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Sample records for proton pump bacteriorhodopsin

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

    Science.gov (United States)

    Chou, K C

    1993-06-01

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

  2. Protons and how they are transported by proton pumps

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Crouch, Rosalie K.; Ebrey, Thomas G.

    2000-02-10

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

  4. Photonic Potential of Haloarchaeal Pigment Bacteriorhodopsin for Future Electronics: A Review.

    Science.gov (United States)

    Ashwini, Ravi; Vijayanand, S; Hemapriya, J

    2017-08-01

    Haloarchaea are known for its adaptation in extreme saline environment. Halophilic archaea produces carotenoid pigments and proton pumps to protect them from extremes of salinity. Bacteriorhodopsin (bR) is a light-driven proton pump that resides in the membrane of haloarchaea Halobacterium salinarum. The photocycle of Bacteriorhodopsin passes through several states from K to O, finally liberating ATP for host's survival. Extensive studies on Bacteriorhodopsin photocycle has provided in depth knowledge on their sequential mechanism of converting solar energy into chemical energy inside the cell. This ability of Bacteriorhodopsin to harvest sunlight has now been experimented to exploit the unexplored and extensively available solar energy in various biotechnological applications. Currently, bacteriorhodopsin finds its importance in dye-sensitized solar cell (DSSC), logic gates (integrated circuits, IC's), optical switching, optical memories, storage devices (random access memory, RAM), biosensors, electronic sensors and optical microcavities. This review deals with the optical and electrical applications of the purple pigment Bacteriorhodopsin.

  5. Protons and how they are transported by proton pumps

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  6. Proton Pumps: Mechanism of Action and Applications

    Science.gov (United States)

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

    2001-01-01

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

  7. Crystallographic Structure of Xanthorhodopsin, the Light-Driven Proton Pump With a Dual Chromophore

    International Nuclear Information System (INIS)

    Luecke, H.; Schobert, B.; Stagno, J.; Imasheva, E.S.; Wang, J.M.; Balashov, S.P.; Lanyi, J.K

    2008-01-01

    Homologous to bacteriorhodopsin and even more to proteorhodopsin, xanthorhodopsin is a light-driven proton pump that, in addition to retinal, contains a noncovalently bound carotenoid with a function of a light-harvesting antenna. We determined the structure of this eubacterial membrane protein-carotenoid complex by X-ray diffraction, to 1.9-(angstrom) resolution. Although it contains 7 transmembrane helices like bacteriorhodopsin and archaerhodopsin, the structure of xanthorhodopsin is considerably different from the 2 archaeal proteins. The crystallographic model for this rhodopsin introduces structural motifs for proton transfer during the reaction cycle, particularly for proton release, that are dramatically different from those in other retinal-based transmembrane pumps. Further, it contains a histidine-aspartate complex for regulating the pK a of the primary proton acceptor not present in archaeal pumps but apparently conserved in eubacterial pumps. In addition to aiding elucidation of a more general proton transfer mechanism for light-driven energy transducers, the structure defines also the geometry of the carotenoid and the retinal. The close approach of the 2 polyenes at their ring ends explains why the efficiency of the excited-state energy transfer is as high as ∼45%, and the 46 o angle between them suggests that the chromophore location is a compromise between optimal capture of light of all polarization angles and excited-state energy transfer

  8. Reconstitution of Biological Molecular generators of electric current. Bacteriorhodopsin.

    Science.gov (United States)

    Drachev, L A; Frolov, V N; Kaulen, A D; Liberman, E A; Ostroumov, S A; Plakunova, V G; Semenov, A Y; Skulachev, V P

    1976-11-25

    1. Photoinduced generation of electric current by bacteriorhodopsin, incorporated into the planar phospholipid membrane, has been directly measured with conventional electrometer techniques. 2. Two methods for bacteriorhodopsin incorporation have been developed: (a) formation of planar membrane from a mixture of decane solution of phospholipids and of the fraction of violet fragments of the Halobacterium halobium membrane (bacteriorhodopsin sheets), and (b) adhesion of bacteriorhodopsin-containing reconstituted spherical membranes (proteoliposomes) to the planar membrane in the presence of Ca2+ or some other cations. In both cases, illumination was found to induce electric current generation directed across the planar membrane, an effect which was measured by macroelectrodes immersed into electrolyte solutions on both sides of the membrane. 3. The maximal values of the transmembrane electric potential were of about 150 mV at a current of about 10(-11) A. The electromotive force measured by means of counterbalancing the photoeffect by an external battery, was found to reach the value of 300 mV. 4. The action spectrum of the photoeffect coincides with the bacteriorhodopsin absorption spectrum (maximum about 570 nm). 5. Both components of the electrochemical potential of H+ ions (electric potential and delta pH) across the planar membrane affect the bacteriorhodopsin photoelectric response in a fashion which could be expected if bacteriorhodopsin were a light-dependent electrogenic proton pump. 6. La3+ ions were shown to inhibit operation of those bacteriorhodopsin which pump out H+ ions from the La3+-containing compartment. 7. The photoeffect, mediated by proteoliposomes associated with thick planar membrane, is decreased by gramicidin A at concentrations which do not influence the planar membrane resistance in the light. On the contrary, a protonophorous uncoupler, trichlorocarbonylcyanidephenylhydrazone, decreases the photoeffect only if it is added at a

  9. Studies on light transduction by bacteriorhodopsin and rhodopsin

    International Nuclear Information System (INIS)

    Braiman, M.; Bubis, J.; Doi, T.; Chen, H.B.; Flitsch, S.L.; Franke, R.R.; Gilles-Gonzalez, M.A.; Graham, R.M.; Karnik, S.S.; Khorana, H.G.; Knox, B.E.; Krebs, M.P.; Marti, T.; Mogi, T.; Nakayama, T.; Oprian, D.D.; Puckett, K.L.; Sakmar, T.P.; Stern, L.J.; Subramaniam, S.; Thompson, D.A.

    1988-01-01

    The visual photoreceptor pigments in vertebrates and invertebrates all use retinal (vitamin A aldehyde) as the light-absorbing molecule. Recently, Stoeckenius et al. discovered bacteriorhodopsin (bR) in the purple membrane of the extreme halophile, Halobacterium halobium, which also contains all-trans retinal as the chromophore, bR carries out light-dependent proton translocation from the inside to the outside of the H. halobium cell. Since the discovery of bR, H. halobium has been found to elaborate three more retinal-based light-transducing proteins. These are halorhodopsin, a chloride ion pump, and sensory rhodopsins I and II. The authors are carrying out structure-function studies of bacteriorhodopsin, bovine rhodopsin, and related proteins primarily by the technique of recombinant DNA; they summarize below the results they have obtained recently

  10. Ionic Polymer Microactuator Activated by Photoresponsive Organic Proton Pumps

    Directory of Open Access Journals (Sweden)

    Khaled M. Al-Aribe

    2015-10-01

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

  11. Tyrosine and carboxyl protonation changes in the bacteriorhodopsin photocycle. 1. M412 and L550 intermediates

    International Nuclear Information System (INIS)

    Roepe, P.; Ahl, P.L.; Gupta, S.K.D.; Herzfeld, J.; Rothschild, K.J.

    1987-01-01

    The role of tyrosines in the bacteriorhodopsin (bR) photocycle has been investigated by using Fourier transform infrared (FTIR) and UV difference spectroscopies. Tyrosine contributions to the BR 570 → M 412 FTIR difference spectra recorded at several temperatures and pH's were identified by isotopically labeling tyrosine residues in bacteriorhodopsin. The frequencies and deuterium/hydrogen exchange sensitivities of these peaks and of peaks in spectra of model compounds in several environments suggest that at least two different tyrosine groups participate in the bR photocycle during the formation of M 412 . One group undergoes a tyrosinate → tyrosine conversion during the BR 570 → K 630 transition. A second tyrosine group deprotonates between L 550 and M 412 . Low-temperature UV difference spectra in the 220-350-nm region of both purple membrane suspensions and rehydrated films support these conclusions. The UV spectra also indicate perturbations(s) of one or more tryptophan group(s). Several carboxyl groups appear to undergo a series of protonation changes between BR 570 and M 412 , as indicated by infrared absorption changes in the 1770-1720-cm -1 region. These results are consistent with the existence of a proton wire in bacteriorhodopsin that involves both tyrosine and carboxyl groups

  12. Analyzing a steady-state phenomenon using an ensemble of sequential transient events: A proof of concept on photocurrent of bacteriorhodopsin upon continuous photoexcitation

    Energy Technology Data Exchange (ETDEWEB)

    Hung, Chang-Wei; Chu, Li-Kang, E-mail: lkchu@mx.nthu.edu.tw [Department of Chemistry, National Tsing Hua University, 101, Sec. 2, Kuang-Fu Rd., Hsinchu 30013, Taiwan (China); Ho, Ching-Hwa [Interdisplinary Program of Science, National Tsing Hua University, 101, Sec. 2, Kuang-Fu Rd., Hsinchu 30013, Taiwan (China)

    2014-10-14

    The proton pump activity of bacteriorhodopsin in aqueous solution upon excitation with modulated continuous light was monitored electrochemically and analyzed by superimposing a series of transient proton translocation events Hᵢ⁺(t). An evolution function f(t)=(he{sup –lt}+k)/(h+k) , including a decay and a stationary offset, was introduced to weight the contribution of the individual transient events evolving with time in the envelope of the steady-state event. The evolution of the total proton concentration can be treated as an ensemble of weighted sequential transient events, H{sub total}⁺(t)=Σ{{sub i=0}sup n}Hᵢ⁺(t)∙f(t), and the temporal profile of the photocurrent is derived by differentiating the proton concentration with respect to time, (table) . The temporal profiles of the bacteriorhodopsin photocurrent in pH range of 6.3–8.1 were analyzed using a well-defined kinetics model and restricted mathematical formulization, and fitted temporal behaviors agreed with the observations. This successful proof-of-concept study on analyzing a steady-state phenomenon using an ensemble of sequential transient events can be generalized to quantify other phenomena upon continuous stimulation, such as estimation of the light-driven ion pump activities of the photosynthetic proteins upon illumination.

  13. Evidence for a tyrosine protonation change during the primary phototransition of bacteriorhodopsin at low temperature.

    OpenAIRE

    Rothschild, K J; Roepe, P; Ahl, P L; Earnest, T N; Bogomolni, R A; Das Gupta, S K; Mulliken, C M; Herzfeld, J

    1986-01-01

    Isotopically labeled tyrosines have been selectively incorporated into bacteriorhodopsin (bR). A comparison of the low-temperature bR570 to K Fourier transform infrared-difference spectra of these samples and normal bR provides information about the role of tyrosine in the primary phototransition. Several tyrosine contributions to the difference spectrum are found. These results and comparison with the spectra of model compounds suggest that a tyrosinate group protonates during the bR570 to K...

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

    Science.gov (United States)

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

    1977-01-01

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

  15. Enhanced photocurrent in engineered bacteriorhodopsin monolayer.

    Science.gov (United States)

    Patil, Amol V; Premaruban, Thenhuan; Berthoumieu, Olivia; Watts, Anthony; Davis, Jason J

    2012-01-12

    The integration of the transmembrane protein bacteriorhodopsin (BR) with man-made electrode surfaces has attracted a great deal of interest for some two decades or more and holds significant promise from the perspective of derived photoresponse or energy capture interfaces. Here we demonstrate that a novel and strategically engineered cysteine site (M163C) can be used to intimately and effectively couple delipidated BR to supporting metallic electrode surfaces. By virtue of the combined effects of the greater surface molecular density afforded by delipidation, and the vicinity of the electrostatic changes associated with proton pumping to the transducing metallic continuum, the resulting films generate a considerably greater photocurrent density on wavelength-selective illumination than previously achievable with monolayers of BR. Given the uniquely photoresponsive, wavelength-selective, and photostable characteristics of this protein, the work has implications for utilization in solar energy capture and photodetector devices.

  16. Effective atomic numbers and electron densities of bacteriorhodopsin and its comprising amino acids in the energy range 1 keV–100 GeV

    Energy Technology Data Exchange (ETDEWEB)

    Ahmadi, Morteza; Lunscher, Nolan [Waterloo Institute for Nanotechnology and Department of Systems Design Engineering, University of Waterloo, 200 University Ave., W., Waterloo, Ontario, Canada N2L 3G1 (Canada); Yeow, John T.W., E-mail: jyeow@uwaterloo.ca [Waterloo Institute for Nanotechnology and Department of Systems Design Engineering, University of Waterloo, 200 University Ave., W., Waterloo, Ontario, Canada N2L 3G1 (Canada)

    2013-04-01

    Recently, there has been an interest in fabrication of X-ray sensors based on bacteriorhodopsin, a proton pump protein in cell membrane of Halobacterium salinarium. Therefore, a better understanding of interaction of X-ray photons with bacteriorhodopsin is required. We use WinXCom program to calculate the mass attenuation coefficient of bacteriorhodopsin and its comprising amino acids for photon energies from 1 keV to 100 GeV. These amino acids include alanine, arginine, asparagine, aspartic acid, glutamine, glutamic acid, glycine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, Asx1, Asx2, Glx1 and Glx2. We then use that data to calculate effective atomic number and electron densities for the same range of energy. We also emphasize on two ranges of energies (10–200 keV and 1–20 MeV) in which X-ray imaging and radiotherapy machines work.

  17. Production of functional bacteriorhodopsin by an Escherichia coli cell-free protein synthesis system supplemented with steroid detergent and lipid

    OpenAIRE

    Shimono, Kazumi; Goto, Mie; Kikukawa, Takashi; Miyauchi, Seiji; Shirouzu, Mikako; Kamo, Naoki; Yokoyama, Shigeyuki

    2009-01-01

    Cell-free expression has become a highly promising tool for the efficient production of membrane proteins. In this study, we used a dialysis-based Escherichia coli cell-free system for the production of a membrane protein actively integrated into liposomes. The membrane protein was the light-driven proton pump bacteriorhodopsin, consisting of seven transmembrane α-helices. The cell-free expression system in the dialysis mode was supplemented with a combination of a detergent and a natural lip...

  18. Development and Characterization of Titanium Dioxide Gel with Encapsulated Bacteriorhodopsin for Hydrogen Production.

    Science.gov (United States)

    Johnson, Kaitlin E; Gakhar, Sukriti; Risbud, Subhash H; Longo, Marjorie L

    2018-06-06

    We study bacteriorhodopsin (BR) in its native purple membrane encapsulated within amorphous titanium dioxide, or titania, gels and in the presence of titania sol-particles to explore this system for hydrogen production. Förster resonance energy transfer between BR and titanium dioxide sol particles was used to conclude that there is nanometer-scale proximity of bacteriorhodopsin to the titanium dioxide. The detection of BR-titania sol aggregates by fluorescence anisotropy and particle sizing indicated the affinity amorphous titania has for BR without the use of additional cross-linkers. UV-Visible spectroscopy of BR-titania gels show that methanol addition did not denature BR at a 25 mM concentration presence as a sacrificial electron donor. Additionally, confinement of BR in the gels significantly limited protein denaturation at higher concentration of added methanol or ethanol. Subsequently, titania gels fabricated through the sol-gel process using a titanium ethoxide precursor, water and the addition of 25 mM methanol were used to encapsulate BR and a platinum reduction catalyst for the production of hydrogen gas under white light irradiation. The inclusion of 5 µM bacteriorhodopsin resulted in a hydrogen production rate of about 3.8 µmole hydrogen mL -1 hr -1 , an increase of 52% compared to gels containing no protein. Electron transfer and proton pumping by BR in close proximity to the titania gel surface are feasible explanations for the enhanced production of hydrogen without the need to crosslink BR to the titania gel. This work sets the stage for further developments of amorphous, rather than crystalline, titania-encapsulated bacteriorhodopsin for solar-driven hydrogen production through water-splitting.

  19. The safety of proton pump inhibitors in pregnancy

    DEFF Research Database (Denmark)

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

    1999-01-01

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

  20. Production of functional bacteriorhodopsin by an Escherichia coli cell-free protein synthesis system supplemented with steroid detergent and lipid.

    Science.gov (United States)

    Shimono, Kazumi; Goto, Mie; Kikukawa, Takashi; Miyauchi, Seiji; Shirouzu, Mikako; Kamo, Naoki; Yokoyama, Shigeyuki

    2009-10-01

    Cell-free expression has become a highly promising tool for the efficient production of membrane proteins. In this study, we used a dialysis-based Escherichia coli cell-free system for the production of a membrane protein actively integrated into liposomes. The membrane protein was the light-driven proton pump bacteriorhodopsin, consisting of seven transmembrane alpha-helices. The cell-free expression system in the dialysis mode was supplemented with a combination of a detergent and a natural lipid, phosphatidylcholine from egg yolk, in only the reaction mixture. By examining a variety of detergents, we found that the combination of a steroid detergent (digitonin, cholate, or CHAPS) and egg phosphatidylcholine yielded a large amount (0.3-0.7 mg/mL reaction mixture) of the fully functional bacteriorhodopsin. We also analyzed the process of functional expression in our system. The synthesized polypeptide was well protected from aggregation by the detergent-lipid mixed micelles and/or lipid disks, and was integrated into liposomes upon detergent removal by dialysis. This approach might be useful for the high yield production of functional membrane proteins.

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

    Science.gov (United States)

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

    2014-01-01

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

  2. Fourier transform infrared difference spectroscopy of bacteriorhodopsin and its photoproducts regenerated with deuterated tyrosine

    International Nuclear Information System (INIS)

    Dollinger, G.; Eisenstein, L.; Lin, S.L.; Nakanishi, K.; Termini, J.

    1986-01-01

    Fourier transform infrared (FTIR) difference spectroscopy has been used to detect the vibrational modes due to tyrosine residues in the protein that change in position or intensity between light-adapted bacteriorhodopsin (LA) and other species, namely, the K and M intermediates and dark-adapted bacteriorhodopsin (DA). To aid in the identification of the bands that change in these various species, the FTIR spectra of the free amino acids Tyr-d0, Tyr-d2 ( 2 H at positions ortho to OH), and Tyr-d4 ( 2 H at positions ortho and meta to OH) were measured in H 2 O and D 2 O at low and high pH. The characteristic frequencies of the Tyr species obtained in this manner were then used to identify the changes in protonation state of the tyrosine residues in the various bacteriorhodopsin species. The two diagnostically most useful bands were the approximately 1480-cm-1 band of Tyr(OH)-d2 and the approximately 1277-cm-1 band of Tyr(O-)-d0. Mainly by observing the appearance or disappearance of these bands in the difference spectra of pigments incorporating the tyrosine isotopes, it was possible to identify the following: in LA, one tyrosine and one tyrosinate; in the K intermediate, two tyrosines; in the M intermediate, one tyrosine and one tyrosinate; and in DA, two tyrosines. Since these residues were observed in the difference spectra K/LA, M/LA, and DA/LA, they represent the tyrosine or tyrosinate groups that most likely undergo changes in protonation state due to the conversions. These changes are most likely linked to the proton translocation process of bacteriorhodopsin

  3. Photochemical cycle of bacteriorhodopsin studied by resonance Raman spectroscopy.

    Science.gov (United States)

    Stockburger, M; Klusmann, W; Gattermann, H; Massig, G; Peters, R

    1979-10-30

    Individual species of the photochemical cycle of bacteriorhodopsin, a retinal-protein complex of Halobacteria, were studied in aqueous suspensions of the "purple membrane" at room temperature by resonance Raman (RR) spectroscopy with flow systems. Two pronounced deuterium shifts were found in the RR spectra of the all-trans complex BR-570 in H2O-D2O suspensions. The first is ascribed to C=NH+ (C=ND+) stretching vibrations of the protonated Schiff base which links retinal to opsin. The second is assigned tentatively to an "X-H" ("X-D") bending mode, where "X" is an atom which carries an exchangeable proton. A RR spectrum of the 13-cis-retinal complex "BR-548" could be deduced from spectra of the dark-adapted purple membrane. The RR spectrum of the M-412 intermediate was monitored in a double-beam pump-probe experiment. The main vibrational features of the intermediate M' in the reaction M-412 in equilibrium hv M' leads to delta BR-570 could be deduced from a photostationary mixture of M-412 and M'. Difference procedures were applied to obtain RR spectra of the L-550 intermediate and of two new long-lived species, R1'-590 and R2-550. From kinetic data it is suggested that T1'-590 links the proton-translocating cycle to the "13-cis" cycle of BR-548. The protonation and isomeric states of the different species are discussed in light of the new spectroscopic and kinetic data. It is found that conformational changes during the photochemical cycle play an important role.

