point. The code contains two major parts: one for an axial-rotor/inducer and one for a multistage centrifugal pump. The inducer and the centrifugal pump are functionally integrated. The code can be used in designing and/or evaluating the inducer/centrifugal-pump combination or the centrifugal pump alone. The code is written in standard Fortran 77.

  9. Supercritical waste oxidation pump investigation

    SciTech Connect

    Thurston, G.; Garcia, K.

    1993-02-01

    This report investigates the pumping techniques and pumping equipment that would be appropriate for a 5,000 gallon per day supercritical water oxidation waste disposal facility. The pumps must boost water, waste, and additives from atmospheric pressure to approximately 27.6 MPa (4,000 psia). The required flow ranges from 10 gpm to less than 0.1 gpm. For the higher flows, many commercial piston pumps are available. These pumps have packing and check-valves that will require periodic maintenance; probably at 2 to 6 month intervals. Several commercial diaphragm pumps were also discovered that could pump the higher flow rates. Diaphragm pumps have the advantage of not requiring dynamic seals. For the lower flows associated with the waste and additive materials, commercial diaphragm pumps. are available. Difficult to pump materials that are sticky, radioactive, or contain solids, could be injected with an accumulator using an inert gas as the driving mechanism. The information presented in this report serves as a spring board for trade studies and the development of equipment specifications.

  10. At 1050 Gallery, Block 12, two centrifugal pumps, Buffalo Pumps, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    At 1050 Gallery, Block 12, two centrifugal pumps, Buffalo Pumps, Buffalo, NY, driven by Allis Chalmers motors (size 3 HSO, head 230, 120 cpm, 1750, rpm, Impulse dia. 15) installed in the 1960s and used for water-cooling system for 230-kv cable; the cables have been removed and the pumps are not currently used. - Columbia Basin Project, Grand Coulee Dam & Franklin D. Roosevelt Lake, Across Columbia River, Southeast of Town of Grand Coulee, Grand Coulee, Grant County, WA

  11. Proton pump inhibitory therapy: then and now.

    PubMed Central

    Schepp, W.

    1996-01-01

    Proton pump inhibitors (PPIs) have been established as the new "gold standard" for traditional acid-inhibitory treatment of the so called "peptic" diseases. Due to the high antisecretory and ulcer-healing potency of omeprazole, no major improvements of the efficacy in ulcer healing and pain relief can be expected. Pantoprazole, as a further development in PPIs, is characterized by improved pharmacokinetic behavior as well as by higher tissue selectivity and binding specificity and by a very low potential to interact with the cytochrome P450 enzyme system. These characteristics may provide the basis for a low potential for side effects and for a more favorable interaction profile, although the clinical relevance of these potential advantages remains to be proven. Reflux esophagitis will also remain a domain for the traditional use of PPIs in the future. However, in the treatment of gastroduodenal ulcers, the acid inhibitory potential of PPIs will be used mainly to facilitate the eradication of H. pylori. PMID:9112749

  12. First evidence for the presence of efflux pump in the earthworm Eisenia andrei.

    PubMed

    Hackenberger, Branimir K; Velki, Mirna; Stepić, Sandra; Hackenberger, Davorka K

    2012-01-01

    Efflux pumps are transport proteins involved in the extrusion of toxic substrates from cells to the external environment. Activities of efflux pumps have been found in many organisms, however such activity has not been evidenced in earthworms. Adult Eisenia andrei earthworms were exposed to efflux modulators - verapamil (a known inhibitor of efflux pump protein) and dexamethasone (a known inducer of efflux activity) - and the amount of absorbed fluorescent dye rhodamine B was measured. The results showed that verapamil inhibited efflux activity and decreased removal of rhodamine B, whereas dexamethasone induced efflux activity and increased removal of rhodamine B. This is the first evidence of the presence of efflux pump in earthworm Eisenia andrei. Since earthworms are often used as test organisms due to their sensitive reactions towards environmental influences, the discovery of efflux pump activity can contribute to the better understanding of toxicity of certain pollutants. PMID:22033226