  4. RENAL SAFETY OF PROTON PUMP INHIBITORS

    Directory of Open Access Journals (Sweden)

    A. I. Dyadyk

    2017-01-01

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

  5. H+-type and OH- -type biological protonic semiconductors and complementary devices.

    Science.gov (United States)

    Deng, Yingxin; Josberger, Erik; Jin, Jungho; Roudsari, Anita Fadavi; Rousdari, Anita Fadavi; Helms, Brett A; Zhong, Chao; Anantram, M P; Rolandi, Marco

    2013-10-03

    Proton conduction is essential in biological systems. Oxidative phosphorylation in mitochondria, proton pumping in bacteriorhodopsin, and uncoupling membrane potentials by the antibiotic Gramicidin are examples. In these systems, H(+) hop along chains of hydrogen bonds between water molecules and hydrophilic residues - proton wires. These wires also support the transport of OH(-) as proton holes. Discriminating between H(+) and OH(-) transport has been elusive. Here, H(+) and OH(-) transport is achieved in polysaccharide- based proton wires and devices. A H(+)- OH(-) junction with rectifying behaviour and H(+)-type and OH(-)-type complementary field effect transistors are demonstrated. We describe these devices with a model that relates H(+) and OH(-) to electron and hole transport in semiconductors. In turn, the model developed for these devices may provide additional insights into proton conduction in biological systems.

  6. Crystal structure of the plasma membrane proton pump

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  7. Determination of retinal chromophore structure in bacteriorhodopsin with resonance Raman spectroscopy.

    Science.gov (United States)

    Smith, S O; Lugtenburg, J; Mathies, R A

    1985-01-01

    The analysis of the vibrational spectrum of the retinal chromophore in bacteriorhodopsin with isotopic derivatives provides a powerful "structural dictionary" for the translation of vibrational frequencies and intensities into structural information. Of importance for the proton-pumping mechanism is the unambiguous determination of the configuration about the C13=C14 and C=N bonds, and the protonation state of the Schiff base nitrogen. Vibrational studies have shown that in light-adapted BR568 the Schiff base nitrogen is protonated and both the C13=C14 and C=N bonds are in a trans geometry. The formation of K625 involves the photochemical isomerization about only the C13=C14 bond which displaces the Schiff base proton into a different protein environment. Subsequent Schiff base deprotonation produces the M412 intermediate. Thermal reisomerization of the C13=C14 bond and reprotonation of the Schiff base occur in the M412------O640 transition, resetting the proton-pumping mechanism. The vibrational spectra can also be used to examine the conformation about the C--C single bonds. The frequency of the C14--C15 stretching vibration in BR568, K625, L550 and O640 argues that the C14--C15 conformation in these intermediates is s-trans. Conformational distortions of the chromophore have been identified in K625 and O640 through the observation of intense hydrogen out-of-plane wagging vibrations in the Raman spectra (see Fig. 2). These two intermediates are the direct products of chromophore isomerization. Thus it appears that following isomerization in a tight protein binding pocket, the chromophore cannot easily relax to a planar geometry. The analogous observation of intense hydrogen out-of-plane modes in the primary photoproduct in vision (Eyring et al., 1982) suggests that this may be a general phenomenon in protein-bound isomerizations. Future resonance Raman studies should provide even more details on how bacterio-opsin and retinal act in concert to produce an

  8. H+-type and OH−-type biological protonic semiconductors and complementary devices

    Science.gov (United States)

    Deng, Yingxin; Josberger, Erik; Jin, Jungho; Rousdari, Anita Fadavi; Helms, Brett A.; Zhong, Chao; Anantram, M. P.; Rolandi, Marco

    2013-01-01

    Proton conduction is essential in biological systems. Oxidative phosphorylation in mitochondria, proton pumping in bacteriorhodopsin, and uncoupling membrane potentials by the antibiotic Gramicidin are examples. In these systems, H+ hop along chains of hydrogen bonds between water molecules and hydrophilic residues – proton wires. These wires also support the transport of OH− as proton holes. Discriminating between H+ and OH− transport has been elusive. Here, H+ and OH− transport is achieved in polysaccharide- based proton wires and devices. A H+- OH− junction with rectifying behaviour and H+-type and OH−-type complementary field effect transistors are demonstrated. We describe these devices with a model that relates H+ and OH− to electron and hole transport in semiconductors. In turn, the model developed for these devices may provide additional insights into proton conduction in biological systems. PMID:24089083

  9. The kinetics of the photochemical reaction cycle of deuterated bacteriorhodopsin and pharaonis halorhodopsin

    International Nuclear Information System (INIS)

    Szakacs, Julianna; Lakatos, Melinda; Varo, Gy.; Ganea, Constanta

    2005-01-01

    Kinetic isotope effects in the photochemical reaction cycle of bacteriorhodopsin and pharaonis halorhodopsin were determined in H 2 O and D 2 O at normal pH, to get insight in the proton dependent steps of the transport process. All the steps of the bacteriorhodopsin photocycle at normal pH exhibited a strong isotope effect. In the case of halorhodopsin in both the chloride and nitrate transporting conditions the photocycle was not strongly affected by the deuterium exchange. In the case of chloride, a slight slow down of the photocycle could be observed. On the opposite, in the nitrate transport conditions a reverse effect is present. (author)

  10. Tyrosine and carboxyl protonation changes in the bacteriorhodopsin photocycle. 2. Tyrosine-26 and -64

    International Nuclear Information System (INIS)

    Roepe, P.; Scherrer, P.; Ahl, P.L.; Gupta, S.K.D.; Bogomolni, R.A.; Herzfeld, J.; Rothschild, K.J.

    1987-01-01

    Low-temperature Fourier transform infrared (FTIR) and UV difference spectroscopies combined with selective tyrosine nitration and tyrosine isotopic labeling have been used to investigate the participation of tyrosines-26 and -64 in the bacteriorhodopsin (bR) photocycle. Nitration of Tyr-26 has no detectable effect on the FTIR or UV difference spectra of the BR 570 → K 630 or BR 570 → M 412 transitions. In contrast, nitration of Tyr-64 causes changes in both the FTIR and UV spectra of these transitions. However, this nitration does not alter tyrosine peaks in the FTIR difference spectra which have previously been associated with the protonation of a tyrosinate by K 630 and the deprotonation of a tyrosine by M 412 . Instead, Tyr-64 nitration appears to affect other tyrosine peaks. These results and changes in UV difference spectra upon Tyr-64 nitration are consistent with the deprotonation of Tyr-64 by M 412 as concluded previously. Effects on chromophore vibrations caused by Tyr-64 nitration are unaltered upon reducing the nitrotyrosine to aminotyrosine with sodium dithionite. Finally, nitro-Tyr-64 causes a shift in the frequency of a positive peak at 1739 cm -1 in the BR 570 → M 412 FTIR difference spectrum which reflects the protonation of a carboxyl-containing residue. The shift does not occur for samples containing amino-Tyr-64. These data suggest that Tyr-64 may interact with this carboxyl group

  11. Proton pump inhibitors inhibit pancreatic secretion

    DEFF Research Database (Denmark)

    Wang, Jing; Barbuskaite, Dagne; Tozzi, Marco

    2015-01-01

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

  12. Branching pathways in the photocycle of bacteriorhodopsin

    International Nuclear Information System (INIS)

    Kalisky, O.; Ottolenghi, M.

    1982-01-01

    The pulsed laser photolysis of light-adapted bacteriorhodopsin (BR 570 ) is carried out between 25 C and -92 C in neutral and alkaline water-glycerol solutions. At relatively low temperatures the primary photoproduct K 610 equilibrates with a blue-shifted species, Ksub(p). Both K 610 and the new intermediate subsequently decay into another species, K'sub(p), in a process which competes with the formation of L 550 . Finally, K'sub(p) converts very slowly to L 550 . This branched pathway delays the formation of L 550 and thus of M 412 , without affecting the final yield of either species. A thermal back-reaction regenerating BR 570 takes place at the stage of L 550 , inhibiting the formation of M 412 . The reaction which also predominates at low temperatures, is relatively inefficient at high pH when the forward L 550 → M 412 step is highly catalyzed. It is the superposition of both these branching mechanisms which accounts for the complex effects of temperature and pH on the photocycle of BR 570 . The latter mechanism is accounted for by a molecular scheme in which deprotonation of a tyrosine moiety at the stage of L 550 constitutes a prerequisite for deprotonation of the retinal-lysine schiff-base as required for forming M 412 . This scheme appears to be directly related to the proton pump. (author)

  13. Protein changes associated with reprotonation of the Schiff base in the photocycle of Asp96-->Asn bacteriorhodopsin. The MN intermediate with unprotonated Schiff base but N-like protein structure

    Science.gov (United States)

    Sasaki, J.; Shichida, Y.; Lanyi, J. K.; Maeda, A.

    1992-01-01

    The difference Fourier transform infrared spectrum for the N intermediate in the photoreaction of the light-adapted form of bacteriorhodopsin can be recorded at pH 10 at 274 K (Pfefferle, J.-M., Maeda, A., Sasaki, J., and Yoshizawa, T. (1991) Biochemistry 30, 6548-6556). Under these conditions, Asp96-->Asn bacteriorhodopsin gives a photoproduct which shows changes in protein structure similar to those observed in N of wild-type bacteriorhodopsin. However, decreased intensity of the chromophore bands and the single absorbance maximum at about 400 nm indicate that the Schiff base is unprotonated, as in the M intermediate. This photoproduct was named MN. At pH 7, where the supply of proton is not as restricted as at pH 10, Asp96-->Asn bacteriorhodopsin yields N with a protonated Schiff base. The Asn96 residue, which cannot deprotonate as Asp96 in wild-type bacteriorhodopsin, is perturbed upon formation of both MN at pH 10 and N at pH 7. We suggest that the reprotonation of the Schiff base is preceded by a large change in the protein structure including perturbation of the residue at position 96.

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

    Science.gov (United States)

    Inoue, Keiichi; Nomura, Yurika; Kandori, Hideki

    2016-01-01

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

  15. Design and modeling of a light powered biomimicry micropump

    Science.gov (United States)

    Sze, Tsun-kay Jackie; Liu, Jin; Dutta, Prashanta

    2015-06-01

    The design of compact micropumps to provide steady flow has been an on-going challenge in the field of microfluidics. In this work, a novel micropump concept is introduced utilizing bacteriorhodopsin and sugar transporter proteins. The micropump utilizes light energy to activate the transporter proteins, which create an osmotic pressure gradient and drive the fluid flow. The capability of the bio inspired micropump is demonstrated using a quasi 1D numerical model, where the contributions of bacteriorhodopsin and sugar transporter proteins are taken care of by appropriate flux boundary conditions in the flow channel. Proton flux created by the bacteriorhodopsin proteins is compared with experimental results to obtain the appropriate working conditions of the proteins. To identify the pumping capability, we also investigate the influences of several key parameters, such as the membrane fraction of transporter proteins, membrane proton permeability and the presence of light. Our results show that there is a wide bacteriorhodopsin membrane fraction range (from 0.2 to 10%) at which fluid flow stays nearly at its maximum value. Numerical results also indicate that lipid membranes with low proton permeability can effectively control the light source as a method to turn on/off fluid flow. This capability allows the micropump to be activated and shut off remotely without bulky support equipment. In comparison with existing micropumps, this pump generates higher pressures than mechanical pumps. It can produce peak fluid flow and shutoff head comparable to other non-mechanical pumps.

  16. Design and modeling of a light powered biomimicry micropump

    International Nuclear Information System (INIS)

    Sze, Tsun-kay Jackie; Liu, Jin; Dutta, Prashanta

    2015-01-01

    The design of compact micropumps to provide steady flow has been an on-going challenge in the field of microfluidics. In this work, a novel micropump concept is introduced utilizing bacteriorhodopsin and sugar transporter proteins. The micropump utilizes light energy to activate the transporter proteins, which create an osmotic pressure gradient and drive the fluid flow. The capability of the bio inspired micropump is demonstrated using a quasi 1D numerical model, where the contributions of bacteriorhodopsin and sugar transporter proteins are taken care of by appropriate flux boundary conditions in the flow channel. Proton flux created by the bacteriorhodopsin proteins is compared with experimental results to obtain the appropriate working conditions of the proteins. To identify the pumping capability, we also investigate the influences of several key parameters, such as the membrane fraction of transporter proteins, membrane proton permeability and the presence of light. Our results show that there is a wide bacteriorhodopsin membrane fraction range (from 0.2 to 10%) at which fluid flow stays nearly at its maximum value. Numerical results also indicate that lipid membranes with low proton permeability can effectively control the light source as a method to turn on/off fluid flow. This capability allows the micropump to be activated and shut off remotely without bulky support equipment. In comparison with existing micropumps, this pump generates higher pressures than mechanical pumps. It can produce peak fluid flow and shutoff head comparable to other non-mechanical pumps. (paper)

  17. Branching pathways in the photocycle of bacteriorhodopsin

    Energy Technology Data Exchange (ETDEWEB)

    Kalisky, O.; Ottolenghi, M. (Hebrew Univ., Jerusalem (Israel). Dept. of Physical Chemistry)

    1982-01-01

    The pulsed laser photolysis of light-adapted bacteriorhodopsin (BR/sub 570/) is carried out between 25 C and -92 C in neutral and alkaline water-glycerol solutions. At relatively low temperatures the primary photoproduct K/sub 610/ equilibrates with a blue-shifted species, Ksub(p). Both K/sub 610/ and the new intermediate subsequently decay into another species, K'sub(p), in a process which competes with the formation of L/sub 550/. Finally, K'sub(p) converts very slowly to L/sub 550/. This branched pathway delays the formation of L/sub 550/ and thus of M/sub 412/, without affecting the final yield of either species. A thermal back-reaction regenerating BR/sub 570/ takes place at the stage of L/sub 550/, inhibiting the formation of M/sub 412/. The reaction which also predominates at low temperatures, is relatively inefficient at high pH when the forward L/sub 550/ ..-->.. M/sub 412/ step is highly catalyzed. It is the superposition of both these branching mechanisms which accounts for the complex effects of temperature and pH on the photocycle of BR/sub 570/. The latter mechanism is accounted for by a molecular scheme in which deprotonation of a tyrosine moiety at the stage of L/sub 550/ constitutes a prerequisite for deprotonation of the retinal-lysine schiff-base as required for forming M/sub 412/. This scheme appears to be directly related to the proton pump.

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

    Science.gov (United States)

    Azimi, Leila; Rastegar Lari, Abdolaziz

    2017-11-01

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

  19. Electrostatic coupling of ion pumps.

    Science.gov (United States)

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

    1992-01-01

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

  20. Molecular dynamics of bacteriorhodopsin.

    Science.gov (United States)

    Lupo, J A; Pachter, R

    1997-02-01

    A model of bacteriorhodopsin (bR), with a retinal chromophore attached, has been derived for a molecular dynamics simulation. A method for determining atomic coordinates of several ill-defined strands was developed using a structure prediction algorithm based on a sequential Kalman filter technique. The completed structure was minimized using the GROMOS force field. The structure was then heated to 293 K and run for 500 ps at constant temperature. A comparison with the energy-minimized structure showed a slow increase in the all-atom RMS deviation over the first 200 ps, leveling off to approximately 2.4 A relative to the starting structure. The final structure yielded a backbone-atom RMS deviation from the crystallographic structure of 2.8 A. The residue neighbors of the chromophore atoms were followed as a function of time. The set of persistent near-residue neighbors supports the theory that differences in pKa values control access to the Schiff base proton, rather than formation of a counterion complex.

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

    Science.gov (United States)

    Moriyama, Y; Nelson, N

    1987-07-05

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

  2. Time-resolved resonance Raman spectroscopy of intermediates of bacteriorhodopsin: The bK(590) intermediate.

    Science.gov (United States)

    Terner, J; Hsieh, C L; Burns, A R; El-Sayed, M A

    1979-07-01

    We have combined microbeam and flow techniques with computer subtraction methods to obtain the resonance Raman spectrum of the short lived batho-intermediate (bK(590)) of bacteriorhodopsin. Comparison of the spectra obtained in (1)H(2)O and (2)H(2)O, as well as the fact that the bK(590) intermediate shows large optical red shifts, suggests that the Schiff base linkage of this intermediate is protonated. The fingerprint region of the spectrum of bK(590), sensitive to the isomeric configuration of the retinal chromophore, does not resemble the corresponding region of the parent bR(570) form. The resonance Raman spectrum of bK(590) as well as the spectra of all of the other main intermediates in the photoreaction cycle of bacteriorhodopsin are discussed and compared with resonance Raman spectra of published model compounds.

  3. Bacteriorhodopsin-based photochromic pigments for optical security applications

    Science.gov (United States)

    Hampp, Norbert A.; Fischer, Thorsten; Neebe, Martin

    2002-04-01

    Bacteriorhodopsin is a two-dimensional crystalline photochromic protein which is astonishingly stable towards chemical and thermal degradation. This is one of the reasons why this is one of the very few proteins which may be used as a biological pigment in printing inks. Variants of the naturally occurring bacteriorhodopsin have been developed which show a distinguished color change even with low light intensities and without the requirement of UV-light. Several pigments with different color changes are available right now. In addition to this visual detectable feature, the photochromism, the proteins amino acid sequence can be genetically altered in order to code and identify specific production lots. For advanced applications the data storage capability of bacteriorhodopsin will be useful. Write-once-read-many (WORM) recording of digital data is accomplished by laser excitation of printed bacteriorhodopsin inks. A density of 1 MBit per square inch is currently achieved. Several application examples for this biological molecule are described where low and high level features are used in combination. Bacteriorhodopsin-based inks are a new class of optical security pigments.

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

    Science.gov (United States)

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

    2014-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Stefan Dröse

    2011-08-01

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

  6. Proton pump inhibitors and osteoporosis

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  7. Strategies for discontinuation of proton pump inhibitors

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  8. Fourier Transform Infrared and Resonance Raman Spectroscopic Studies of Bacteriorhodopsin.