  13. Chemical heat pump

    DOEpatents

    Greiner, Leonard

    1980-01-01

    A chemical heat pump system is disclosed for use in heating and cooling structures such as residences or commercial buildings. The system is particularly adapted to utilizing solar energy, but also increases the efficiency of other forms of thermal energy when solar energy is not available. When solar energy is not available for relatively short periods of time, the heat storage capacity of the chemical heat pump is utilized to heat the structure as during nighttime hours. The design also permits home heating from solar energy when the sun is shining. The entire system may be conveniently rooftop located. In order to facilitate installation on existing structures, the absorber and vaporizer portions of the system may each be designed as flat, thin wall, thin pan vessels which materially increase the surface area available for heat transfer. In addition, this thin, flat configuration of the absorber and its thin walled (and therefore relatively flexible) construction permits substantial expansion and contraction of the absorber material during vaporization and absorption without generating voids which would interfere with heat transfer. The heat pump part of the system heats or cools a house or other structure through a combination of evaporation and absorption or, conversely, condensation and desorption, in a pair of containers. A set of automatic controls change the system for operation during winter and summer months and for daytime and nighttime operation to satisfactorily heat and cool a house during an entire year. The absorber chamber is subjected to solar heating during regeneration cycles and is covered by one or more layers of glass or other transparent material. Daytime home air used for heating the home is passed at appropriate flow rates between the absorber container and the first transparent cover layer in heat transfer relationship in a manner that greatly reduce eddies and resultant heat loss from the absorbant surface to ambient atmosphere.

  14. Absorption heat pump system

    DOEpatents

    Grossman, Gershon; Perez-Blanco, Horacio

    1984-01-01

    An improvement in an absorption heat pump cycle is obtained by adding adiabatic absorption and desorption steps to the absorber and desorber of the system. The adiabatic processes make it possible to obtain the highest temperature in the absorber before any heat is removed from it and the lowest temperature in the desorber before heat is added to it, allowing for efficient utilization of the thermodynamic availability of the heat supply stream. The improved system can operate with a larger difference between high and low working fluid concentrations, less circulation losses, and more efficient heat exchange than a conventional system.

  15. Electromagnetic pump stator coil

    DOEpatents

    Fanning, Alan W.; Dahl, Leslie R.

    1996-01-01

    An electrical stator coil for an electromagnetic pump includes a continuous conductor strip having first and second terminals at opposite ends thereof and an intermediate section disposed therebetween. The strip is configured in first and second coil halves, with the first coil half including a plurality of windings extending from the first terminal to the intermediate section, and the second coil half including a plurality of windings extending from the second terminal to the intermediate section. The first and second coil halves are disposed coaxially, and the first and second terminals are disposed radially inwardly therefrom with the intermediate section being disposed radially outwardly therefrom.

  16. Electromagnetic pump stator coil

    DOEpatents

    Fanning, A.W.; Dahl, L.R.

    1996-06-25

    An electrical stator coil for an electromagnetic pump includes a continuous conductor strip having first and second terminals at opposite ends thereof and an intermediate section disposed therebetween. The strip is configured in first and second coil halves, with the first coil half including a plurality of windings extending from the first terminal to the intermediate section, and the second coil half including a plurality of windings extending from the second terminal to the intermediate section. The first and second coil halves are disposed coaxially, and the first and second terminals are disposed radially inwardly therefrom with the intermediate section being disposed radially outwardly therefrom. 9 figs.

  17. Stirling and Vuilleumier heat pumps

    SciTech Connect

    Wurm, J.

    1990-01-01

    The book discuses the design, application, and performance evaluation of integrated engine-refrigerator heat pumps and provides an overview of heat pump theory, including a unique comparative analysis of six integrated Stirling and Vuilleumier heat pumps and their advantages in applications. It also evaluates the effect of key components on performance; lists and documents computer programs for comparative analysis; and summarizes current hardware development programs.

  18. Autonomous pump against concentration gradient

    NASA Astrophysics Data System (ADS)

    Xu, Zhi-Cheng; Zheng, Dong-Qin; Ai, Bao-Quan; Zhong, Wei-Rong

    2016-03-01

    Using non-equilibrium molecular dynamics and Monte Carlo methods, we have studied the molecular transport in asymmetric nanochannels. The efficiency of the molecular pump depends on the angle and apertures of the asymmetric channel, the environmental temperature and average concentration of the particles. The pumping effect can be explained as the competition between the molecular force field and the thermal disturbance. Our results provide a green approach for pumping fluid particles against the concentration gradient through asymmetric nanoscale thin films without any external forces. It indicates that pumping vacuum can be a spontaneous process.

  19. Fan and pump noise control

    NASA Technical Reports Server (NTRS)

    Misoda, J.; Magliozzi, B.

    1973-01-01

    The development is described of improved, low noise level fan and pump concepts for the space shuttle. In addition, a set of noise design criteria for small fans and pumps was derived. The concepts and criteria were created by obtaining Apollo hardware test data to correlate and modify existing noise estimating procedures. A set of space shuttle selection criteria was used to determine preliminary fan and pump concepts. These concepts were tested and modified to obtain noise sources and characteristics which yield the design criteria and quiet, efficient space shuttle fan and pump concepts.

  20. Bioinspired artificial single ion pump.

    PubMed

    Zhang, Huacheng; Hou, Xu; Zeng, Lu; Yang, Fu; Li, Lin; Yan, Dadong; Tian, Ye; Jiang, Lei

    2013-10-30

    Bioinspired artificial functional nanochannels for intelligent molecular and ionic transport control at the nanoscale have wide potential applications in nanofluidics, energy conversion, and biosensors. Although various smart passive ion transport properties of ion channels have been artificially realized, it is still hugely challenging to achieve high level intelligent ion transport features in biological ion pumps. Here we show a unique bioinspired single ion pump based on a cooperative pH response double-gate nanochannel, whose gates could be opened and closed alternately/simultaneously under symmetric/asymmetric pH environments. With the stimulation of the double-gate nanochannel by continuous switching of the symmetric/asymmetric pH stimuli, the bioinspired system systematically realized three key ionic transport features of biological ion pumps, including an alternating gates ion pumping process under symmetric pH stimuli, transformation of the ion pump into an ion channel under asymmetric pH stimuli, and a fail-safe ion pumping feature under both symmetric and asymmetric pH stimuli. The ion pumping processes could well be reproduced under a concentration gradient. With the advantages of the extraordinary ionic transport functions of biological ion pumps, the bioinspired ion pump should find widespread applicability in active transportation-controlling smart nanofluidic devices, efficient energy conversions, and seawater desalinization, and open the way to design and develop novel bioinspired intelligent artificial nanochannel materials. PMID:23773031

  1. Autonomous pump against concentration gradient

    PubMed Central

    Xu, Zhi-cheng; Zheng, Dong-qin; Ai, Bao-quan; Zhong, Wei-rong

    2016-01-01

    Using non-equilibrium molecular dynamics and Monte Carlo methods, we have studied the molecular transport in asymmetric nanochannels. The efficiency of the molecular pump depends on the angle and apertures of the asymmetric channel, the environmental temperature and average concentration of the particles. The pumping effect can be explained as the competition between the molecular force field and the thermal disturbance. Our results provide a green approach for pumping fluid particles against the concentration gradient through asymmetric nanoscale thin films without any external forces. It indicates that pumping vacuum can be a spontaneous process. PMID:26996204

  2. Long life coolant pump technology

    NASA Technical Reports Server (NTRS)

    1976-01-01

    Design concepts were investigated to improve space system coolant pump technology to be suitable for mission durations of two years and greater. These design concepts included an improved bearing system for the pump rotating elements, consisting of pressurized conical bearings. This design was satisfactorily endurance tested as was a new prototype pump built using various other improved design concepts. Based upon an overall assessment of the results of the program it is concluded that reliable coolant pumps can be designed for three year space missions.

  3. Resonant Tunneling Spin Pump

    NASA Technical Reports Server (NTRS)

    Ting, David Z.

    2007-01-01

    The resonant tunneling spin pump is a proposed semiconductor device that would generate spin-polarized electron currents. The resonant tunneling spin pump would be a purely electrical device in the sense that it would not contain any magnetic material and would not rely on an applied magnetic field. Also, unlike prior sources of spin-polarized electron currents, the proposed device would not depend on a source of circularly polarized light. The proposed semiconductor electron-spin filters would exploit the Rashba effect, which can induce energy splitting in what would otherwise be degenerate quantum states, caused by a spin-orbit interaction in conjunction with a structural-inversion asymmetry in the presence of interfacial electric fields in a semiconductor heterostructure. The magnitude of the energy split is proportional to the electron wave number. Theoretical studies have suggested the possibility of devices in which electron energy states would be split by the Rashba effect and spin-polarized currents would be extracted by resonant quantum-mechanical tunneling.

  4. Heat pump apparatus

    DOEpatents

    Nelson, Paul A.; Horowitz, Jeffrey S.

    1983-01-01

    A heat pump apparatus including a compact arrangement of individual tubular reactors containing hydride-dehydride beds in opposite end sections, each pair of beds in each reactor being operable by sequential and coordinated treatment with a plurality of heat transfer fluids in a plurality of processing stages, and first and second valves located adjacent the reactor end sections with rotatable members having multiple ports and associated portions for separating the hydride beds at each of the end sections into groups and for simultaneously directing a plurality of heat transfer fluids to the different groups. As heat is being generated by a group of beds, others are being regenerated so that heat is continuously available for space heating. As each of the processing stages is completed for a hydride bed or group of beds, each valve member is rotated causing the heat transfer fluid for the heat processing stage to be directed to that bed or group of beds. Each of the end sections are arranged to form a closed perimeter and the valve member may be rotated repeatedly about the perimeter to provide a continuous operation. Both valves are driven by a common motor to provide a coordinated treatment of beds in the same reactors. The heat pump apparatus is particularly suitable for the utilization of thermal energy supplied by solar collectors and concentrators but may be used with any source of heat, including a source of low-grade heat.