    Science.gov (United States)

    Earnest, Thomas Nixon

    Fourier transform infrared and resonance Raman spectroscopy were used to investigate the structure and function of the light-activated, transmembrane proton pump, bacteriorhodopsin, from the purple membrane of Halobacterium halobium. Bacteriorhodopsin (bR) is a 27,000 dalton integral membrane protein consisting of 248 amino acids with a retinylidene chromophore. Absorption of a photon leads to the translocation of one or two protons from the inside of the cell to the outside. Resonance Raman spectroscopy allows for the study of the configuration of retinal in bR and its photointermediates by the selective enhancement of vibrational modes of the chromophore. This technique was used to determine that the chromophore is attached to lysine-216 in both the bR _{570} and the M _{412} intermediates. In bR with tyrosine-64 selectively nitrated or aminated, the chromophore appears to have the same configuration in that bR _{570} (all- trans) and M _{412} (13- cis) states as it does in unmodified bR. Polarized Fourier transform infrared spectroscopy (FTIR) permits the study of the direction of transition dipole moments arising from molecular vibrations of the protein and the retinal chromophore. The orientation of alpha helical and beta sheet components was determined for bR with the average helical tilt found to lie mostly parallel to the membrane normal. The beta sheet structures also exhibit an IR linear dichroism for the amide I and amide II bands which suggest that the peptide backbone is mostly perpendicular to the membrane plane although it is difficult to determine whether the bands originate from sheet or turn components. The orientation of secondary structure components of the C-1 (residues 72-248) and C-2 (residues 1-71) fragments were also investigated to determine the structure of these putative membrane protein folding intermediates. Polarized, low temperature FTIR -difference spectroscopy was then used to investigate the structure of bR as it undergoes

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

    Science.gov (United States)

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

    1986-02-25

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

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

    Science.gov (United States)

    Mourokh, Lev; Filonenko, Ilan

    2014-03-01

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

  11. Proton pump inhibitors affect the gut microbiome

    NARCIS (Netherlands)

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

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

  12. Rate Constant Change of Photo Reaction of Bacteriorhodopsin Observed in Trimeric Molecular System.

    Science.gov (United States)

    Tsujiuchi, Yutaka; Masumoto, Hiroshi; Goto, Takashi

    2016-04-01

    To elucidate the time evolution of photo reaction of bacteriorhodopsin in glycerol mixed purple membrane at around 196 K under irradiation by red light, a kinetic model was constructed. The change of absorption with irradiation at times of 560 nm and 412 nm was analyzed for the purpose of determining reaction rates of photo reaction of bacteriorhodopsin and its product M intermediate. In this study it is shown that reaction rates of conversion from bacteriorhodopsin to the M intermediate can be explained by a set of linear differential equations. This model analysis concludes that bacteriorhodopsin in which constitutes a trimer unit with other two bacteriorhodopsin molecules changes into M intermediates in the 1.73 of reaction rate, in the initial step, and according to the number of M intermediate in a trimer unit, from three to one, the reaction rate of bacteriorhodopsin into M intermediates smaller as 1.73, 0.80, 0.19 which caused by influence of inter-molecular interaction between bacteriorhodopsin.

  13. Liposome Model Systems to Study the Endosomal Escape of Cell-Penetrating Peptides: Transport across Phospholipid Membranes Induced by a Proton Gradient

    Directory of Open Access Journals (Sweden)

    Fatemeh Madani

    2011-01-01

    Full Text Available Detergent-mediated reconstitution of bacteriorhodopsin (BR into large unilamellar vesicles (LUVs was investigated, and the effects were carefully characterized for every step of the procedure. LUVs were prepared by the extrusion method, and their size and stability were examined by dynamic light scattering. BR was incorporated into the LUVs using the detergent-mediated reconstitution method and octyl glucoside (OG as detergent. The result of measuring pH outside the LUVs suggested that in the presence of light, BR pumps protons from the outside to the inside of the LUVs, creating acidic pH inside the vesicles. LUVs with 20% negatively charged headgroups were used to model endosomes with BR incorporated into the membrane. The fluorescein-labeled cell-penetrating peptide penetratin was entrapped inside these BR-containing LUVs. The light-induced proton pumping activity of BR has allowed us to observe the translocation of fluorescein-labeled penetratin across the vesicle membrane.

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

    Science.gov (United States)

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

    2008-05-01

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

  15. Steady-State Characterization of Bacteriorhodopsin-D85N Photocycle

    Science.gov (United States)

    Timucin, Dogan A.; Downie, John D.; Norvig, Peter (Technical Monitor)

    1999-01-01

    An operational characterization of the photocycle of the genetic mutant D85N of bacteriorhodopsin, BR-D85N, is presented. Steady-state bleach spectra and pump-probe absorbance data are obtained with thick hydrated films containing BR-D85N embedded in a gelatin host. Simple two- and three-state models are used to analyze the photocycle dynamics and extract relevant information such as pure-state absorption spectra, photochemical-transition quantum efficiencies, and thermal lifetimes of dominant states appearing in the photocycle, the knowledge of which should aid in the analysis of optical recording and retrieval of data in films incorporating this photochromic material. The remarkable characteristics of this material and their implications from the viewpoint of optical data storage and processing are discussed.

  16. Formation of M-Like Intermediates in Proteorhodopsin in Alkali Solutions (pH ≥ ∼8.5) Where the Proton Release Occurs First in Contrast to the Sequence at Lower pH.

    Science.gov (United States)

    Tamogami, Jun; Sato, Keitaro; Kurokawa, Sukuna; Yamada, Takumi; Nara, Toshifumi; Demura, Makoto; Miyauchi, Seiji; Kikukawa, Takashi; Muneyuki, Eiro; Kamo, Naoki

    2016-02-23

    Proteorhodopsin (PR) is an outward light-driven proton pump observed in marine eubacteria. Despite many structural and functional similarities to bacteriorhodopsin (BR) in archaea, which also acts as an outward proton pump, the mechanism of the photoinduced proton release and uptake is different between two H(+)-pumps. In this study, we investigated the pH dependence of the photocycle and proton transfer in PR reconstituted with the phospholipid membrane under alkaline conditions. Under these conditions, as the medium pH increased, a blue-shifted photoproduct (defined as Ma), which is different from M, with a pKa of ca. 9.2 was produced. The sequence of the photoinduced proton uptake and release during the photocycle was inverted with the increase in pH. A pKa value of ca. 9.5 was estimated for this inversion and was in good agreement with the pKa value of the formation of Ma (∼ 9.2). In addition, we measured the photoelectric current generated by PRs attached to a thin polymer film at varying pH. Interestingly, increases in the medium pH evoked bidirectional photocurrents, which may imply a possible reversal of the direction of the proton movement at alkaline pH. On the basis of these findings, a putative photocycle and proton transfer scheme in PR under alkaline pH conditions was proposed.

  17. Shortcomings of the first-generation proton pump inhibitors

    NARCIS (Netherlands)

    Tytgat, G. N.

    2001-01-01

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

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

    Science.gov (United States)

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

    2014-08-01

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

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

    Science.gov (United States)

    Fais, S

    2010-05-01

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

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

    Science.gov (United States)

    Vedovato, Natascia; Gadsby, David C

    2014-04-01

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

  1. Coordinating the Structural Rearrangements Associated with Unidirectional Proton Transfer in the Bacteriorhodopsin Photocycle Induced by Deprotonation of the Proton-Release Group: A Time-Resolved Difference FTIR Spectroscopic Study†

    Science.gov (United States)

    Morgan, Joel E.; Vakkasoglu, Ahmet S.; Lanyi, Janos K.; Gennis, Robert B.; Maeda, Akio

    2014-01-01

    In the photocycle of bacteriorhodopsin at pH 7, proton release from the proton releasing group (PRG) to the extracellular medium occurs during formation of the M intermediate. This proton release is inhibited at acidic pH, below the pKa of the PRG, ∼6 in M, and instead occurs later in the cycle as the initial state is restored from the O intermediate. Here, structural changes related to deprotonation of the PRG have been investigated by time-resolved FTIR spectroscopy at 25°C. The vibrational features at 2100-1790 cm-1, 1730-1685 cm-1, 1661 cm-1, and 1130-1045 cm-1 have greater negative intensity in the pure M-minus-BR spectrum and even in the M-minus-BR spectrum, that is present earlier together with the L-minus-BR spectrum, at pH 7, than in the corresponding M-minus-BR spectra at pH 5 or pH 4. The D212N mutation abolishes the decreases in the intensities of the broad feature between 1730 and 1685 cm-1 and the band at 1661 cm-1. The 1730-1685 cm-1 feature may arise from transition dipole coupling of the backbone carbonyl groups of Glu204, Phe208, Asp212 and Lys216 interacting with Tyr57 and C15-H of the chromophore. The 1661 cm-1 band, which is insensitive to D2O substitution, may arise by interaction of the backbone carbonyl of Asp212 with C15-H. The 2100-1790 cm-1 feature with a trough at 1885 cm-1 could be due to a water cluster. Depletion of these bands upon deprotonation of the PRG is attributable to disruption of a coordinated structure, held in place by interactions of Asp212. Deprotonation of the PRG is accompanied also by disruption of the interaction of the water molecule near Arg82. The liberated Asp212 may stabilize the protonated state of Asp85, and thus confer uni-directionality to the transport. PMID:20232848

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

    Science.gov (United States)

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

    2010-05-08

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

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

    Directory of Open Access Journals (Sweden)

    Fais Stefano

    2010-05-01

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

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

    Science.gov (United States)

    Vedovato, Natascia

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Science.gov (United States)

    Simon, Mireille; Zerbib, Frank

    2013-01-01

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

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

    African Journals Online (AJOL)

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

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

    Science.gov (United States)

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

    2018-04-15

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

  9. 1-Arylsulfonyl-2-(Pyridylmethylsulfinyl) Benzimidazoles as New Proton Pump Inhibitor Prodrugs

    Science.gov (United States)

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

    2010-01-01

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

  10. Fractal morphological analysis of Bacteriorhodopsin (bR) layers deposited onto Indium Tin Oxide (ITO) electrodes

    International Nuclear Information System (INIS)

    Vengadesh, P.; Muniandy, S.V.; Majid, W.H. Abd.

    2009-01-01

    Uniform Bacteriorhodopsin layers for the purpose of fabricating Bacteriorhodopsin-based biosensors were prepared by allowing drying of the layers under a constant electric field. To properly observe and understand the 'electric field effect' on the protein Bacteriorhodopsin, the electric and non-electric field influenced Bacteriorhodopsin layers prepared using a manual syringe-deposition method applied onto Indium Tin Oxide electrodes were structurally investigated using Scanning Electron Microscopy and Atomic Force Microscopy. The results yield obvious morphological differences between the electric and non-electric field assisted Bacteriorhodopsin layers and brings to attention the occurrence of the so-called 'coffee-ring' effect in the latter case. We applied stochastic fractal method based on the generalized Cauchy process to describe the morphological features surrounding the void. Fractal dimension is used to characterize the local regularity of the Bacteriorhodopsin clusters and the correlation exponent is used to describe the long-range correlation between the clusters. It is found that the Bacteriorhodopsin protein tends to exhibit with strong spatial correlation in the presence of external electric field compared to in absence of the electric field. Long-range correlation in the morphological feature may be associated to the enhancement of aggregation process of Bacteriorhodopsin protein in the presence of electric field, thereby inhibiting the formation of the so-called 'coffee-ring' effect. As such, the observations discussed in this work suggest some amount of control of surface uniformity when forming layers.

  11. A quantum chemical study of the mechanism for proton-coupled electron transfer leading to proton pumping in cytochrome c oxidase

    Science.gov (United States)

    Blomberg, Margareta R. A.; Siegbahn, Per E. M.

    2010-10-01

    The proton pumping mechanism in cytochrome c oxidase, the terminal enzyme in the respiratory chain, has been investigated using hybrid DFT with large chemical models. In previous studies, a gating mechanism was suggested based on electrostatic interpretations of kinetic experiments. The predictions from that analysis are tested here. The main result is that the suggestion of a positively charged transition state for proton transfer is confirmed, while some other suggestions for the gating are not supported. It is shown that a few critical relative energy values from the earlier studies are reproduced with quite high accuracy using the present model calculations. Examples are the forward barrier for proton transfer from the N-side of the membrane to the pump-loading site when the heme a cofactor is reduced, and the corresponding back leakage barrier when heme a is oxidised. An interesting new finding is an unexpected double-well potential for proton transfer from the N-side to the pump-loading site. In the intermediate between the two transition states found, the proton is bound to PropD on heme a. A possible purpose of this type of potential surface is suggested here. The accuracy of the present values are discussed in terms of their sensitivity to the choice of dielectric constant. Only one energy value, which is not critical for the present mechanism, varies significantly with this choice and is therefore less certain.

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

    Directory of Open Access Journals (Sweden)

    Munazah Fazal Qureshi

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    LENUS (Irish Health Repository)

    Cahir, Caitriona

    2012-01-01

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

  15. The Improved Method for Isolation of Photochrome Trans-membrane Protein Bacteriorhodopsin from Purple Membranes of Halobacterium Halobacterium Halobium ET 1001

    OpenAIRE

    Oleg Mosin; Ignat Ignatov

    2015-01-01

    It was developed the improved method for isolation of photochrome trans-membraine protein bacteriorhodopsin (output – 5 mg from 100 g of wet biomass) capable to transform light energy to electrochemical energy of generated protons H+ and АТP. The protein was isolated from purple membranes of photo-organotrophic halobacterium Halobacterium halobium ET 1001 by cellular autolysis by distilled water, processing of bacterial biomass by ultrasound at 22 KHz, alcohol extraction of low and high-weigh...

  16. Evolution of rhodopsin ion pumps in haloarchaea

    Directory of Open Access Journals (Sweden)

    Ford Doolittle W

    2007-05-01

    Full Text Available Abstract Background The type 1 (microbial rhodopsins are a diverse group of photochemically reactive proteins that display a broad yet patchy distribution among the three domains of life. Recent work indicates that this pattern is likely the result of lateral gene transfer (LGT of rhodopsin genes between major lineages, and even across domain boundaries. Within the lineage in which the microbial rhodopsins were initially discovered, the haloarchaea, a similar patchy distribution is observed. In this initial study, we assess the roles of LGT and gene loss in the evolution of haloarchaeal rhodopsin ion pump genes, using phylogenetics and comparative genomics approaches. Results Mapping presence/absence of rhodopsins onto the phylogeny of the RNA polymerase B' subunit (RpoB' of the haloarchaea supports previous notions that rhodopsins are patchily distributed. The phylogeny for the bacteriorhodopsin (BR protein revealed two discrepancies in comparison to the RpoB' marker, while the halorhodopsin (HR tree showed incongruence to both markers. Comparative analyses of bacteriorhodopsin-linked regions of five haloarchaeal genomes supported relationships observed in the BR tree, and also identified two open reading frames (ORFs that were more frequently linked to the bacteriorhodopsin gene than those genes previously shown to be important to the function and expression of BR. Conclusion The evidence presented here reveals a complex evolutionary history for the haloarchaeal rhodopsins, with both LGT and gene loss contributing to the patchy distribution of rhodopsins within this group. Similarities between the BR and RpoB' phylogenies provide supportive evidence for the presence of bacteriorhodopsin in the last common ancestor of haloarchaea. Furthermore, two loci that we have designated bacterio-opsin associated chaperone (bac and bacterio-opsin associated protein (bap are inferred to have important roles in BR biogenesis based on frequent linkage and co

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-04-01

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

  18. Vibrational motions associated with primary processes in bacteriorhodopsin studied by coherent infrared emission spectroscopy.

    Science.gov (United States)

    Groma, Géza I; Colonna, Anne; Martin, Jean-Louis; Vos, Marten H

    2011-03-16

    The primary energetic processes driving the functional proton pump of bacteriorhodopsin take place in the form of complex molecular dynamic events after excitation of the retinal chromophore into the Franck-Condon state. These early events include a strong electronic polarization, skeletal stretching, and all-trans-to-13-cis isomerization upon formation of the J intermediate. The effectiveness of the photoreaction is ensured by a conical intersection between the electronic excited and ground states, providing highly nonadiabatic coupling to nuclear motions. Here, we study real-time vibrational coherences associated with these motions by analyzing light-induced infrared emission from oriented purple membranes in the 750-1400 cm(-)(1) region. The experimental technique applied is based on second-order femtosecond difference frequency generation on macroscopically ordered samples that also yield information on phase and direction of the underlying motions. Concerted use of several analysis methods resulted in the isolation and characterization of seven different vibrational modes, assigned as C-C stretches, out-of-plane methyl rocks, and hydrogen out-of-plane wags, whereas no in-plane H rock was found. Based on their lifetimes and several other criteria, we deduce that the majority of the observed modes take place on the potential energy surface of the excited electronic state. In particular, the direction sensitivity provides experimental evidence for large intermediate distortions of the retinal plane during the excited-state isomerization process. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  1. Surface proton transport of fully protonated poly(aspartic acid) thin films on quartz substrates

    Energy Technology Data Exchange (ETDEWEB)

    Nagao, Yuki, E-mail: ynagao@jaist.ac.jp; Kubo, Takahiro

    2014-12-30

    Graphical abstract: - Highlights: • Proton transport of fully protonated poly(aspartic acid) thin film was investigated. • The thin film structure differed greatly from the partially protonated one. • Proton transport occurs on the surface, not inside of the thin film. • This result contributes to biological transport systems such as bacteriorhodopsin. - Abstract: Thin film structure and the proton transport property of fully protonated poly(aspartic acid) (P-Asp100) have been investigated. An earlier study assessed partially protonated poly(aspartic acid), highly oriented thin film structure and enhancement of the internal proton transport. In this study of P-Asp100, IR p-polarized multiple-angle incidence resolution (P-MAIR) spectra were measured to investigate the thin film structure. The obtained thin films, with thicknesses of 120–670 nm, had no oriented structure. Relative humidity dependence of the resistance, proton conductivity, and normalized resistance were examined to ascertain the proton transport property of P-Asp100 thin films. The obtained data showed that the proton transport of P-Asp100 thin films might occur on the surface, not inside of the thin film. This phenomenon might be related with the proton transport of the biological system.

  2. Surface proton transport of fully protonated poly(aspartic acid) thin films on quartz substrates

    International Nuclear Information System (INIS)

    Nagao, Yuki; Kubo, Takahiro

    2014-01-01

    Graphical abstract: - Highlights: • Proton transport of fully protonated poly(aspartic acid) thin film was investigated. • The thin film structure differed greatly from the partially protonated one. • Proton transport occurs on the surface, not inside of the thin film. • This result contributes to biological transport systems such as bacteriorhodopsin. - Abstract: Thin film structure and the proton transport property of fully protonated poly(aspartic acid) (P-Asp100) have been investigated. An earlier study assessed partially protonated poly(aspartic acid), highly oriented thin film structure and enhancement of the internal proton transport. In this study of P-Asp100, IR p-polarized multiple-angle incidence resolution (P-MAIR) spectra were measured to investigate the thin film structure. The obtained thin films, with thicknesses of 120–670 nm, had no oriented structure. Relative humidity dependence of the resistance, proton conductivity, and normalized resistance were examined to ascertain the proton transport property of P-Asp100 thin films. The obtained data showed that the proton transport of P-Asp100 thin films might occur on the surface, not inside of the thin film. This phenomenon might be related with the proton transport of the biological system

  3. Probing specific molecular processes and intermediates by time-resolved Fourier transform infrared spectroscopy: application to the bacteriorhodopsin photocycle.

    Science.gov (United States)

    Lórenz-Fonfría, Víctor A; Kandori, Hideki; Padrós, Esteve

    2011-06-23

    We present a general approach for probing the kinetics of specific molecular processes in proteins by time-resolved Fourier transform infrared (IR) spectroscopy. Using bacteriorhodopsin (bR) as a model we demonstrate that by appropriately monitoring some selected IR bands it is possible obtaining the kinetics of the most important events occurring in the photocycle, namely changes in the chromophore and the protein backbone conformation, and changes in the protonation state of the key residues implicated in the proton transfers. Besides confirming widely accepted views of the bR photocycle, our analysis also sheds light into some disputed issues: the degree of retinal torsion in the L intermediate to respect the ground state; the possibility of a proton transfer from Asp85 to Asp212; the relationship between the protonation/deprotonation of Asp85 and the proton release complex; and the timing of the protein backbone dynamics. By providing a direct way to estimate the kinetics of photocycle intermediates the present approach opens new prospects for a robust quantitative kinetic analysis of the bR photocycle, which could also benefit the study of other proteins involved in photosynthesis, in phototaxis, or in respiratory chains.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

    Rauws, E. A.