  5. The terrestrial silica pump.

    PubMed

    Carey, Joanna C; Fulweiler, Robinson W

    2012-01-01

    Silicon (Si) cycling controls atmospheric CO(2) concentrations and thus, the global climate, through three well-recognized means: chemical weathering of mineral silicates, occlusion of carbon (C) to soil phytoliths, and the oceanic biological Si pump. In the latter, oceanic diatoms directly sequester 25.8 Gton C yr(-1), accounting for 43% of the total oceanic net primary production (NPP). However, another important link between C and Si cycling remains largely ignored, specifically the role of Si in terrestrial NPP. Here we show that 55% of terrestrial NPP (33 Gton C yr(-1)) is due to active Si-accumulating vegetation, on par with the amount of C sequestered annually via marine diatoms. Our results suggest that similar to oceanic diatoms, the biological Si cycle of land plants also controls atmospheric CO(2) levels. In addition, we provide the first estimates of Si fixed in terrestrial vegetation by major global biome type, highlighting the ecosystems of most dynamic Si fixation. Projected global land use change will convert forests to agricultural lands, increasing the fixation of Si by land plants, and the magnitude of the terrestrial Si pump. PMID:23300825

  6. Chemical heat pump

    DOEpatents

    Greiner, Leonard

    1984-01-01

    A chemical heat pump system is disclosed for use in heating and cooling structures such as residences or commercial buildings. The system is particularly adapted to utilizing solar energy, but also increases the efficiency of other forms of thermal energy when solar energy is not available. When solar energy is not available for relatively short periods of time, the heat storage capacity of the chemical heat pump is utilized to heat the structure, as during nighttime hours. The design also permits home heating from solar energy when the sun is shining. The entire system may be conveniently rooftop located. In order to facilitate installation on existing structures, the absorber and vaporizer portions of the system may each be designed as flat, thin wall, thin pan vessels which materially increase the surface area available for heat transfer. In addition, this thin, flat configuration of the absorber and its thin walled (and therefore relatively flexible) construction permits substantial expansion and contraction of the absorber material during vaporization and absorption without generating voids which would interfere with heat transfer.

  7. Chemical heat pump

    DOEpatents

    Greiner, Leonard

    1981-01-01

    A chemical heat pump system is disclosed for use in heating and cooling structures such as residences or commercial buildings. The system is particularly adapted to utilizing solar energy, but also increases the efficiency of other forms of thermal energy when solar energy is not available. When solar energy is not available for relatively short periods of time, the heat storage capacity of the chemical heat pump is utilized to heat the structure, as during nighttime hours. The design also permits home heating from solar energy when the sun is shining. The entire system may be conveniently rooftop located. In order to facilitate installation on existing structures, the absorber and vaporizer portions of the system may each be designed as flat, thin wall, thin pan vessels which materially increase the surface area available for heat transfer. In addition, this thin, flat configuration of the absorber and its thin walled (and therefore relatively flexible) construction permits substantial expansion and contraction of the absorber material during vaporization and absorption without generating voids which would interfere with heat transfer.

  8. Chemical heat pump

    DOEpatents

    Greiner, Leonard

    1984-01-01

    A chemical heat pump system is disclosed for use in heating and cooling structures such as residences or commercial buildings. The system is particularly adapted to utilizing solar energy, but also increases the efficiency of other forms of thermal energy when solar energy is not available. When solar energy is not available for relatively short periods of time, the heat storage capacity of the chemical heat pump is utilized to heat the structure, as during nighttime hours. The design also permits home heating from solar energy when the sun is shining. The entire system may be conveniently rooftop located. In order to faciliate installation on existing structures, the absorber and vaporizer portions of the system may each be designed as flat, thin wall, thin pan vessels which materially increase the surface area available for heat transfer. In addition, this thin, flat configuration of the absorber and its thin walled (and therefore relatively flexible) construction permits substantial expansion and contraction of the absorber material during vaporization and absorption without generating voids which would interfere with heat transfer.

  9. Chemical heat pump

    DOEpatents

    Greiner, Leonard

    1984-01-01

    A chemical heat pump system is disclosed for use in heating and cooling structures such as residences or commercial buildings. The system is particularly adapted to utilizing solar energy, but also increases the efficiency of other forms of thermal energy when solar energy is not available. When solar energy is not available for relatively short periods of time, the heat storage capacity of the chemical heat pump is utilized to heat the structure, as during nighttime hours. The design also permits home heating from solar energy when the sun is shining. The entire system may be conveniently rooftop located. In order to facilitate intallation on existing structures, the absorber and vaporizer portions of the system may each be designed as flat, thin wall, thin pan vessels which materially increase the surface area available for heat transfer. In addition, this thin, flat configuration of the absorber and its thin walled (and therefore relatively flexible) construction permits substantial expansion and contraction of the absorber material during vaporization and absorption without generating voids which would interfere with heat transfer.

  10. The Terrestrial Silica Pump

    PubMed Central

    Carey, Joanna C.; Fulweiler, Robinson W.