    1997-01-01

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

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

    DEFF Research Database (Denmark)

    Justesen, Bo Højen

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-03-15

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

  8. Schiff base switch II precedes the retinal thermal isomerization in the photocycle of bacteriorhodopsin.

    Directory of Open Access Journals (Sweden)

    Ting Wang

    Full Text Available In bacteriorhodopsin, the order of molecular events that control the cytoplasmic or extracellular accessibility of the Schiff bases (SB are not well understood. We use molecular dynamics simulations to study a process involved in the second accessibility switch of SB that occurs after its reprotonation in the N intermediate of the photocycle. We find that once protonated, the SB C15 = NZ bond switches from a cytoplasmic facing (13-cis, 15-anti configuration to an extracellular facing (13-cis, 15-syn configuration on the pico to nanosecond timescale. Significantly, rotation about the retinal's C13 = C14 double bond is not observed. The dynamics of the isomeric state transitions of the protonated SB are strongly influenced by the surrounding charges and dielectric effects of other buried ions, particularly D96 and D212. Our simulations indicate that the thermal isomerization of retinal from 13-cis back to all-trans likely occurs independently from and after the SB C15 = NZ rotation in the N-to-O transition.

  9. Studying of Phototransformation of Light Signal by Photoreceptor Pigments - Rhodopsin, Iodopsin and Bacteriorhodopsin

    OpenAIRE

    Ignat Ignatov; Oleg Mosin

    2014-01-01

    This review article views predominately the structure and function of animal and bacterial photoreceptor pigments (rhodopsin, iodopsin, bacteriorhodopsin) and their aspects of nano- and biotechnological usage. On an example of bacteriorhodopsin is described the method of its isolation from purple membranes of photo-organotrophic halobacterium Halobacterium halobium by cellular autolysis by distilled water, processing of bacterial biomass by ultrasound at 22 KHz, alcohol extraction of low and ...

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

    Directory of Open Access Journals (Sweden)

    M. V. Markina

    2010-04-01

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

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

    Science.gov (United States)

    MacLaren, Robert; Campbell, Jon

    2014-04-01

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

  12. Occupational Airborne Contact Dermatitis From Proton Pump Inhibitors.

    Science.gov (United States)

    DeKoven, Joel G; Yu, Ashley M

    2015-01-01

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

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

    Science.gov (United States)

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

    2018-02-01

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

  14. Pharmacokinetics and pharmacodynamics of the proton pump inhibitors.

    Science.gov (United States)

    Shin, Jai Moo; Kim, Nayoung

    2013-01-01

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

  15. Modulation of proton pumping across proteoliposome membranes reconstituted with tonoplast H(+)-ATPase from cultured rice (Oryza sativa L. var. Boro) cells by acyl steryl glucoside and steryl glucoside.

    Science.gov (United States)

    Yamaguchi, Mineo; Kasamo, Kunihiro

    2002-07-01

    Tonoplast H(+)-ATPase purified from cultured rice cells (Oryza sativa L. var. Boro) was reconstituted into asolectin liposomes containing steryl glucoside (SG) or acyl steryl glucoside (ASG), and the effects of SG and ASG on proton pumping, ATP-hydrolysis activity and proton permeability of the proteoliposome membranes were investigated. In the proteoliposomes containing 10 mol% SG, proton pumping and ATP-hydrolysis activity were increased to around 140% of those in SG-free proteoliposomes. In the proteoliposomes containing ASG, proton pumping and ATP-hydrolysis activity were decreased to one-tenth of those in ASG-free proteoliposomes at 15 mol% ASG; however, activity increased again slightly in the range between 20 and 40 mol% ASG. The change in proton pumping across the proteoliposome membrane is not due to a change of proteoliposome size nor to the location of the catalytic site of the tonoplast H(+)-ATPase in the proteoliposomes. SG and ASG also reduced the passive proton permeability of the proteoliposomes. These results show that SG and ASG modulate proton pumping across the tonoplast toward stimulation and depression, respectively, and they reduce the passive proton permeability of the tonoplast.

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

    Directory of Open Access Journals (Sweden)

    Mélissa Ratelle

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2016-09-15

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

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

    DEFF Research Database (Denmark)

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

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

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

    Directory of Open Access Journals (Sweden)

    Milutinović Jelena D.

    2015-01-01

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

  1. Cell-free expressed bacteriorhodopsin in different soluble membrane mimetics: biophysical properties and NMR accessibility.

    Science.gov (United States)

    Etzkorn, Manuel; Raschle, Thomas; Hagn, Franz; Gelev, Vladimir; Rice, Amanda J; Walz, Thomas; Wagner, Gerhard

    2013-03-05

    Selecting a suitable membrane-mimicking environment is of fundamental importance for the investigation of membrane proteins. Nonconventional surfactants, such as amphipathic polymers (amphipols) and lipid bilayer nanodiscs, have been introduced as promising environments that may overcome intrinsic disadvantages of detergent micelle systems. However, structural insights into the effects of different environments on the embedded protein are limited. Here, we present a comparative study of the heptahelical membrane protein bacteriorhodopsin in detergent micelles, amphipols, and nanodiscs. Our results confirm that nonconventional environments can increase stability of functional bacteriorhodopsin, and demonstrate that well-folded heptahelical membrane proteins are, in principle, accessible by solution-NMR methods in amphipols and phospholipid nanodiscs. Our data distinguish regions of bacteriorhodopsin that mediate membrane/solvent contacts in the tested environments, whereas the protein's functional inner core remains almost unperturbed. The presented data allow comparing the investigated membrane mimetics in terms of NMR spectral quality and thermal stability required for structural studies. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Irfan Ahmad

    2013-12-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  5. Active glucose transport and proton pumping in tonoplast membrane of Zea mays L. coleoptiles are inhibited by anti-H+-ATPase antibodies

    International Nuclear Information System (INIS)

    Rausch, T.; Butcher, D.N.; Taiz, L.

    1987-01-01

    A tonoplast enriched fraction was obtained from Zea mays L. coleoptiles by isopycnic centrifugation of microsomal membranes in a sucrose step gradient. At the 18/26% interface chloride-stimulated and nitrate-inhibited proton pumping activity coincided with a Mg 2+ -ATP dependent accumulation of 3-O-methyl-D-glucose (OMG) as determined by a membrane filtration technique using 14 C-labeled substrate. OMG transport showed an apparently saturable component with a K/sub m/ of 110 micromolar, and was completely inhibited by 10 micromolar carbonyl cyanide m-chlorophenylhydrazone. Polyclonal antibodies against solubilized native tonoplast H + -ATPase and its 62 and 72 kilodalton subunits were assayed for their ability to inhibit proton pumping and OMG accumulation. Antibodies against both the native enzyme and the putative catalytic subunit strongly inhibited proton pumping and OMG transport whereas antibodies against the 62 kilodalton subunit had only a slight effect on both processes

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

    NARCIS (Netherlands)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

    Bytzer, Peter; Jones, Roger; Vakil, Nimish

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2018-04-01

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

  11. Effects of membrane curvature and pH on proton pumping activity of single cytochrome bo3 enzymes

    DEFF Research Database (Denmark)

    Li, Mengqiu; Khan, Sanobar; Rong, Honglin

    2017-01-01

    The molecular mechanism of proton pumping by heme-copper oxidases (HCO) has intrigued the scientific community since it was first proposed. We have recently reported a novel technology that enables the continuous characterisation of proton transport activity of a HCO and ubiquinol oxidase from...... Escherichia coli, cytochrome bo3, for hundreds of seconds on the single enzyme level (Li et al. J Am Chem Soc 137 (2015) 16055–16063). Here, we have extended these studies by additional experiments and analyses of the proton transfer rate as a function of proteoliposome size and pH at the N- and P......-side of single HCOs. Proton transport activity of cytochrome bo3 was found to decrease with increased curvature of the membrane. Furthermore, proton uptake at the N-side (proton entrance) was insensitive to pH between pH 6.4–8.4, while proton release at the P-side had an optimum pH of ~ 7.4, suggesting...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-01-01

    To reach the mammalian gut, enteric bacteria must pass through the stomach. Many such organisms survive exposure to the harsh gastric environment (pH 1.5-4) by mounting extreme acid-resistance responses, one of which, the arginine-dependent system of Escherichia coli, has been studied at levels of cellular physiology, molecular genetics and protein biochemistry. This multiprotein system keeps the cytoplasm above pH 5 during acid challenge by continually pumping protons out of the cell using the free energy of arginine decarboxylation. At the heart of the process is a 'virtual proton pump' in the inner membrane, called AdiC, that imports L-arginine from the gastric juice and exports its decarboxylation product agmatine. AdiC belongs to the APC superfamily of membrane proteins, which transports amino acids, polyamines and organic cations in a multitude of biological roles, including delivery of arginine for nitric oxide synthesis, facilitation of insulin release from pancreatic beta-cells, and, when inappropriately overexpressed, provisioning of certain fast-growing neoplastic cells with amino acids. High-resolution structures and detailed transport mechanisms of APC transporters are currently unknown. Here we describe a crystal structure of AdiC at 3.2 A resolution. The protein is captured in an outward-open, substrate-free conformation with transmembrane architecture remarkably similar to that seen in four other families of apparently unrelated transport proteins.

  13. Structure of a prokaryotic virtual proton pump at 3.2 Å resolution

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Yiling; Jayaram, Hariharan; Shane, Tania; Kolmakova-Partensky, Ludmila; Wu, Fang; Williams, Carole; Xiong, Yong; Miller, Christopher; (Yale); (Brandeis)

    2009-09-15

    To reach the mammalian gut, enteric bacteria must pass through the stomach. Many such organisms survive exposure to the harsh gastric environment (pH 1.5-4) by mounting extreme acid-resistance responses, one of which, the arginine-dependent system of Escherichia coli, has been studied at levels of cellular physiology, molecular genetics and protein biochemistry. This multiprotein system keeps the cytoplasm above pH 5 during acid challenge by continually pumping protons out of the cell using the free energy of arginine decarboxylation. At the heart of the process is a 'virtual proton pump' in the inner membrane, called AdiC, that imports L-arginine from the gastric juice and exports its decarboxylation product agmatine. AdiC belongs to the APC superfamily of membrane proteins, which transports amino acids, polyamines and organic cations in a multitude of biological roles, including delivery of arginine for nitric oxide synthesis, facilitation of insulin release from pancreatic {beta}-cells, and, when inappropriately overexpressed, provisioning of certain fast-growing neoplastic cells with amino acids. High-resolution structures and detailed transport mechanisms of APC transporters are currently unknown. Here we describe a crystal structure of AdiC at 3.2 {angstrom} resolution. The protein is captured in an outward-open, substrate-free conformation with transmembrane architecture remarkably similar to that seen in four other families of apparently unrelated transport proteins.

  14. Proton pump inhibitors and gastroenteritis

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    NARCIS (Netherlands)

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

    2006-01-01

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

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

    OpenAIRE

    Kinoshita, Yoshikazu; Ishihara, Shunji

    2008-01-01

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

  17. Structures of aspartic acid-96 in the L and N intermediates of bacteriorhodopsin: analysis by Fourier transform infrared spectroscopy

    Science.gov (United States)

    Maeda, A.; Sasaki, J.; Shichida, Y.; Yoshizawa, T.; Chang, M.; Ni, B.; Needleman, R.; Lanyi, J. K.

    1992-01-01

    The light-induced difference Fourier transform infrared spectrum between the L or N intermediate minus light-adapted bacteriorhodopsin (BR) was measured in order to examine the protonated states and the changes in the interactions of carboxylic acids of Asp-96 and Asp-115 in these intermediates. Vibrational bands due to the protonated and unprotonated carboxylic acid were identified by isotope shift and band depletion upon substitution of Asp-96 or -115 by asparagine. While the signal due to the deprotonation of Asp-96 was clearly observed in the N intermediate, this residue remained protonated in L. Asp-115 was partially deprotonated in L. The C = O stretching vibration of protonated Asp-96 of L showed almost no shift upon 2H2O substitution, in contrast to the corresponding band of Asp-96 or Asp-115 of BR, which shifted by 9-12 cm-1 under the same conditions. In the model system of acetic acid in organic solvents, such an absence of the shift of the C = O stretching vibration of the protonated carboxylic acid upon 2H2O substitution was seen only when the O-H of acetic acid is hydrogen-bonded. The non-hydrogen-bonded monomer showed the 2H2O-dependent shift. Thus, the O-H bond of Asp-96 enters into hydrogen bonding upon conversion of BR to L. Its increased hydrogen bonding in L is consistent with the observed downshift of the O-H stretching vibration of the carboxylic acid of Asp-96.

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  19. The appropriateness of a proton pump inhibitor prescription.

    LENUS (Irish Health Repository)

    Moran, N

    2014-11-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-10-01

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

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

    Science.gov (United States)

    Otremba, Iwona; Wilczyński, Krzysztof; Szewieczek, Jan

    2016-01-01

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

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

    LENUS (Irish Health Repository)

    O'Leary, C

    2012-02-03

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

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

    Directory of Open Access Journals (Sweden)

    Mermelstein J

    2016-07-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Science.gov (United States)

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

    2010-10-08

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

  7. Plant proton pumps

    DEFF Research Database (Denmark)

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

    2007-01-01

    Chemiosmotic circuits of plant cells are driven by proton (H+) gradients that mediate secondary active transport of compounds across plasma and endosomal membranes. Furthermore, regulation of endosomal acidification is critical for endocytic and secretory pathways. For plants to react...

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

    LENUS (Irish Health Repository)

    Drepper, Michael D

    2012-05-14

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

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

    Science.gov (United States)

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

    2013-01-01

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

  10. Hydrogen exchange mass spectrometry of bacteriorhodopsin reveals light-induced changes in the structural dynamics of a biomolecular machine.

    Science.gov (United States)

    Pan, Yan; Brown, Leonid; Konermann, Lars

    2011-12-21

    Many proteins act as molecular machines that are fuelled by a nonthermal energy source. Examples include transmembrane pumps and stator-rotor complexes. These systems undergo cyclic motions (CMs) that are being driven along a well-defined conformational trajectory. Superimposed on these CMs are thermal fluctuations (TFs) that are coupled to stochastic motions of the solvent. Here we explore whether the TFs of a molecular machine are affected by the occurrence of CMs. Bacteriorhodopsin (BR) is a light-driven proton pump that serves as a model system in this study. The function of BR is based on a photocycle that involves trans/cis isomerization of a retinal chromophore, as well as motions of transmembrane helices. Hydrogen/deuterium exchange (HDX) mass spectrometry was used to monitor the TFs of BR, focusing on the monomeric form of the protein. Comparative HDX studies were conducted under illumination and in the dark. The HDX kinetics of BR are dramatically accelerated in the presence of light. The isotope exchange rates and the number of backbone amides involved in EX2 opening transitions increase roughly 2-fold upon illumination. In contrast, light/dark control experiments on retinal-free protein produced no discernible differences. It can be concluded that the extent of TFs in BR strongly depends on photon-driven CMs. The light-induced differences in HDX behavior are ascribed to protein destabilization. Specifically, the thermodynamic stability of the dark-adapted protein is estimated to be 5.5 kJ mol(-1) under the conditions of our work. This value represents the free energy difference between the folded state F and a significantly unfolded conformer U. Illumination reduces the stability of F by 2.2 kJ mol(-1). Mechanical agitation caused by isomerization of the chromophore is transferred to the surrounding protein scaffold, and subsequently, the energy dissipates into the solvent. Light-induced retinal motions therefore act analogously to an internal heat

  11. Proton Pump Inhibitors and Risk of Rhabdomyolysis.

    Science.gov (United States)

    Duncan, Scott J; Howden, Colin W

    2017-01-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Carlo A Fallone

    2013-01-01

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

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

    Science.gov (United States)

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

    2006-12-01

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

  15. Inhibition of the coated vesicle proton pump and labeling of a 17,000-dalton polypeptide by N,N'-dicyclohexylcarbodiimide

    International Nuclear Information System (INIS)

    Arai, H.; Berne, M.; Forgac, M.

    1987-01-01

    N,N'-Dicyclohexylcarbodiimide (DCCD) inhibits 100% of proton transport and 80-85% of (Mg2+)-ATPase activity in clathrin-coated vesicles. Half-maximum inhibition of proton transport is observed at 10 microM DCCD after 30 min. Although treatment of the coated vesicle (H+)-ATPase with DCCD has no effect on ATP hydrolysis in the detergent-solubilized state, sensitivity of proton transport and ATPase activity to DCCD is restored following reconstitution into phospholipid vesicles. In addition, treatment of the detergent-solubilized enzyme with DCCD followed by reconstitution gives a preparation that is blocked in both proton transport and ATP hydrolysis. These results suggest that although the coated vesicle (H+)-ATPase can react with DCCD in either a membrane-bound or detergent-solubilized state, inhibition of ATPase activity is only manifested when the pump is present in sealed membrane vesicles. To identify the subunit responsible for inhibition of the coated vesicle (H+)-ATPase by DCCD, we have labeled the partially purified enzyme with [ 14 C]DCCD. A single polypeptide of molecular weight 17,000 is labeled. The extremely hydrophobic nature of this polypeptide is indicated by its extraction with chloroform:methanol. The 17,000-dalton protein can be labeled to a maximum stoichiometry of 0.99 mol of DCCD/mol of protein with 100% inhibition of proton transport occurring at a stoichiometry of 0.15-0.20 mol of DCCD/mol of protein. Amino acid analysis of the chloroform:methanol extracted 17,000-dalton polypeptide reveals a high percentage of nonpolar amino acids. The similarity in properties of this protein and the DCCD-binding subunit of the coupling factor (H+)-ATPases suggests that the 17,000-dalton polypeptide may function as part of a proton channel in the coated vesicle proton pump

  16. Characterization and isolation of a light driven sodium pump from membranes of Halobacterium halobium. Final technical progress report

    International Nuclear Information System (INIS)

    MacDonald, R.E.

    1982-01-01

    We investigated three aspects of the light driven sodium pump (halorhodopsin, which appear to be crucial to our understanding of the mechanisms employed by Halobacterium halobium and to further investigate this unique system of energy conservation. We characterized the molecular mechanisms of transmembrane sodium transport in vesicles from H. halobium with particular reference to the mechanism of couplins of light energy to net sodium translocation. We develop procedures and techniques for extracting the components of the light driven sodium pump from membranes and incorporating them into artificial membrane systems. We examine the mechanism of conversion of bacteriorhodopsin from an active to an inactive form in membrane vesicles and to relate this alternative state of this pigment to the presence of the light driven sodium pump

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2011-09-11

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

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

    Science.gov (United States)

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

    2018-01-01

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

  20. Alpha-helical hydrophobic polypeptides form proton-selective channels in lipid bilayers

    Science.gov (United States)

    Oliver, A. E.; Deamer, D. W.