    2012-01-01

    Silicon (Si) cycling controls atmospheric CO2 concentrations and thus, the global climate, through three well-recognized means: chemical weathering of mineral silicates, occlusion of carbon (C) to soil phytoliths, and the oceanic biological Si pump. In the latter, oceanic diatoms directly sequester 25.8 Gton C yr−1, accounting for 43% of the total oceanic net primary production (NPP). However, another important link between C and Si cycling remains largely ignored, specifically the role of Si in terrestrial NPP. Here we show that 55% of terrestrial NPP (33 Gton C yr−1) is due to active Si-accumulating vegetation, on par with the amount of C sequestered annually via marine diatoms. Our results suggest that similar to oceanic diatoms, the biological Si cycle of land plants also controls atmospheric CO2 levels. In addition, we provide the first estimates of Si fixed in terrestrial vegetation by major global biome type, highlighting the ecosystems of most dynamic Si fixation. Projected global land use change will convert forests to agricultural lands, increasing the fixation of Si by land plants, and the magnitude of the terrestrial Si pump. PMID:23300825

  11. [Inhibitors of xanthine oxidoreductase].

    PubMed

    Okamoto, Ken

    2008-04-01

    Inhibitors of xanthine oxidoreductase decrease production of uric acid, thus they act as hypouricemic drugs. Allopurinol, a prototypical xanthine oxidoreductase inhibitor, has been widely prescribed for treatment of gout and hyperuricemia. However, severe side effects of allopurinol may occur in patients with renal insufficiency. Recently, novel nonpurine selective inhibitors of xanthine oxidoreductase have been developed as potential alternatives to allopurinol. They have different inhibition mechanisms, utilizing the enzyme structure and the reaction mechanism. Such variation of the inhibition mechanism affects/in vivo/hypouricemic effects of the inhibitors. PMID:18409526

  12. A pump monitoring approach to irrigation pumping plant testing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The conventional approach for evaluating irrigation pumping plant performance has been an instantaneous spot measurement approach. Using this method, the tester measures the necessary work and energy use parameters to determine overall pumping plant performance. The primary limitation of this appr...

  13. Diode-pumped laser with improved pumping system

    DOEpatents

    Chang, Jim J.

    2004-03-09

    A laser wherein pump radiation from laser diodes is delivered to a pump chamber and into the lasing medium by quasi-three-dimensional compound parabolic concentrator light channels. The light channels have reflective side walls with a curved surface and reflective end walls with a curved surface. A flow tube between the lasing medium and the light channel has a roughened surface.

  14. 123. UMBILICAL MAST PUMP ROOM (209), LSB (BLDG. 751). PUMP ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    123. UMBILICAL MAST PUMP ROOM (209), LSB (BLDG. 751). PUMP ON LEFT; HYDRAULIC CONTROL PANEL FOR UMBILICAL MAST AND TRENCH DOORS IN CENTER OF ROOM, FACING WEST. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  15. Pump Operation Workshop. Third Edition (Revised).

    ERIC Educational Resources Information Center

    Ontario Ministry of the Environment, Toronto.

    Presented is the learner's manual for a five-day workshop designed to supplement the skills of water and wastewater treatment personnel. The program consists of lecture-discussions and hands-on sessions covering the operation of water and wastewater pumps. Areas addressed include: material pumped, pump systems, types of pumps, pump controls,…

  16. 46 CFR 154.1135 - Pumps.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Pumps. 154.1135 Section 154.1135 Shipping COAST GUARD... Pumps. (a) Water to the water spray system must be supplied by: (1) A pump that is only for the use of the system; (2) A fire pump; or (3) A pump specially approved by the Commandant (CG-522)....

  17. 46 CFR 119.520 - Bilge pumps.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Bilge pumps. 119.520 Section 119.520 Shipping COAST... Ballast Systems § 119.520 Bilge pumps. (a) Each vessel must be provided with bilge pumps in accordance... have a portable hand bilge pump that must be: (1) Capable of pumping water, but not...

  18. 46 CFR 154.1135 - Pumps.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Pumps. 154.1135 Section 154.1135 Shipping COAST GUARD... Pumps. (a) Water to the water spray system must be supplied by: (1) A pump that is only for the use of the system; (2) A fire pump; or (3) A pump specially approved by the Commandant (CG-OES)....

  19. 46 CFR 154.1135 - Pumps.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Pumps. 154.1135 Section 154.1135 Shipping COAST GUARD... Pumps. (a) Water to the water spray system must be supplied by: (1) A pump that is only for the use of the system; (2) A fire pump; or (3) A pump specially approved by the Commandant (CG-OES)....

  20. 46 CFR 119.520 - Bilge pumps.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Bilge pumps. 119.520 Section 119.520 Shipping COAST... Ballast Systems § 119.520 Bilge pumps. (a) Each vessel must be provided with bilge pumps in accordance... have a portable hand bilge pump that must be: (1) Capable of pumping water, but not...