    1994-01-01

    Proton translocation is important in membrane-mediated processes such as ATP-dependent proton pumps, ATP synthesis, bacteriorhodopsin, and cytochrome oxidase function. The fundamental mechanism, however, is poorly understood. To test the theoretical possibility that bundles of hydrophobic alpha-helices could provide a low energy pathway for ion translocation through the lipid bilayer, polyamino acids were incorporated into extruded liposomes and planar lipid membranes, and proton translocation was measured. Liposomes with incorporated long-chain poly-L-alanine or poly-L-leucine were found to have proton permeability coefficients 5 to 7 times greater than control liposomes, whereas short-chain polyamino acids had relatively little effect. Potassium permeability was not increased markedly by any of the polyamino acids tested. Analytical thin layer chromatography measurements of lipid content and a fluorescamine assay for amino acids showed that there were approximately 135 polyleucine or 65 polyalanine molecules associated with each liposome. Fourier transform infrared spectroscopy indicated that a major fraction of the long-chain hydrophobic peptides existed in an alpha-helical conformation. Single-channel recording in both 0.1 N HCl and 0.1 M KCl was also used to determine whether proton-conducting channels formed in planar lipid membranes (phosphatidylcholine/phosphatidylethanolamine, 1:1). Poly-L-leucine and poly-L-alanine in HCl caused a 10- to 30-fold increase in frequency of conductive events compared to that seen in KCl or by the other polyamino acids in either solution. This finding correlates well with the liposome observations in which these two polyamino acids caused the largest increase in membrane proton permeability but had little effect on potassium permeability. Poly-L-leucine was considerably more conductive than poly-L-alanine due primarily to larger event amplitudes and, to a lesser extent, a higher event frequency. Poly-L-leucine caused two

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

    Science.gov (United States)

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

    2017-01-17

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

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

    Directory of Open Access Journals (Sweden)

    Nabil Sultan

    2008-01-01

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

  3. Evidence of multipolar response of Bacteriorhodopsin by noncollinear second harmonic generation.

    Science.gov (United States)

    Bovino, F A; Larciprete, M C; Sibilia, C; Váró, G; Gergely, C

    2012-06-18

    Noncollinear second harmonic generation from a Bacteriorhodopsin (BR) oriented multilayer film was systematically investigated by varying the polarization state of both fundamental beams. Both experimental results and theoretical simulations, show that the resulting polarization mapping is an useful tool to put in evidence the optical chirality of the investigated film as well as the corresponding multipolar contributions to the nonlinear.

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Carolina Gutiérrez-Junquera

    2018-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Naser Ashraf Tadvi

    2016-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

    Gyawali, C Prakash

    2017-09-01

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    Science.gov (United States)

    Rui, Huan; Artigas, Pablo; Roux, Benoît

    2016-08-04

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

  11. Improved free-energy landscape reconstruction of bacteriorhodopsin highlights local variations in unfolding energy.

    Science.gov (United States)

    Heenan, Patrick R; Yu, Hao; Siewny, Matthew G W; Perkins, Thomas T

    2018-03-28

    Precisely quantifying the energetics that drive the folding of membrane proteins into a lipid bilayer remains challenging. More than 15 years ago, atomic force microscopy (AFM) emerged as a powerful tool to mechanically extract individual membrane proteins from a lipid bilayer. Concurrently, fluctuation theorems, such as the Jarzynski equality, were applied to deduce equilibrium free energies (ΔG 0 ) from non-equilibrium single-molecule force spectroscopy records. The combination of these two advances in single-molecule studies deduced the free-energy of the model membrane protein bacteriorhodopsin in its native lipid bilayer. To elucidate this free-energy landscape at a higher resolution, we applied two recent developments. First, as an input to the reconstruction, we used force-extension curves acquired with a 100-fold higher time resolution and 10-fold higher force precision than traditional AFM studies of membrane proteins. Next, by using an inverse Weierstrass transform and the Jarzynski equality, we removed the free energy associated with the force probe and determined the molecular free-energy landscape of the molecule under study, bacteriorhodopsin. The resulting landscape yielded an average unfolding free energy per amino acid (aa) of 1.0 ± 0.1 kcal/mol, in agreement with past single-molecule studies. Moreover, on a smaller spatial scale, this high-resolution landscape also agreed with an equilibrium measurement of a particular three-aa transition in bacteriorhodopsin that yielded 2.7 kcal/mol/aa, an unexpectedly high value. Hence, while average unfolding ΔG 0 per aa is a useful metric, the derived high-resolution landscape details significant local variation from the mean. More generally, we demonstrated that, as anticipated, the inverse Weierstrass transform is an efficient means to reconstruct free-energy landscapes from AFM data.

  12. Photoaffinity labeling of bacteriorhodopsin

    International Nuclear Information System (INIS)

    Ding, Weidong; Tsipouras, Athanasios; Ok, Hyun; Yamamoto, Toshihiro; Gawinowicz, M.A.; Nakanishi, Koji

    1990-01-01

    14 C-Labeled optically pure 3S- and 3R-(diazoacetoxy)-all-trans-retinals were incorporated separately into bacterioopsin to reconstitute functional bacteriorhodopsin (bR) analogues, 3S- and 3R-diazo-bRs. UV irradiation at 254 nm generated highly reactive carbenes, which cross-linked the radiolabeled retinals to amino acid residues in the vicinity of the β-ionone ring. The 3S- and 3R-diazo analogues were found to cross-link, respectively, to cyanogen bromide fragments CN 7/CN 9 and CN 8/CN 9. More specifically, Thr121 and Gly122 in fragment CN 7 were found to be cross-linked to the 3S-diazo analogue. The identification of cross-linked residues and fragments favors assignments of the seven helices A-G-F-E-D-C-B or B-C-D-E-F-G-A to helices 1-2-3-4-5-6-7 in the two-dimensional electron density map. The present results show that the chromophore chain is oriented with the ionone ring inclined toward the outside of the membrane (the 9-methyl group also faces the extracellular side of the membrane)

  13. Pancreatic bicarbonate secretion involves two proton pumps.

    Science.gov (United States)

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

    2011-01-07

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

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

    OpenAIRE

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

    2012-01-01

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

  15. Polarized proton and deuteron targets for the usage in intensive proton beams

    International Nuclear Information System (INIS)

    Get'man, V.A.; Derkach, A.Ya.; Karnaukhov, I.M.; Lukhanin, A.A.; Razumnyj, A.A.; Sorokin, P.V.; Sporo, E.A.; Telegin, Yu.N.

    1982-01-01

    Polarized proton and deuteron targets are developed and tested for conducting investigations in intense photon beams. A flowsheet of polarization targets which includes: working agent of the target, superconducting magnet, cryostat of 3 He evaporation with 3 He pumping and recirculation systems, SHF system of 4 mm range for polarization pumping, measuring system of target polarization protons is presented. Working agent of the targets includes frozen balls with 1.5 mm diameter. Ethylene-glucol and 1.2-propylene-glycol were used as a working substance for proton targets. Completely deuterated ethylene-glycol was used for the deuteron target. Vertical magnetic field with 2.7 T intensity is produced by a superconducting magnetic system. Polarization pumping is exercised at 75 GHz frequency. Q-meter of direct current is used for determination of polarization. Working temperature of the cryostat is approximately 0.5 K. The lock device permits to exercise replacement of the target working agent during 30 minutes

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

    Directory of Open Access Journals (Sweden)

    Nobata Kouichi

    2007-08-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  19. Chimeric microbial rhodopsins for optical activation of Gs-proteins

    Science.gov (United States)

    Yoshida, Kazuho; Yamashita, Takahiro; Sasaki, Kengo; Inoue, Keiichi; Shichida, Yoshinori; Kandori, Hideki

    2017-01-01

    We previously showed that the chimeric proteins of microbial rhodopsins, such as light-driven proton pump bacteriorhodopsin (BR) and Gloeobacter rhodopsin (GR) that contain cytoplasmic loops of bovine rhodopsin, are able to activate Gt protein upon light absorption. These facts suggest similar protein structural changes in both the light-driven proton pump and animal rhodopsin. Here we report two trials to engineer chimeric rhodopsins, one for the inserted loop, and another for the microbial rhodopsin template. For the former, we successfully activated Gs protein by light through the incorporation of the cytoplasmic loop of β2-adrenergic receptor (β2AR). For the latter, we did not observe any G-protein activation for the light-driven sodium pump from Indibacter alkaliphilus (IndiR2) or a light-driven chloride pump halorhodopsin from Natronomonas pharaonis (NpHR), whereas the light-driven proton pump GR showed light-dependent G-protein activation. This fact suggests that a helix opening motion is common to G protein coupled receptor (GPCR) and GR, but not to IndiR2 and NpHR. Light-induced difference FTIR spectroscopy revealed similar structural changes between WT and the third loop chimera for each light-driven pump. A helical structural perturbation, which was largest for GR, was further enhanced in the chimera. We conclude that similar structural dynamics that occur on the cytoplasmic side of GPCR are needed to design chimeric microbial rhodopsins. PMID:29362703

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

    Science.gov (United States)

    Gabardi, Steven; Olyaei, Ali

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Otremba I

    2016-04-01

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

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

    NARCIS (Netherlands)

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

    2004-01-01

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

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

    NARCIS (Netherlands)

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

    2004-01-01

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    DEFF Research Database (Denmark)

    Wod, Mette; Hallas, Jesper; Andersen, Kjeld

    2018-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sander Veldhuyzen van Zanten

    2004-01-01

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

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

    Science.gov (United States)

    Rui, Huan; Artigas, Pablo; Roux, Benoît

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Lara Aguilera-Castro

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

  9. Efficient production and purification of functional bacteriorhodopsin with a wheat-germ cell-free system and a combination of Fos-choline and CHAPS detergents.

    Science.gov (United States)

    Genji, Takahisa; Nozawa, Akira; Tozawa, Yuzuru

    2010-10-01

    Cell-free translation is one potential approach to the production of functional transmembrane proteins. We have now examined various detergents as supplements to a wheat-germ cell-free system in order to optimize the production and subsequent purification of a functional model transmembrane protein, bacteriorhodopsin. We found that Fos-choline and CHAPS detergents counteracted each other's inhibitory effects on cell-free translation activity and thereby allowed the efficient production and subsequent purification of functional bacteriorhodopsin in high yield. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Tuning biomimetic membrane barrier properties by hydrocarbon, cholesterol and polymeric additives

    DEFF Research Database (Denmark)

    Palanco, Marta Espina; Skovgaard, Nils; Hansen, Jesper Søndergaard

    2017-01-01

    The barrier properties of cellular membranes are increasingly attracting attention as a source of inspiration for designing biomimetic membranes. The broad range of potential technological applications makes the use of lipid and lately also polymeric materials a popular choice for constructing...... biomimetic membranes, where the barrier properties can be controlled by the composition of the membrane constituent elements. Here we investigate the membrane properties reported by the light-induced proton pumping activity of bacteriorhodopsin (bR) reconstituted in three vesicle systems of different...... membrane composition. Specifically we quantify how the resulting proton influx and efflux rates are influenced by the membrane composition using a variety of membrane modulators. We demonstrate that by adding hydrocarbons to vesicles with reconstituted bR formed from asolectin lipids the resulting...

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

    Science.gov (United States)

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

    2013-09-21

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

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

    Science.gov (United States)

    Fais, Stefano

    2015-11-24

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

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

    OpenAIRE

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2012-10-01

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2010-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Gwee KA

    2018-02-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  19. Modeling and design of light powered biomimicry micropump utilizing transporter proteins

    Science.gov (United States)

    Liu, Jin; Sze, Tsun-Kay Jackie; Dutta, Prashanta

    2014-11-01

    The creation of compact micropumps to provide steady flow has been an on-going challenge in the field of microfluidics. We present a mathematical model for a micropump utilizing Bacteriorhodopsin and sugar transporter proteins. This micropump utilizes transporter proteins as method to drive fluid flow by converting light energy into chemical potential. The fluid flow through a microchannel is simulated using the Nernst-Planck, Navier-Stokes, and continuity equations. Numerical results show that the micropump is capable of generating usable pressure. Designing parameters influencing the performance of the micropump are investigated including membrane fraction, lipid proton permeability, illumination, and channel height. The results show that there is a substantial membrane fraction region at which fluid flow is maximized. The use of lipids with low membrane proton permeability allows illumination to be used as a method to turn the pump on and off. This capability allows the micropump to be activated and shut off remotely without bulky support equipment. This modeling work provides new insights on mechanisms potentially useful for fluidic pumping in self-sustained bio-mimic microfluidic pumps. This work is supported in part by the National Science Fundation Grant CBET-1250107.

  20. Proton Pumping and Slippage Dynamics of a Eukaryotic P-Type ATPase Studied at the Single-Molecule Level

    DEFF Research Database (Denmark)

    Veshaguri, Salome

    In all eukaryotes the plasma membrane potential and secondary transport systems are energized by P-type ATPases whose regulation however remains poorly understood. Here we monitored at the single-molecule level the activity of the prototypic proton pumping P-type ATPase Arabidopsis thaliana isoform....... We propose that variable ATP/H+ stoichiometry emerges as a novel mechanism for adaptation when challenged with depletion of ATP that is likely relevant for other ATPases. Such measurements will provide indispensable insights into the mechanisms of function and regulation of many other ion...

  1. Low-power bacteriorhodopsin-silicon n-channel metal-oxide field-effect transistor photoreceiver.

    Science.gov (United States)

    Shin, Jonghyun; Bhattacharya, Pallab; Yuan, Hao-Chih; Ma, Zhenqiang; Váró, György

    2007-03-01

    A bacteriorhodopsin (bR)-silicon n-channel metal-oxide field-effect transistor (NMOSFET) monolithically integrated photoreceiver is demonstrated. The bR film is selectively formed on an external gate electrode of the transistor by electrophoretic deposition. A modified biasing circuit is incorporated, which helps to match the resistance of the bR film to the input impedance of the NMOSFET and to shift the operating point of the transistor to coincide with the maximum gain. The photoreceiver exhibits a responsivity of 4.7 mA/W.

  2. Chimeric Proton-Pumping Rhodopsins Containing the Cytoplasmic Loop of Bovine Rhodopsin

    Science.gov (United States)

    Sasaki, Kengo; Yamashita, Takahiro; Yoshida, Kazuho; Inoue, Keiichi; Shichida, Yoshinori; Kandori, Hideki

    2014-01-01

    G-protein-coupled receptors (GPCRs) transmit stimuli to intracellular signaling systems. Rhodopsin (Rh), which is a prototypical GPCR, possesses an 11-cis retinal. Photoisomerization of 11-cis to all-trans leads to structural changes in the protein of cytoplasmic loops, activating G-protein. Microbial rhodopsins are similar heptahelical membrane proteins that function as bacterial sensors, light-driven ion-pumps, or light-gated channels. They possess an all-trans retinal, and photoisomerization to 13-cis triggers structural changes in protein. Despite these similarities, there is no sequence homology between visual and microbial rhodopsins, and microbial rhodopsins do not activate G-proteins. In this study, new chimeric proton-pumping rhodopsins, proteorhodopsin (PR) and Gloeobacter rhodopsin (GR) were designed by replacing cytoplasmic loops with bovine Rh loops. Although G-protein was not activated by the PR chimeras, all 12 GR chimeras activated G-protein. The GR chimera containing the second cytoplasmic loop of bovine Rh did not activate G-protein. However, the chimera with a second and third double-loop further enhanced G-protein activation. Introduction of an E132Q mutation slowed the photocycle 30-fold and enhanced activation. The highest catalytic activity of the GR chimera was still 3,200 times lower than bovine Rh but only 64 times lower than amphioxus Go-rhodopsin. This GR chimera showed a strong absorption change of the amide-I band on a light-minus-dark difference FTIR spectrum which could represent a larger helical opening, important for G-protein activation. The light-dependent catalytic activity of this GR chimera makes it a potential optogenetic tool for enzymatic activation by light. PMID:24621599

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

    Science.gov (United States)

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

    2013-10-21

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

  4. Energizing porters by proton-motive force.

    Science.gov (United States)

    Nelson, N

    1994-11-01

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

  5. -pumping pyrophosphatase in pepper plants

    KAUST Repository

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

    2018-01-01

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

  6. -pumping pyrophosphatase in pepper plants

    KAUST Repository

    Vigani, Gianpiero

    2018-05-22

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  8. Prospects for hybrid pixel detectors in electron microscopy

    International Nuclear Information System (INIS)

    Faruqi, A.R.

    2001-01-01

    The current status of CCD-based detectors for cryo-electron microscopy of membrane and other proteins is described briefly, highlighting the strengths and weaknesses of the technique. Over the past few years CCD detectors have been used extensively in electron crystallography of membrane proteins, and in particular, in the study of the molecular transitions which take place during the photo-cycle of the light-driven proton pump bacteriorhodopsin. Direct-detection methods, which avoid the intermediate stages of converting the electron energy into light, offer the possibility of improved spatial resolution compared to CCD detectors; in addition, photon counting and noise-free readout should improve the signal-to-noise ratio

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

    Science.gov (United States)

    Kinoshita, Yoshikazu; Ishimura, Norihisa; Ishihara, Shunji

    2018-04-30

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

  10. The reaction of hydroxylamine with bacteriorhodopsin studied with mutants that have altered photocycles: selective reactivity of different photointermediates.

    Science.gov (United States)

    Subramaniam, S; Marti, T; Rösselet, S J; Rothschild, K J; Khorana, H G

    1991-01-01

    The reaction of the retinylidene Schiff base in bacteriorhodopsin (bR) to the water-soluble reagent hydroxylamine is enhanced by greater than 2 orders of magnitude under illumination. We have used this reaction as a probe for changes in Schiff base reactivity during the photocycle of wild-type bR and mutants defective in proton transport. We report here that under illumination at pH 6, the D85N mutant has a 20-fold lower rate and the D212N mutant has a greater than 4-fold higher rate for the light-dependent reaction with hydroxylamine compared with wild-type bR. In contrast, the reactivities of wild-type bR and the D96N and T46V mutants are similar. It has been previously shown that the D96N and T46V replacements have no significant effect on the kinetics of "M" formation but have dramatic effects on rate of the decay of M. We therefore conclude that the hydroxylamine reaction occurs before formation of the M intermediate. Most likely it occurs at the "L" stage of the cycle and reflects increased water accessibility to the Schiff base due to a light-driven change in protein conformation. PMID:2006195

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

    Science.gov (United States)

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

    2015-10-01

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

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

    NARCIS (Netherlands)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

  14. Lipidic cubic phase serial millisecond crystallography using synchrotron radiation

    Directory of Open Access Journals (Sweden)

    Przemyslaw Nogly

    2015-03-01

    Full Text Available Lipidic cubic phases (LCPs have emerged as successful matrixes for the crystallization of membrane proteins. Moreover, the viscous LCP also provides a highly effective delivery medium for serial femtosecond crystallography (SFX at X-ray free-electron lasers (XFELs. Here, the adaptation of this technology to perform serial millisecond crystallography (SMX at more widely available synchrotron microfocus beamlines is described. Compared with conventional microcrystallography, LCP-SMX eliminates the need for difficult handling of individual crystals and allows for data collection at room temperature. The technology is demonstrated by solving a structure of the light-driven proton-pump bacteriorhodopsin (bR at a resolution of 2.4 Å. The room-temperature structure of bR is very similar to previous cryogenic structures but shows small yet distinct differences in the retinal ligand and proton-transfer pathway.

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

    OpenAIRE

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

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Satoshi Shinozaki

    2016-05-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  18. Nanoscale Electric Characteristics and Oriented Assembly of Halobacterium salinarum Membrane Revealed by Electric Force Microscopy

    Directory of Open Access Journals (Sweden)

    Denghua Li

    2016-11-01

    Full Text Available Purple membranes (PM of the bacteria Halobacterium salinarum are a unique natural membrane where bacteriorhodopsin (BR can convert photon energy and pump protons. Elucidating the electronic properties of biomembranes is critical for revealing biological mechanisms and developing new devices. We report here the electric properties of PMs studied by using multi-functional electric force microscopy (EFM at the nanoscale. The topography, surface potential, and dielectric capacity of PMs were imaged and quantitatively measured in parallel. Two orientations of PMs were identified by EFM because of its high resolution in differentiating electrical characteristics. The extracellular (EC sides were more negative than the cytoplasmic (CP side by 8 mV. The direction of potential difference may facilitate movement of protons across the membrane and thus play important roles in proton pumping. Unlike the side-dependent surface potentials observed in PM, the EFM capacitive response was independent of the side and was measured to be at a dC/dz value of ~5.25 nF/m. Furthermore, by modification of PM with de novo peptides based on peptide-protein interaction, directional oriented PM assembly on silicon substrate was obtained for technical devices. This work develops a new method for studying membrane nanoelectronics and exploring the bioelectric application at the nanoscale.

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

    Science.gov (United States)

    Spugnini, Enrico; Fais, Stefano

    2017-04-01

    One of the unsolved mysteries in oncology includes the strategies that cancer cells adopt to cope with an adverse microenvironment. However, we knew, from the Warburg's discovery that through their metabolism based on sugar fermentation, cancer cells acidify their microenvironment and this progressive acidification induces a selective pressure, leading to the development of very malignant cells entirely armed to survive in the hostile microenvironment generated by their own metabolism. In the last decades a primordial role for proton exchangers has been supported as a key tumor advantage in facing off the acidic milieu. Proton exchangers do not allow intracellular acidification through a continuous elimination of H+ either outside the cells or within the internal vacuoles. This article wants to comment a translational process through that led to the preclinical demonstration that a class of proton pump inhibitors (PPI) exploited worldwide for peptic ulcer treatment and gastroprotection are indeed powerful chemosensitizers as well. In this process we achieved the clinical proof of concept that PPI may well be included in new anti-cancer strategies with a solid background and rationale. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Polarized proton target-IV. Operations manual

    International Nuclear Information System (INIS)

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

    1976-01-01

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  2. Photolytic interruptions of the bacteriorhodopsin photocycle examined by time-resolved resonance raman spectroscopy.

    Science.gov (United States)

    Grieger, I; Atkinson, G H

    1985-09-24

    An investigation of the photolytic conditions used to initiate and spectroscopically monitor the bacteriorhodopsin (BR) photocycle utilizing time-resolved resonance Raman (TR3) spectroscopy has revealed and characterized two photoinduced reactions that interrupt the thermal pathway. One reaction involves the photolytic interconversion of M-412 and M', and the other involves the direct photolytic conversion of the BR-570/K-590 photostationary mixture either to M-412 and M' or to M-like intermediates within 10 ns. The photolytic threshold conditions describing both reactions have been quantitatively measured and are discussed in terms of experimental parameters.

  3. Multifunctional optical security features based on bacteriorhodopsin

    Science.gov (United States)

    Hampp, Norbert A.; Neebe, Martin; Juchem, Thorsten; Wolperdinger, Markus; Geiger, Markus; Schmuck, Arno

    2004-06-01

    Bacteriorhodopsin (BR), a photochromic retinal protein, has been developed into a new materials platform for applications in anti-counterfeiting. The combination of three different properties of the material on its molecular level, a light-inducible color change, photochemical data storage and traceability of the protein due to molecular marker sequences make this protein a promising material for security applications. The crystalline structure of the biopigment combines these properties with high stability. As BR is a biological material specialized knowledge for modification, cost- effective production and suitable processing of the material is required. Photochromic BR-based inks have been developed for screen printing, pad printing and ink jet printing. These prints show a high photochromic sensitivity towards variation of illumination. For this reason it is not possible to reproduce the dynamic color by photocopying. In addition to such visual inspection the printed symbols offer the possibility for digital write-once-read-many (WORM) data storage. Photochemical recording is accomplished by a two-photon process. Recording densities in a range from 106 bit/cm2 to 108 bit/cm2 have been achieved. Data structures are stored in a polarization sensitive mode which allows an easy and efficient data encryption.

  4. Engineering bacterial efflux pumps for solar-powered bioremediation of surface waters.

    Science.gov (United States)

    Kapoor, Vikram; Wendell, David

    2013-05-08

    Antibiotics are difficult to selectively remove from surface waters by present treatment methods. Bacterial efflux pumps have evolved the ability to discriminately expel antibiotics and other noxious agents via proton and ATP driven pathways. Here, we describe light-dependent removal of antibiotics by engineering the bacterial efflux pump AcrB into a proteovesicle system. We have created a chimeric protein with the requisite proton motive force by coupling AcrB to the light-driven proton pump Delta-rhodopsin (dR) via a glycophorin A transmembrane domain. This creates a solar powered protein material capable of selectively capturing antibiotics from bulk solutions. Using environmental water and direct sunlight, our AcrB-dR vesicles removed almost twice as much antibiotic as the treatment standard, activated carbon. Altogether, the AcrB-dR system provides an effective means of extracting antibiotics from surface waters as well as potential antibiotic recovery through vesicle solubilization.

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

    Science.gov (United States)

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

    2016-06-01

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

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

    OpenAIRE

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

    2018-01-01

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

  7. Excited state proton transfer in strongly enhanced GFP (sGFP2).

    Science.gov (United States)

    van Oort, Bart; ter Veer, Mirelle J T; Groot, Marie Louise; van Stokkum, Ivo H M

    2012-07-07

    Proton transfer is an elementary process in biology. Green fluorescent protein (GFP) has served as an important model system to elucidate the mechanistic details of this reaction, because in GFP proton transfer can be induced by light absorption. We have used pump-dump-probe spectroscopy to study how proton transfer through the 'proton-wire' around the chromophore is affected by a combination of mutations in a modern GFP variety (sGFP2). The results indicate that in H(2)O, after absorption of a photon, a proton is transferred (A* → I*) in 5 ps, and back-transferred from a ground state intermediate (I → A) in 0.3 ns, similar to time constants found with GFPuv, although sGFP2 shows less heterogeneous proton transfer. This suggests that the mutations left the proton-transfer largely unchanged, indicating the robustness of the proton-wire. We used pump-dump-probe spectroscopy in combination with target analysis to probe suitability of the sGFP2 fluorophore for super-resolution microscopy.

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

    Science.gov (United States)

    Heading, Robert C

    2017-04-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Usman Hammawa Malabu

    2011-01-01

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

  11. Molecular basis of proton uptake in single and double mutants of cytochrome c oxidase

    Energy Technology Data Exchange (ETDEWEB)

    Henry, Rowan M; Caplan, David; Pomes, Regis [Molecular Structure and Function, Hospital for Sick Children, Toronto, ON, M5G 1X8 (Canada); Fadda, Elisa, E-mail: pomes@sickkids.ca [Department of Chemistry, University of Galway (Ireland)

    2011-06-15

    Cytochrome c oxidase, the terminal enzyme of the respiratory chain, utilizes the reduction of dioxygen into water to pump protons across the mitochondrial inner membrane. The principal pathway of proton uptake into the enzyme, the D channel, is a 2.5 nm long channel-like cavity named after a conserved, negatively charged aspartic acid (D) residue thought to help recruiting protons to its entrance (D132 in the first subunit of the S. sphaeroides enzyme). The single-point mutation of D132 to asparagine (N), a neutral residue, abolishes enzyme activity. Conversely, replacing conserved N139, one-third into the D channel, by D, induces a decoupled phenotype, whereby oxygen reduction proceeds but not proton pumping. Intriguingly, the double mutant D132N/N139D, which conserves the charge of the D channel, restores the wild-type phenotype. We use molecular dynamics simulations and electrostatic calculations to examine the structural and physical basis for the coupling of proton pumping and oxygen chemistry in single and double N139D mutants. The potential of mean force for the conformational isomerization of N139 and N139D side chains reveals the presence of three rotamers, one of which faces the channel entrance. This out-facing conformer is metastable in the wild-type and in the N139D single mutant, but predominant in the double mutant thanks to the loss of electrostatic repulsion with the carboxylate group of D132. The effects of mutations and conformational isomerization on the pKa of E286, an essential proton-shuttling residue located at the top of the D channel, are shown to be consistent with the electrostatic control of proton pumping proposed recently (Fadda et al 2008 Biochim. Biophys. Acta 1777 277-84). Taken together, these results suggest that preserving the spatial distribution of charges at the entrance of the D channel is necessary to guarantee both the uptake and the relay of protons to the active site of the enzyme. These findings highlight the interplay

  12. Molecular basis of proton uptake in single and double mutants of cytochrome c oxidase

    International Nuclear Information System (INIS)

    Henry, Rowan M; Caplan, David; Pomes, Regis; Fadda, Elisa

    2011-01-01

    Cytochrome c oxidase, the terminal enzyme of the respiratory chain, utilizes the reduction of dioxygen into water to pump protons across the mitochondrial inner membrane. The principal pathway of proton uptake into the enzyme, the D channel, is a 2.5 nm long channel-like cavity named after a conserved, negatively charged aspartic acid (D) residue thought to help recruiting protons to its entrance (D132 in the first subunit of the S. sphaeroides enzyme). The single-point mutation of D132 to asparagine (N), a neutral residue, abolishes enzyme activity. Conversely, replacing conserved N139, one-third into the D channel, by D, induces a decoupled phenotype, whereby oxygen reduction proceeds but not proton pumping. Intriguingly, the double mutant D132N/N139D, which conserves the charge of the D channel, restores the wild-type phenotype. We use molecular dynamics simulations and electrostatic calculations to examine the structural and physical basis for the coupling of proton pumping and oxygen chemistry in single and double N139D mutants. The potential of mean force for the conformational isomerization of N139 and N139D side chains reveals the presence of three rotamers, one of which faces the channel entrance. This out-facing conformer is metastable in the wild-type and in the N139D single mutant, but predominant in the double mutant thanks to the loss of electrostatic repulsion with the carboxylate group of D132. The effects of mutations and conformational isomerization on the pKa of E286, an essential proton-shuttling residue located at the top of the D channel, are shown to be consistent with the electrostatic control of proton pumping proposed recently (Fadda et al 2008 Biochim. Biophys. Acta 1777 277-84). Taken together, these results suggest that preserving the spatial distribution of charges at the entrance of the D channel is necessary to guarantee both the uptake and the relay of protons to the active site of the enzyme. These findings highlight the interplay

  13. Molecular basis of proton uptake in single and double mutants of cytochrome c oxidase

    Science.gov (United States)

    Henry, Rowan M.; Caplan, David; Fadda, Elisa; Pomès, Régis

    2011-06-01

    Cytochrome c oxidase, the terminal enzyme of the respiratory chain, utilizes the reduction of dioxygen into water to pump protons across the mitochondrial inner membrane. The principal pathway of proton uptake into the enzyme, the D channel, is a 2.5 nm long channel-like cavity named after a conserved, negatively charged aspartic acid (D) residue thought to help recruiting protons to its entrance (D132 in the first subunit of the S. sphaeroides enzyme). The single-point mutation of D132 to asparagine (N), a neutral residue, abolishes enzyme activity. Conversely, replacing conserved N139, one-third into the D channel, by D, induces a decoupled phenotype, whereby oxygen reduction proceeds but not proton pumping. Intriguingly, the double mutant D132N/N139D, which conserves the charge of the D channel, restores the wild-type phenotype. We use molecular dynamics simulations and electrostatic calculations to examine the structural and physical basis for the coupling of proton pumping and oxygen chemistry in single and double N139D mutants. The potential of mean force for the conformational isomerization of N139 and N139D side chains reveals the presence of three rotamers, one of which faces the channel entrance. This out-facing conformer is metastable in the wild-type and in the N139D single mutant, but predominant in the double mutant thanks to the loss of electrostatic repulsion with the carboxylate group of D132. The effects of mutations and conformational isomerization on the pKa of E286, an essential proton-shuttling residue located at the top of the D channel, are shown to be consistent with the electrostatic control of proton pumping proposed recently (Fadda et al 2008 Biochim. Biophys. Acta 1777 277-84). Taken together, these results suggest that preserving the spatial distribution of charges at the entrance of the D channel is necessary to guarantee both the uptake and the relay of protons to the active site of the enzyme. These findings highlight the interplay

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

    Science.gov (United States)

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

    2018-04-01

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

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Science.gov (United States)

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

    2013-09-01

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

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

    Science.gov (United States)

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

    2017-07-04

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

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

    Directory of Open Access Journals (Sweden)

    Meritxell Pujal Herranz

    2016-09-01

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

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

    DEFF Research Database (Denmark)

    Krag, Mette; Perner, Anders; Wetterslev, Jørn

    2016-01-01

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

  20. Activation of acid-sensing ion channels by localized proton transient reveals their role in proton signaling.

    Science.gov (United States)

    Zeng, Wei-Zheng; Liu, Di-Shi; Liu, Lu; She, Liang; Wu, Long-Jun; Xu, Tian-Le

    2015-09-15

    Extracellular transients of pH alterations likely mediate signal transduction in the nervous system. Neuronal acid-sensing ion channels (ASICs) act as sensors for extracellular protons, but the mechanism underlying ASIC activation remains largely unknown. Here, we show that, following activation of a light-activated proton pump, Archaerhodopsin-3 (Arch), proton transients induced ASIC currents in both neurons and HEK293T cells co-expressing ASIC1a channels. Using chimera proteins that bridge Arch and ASIC1a by a glycine/serine linker, we found that successful coupling occurred within 15 nm distance. Furthermore, two-cell sniffer patch recording revealed that regulated release of protons through either Arch or voltage-gated proton channel Hv1 activated neighbouring cells expressing ASIC1a channels. Finally, computational modelling predicted the peak proton concentration at the intercellular interface to be at pH 6.7, which is acidic enough to activate ASICs in vivo. Our results highlight the pathophysiological role of proton signalling in the nervous system.

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

    Science.gov (United States)

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

    2013-08-21

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

  2. Reconstitution of halorhodopsin

    Energy Technology Data Exchange (ETDEWEB)

    Kong, T.

    1989-11-01

    Halobacterium halobium contains a family of retinal-bound proteins: bacteriorhodopsin (bR) which mediates phototrophic growth as a light-riven proton pump, halorhodopsin (hR) which is a light-driven chloride pump, and one or more sensory rhodopsins (sR) which mediate a phototactic response. Two-dimensional crystallization of halorhodopsin has been attempted though the reconstitution of purified halorhodopsin with purple membrane lipid for electron microscopy work. The first important step for crystallization is to get a homogeneous protein which is pure and not denatured. Homogeneous halorhodopsin has been obtained by a modification of existing purification methods. Some nice looking membrane patches which have the same density as purple membrane have been obtained. But unfortunately, they are not crystalline. The procedure of hR reconstitution is described in detail and some other strategies to induce the protein crystal in the reconstituted membrane are discussed in this dissertation. 76 refs., 20 figs., 6 tabs.

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

    Science.gov (United States)

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

    2013-10-24

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

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

    Science.gov (United States)

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

    2015-09-01

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

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

    Science.gov (United States)

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

    2007-06-01

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

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

    Science.gov (United States)

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

    2015-05-28

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

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

    Science.gov (United States)

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

    2014-12-24

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

  8. Proton transfer events in GFP.

    Science.gov (United States)

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

    2011-09-28

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

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

    Science.gov (United States)

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

    2013-01-01

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

  10. Observation of helix associations for insertion of a retinal molecule and distortions of helix structures in bacteriorhodopsin

    Science.gov (United States)

    Urano, Ryo; Okamoto, Yuko

    2015-12-01

    We applied a newly proposed prediction method for membrane protein structures to bacteriorhodopsin that has distorted transmembrane helices in the native structure. This method uses an implicit membrane model, which restricts sampling space during folding in a membrane region, and includes helix bending. Replica-exchange simulations were performed with seven transmembrane helices only without a retinal molecule. Obtained structures were classified into clusters of similar structures, which correspond to local-minimum free energy states. The two lowest free energy states corresponded to a native-like structure with the correct empty space for retinal and a structure with this empty space filled with a helix. Previous experiments of bacteriorhodopsin suggested that association of transmembrane helices enables them to make a room for insertion of a retinal. Our results are consistent with these results. Moreover, distortions of helices in the native-like structures were successfully reproduced. In the distortions, whereas the locations of kinks for all helices were similar to those of Protein Data Bank's data, the amount of bends was more similar for helices away from the retinal than for those close to the retinal in the native structure. This suggests a hypothesis that the amino-acid sequence specifies the location of kinks in transmembrane helices and that the amount of distortions depends on the interactions with the surrounding molecules such as neighboring helices, lipids, and retinal.

  11. Surface pH controls purple-to-blue transition of bacteriorhodopsin. A theoretical model of purple membrane surface

    OpenAIRE

    Szundi, I.; Stoeckenius, W.

    1989-01-01

    We have developed a surface model of purple membrane and applied it in an analysis of the purple-to-blue color change of bacteriorhodopsin which is induced by acidification or deionization. The model is based on dissociation and double layer theory and the known membrane structure. We calculated surface pH, ion concentrations, charge density, and potential as a function of bulk pH and concentration of mono- and divalent cations. At low salt concentrations, the surface pH is significantly lowe...

  12. An analysis of 3D solvation structure in biomolecules: application to coiled coil serine and bacteriorhodopsin.

    Science.gov (United States)

    Hirano, Kenji; Yokogawa, Daisuke; Sato, Hirofumi; Sakaki, Shigeyoshi

    2010-06-17

    Three-dimensional (3D) solvation structure around coiled coil serine (Coil-Ser) and inner 3D hydration structure in bacteriorhodopsin (bR) were studied using a recently developed method named multicenter molecular Ornstein-Zernike equation (MC-MOZ) theory. In addition, a procedure for analyzing the 3D solvent distribution was proposed. The method enables us to calculate the coordination number of solvent water as well as the strength of hydrogen bonding between the water molecule and the protein. The results for Coil-Ser and bR showed very good agreement with the experimental observations.

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

    Directory of Open Access Journals (Sweden)

    Rok Orel

    2017-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Ranstam Jonas

    2009-04-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-09-30

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

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

    OpenAIRE

    Takahashi, Megumi; Takagi, Shin

    2017-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sorena Keihani

    2018-01-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

  2. The Toolbox of Proton Spin Physics in Historical Perspective

    International Nuclear Information System (INIS)

    Haeberli, Willy

    2008-01-01

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

  3. Transcriptome analysis of Haloquadratum walsbyi: vanity is but the surface.

    Science.gov (United States)

    Bolhuis, Henk; Martín-Cuadrado, Ana Belén; Rosselli, Riccardo; Pašić, Lejla; Rodriguez-Valera, Francisco

    2017-07-03

    Haloquadratum walsbyi dominates saturated thalassic lakes worldwide where they can constitute up to 80-90% of the total prokaryotic community. Despite the abundance of the enigmatic square-flattened cells, only 7 isolates are currently known with 2 genomes fully sequenced and annotated due to difficulties to grow them under laboratory conditions. We have performed a transcriptomic analysis of one of these isolates, the Spanish strain HBSQ001 in order to investigate gene transcription under light and dark conditions. Despite a potential advantage for light as additional source of energy, no significant differences were found between light and dark expressed genes. Constitutive high gene expression was observed in genes encoding surface glycoproteins, light mediated proton pumping by bacteriorhodopsin, several nutrient uptake systems, buoyancy and storage of excess carbon. Two low expressed regions of the genome were characterized by a lower codon adaptation index, low GC content and high incidence of hypothetical genes. Under the extant cultivation conditions, the square hyperhalophile devoted most of its transcriptome towards processes maintaining cell integrity and exploiting solar energy. Surface glycoproteins are essential for maintaining the large surface to volume ratio that facilitates light and organic nutrient harvesting whereas constitutive expression of bacteriorhodopsin warrants an immediate source of energy when light becomes available.

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-07-07

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

  6. Arabidopsis type I proton-pumping pyrophosphatase expresses strongly in phloem, where it is required for pyrophosphate metabolism and photosynthate partitioning.