  1. 46 CFR 119.520 - Bilge pumps.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Bilge pumps. 119.520 Section 119.520 Shipping COAST... Ballast Systems § 119.520 Bilge pumps. (a) Each vessel must be provided with bilge pumps in accordance... have a portable hand bilge pump that must be: (1) Capable of pumping water, but not...

  2. 46 CFR 119.520 - Bilge pumps.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Bilge pumps. 119.520 Section 119.520 Shipping COAST... Ballast Systems § 119.520 Bilge pumps. (a) Each vessel must be provided with bilge pumps in accordance... have a portable hand bilge pump that must be: (1) Capable of pumping water, but not...

  3. 46 CFR 64.93 - Pump controls.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Pump controls. 64.93 Section 64.93 Shipping COAST GUARD... SYSTEMS Cargo Handling System § 64.93 Pump controls. (a) A pressure gauge must be installed— (1) On the pump discharge; (2) Near the pump controls; and (3) Visible to the operator. (b) A pump must have...

  4. 46 CFR 64.93 - Pump controls.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Pump controls. 64.93 Section 64.93 Shipping COAST GUARD... SYSTEMS Cargo Handling System § 64.93 Pump controls. (a) A pressure gauge must be installed— (1) On the pump discharge; (2) Near the pump controls; and (3) Visible to the operator. (b) A pump must have...

  5. 46 CFR 64.93 - Pump controls.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Pump controls. 64.93 Section 64.93 Shipping COAST GUARD... SYSTEMS Cargo Handling System § 64.93 Pump controls. (a) A pressure gauge must be installed— (1) On the pump discharge; (2) Near the pump controls; and (3) Visible to the operator. (b) A pump must have...

  6. 46 CFR 64.93 - Pump controls.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Pump controls. 64.93 Section 64.93 Shipping COAST GUARD... SYSTEMS Cargo Handling System § 64.93 Pump controls. (a) A pressure gauge must be installed— (1) On the pump discharge; (2) Near the pump controls; and (3) Visible to the operator. (b) A pump must have...

  7. 46 CFR 64.93 - Pump controls.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Pump controls. 64.93 Section 64.93 Shipping COAST GUARD... SYSTEMS Cargo Handling System § 64.93 Pump controls. (a) A pressure gauge must be installed— (1) On the pump discharge; (2) Near the pump controls; and (3) Visible to the operator. (b) A pump must have...

  8. The Plasma Membrane Calcium Pump

    NASA Technical Reports Server (NTRS)

    Rasmussen, H.

    1983-01-01

    Three aspect of cellular calcium metabolism in animal cells was discussed including the importance of the plasma membrane in calcium homeostasis, experiments dealing with the actual mechanism of the calcium pump, and the function of the pump in relationship to the mitochondria and to the function of calmodulin in the intact cell.

  9. Centrifugal pumps for rocket engines

    NASA Technical Reports Server (NTRS)

    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.

  10. Ion-pumping microbial rhodopsins

    PubMed Central

    Kandori, Hideki

    2015-01-01

    Rhodopsins are light-sensing proteins used in optogenetics. The word “rhodopsin” originates from the Greek words “rhodo” and “opsis,” indicating rose and sight, respectively. Although the classical meaning of rhodopsin is the red-colored pigment in our eyes, the modern meaning of rhodopsin encompasses photoactive proteins containing a retinal chromophore in animals and microbes. Animal and microbial rhodopsins possess 11-cis and all-trans retinal, respectively, to capture light in seven transmembrane α-helices, and photoisomerizations into all-trans and 13-cis forms, respectively, initiate each function. Ion-transporting proteins can be found in microbial rhodopsins, such as light-gated channels and light-driven pumps, which are the main tools in optogenetics. Light-driven pumps, such as archaeal H+ pump bacteriorhodopsin (BR) and Cl− pump halorhodopsin (HR), were discovered in the 1970s, and their mechanism has been extensively studied. On the other hand, different kinds of H+ and Cl− pumps have been found in marine bacteria, such as proteorhodopsin (PR) and Fulvimarina pelagi rhodopsin (FR), respectively. In addition, a light-driven Na+ pump was found, Krokinobacter eikastus rhodopsin 2 (KR2). These light-driven ion-pumping microbial rhodopsins are classified as DTD, TSA, DTE, NTQ, and NDQ rhodopsins for BR, HR, PR, FR, and KR2, respectively. Recent understanding of ion-pumping microbial rhodopsins is reviewed in this paper. PMID:26442282

  11. Multi-path peristaltic pump

    NASA Technical Reports Server (NTRS)

    Chandler, Joseph A. (Inventor)

    1986-01-01

    The instant invention is directed to a peristaltic pump for critical laboratory or hospital applications requiring precise flow rates over an extended period of time. Within the cylindrical barrel pump housing is a single-piece, molded, elastometric, cylindrical liner with a multiplicity of flattened helical channels created therein from one end of the liner to the other. Three cylindrical rollers rotate about the center axis of the pump around the inside surface of the liner selectively compressing the liner, and hence the helical channels between the rollers and the barrel housing, creating a pumping action by forcing trapped fluid in the helical channels axially from one end of the liner to the opposite end. The novelty of the invention appears to lie in the provision of the special liner with multiple helical channels as the pumping chamber, rather than the standard single elastomeric tubing which is squeezed repeatedly by rollers to move the liquid through a typical peristaltic pump. Large, repeated deflections on the standard tubing causes a permanent set in the tubing, thus either changing the flow rate, or requiring a new section of tubing to be positioned in the pump head. Further, this configuration minimizes the amount of outflow pulsation which is characteristic of a typical single tubing peristaltic pump.

  12. Generalized Pump-restriction Theorem

    SciTech Connect

    Sinitsyn, Nikolai A; Chernyak, Vladimir Y

    2008-01-01

    We formulate conditions under which periodic modulations of parameters on a finite graph with stochastic transitions among its nodes do not lead to overall pump currents through any given link. Our theorem unifies previously known results with the new ones and provides a universal approach to explore futher restrictions on stochastic pump effect in non-adiabatically driven systems with detailed balance.

  13. Breast milk - pumping and storing

    MedlinePlus

    ... a medical supply store. Most mothers find electric pumps the best. They create and release suction on their own, and you can easily learn to use one. Either a lactation consultant or the ... help you buy or rent a pump. They can also teach you how to use ...

  14. Diode-pumped laser research

    NASA Technical Reports Server (NTRS)

    Ramos-Izquierdo, L.; Bufton, J. L.; Chan, K.

    1988-01-01

    The Laboratory for Oceans is currently working on the development of compact laser diode array (LD) pumped Nd:YAG lasers for use in space-based altimetry and ranging. Laser diode-array pumping technology promises to increase the electrical to optical efficiency of solid state lasers by an order of magnitude with a lifetime increase of nearly three orders of magnitude relative to today's conventional flashlamp-pumped laser systems. The small size, efficiency, and ruggedness make LD-pumped solid state lasers ideal for space based applications. In an in-house RTOP effort, a novel multiple-pass LD-pumped Nd:YAG laser amplifier was designed and tested to increase the 100 microjoule output pulse energy of the Lightwave laser oscillator. Preliminary results have yielded a round trip amplifier gain of about 15 percent using 7 microjoule LD-pump energy. As a parallel activity, funding was recently obtained to investigate the possible use of custom made fiber optic arrays to obtain an efficient optical coupling mechanism between the emitting laser diode-arrays and the target solid state laser material. Fiber optic coupling arrays would allow for the easy manipulation of the spatial emitting pattern of the diode pump sources to match either an end or side pumping laser configuration.

  15. Heat Pumping in Nanomechanical Systems

    NASA Astrophysics Data System (ADS)

    Chamon, Claudio; Mucciolo, Eduardo R.; Arrachea, Liliana; Capaz, Rodrigo B.

    2011-04-01

    We propose using a phonon pumping mechanism to transfer heat from a cold to a hot body using a propagating modulation of the medium connecting the two bodies. This phonon pump can cool nanomechanical systems without the need for active feedback. We compute the lowest temperature that this refrigerator can achieve.

  16. Variability of Voriconazole Trough Levels in Haematological Patients: Influence of Comedications with cytochrome P450(CYP) Inhibitors and/or with CYP Inhibitors plus CYP Inducers.

    PubMed

    Cojutti, Piergiorgio; Candoni, Anna; Forghieri, Fabio; Isola, Miriam; Zannier, Maria Elena; Bigliardi, Sara; Luppi, Mario; Fanin, Renato; Pea, Federico