    Science.gov (United States)

    Pizzio, Gaston A; Paez-Valencia, Julio; Khadilkar, Aswad S; Regmi, Kamesh; Patron-Soberano, Araceli; Zhang, Shangji; Sanchez-Lares, Jonathan; Furstenau, Tara; Li, Jisheng; Sanchez-Gomez, Concepcion; Valencia-Mayoral, Pedro; Yadav, Umesh P; Ayre, Brian G; Gaxiola, Roberto A

    2015-04-01

    Phloem loading is a critical process in plant physiology. The potential of regulating the translocation of photoassimilates from source to sink tissues represents an opportunity to increase crop yield. Pyrophosphate homeostasis is crucial for normal phloem function in apoplasmic loaders. The involvement of Arabidopsis (Arabidopsis thaliana) type I proton-pumping pyrophosphatase (AVP1) in phloem loading was analyzed at genetic, histochemical, and physiological levels. A transcriptional AVP1 promoter::GUS fusion revealed phloem activity in source leaves. Ubiquitous AVP1 overexpression (35S::AVP1 cassette) enhanced shoot biomass, photoassimilate production and transport, rhizosphere acidification, and expression of sugar-induced root ion transporter genes (POTASSIUM TRANSPORTER2 [KUP2], NITRATE TRANSPORTER2.1 [NRT2.1], NRT2.4, and PHOSPHATE TRANSPORTER1.4 [PHT1.4]). Phloem-specific AVP1 overexpression (Commelina Yellow Mottle Virus promoter [pCOYMV]::AVP1) elicited similar phenotypes. By contrast, phloem-specific AVP1 knockdown (pCoYMV::RNAiAVP1) resulted in stunted seedlings in sucrose-deprived medium. We also present a promoter mutant avp1-2 (SALK046492) with a 70% reduction of expression that did not show severe growth impairment. Interestingly, AVP1 protein in this mutant is prominent in the phloem. Moreover, expression of an Escherichia coli-soluble pyrophosphatase in the phloem (pCoYMV::pyrophosphatase) of avp1-2 plants resulted in severe dwarf phenotype and abnormal leaf morphology. We conclude that the Proton-Pumping Pyrophosphatase AVP1 localized at the plasma membrane of the sieve element-companion cell complexes functions as a synthase, and that this activity is critical for the maintenance of pyrophosphate homeostasis required for phloem function. © 2015 American Society of Plant Biologists. All Rights Reserved.

  7. Structure and operation of bacterial tripartite pumps.

    Science.gov (United States)

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

    2013-01-01

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

  8. Positive Darwinian selection in the piston that powers proton pumps in complex I of the mitochondria of Pacific salmon.

    Science.gov (United States)

    Garvin, Michael R; Bielawski, Joseph P; Gharrett, Anthony J

    2011-01-01

    The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm.

  9. Positive Darwinian Selection in the Piston That Powers Proton Pumps in Complex I of the Mitochondria of Pacific Salmon

    Science.gov (United States)

    Garvin, Michael R.; Bielawski, Joseph P.; Gharrett, Anthony J.

    2011-01-01

    The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm. PMID:21969854

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Science.gov (United States)

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

    2009-03-01

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

  12. Surface pH controls purple-to-blue transition of bacteriorhodopsin. A theoretical model of purple membrane surface.

    Science.gov (United States)

    Szundi, I; Stoeckenius, W

    1989-08-01

    We have developed a surface model of purple membrane and applied it in an analysis of the purple-to-blue color change of bacteriorhodopsin which is induced by acidification or deionization. The model is based on dissociation and double layer theory and the known membrane structure. We calculated surface pH, ion concentrations, charge density, and potential as a function of bulk pH and concentration of mono- and divalent cations. At low salt concentrations, the surface pH is significantly lower than the bulk pH and it becomes independent of bulk pH in the deionized membrane suspension. Using an experimental acid titration curve for neutral, lipid-depleted membrane, we converted surface pH into absorption values. The calculated bacteriohodopsin color changes for acidification of purple, and titrations of deionized blue membrane with cations or base agree well with experimental results. No chemical binding is required to reproduce the experimental curves. Surface charge and potential changes in acid, base and cation titrations are calculated and their relation to the color change is discussed. Consistent with structural data, 10 primary phosphate and two basic surface groups per bacteriorhodopsin are sufficient to obtain good agreement between all calculated and experimental curves. The results provide a theoretical basis for our earlier conclusion that the purple-to-blue transition must be attributed to surface phenomena and not to cation binding at specific sites in the protein.

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

    Directory of Open Access Journals (Sweden)

    Michael J. Van Oosten

    2017-07-01

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

  14. Excited state proton transfer in strongly enhanced GFP (sGFP2)

    NARCIS (Netherlands)

    van Oort, B.F.; ter Veer, M.J.T.; Groot, M.L.; van Stokkum, I.H.M.

    2012-01-01

    Proton transfer is an elementary process in biology. Green fluorescent protein (GFP) has served as an important model system to elucidate the mechanistic details of this reaction, because in GFP proton transfer can be induced by light absorption. We have used pump-dump-probe spectroscopy to study

  15. Two-photon polarization data storage in bacteriorhodopsin films and its potential use in security applications

    Energy Technology Data Exchange (ETDEWEB)

    Imhof, Martin; Hampp, Norbert, E-mail: hampp@staff.uni-marburg.de [Department of Chemistry, Material Sciences Center, University of Marburg, Hans-Meerwein-Str., D-35032 Marburg (Germany); Rhinow, Daniel [Max-Planck-Institute of Biophysics, Max-von-Laue-Straße 3, D-60438 Frankfurt (Germany)

    2014-02-24

    Bacteriorhodopsin (BR) films allow write-once-read-many recording of polarization data by a two-photon-absorption (TPA) process. The optical changes in BR films induced by the TPA recording were measured and the Müller matrix of a BR film was determined. A potential application of BR films in security technology is shown. Polarization data can be angle-selective retrieved with high signal-to-noise ratio. The BR film does not only carry optical information but serves also as a linear polarizer. This enables that polarization features recorded in BR films may be retrieved by merely using polarized light from a mobile phone display.

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

    Science.gov (United States)

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

    2015-02-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  18. Proton gradients and proton-dependent transport processes in the chloroplast

    Directory of Open Access Journals (Sweden)

    Ricarda eHöhner

    2016-02-01

    Full Text Available Proton gradients are fundamental to chloroplast function. Across thylakoid membranes, the light induced proton gradient is essential for ATP synthesis. As a result of proton pumping into the thylakoid lumen, an alkaline stromal pH develops, which is required for full activation of pH-dependent Calvin Benson cycle enzymes. This implies that a pH gradient between the cytosol (pH 7 and the stroma (pH 8 is established upon illumination. To maintain this pH gradient chloroplasts actively extrude protons. More than 30 years ago it was already established that these proton fluxes are electrically counterbalanced by Mg2+, K+ or Cl- fluxes, but only recently the first transport systems that regulate the pH gradient were identified. Notably several (Na+,K+/H+ antiporter systems where identified, that play a role in pH gradient regulation, ion homeostasis, osmoregulation, or coupling of secondary active transport. The established pH gradients are important to drive uptake of essential ions and solutes, but not many transporters involved have been identified to date. In this mini review we summarize the current status in the field and the open questions that need to be addressed in order to understand how pH gradients are maintained, how this is interconnected with other transport processes and what this means for chloroplast function.

  19. Positive Darwinian selection in the piston that powers proton pumps in complex I of the mitochondria of Pacific salmon.

    Directory of Open Access Journals (Sweden)

    Michael R Garvin

    Full Text Available The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm.

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

    Directory of Open Access Journals (Sweden)

    Sloan Sheldon

    2008-05-01

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

  1. Polarized proton target with horizontal spin orientation

    International Nuclear Information System (INIS)

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

    1988-01-01

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

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-04-28

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-05-04

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

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

    Science.gov (United States)

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

    2006-01-01

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

  8. Acidic digestion in a teleost: postprandial and circadian pattern of gastric pH, pepsin activity, and pepsinogen and proton pump mRNAs expression.

    Science.gov (United States)

    Yúfera, Manuel; Moyano, Francisco J; Astola, Antonio; Pousão-Ferreira, Pedro; Martínez-Rodríguez, Gonzalo

    2012-01-01

    Two different modes for regulation of stomach acid secretion have been described in vertebrates. Some species exhibit a continuous acid secretion maintaining a low gastric pH during fasting. Others, as some teleosts, maintain a neutral gastric pH during fasting while the hydrochloric acid is released only after the ingestion of a meal. Those different patterns seem to be closely related to specific feeding habits. However, our recent observations suggest that this acidification pattern could be modified by changes in daily feeding frequency and time schedule. The aim of this study was to advance in understanding the regulation mechanisms of stomach digestion and pattern of acid secretion in teleost fish. We have examined the postprandial pattern of gastric pH, pepsin activity, and mRNA expression for pepsinogen and proton pump in white seabream juveniles maintained under a light/dark 12/12 hours cycle and receiving only one morning meal. The pepsin activity was analyzed according to the standard protocol buffering at pH 2 and using the actual pH measured in the stomach. The results show how the enzyme precursor is permanently available while the hydrochloric acid, which activates the zymogen fraction, is secreted just after the ingestion of food. Results also reveal that analytical protocol at pH 2 notably overestimates true pepsin activity in fish stomach. The expression of the mRNA encoding pepsinogen and proton pump exhibited almost parallel patterns, with notable increases during the darkness period and sharp decreases just before the morning meal. These results indicate that white seabream uses the resting hours for recovering the mRNA stock that will be quickly used during the feeding process. Our data clearly shows that both daily illumination pattern and feeding time are involved at different level in the regulation of the secretion of digestive juices.

  9. Acidic digestion in a teleost: postprandial and circadian pattern of gastric pH, pepsin activity, and pepsinogen and proton pump mRNAs expression.

    Directory of Open Access Journals (Sweden)

    Manuel Yúfera

    Full Text Available Two different modes for regulation of stomach acid secretion have been described in vertebrates. Some species exhibit a continuous acid secretion maintaining a low gastric pH during fasting. Others, as some teleosts, maintain a neutral gastric pH during fasting while the hydrochloric acid is released only after the ingestion of a meal. Those different patterns seem to be closely related to specific feeding habits. However, our recent observations suggest that this acidification pattern could be modified by changes in daily feeding frequency and time schedule. The aim of this study was to advance in understanding the regulation mechanisms of stomach digestion and pattern of acid secretion in teleost fish. We have examined the postprandial pattern of gastric pH, pepsin activity, and mRNA expression for pepsinogen and proton pump in white seabream juveniles maintained under a light/dark 12/12 hours cycle and receiving only one morning meal. The pepsin activity was analyzed according to the standard protocol buffering at pH 2 and using the actual pH measured in the stomach. The results show how the enzyme precursor is permanently available while the hydrochloric acid, which activates the zymogen fraction, is secreted just after the ingestion of food. Results also reveal that analytical protocol at pH 2 notably overestimates true pepsin activity in fish stomach. The expression of the mRNA encoding pepsinogen and proton pump exhibited almost parallel patterns, with notable increases during the darkness period and sharp decreases just before the morning meal. These results indicate that white seabream uses the resting hours for recovering the mRNA stock that will be quickly used during the feeding process. Our data clearly shows that both daily illumination pattern and feeding time are involved at different level in the regulation of the secretion of digestive juices.

  10. Circulating aldosterone induces the apical accumulation of the proton pumping V-ATPase and increases proton secretion in clear cells in the caput epididymis.

    Science.gov (United States)

    Roy, Jeremy W; Hill, Eric; Ruan, Ye Chun; Vedovelli, Luca; Păunescu, Teodor G; Brown, Dennis; Breton, Sylvie

    2013-08-15

    Clear cells express the vacuolar proton-pumping H(+)-ATPase (V-ATPase) and acidify the lumen of the epididymis, a process that is essential for male fertility. The renin-angiotensin-aldosterone system (RAAS) regulates fluid and electrolyte balance in the epididymis, and a previous study showed binding of aldosterone exclusively to epididymal clear cells (Hinton BT, Keefer DA. Steroid Biochem 23: 231-233, 1985). We examined here the role of aldosterone in the regulation of V-ATPase in the epididymis. RT-PCR showed expression of the mineralocorticoid receptor [MR; nuclear receptor subfamily 3, group C member 2 (NR3C2)] and 11-β-dehydrogenase isozyme 2 (HSD11β2) mRNAs specifically in clear cells, isolated by fluorescence-activated cell sorting from B1-enhanced green fluorescent protein (EGFP) mice. Tail vein injection of adult rats with aldosterone, 1,2-dioctanoyl-sn-glycerol (DOG), or 8-(4-chlorophenylthio)-cAMP (cpt-cAMP) induced V-ATPase apical membrane accumulation and extension of V-ATPase-labeled microvilli in clear cells in the caput epididymis but not in the cauda. V-ATPase activity was measured in EGFP-expressing clear cells using the intracellular pH (pHi)-sensing dye seminaphthorhodafluor-5F-5-(and 6)-carboxylic acid, acetoxymethyl ester acetate (SNARF-5F). Aldosterone induced a rapid increase in the rate of Na(+)- and bicarbonate-independent pHi recovery following an NH4Cl-induced acid load in clear cells isolated from the caput but not the cauda. This effect was abolished by concanamycin A, spironolactone, and chelerythrine but not myristoylated-protein kinase inhibitor (mPKI) or mifepristone. Thus aldosterone increases V-ATPase-dependent proton secretion in clear cells in the caput epididymis via MR/NR3C2 and PKC activation. This study, therefore, identifies aldosterone as an active member of the RAAS for the regulation of luminal acidification in the proximal epididymis.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-12-27

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

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

    Science.gov (United States)

    Sheele, Johnathan M

    2017-12-01

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

  14. Nanosecond retinal structure changes in K-590 during the room-temperature bacteriorhodopsin photocycle: picosecond time-resolved coherent anti-stokes Raman spectroscopy

    OpenAIRE

    Weidlich, O.; Ujj, L.; Jäger, F.; Atkinson, G.H.

    1997-01-01

    Time-resolved vibrational spectra are used to elucidate the structural changes in the retinal chromophore within the K-590 intermediate that precedes the formation of the L-550 intermediate in the room-temperature (RT) bacteriorhodopsin (BR) photocycle. Measured by picosecond time-resolved coherent anti-Stokes Raman scattering (PTR/CARS), these vibrational data are recorded within the 750 cm-1 to 1720 cm-1 spectral region and with time delays of 50-260 ns after the RT/BR photocycle is optical...

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

    Science.gov (United States)

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

    2015-04-21

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

  16. Multilayer models of photosynthetic membranes. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Brocklehurst, J R; Flanagan, M T

    1982-01-01

    The primary aim of this project has been to build an artificial membrane in which is incorporated, in a functional state, the protein bacteriorhodopsin responsible for generating an electrical potential difference across the membrane of the photosynthetic bacterium, halobacterium halobium, and to investigate the use of this artificial system as the basis of a solar cell. the bacteriorhodopsin has been incorporated into Langmuir-Blodgett multilayers. If ths supporting filter is then illuminated, a potential difference is generated between the two compartments. The lipid in the filter appears to act as a charge carrier for protons, the charge species that forms the electrochemical gradient generated by the bacteriorhodopsin when this molecule absorbs light. The internal resistances of such solar cells were determined and found to be so high that the cells could not be seriously considered as competitors with classical semiconductor cells. Multilayerswere deposited onto filters in which ion carriers that make the filters permeable to sodium ions had been dissolved in the paraffin. The photovoltage obtained indicated that protons transferred from one side of the filter to the other by the action of the bacteriorhodopsin were bing exchanged for sodium ions. A secondary aim of the project has been to examine the possibility of depositing mixed multilayers of a dye and a long chain quinone onto a semiconductor surface. A sensitizing multilayer has been prepared and the mobility of long chain quinones within the layers is high enough to warrant further research. However, it was found that, with the dyes and quinones used, quenched complexes were formed which would not act as sensitizers.

  17. The Integration of Bacteriorhodopsin Proteins with Semiconductor Heterostructure Devices

    Science.gov (United States)

    Xu, Jian

    2008-03-01

    Bioelectronics has emerged as one of the most rapidly developing fields among the active frontiers of interdisciplinary research. A major thrust in this field is aimed at the coupling of the technologically-unmatched performance of biological systems, such as neural and sensing functions, with the well developed technology of microelectronics and optoelectronics. To this end we have studied the integration of a suitably engineered protein, bacteriorhodopsin (BR), with semiconductor optoelectronic devices and circuits. Successful integration will potentially lead to ultrasensitive sensors with polarization selectivity and built-in preprocessing capabilities that will be useful for high speed tracking, motion and edge detection, biological detection, and artificial vision systems. In this presentation we will summarize our progresses in this area, which include fundamental studies on the transient dynamics of photo-induced charge shift in BR and the coupling mechanism at protein-semiconductor interface for effective immobilizing and selectively integrating light sensitive proteins with microelectronic devices and circuits, and the device engineering of BR-transistor-integrated optical sensors as well as their applications in phototransceiver circuits. Work done in collaboration with Pallab Bhattacharya, Jonghyun Shin, Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI; Robert R. Birge, Department of Chemistry, University of Connecticut, Storrs, CT 06269; and György V'ar'o, Institute of Biophysics, Biological Research Center of the Hungarian Academy of Science, H-6701 Szeged, Hungary.

  18. Tunneling induced electron transfer between separated protons

    Science.gov (United States)

    Vindel-Zandbergen, Patricia; Meier, Christoph; Sola, Ignacio R.

    2018-04-01

    We study electron transfer between two separated protons using local control theory. In this symmetric system one can favour a slow transfer by biasing the algorithm, achieving high efficiencies for fixed nuclei. The solution can be parametrized using a sequence of a pump followed by a dump pulse that lead to tunneling-induced electron transfer. Finally, we study the effect of the nuclear kinetic energy on the efficiency. Even in the absence of relative motion between the protons, the spreading of the nuclear wave function is enough to reduce the yield of electronic transfer to less than one half.

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

    Czech Academy of Sciences Publication Activity Database

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

    2017-01-01

    Roč. 3, č. 9 (2017), č. článku e1603187. ISSN 2375-2548 R&D Projects: GA ČR(CZ) GA17-04828S Institutional support: RVO:60077344 Keywords : sensory rhodopsin * membrane-proteins * purple membrane * proton pump Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology

  20. The proton radius puzzle

    Science.gov (United States)

    Bonesini, Maurizio

    2017-12-01

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

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

    Science.gov (United States)

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

    2015-02-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Andrei Vasile OLTEANU

    2015-12-01

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

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

    Science.gov (United States)

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

    2017-07-01

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

  5. Synthesis of 13C and 2H labelled retinals: spectroscopic investigations on isotopically labelled rhodopsin and bacteriorhodopsin

    International Nuclear Information System (INIS)

    Pardoen, J.A.

    1986-01-01

    In order to develop probes of the structure of chromophores, the author introduces isotopic modifications at specific chromophoric positions as structural probes. To obtain bacteriorhodopsin, rhodopsin and their photoproducts labelled in the chromophore at selected positions, bacterioopsin and opsin were reacted with the appropriate labelled a11-trans and 11-cis retinals. The author describes the synthesis of a11-trans retinal selectively 13 C labelled at different positions. The characterization of these labelled a11-trans retinals by mass spectrometry, 300 MHz 1 H NMR and 75 MHz 13 C NMR spectroscopy is given. The photochemical preparation and isolation of the pure 9-, 11- and 13-cis forms is described in the experimental part. (Auth.)

  6. Role of Asp544 in subunit I for Na+ pumping by Vitreoscilla cytochrome bo

    International Nuclear Information System (INIS)

    Chung, Yeon T.; Stark, Benjamin C.; Webster, Dale A.