    2016-06-01

    Voriconazole plasma exposure greatly varies among haematological patients. The purpose of this study was to identify the magnitude of influence of comedications with CYP inhibitors and/or with CYP inhibitors plus CYP inducers on voriconazole trough level (Cmin ). Voriconazole Cmin was retrospectively assessed among haematological patients who underwent therapeutic drug monitoring (TDM). Univariate and multivariate linear mixed-effect regression analyses were performed to identify the independent predictors of normalized Cmin . Of the 83 included patients, 35 had comedications with CYP inhibitors (omeprazole or pantoprazole) and 21 with CYP inhibitors (omeprazole or pantoprazole) plus CYP inducers (methylprednisolone, dexamethasone, phenobarbital, rifampin or carbamazepine). Median Cmin value (n = 199) was 2.4 mg/L with a wide range of distribution (<0.2-13.5 mg/L). Median (IQR) normalized voriconazole Cmin value was significantly higher in the presence of CYP inhibitors (4.20 mg/L, 3.23-5.51 mg/L) than either in the absence of interacting cotreatments (2.55 mg/L, 1.54-3.47 mg/L) or in the presence of CYP inhibitors plus CYP inducers (2.16 mg/L, 1.19-3.09 mg/L). The presence of CYP inhibitors was highly significantly associated with Cmin >5.5 mg/L (OR: 23.22, 95% CI: 3.01-179.09, p = 0.003). No significant association emerged when CYP inhibitors were coadministered with CYP inducers (OR: 3.53, 95% CI: 0.36-34.95, p = 0.280). The amount of expected Cmin increase was significantly influenced by both the type and the dose of the administered proton pump inhibitor. The study highlights that the benefit from TDM of voriconazole may be maximal in those patients who are cotreated with CYP inhibitors and/or with CYP inhibitors plus CYP inducers, especially when receiving proton pump inhibitors (PPIs) at very high dosages intravenously. PMID:26572687

  17. Metal hydride heat pump

    SciTech Connect

    Nishizaki, T.; Miyamoto, K.; Miyamoto, M.; Nakata, Y.; Yamaji, K.; Yoshida, K.

    1983-12-27

    A metal hydride heat pump is disclosed comprising a first and a second heat medium receptacle having heat media flowing therein and a plurality of closed vessels each containing a hydrogen gas atmosphere and divided into a first chamber having a first metal hydride filled therein and a second chamber having a second metal hydride filled therein. The first and second chambers of each closed vessel are made to communicate with each other so that hydrogen gas passes from one chamber to the other but the metal hydrides do not, and a group of the first chambers of the closed vessels being located within the first heat medium receptacle and a group of the second chambers of the closed vessels being located within the second heat medium receptacle, whereby heat exchange is carried out between the heat media in the first and second heat medium receptacles and the first and second metal hydrides through the external walls of the closed vessels.

  18. SOLAR PUMPED LASER MICROTHRUSTER

    SciTech Connect

    Rubenchik, A M; Beach, R; Dawson, J; Siders, C W

    2010-02-05

    The development of microsatellites requires the development of engines to modify their orbit. It is natural to use solar energy to drive such engines. For an unlimited energy source the optimal thruster must use a minimal amount of expendable material to minimize launch costs. This requires the ejected material to have the maximal velocity and, hence, the ejected atoms must be as light as possible and be ejected by as high an energy density source as possible. Such a propulsion can be induced by pulses from an ultra-short laser. The ultra-short laser provides the high-energy concentration and high-ejected velocity. We suggest a microthruster system comprised of an inflatable solar concentrator, a solar panel, and a diode-pumped fiber laser. We will describe the system design and give weight estimates.

  19. Dual source heat pump

    DOEpatents

    Ecker, Amir L.; Pietsch, Joseph A.

    1982-01-01

    What is disclosed is a heat pump apparatus for conditioning a fluid characterized by a fluid handler and path for circulating the fluid in heat exchange relationship with a refrigerant fluid; at least two refrigerant heat exchangers, one for effecting heat exchange with the fluid and a second for effecting heat exchange between refrigerant and a heat exchange fluid and the ambient air; a compressor for efficiently compressing the refrigerant; at least one throttling valve for throttling liquid refrigerant; a refrigerant circuit; refrigerant; a source of heat exchange fluid; heat exchange fluid circulating device and heat exchange fluid circuit for circulating the heat exchange fluid in heat exchange relationship with the refrigerant; and valves or switches for selecting the heat exchangers and direction of flow of the refrigerant therethrough for selecting a particular mode of operation. The heat exchange fluid provides energy for defrosting the second heat exchanger when operating in the air source mode and also provides a alternate source of heat.

  20. Nanowire liquid pumps

    NASA Astrophysics Data System (ADS)

    Huang, Jian Yu; Lo, Yu-Chieh; Niu, Jun Jie; Kushima, Akihiro; Qian, Xiaofeng; Zhong, Li; Mao, Scott X.; Li, Ju

    2013-04-01

    The ability to form tiny droplets of liquids and control their movements is important in printing or patterning, chemical reactions and biological assays. So far, such nanofluidic capabilities have principally used components such as channels, nozzles or tubes, where a solid encloses the transported liquid. Here, we show that liquids can flow along the outer surface of solid nanowires at a scale of attolitres per second and the process can be directly imaged with in situ transmission electron microscopy. Microscopy videos show that an ionic liquid can be pumped along tin dioxide, silicon or zinc oxide nanowires as a thin precursor film or as beads riding on the precursor film. Theoretical analysis suggests there is a critical film thickness of ~10 nm below which the liquid flows as a flat film and above which it flows as discrete beads. This critical thickness is the result of intermolecular forces between solid and liquid, which compete with liquid surface energy and Rayleigh-Plateau instability.