    2006-01-01

    The conserved Glu540 in subunit I of Escherichia coli cytochrome bo (a H + pump) is replaced by Asp544 in the Vitreoscilla enzyme (a Na + pump). Site-directed mutagenesis of the Vitreoscilla cytochrome bo operon changed this Asp to Glu, and both wild type and mutant cyo's were transformed into E. coli strain GV100, which lacks cytochrome bo. Compared to the wild type transformant the Asp544Glu transformant had decreased ability to pump Na + as well as decreased stimulation in respiratory activity in the presence of Na + . Preliminary experiments indicated that this mutant also had increased ability to pump protons, suggesting that this single change may provide cation pumping specificity in this group of enzymes

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

    Science.gov (United States)

    Saniee, Parastoo; Shahreza, Somayeh; Siavoshi, Farideh

    2016-04-01

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

  8. Proton dynamics in cancer.

    Science.gov (United States)

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

    2010-06-15

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

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

    Science.gov (United States)

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

    2018-03-08

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

  10. Molecular cloning and sequence of cDNA encoding the plasma membrane proton pump (H+-ATPase) of Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Harper, J.F.; Surowy, T.K.; Sussman, M.R.

    1989-01-01

    In plants, the transport of solutes across the plasma membrane is driven by a proton pump (H + -ATPase) that produces an electric potential and pH gradient. The authors isolated and sequenced a full-length cDNA clone that encodes this enzyme in Arabidopsis thaliana. The protein predicted from its nucleotide sequence encodes 959 amino acids and has a molecular mass of 104,207 Da. The plant protein shows structural features common to a family of cation-translocating ATPases found in the plasma membrane of prokaryotic and eukaryotic cells, with the greatest overall identity in amino acid sequence (36%) to the H + -ATPase observed in the plasma membrane of fungi. The structure predicted from a hydropathy plant contains at least eight transmembrane segments, with most of the protein (73%) extending into the cytoplasm and only 5% of the residues exposed on the external surface. Unique features of the plant enzyme include diverged sequences at the amino and carboxyl termini as well as greater hydrophilic character in three extracellular loops

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

    Directory of Open Access Journals (Sweden)

    Jennifer L. Czwornog

    2015-10-01

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

  12. An intelligent displacement pumping film system: A new concept for enhancing heavy metal ion removal efficiency from liquid waste

    International Nuclear Information System (INIS)

    Wang, Zhongde; Feng, Yanting; Hao, Xiaogang; Huang, Wei; Guan, Guoqing; Abudula, Abuliti

    2014-01-01

    Highlights: • A new concept for design of an intelligent displacement pumping film was proposed. • As-prepared ESIX hybrid film system showed excellent Ni 2+ uptake/exclude rate. • Piston-like proton pumping effect existed in the prepared ESIX hybrid film. • The mechanism of the ion pumping effect was proved by XPS analysis. - Abstract: A concept of electrochemically switched ion exchange (ESIX) hybrid film system with piston-like proton pumping effect for the removal of heavy metal ions was proposed. Based on this concept, a novel ESIX hybrid film composed of layered alpha zirconium phosphate (α-Zr(HPO 4 ) 2 ; α-ZrP) nanosheets intercalated with a potential-responsive conducting polyaniline (PANI) was developed for the removal of Ni 2+ ions from wastewater. It is expected that the space between α-ZrP nanosheets acts as the reservoir for the functional ions while the intercalated PANI works as the potential-sensitive function element for piston-like proton pumping in such ESIX hybrid films. The prepared ESIX hybrid film showed an excellent property of rapid removal of Ni 2+ ions from wastewater with a high selectivity. The used film was simply regenerated by only altering the applied potential. The ion pumping effect for the ESIX of Ni 2+ ions using this kind of film was proved via XPS analysis. The proposed ESIX hybrid film should have high potential for the removal of Ni 2+ ions and/or other heavy metal ions from wastewater in various industrial processes

  13. Exchangers man the pumps

    Science.gov (United States)

    Barkla, Bronwyn J; Hirschi, Kendal D

    2008-01-01

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

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

    Science.gov (United States)

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

    2017-03-21

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

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

    Science.gov (United States)

    Barletta, Jeffrey F; Sclar, David A

    2014-01-01

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

  16. Measurements of photoinduced refractive index changes in ...

    Indian Academy of Sciences (India)

    Abstract. We report the pump–probe measurements of nonlinear refractive index changes in photochromic bacteriorhodopsin films. The photoinduced absorption is caused by pump beam at 532 nm and the accompanying refractive index changes are studied using a probe beam at 633 nm. The proposed technique is ...

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

    Directory of Open Access Journals (Sweden)

    Di Pierro F

    2013-03-01

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

  18. Biosolar energy generation and harvesting from biomolecule-copolymer hybrid systems

    Science.gov (United States)

    Chu, Bong-Chieh Benjamin

    Alternative energy sources have become an increasingly important topic as energy needs outpace supply. Furthermore, as the world moves into the digital age of portable electronics, highly efficient and lightweight energy sources will need to be developed. Current technology, such as lithium ion batteries, provide enough power to run portable electronics for hours or days, but can still allow for improvement in their power density (W/kg). Utilizing energy-transducing membrane proteins, which are by nature highly efficient, it is possible to engineer biological-based energy sources with energy densities far greater than any solid-state systems. Furthermore, solar powered membrane proteins have the added benefit of a virtually unlimited supply of energy. This work has developed protein-polymer hybrid films and nanoscale vesicles for a variety of applications from fuel-cell technology to biological-based photovoltaics. Bacteriorhodopsin (BR), a light-activated proton pump, and Cytochrome C Oxidase (COX), a protein involved in the electron transport chain in mitochondria, were reconstituted into biomimetic triblock copolymer membranes. Block copolymer membranes mimic the amphiphilic nature of a natural lipid bilayer but exhibit greater mechanical stability due to UV-polymerizable endgroups. In BR/COX functionalized nanovesicles, proton gradients generated by the light-activated proton pumping of BR are used to drive COX in reverse to generate electrons, providing a hybrid biologically-active polymer to convert solar energy to chemical energy, and finally to electrical energy. This work has found protein activity in planar membranes through the photoelectric current generation by BR and the proton pumping activity of BR-functionalized polymer membranes deposited onto proton exchange membranes, as well as the coupled functionality of BR and COX through current generation in cyclic voltammetry and direct current measurements. Current switching between light and dark

  19. The effects of heavy water in the proteorhodopsin photocycle

    International Nuclear Information System (INIS)

    Szakacs, Juliana; Lakatos, Melinda; Ganea, Constanta; Varo, Gy.

    2005-01-01

    The proton transporting photocycle of the proteorhodopsin at its normal pH (9.5) shows a marked deuterium effect. It was shown earlier that the intermediates N and PR' are responsible for the proton uptake and release. By proton-deuteron exchange the M 2 -N and N-PR' transitions become 2-3 times slower. On the contrary, the early μs domain is less affected than the decay part of the photocycle. The effects measured on proteorhodopsin are very similar to those measured on bacteriorhodopsin. (authors)

  20. Proton dynamics in cancer

    Directory of Open Access Journals (Sweden)

    Pouysségur Jacques

    2010-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Nigam H Shah

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

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

    Science.gov (United States)

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

    2010-07-01

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

  3. Cytochrome cbb3 of Thioalkalivibrio is a Na+-pumping cytochrome oxidase

    NARCIS (Netherlands)

    Muntyan, M.S.; Cherepanov, D.A.; Malinen, A.M.; Bloch, D.A.; Sorokin, D.Y.; Severina, I.I.; Ivashina, T.V.; Lahti, R.; Muyzer, G.; Skulachev, V.P.

    2015-01-01

    Cytochrome c oxidases (Coxs) are the basic energy transducers in the respiratory chain of the majority of aerobic organisms. Coxs studied to date are redox-driven proton-pumping enzymes belonging to one of three subfamilies: A-, B-, and C-type oxidases. The C-type oxidases (cbb3 cytochromes), which

  4. Coherent evolution of parahydrogen induced polarisation using laser pump, NMR probe spectroscopy: Theoretical framework and experimental observation.

    Science.gov (United States)

    Halse, Meghan E; Procacci, Barbara; Henshaw, Sarah-Louise; Perutz, Robin N; Duckett, Simon B

    2017-05-01

    We recently reported a pump-probe method that uses a single laser pulse to introduce parahydrogen (p-H 2 ) into a metal dihydride complex and then follows the time-evolution of the p-H 2 -derived nuclear spin states by NMR. We present here a theoretical framework to describe the oscillatory behaviour of the resultant hyperpolarised NMR signals using a product operator formalism. We consider the cases where the p-H 2 -derived protons form part of an AX, AXY, AXYZ or AA'XX' spin system in the product molecule. We use this framework to predict the patterns for 2D pump-probe NMR spectra, where the indirect dimension represents the evolution during the pump-probe delay and the positions of the cross-peaks depend on the difference in chemical shift of the p-H 2 -derived protons and the difference in their couplings to other nuclei. The evolution of the NMR signals of the p-H 2 -derived protons, as well as the transfer of hyperpolarisation to other NMR-active nuclei in the product, is described. The theoretical framework is tested experimentally for a set of ruthenium dihydride complexes representing the different spin systems. Theoretical predictions and experimental results agree to within experimental error for all features of the hyperpolarised 1 H and 31 P pump-probe NMR spectra. Thus we establish the laser pump, NMR probe approach as a robust way to directly observe and quantitatively analyse the coherent evolution of p-H 2 -derived spin order over micro-to-millisecond timescales. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Proton transfers in a channelrhodopsin-1 studied by Fourier transform infrared (FTIR) difference spectroscopy and site-directed mutagenesis.

    Science.gov (United States)

    Ogren, John I; Yi, Adrian; Mamaev, Sergey; Li, Hai; Spudich, John L; Rothschild, Kenneth J

    2015-05-15

    Channelrhodopsin-1 from the alga Chlamydomonas augustae (CaChR1) is a low-efficiency light-activated cation channel that exhibits properties useful for optogenetic applications such as a slow light inactivation and a red-shifted visible absorption maximum as compared with the more extensively studied channelrhodopsin-2 from Chlamydomonas reinhardtii (CrChR2). Previously, both resonance Raman and low-temperature FTIR difference spectroscopy revealed that unlike CrChR2, CaChR1 under our conditions exhibits an almost pure all-trans retinal composition in the unphotolyzed ground state and undergoes an all-trans to 13-cis isomerization during the primary phototransition typical of other microbial rhodopsins such as bacteriorhodopsin (BR). Here, we apply static and rapid-scan FTIR difference spectroscopy along with site-directed mutagenesis to characterize the proton transfer events occurring upon the formation of the long-lived conducting P2 (380) state of CaChR1. Assignment of carboxylic C=O stretch bands indicates that Asp-299 (homolog to Asp-212 in BR) becomes protonated and Asp-169 (homolog to Asp-85 in BR) undergoes a net change in hydrogen bonding relative to the unphotolyzed ground state of CaChR1. These data along with earlier FTIR measurements on the CaChR1 → P1 transition are consistent with a two-step proton relay mechanism that transfers a proton from Glu-169 to Asp-299 during the primary phototransition and from the Schiff base to Glu-169 during P2 (380) formation. The unusual charge neutrality of both Schiff base counterions in the P2 (380) conducting state suggests that these residues may function as part of a cation selective filter in the open channel state of CaChR1 as well as other low-efficiency ChRs. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Science.gov (United States)

    Niioka, Takenori

    2011-03-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    OpenAIRE

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mody R

    2013-04-01

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

  12. Transient Fourier holography with bacteriorhodopsin films for breast cancer diagnostics

    Science.gov (United States)

    Rao, Devulapalli; Kothapalli, Sri-Rajasekar; Wu, Pengfei; Yelleswarapu, Chandra

    X-ray mammography is the current gold standard for breast cancer screening. Microcalcifications and other features which are helpful to the radiologist for early diagnostics are often buried in the noise generated by the surrounding dense tissue. So image processing techniques are required to enhance these important features to improve the sensitivity of detection. An innovative technique is demonstrated for recording a hologram of the mammogram. It is recorded on a thin polymer film of Bacteriorhodopsin (bR) as photo induced isomerization grating containing the interference pattern between the object beam containing the Fourier spatial frequency components of the mammogram and a reference beam. The hologram contains all the enhanced features of the mammogram. A significant innovation of the technique is that the enhanced components in the processed image can be viewed by the radiologist in time scale. A technician can record the movie and when the radiologist looks at the movie at his convenience, freezing the frame as and when desired, he would see the microcalcifications as the brightest and last long in time. He would also observe lesions with intensity decreasing as their size increases. The same bR film can be used repeatedly for recording holograms with different mammograms. The technique is versatile and a different frequency band can be chosen to be optimized by changing the reference beam intensity. The experimental arrangement can be used for mammograms in screen film or digital format.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  15. Evaluation of reciprocating electromagnetic air pumping for portable PEMFC

    International Nuclear Information System (INIS)

    Kwon, Kilsung; Kang, Ho; Kang, Seongwon; Kim, Daejoong

    2013-01-01

    In this paper, we present a proton exchange membrane fuel cell (PEMFC) integrated with an electromagnetic (EM) air pump. The EM air pump provides the PEMFC with air by reciprocating motions of the permanent magnet attached to a flexible membrane. We performed a parametric study to decide the optimal dimensions of the reciprocating EM air pump. The effects of various operating parameters on the EM air pump were investigated with the root-mean-square (RMS) flow rate and current. A core with a higher relative permeability shows better performance. The RMS current linearly increases with the applied voltage and shows no dependence on the frequency. The RMS flow rate also increases with the voltage. The RMS flow rate per power consumption is highest at the frequency around 20 Hz and decreases as the applied voltage increases. When the reciprocating EM air pump was used to supply air to the portable PEMFC, it was found that the power density of the PEMFC increases with the applied voltage and shows the highest performance at the frequency of 10 Hz. We compared the performance of the PEMFC between the flow meter and the EM air pump used as an air supplier. About 81% of the output power using the flow meter was obtained when the EM air pump is operated at the applied voltage of 5 V. The parasitic power ratio reaches at its minimum value about 0.1 with an EM applied voltage of 0.25V. (paper)

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

    Directory of Open Access Journals (Sweden)

    Kenji Ikemura

    2017-12-01

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

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

    Science.gov (United States)

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

    2013-04-01

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

  18. How It's Made - Polarized Proton Beam (444th Brookhaven Lecture)

    International Nuclear Information System (INIS)

    Zelenski, Anatoli

    2008-01-01

    Experiments with polarized beams at RHIC will provide fundamental tests of QCD, and the electro-weak interaction reveal the spin structure of the proton. Polarization asymmetries and parity violation are the strong signatures for identification of the fundamental processes, which are otherwise inaccessible. Such experiments require the maximum available luminosity and therefore polarization must be obtained as an extra beam quality without sacrificing intensity. There are proposals to polarize the high-energy proton beam in the storage rings by the Stern-Gerlach effect or spin-filter techniques. But so far, the only practically available option is acceleration of the polarized beam produced in the source and taking care of polarization survival during acceleration and storage. Two major innovations -- the 'Siberian Snake' technique for polarization preservation during acceleration and high current polarized proton sources make spin physics with the high-energy polarized beams feasible. The RHIC is the first high-energy collider, where the 'Siberian Snake' technique allowed of polarized proton beam acceleration up-to 250 GeV energy. The RHIC unique Optically Pumped Polarized Ion Source produces sufficient polarized beam intensity for complete saturation of the RHIC acceptance. This polarization technique is based on spin-transfer collisions between a proton or atomic hydrogen beam of a few keV beam energy and optically pumped alkali metal vapors. From the first proposal and feasibility studies to the operational source this development can be considered as example of successful unification of individual scientists ingenuity, international collaboration and modern technology application for creation of a new polarization technique, which allowed of two-to-three order of magnitude polarized beam intensity increase sufficient for loading the RHIC to its full capacity for polarization studies.

  19. Reaction pathways of photoexcited retinal in proteorhodopsin studied by pump-dump-probe spectroscopy

    NARCIS (Netherlands)

    Rupenyan, A.; van Stokkum, I.H.M.; Arents, J.C.; van Grondelle, R.; Hellingwerf, K.J.; Groot, M.L.

    2009-01-01

    Proteorhodopsin (pR) is a membrane-embedded proton pump from the microbial rhodopsin family. Light absorption by its retinal chromophore initiates a photocycle, driven by trans/cis isomerization on the femtosecond to picosecond time scales. Here, we report a study on the photoisomerization dynamics

  20. Drug transport mechanism of the AcrB efflux pump.

    Science.gov (United States)

    Pos, Klaas M

    2009-05-01

    In Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa, tripartite multidrug efflux systems extrude cytotoxic substances from the cell directly into the medium bypassing periplasm and the outer membrane. In E. coli, the tripartite efflux system AcrA/AcrB/TolC is the pump that extrudes multiple antibiotics, dyes, bile salts and detergents. The inner membrane component AcrB, a member of the Resistance Nodulation cell Division (RND) family, is the major site for substrate recognition and energy transduction of the entire tripartite system. The drug/proton antiport processes in this secondary transporter are suggested to be spatially separated, a feature frequently observed for primary transporters like membrane-bound ATPases. The recently elucidated asymmetric structure of the AcrB trimer reveals three different monomer conformations proposed to represent consecutive states in a directional transport cycle. Each monomer shows a distinct tunnel system with entrances located at the boundary of the outer leaflet of the inner membrane and the periplasm through the periplasmic porter (pore) domain towards the funnel of the trimer and TolC. In one monomer a hydrophobic pocket is present which has been shown to bind the AcrB substrates minocyclin and doxorubicin. The energy conversion from the proton motive force into drug efflux includes proton binding in (and release from) the transmembrane part. The conformational changes observed within a triad of essential, titratable residues (D407/D408/K940) residing in the hydrophobic transmembrane domain appear to be transduced by transmembrane helix 8 and associated with the conformational changes seen in the periplasmic domain. From the asymmetric structure a possible peristaltic pump transport mechanism based on a functional rotation of the AcrB trimer has been postulated. The novel drug transport model combines the alternate access pump mechanism with the rotating site catalysis of F(1)F(o) ATPase as

  1. Sodium pumping: pump problems

    International Nuclear Information System (INIS)

    Guer, M.; Guiton, P.

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

  2. Polarized proton Target-III operators manual, revision A

    International Nuclear Information System (INIS)

    Hill, D.; Moretti, A.; Onesto, F.; Rynes, P.

    1976-04-01

    A revision is given of a manual containing standard operating procedures for the vacuum, cryogenic, and electronic systems of a polarized proton target. The discussion includes the target cryostat, the 3 He and 4 He pumping systems, remote monitors and controls, the microwave system, the magnet and power supply, the computerized polarization monitor, the 4 He liquifier and gas recovery system, and miscellaneous auxiliary equipment

  3. All-optical switching based on optical fibre long period gratings modified bacteriorhodopsin

    Science.gov (United States)

    Korposh, S.; James, S.; Partridge, M.; Sichka, M.; Tatam, R.

    2018-05-01

    All-optical switching using an optical fibre long-period gating (LPG) modified with bacteriorhodopsin (bR) is demonstrated. The switching process is based on the photo-induced RI change of bR, which in turn changes the phase matching conditions of the mode coupling by the LPG, leading to modulation of the propagating light. The effect was studied with an LPG immersed into a bR solution and with LPGs coated with the bR films, deposited onto the LPGs using the layer-by-layer electrostatic self-assembly (LbL) method. The dependence of the all-optical switching efficiency upon the concentration of the bR solution and on the grating period of the LPG was also studied. In addition, an in-fibre Mach-Zehnder interferometer (MZI) composed of a cascaded LPG pair separated by 30 mm and modified with bR was used to enhance the wavelength range of all-optical switching. The switching wavelength is determined by the grating period of the LPG. Switching efficiencies of 16% and 35% were observed when an LPG and an MZI were immersed into bR solutions, respectively. The switching time for devices coated with bR-films was within 1 s, 10 times faster than that observed for devices immersed into bR solution.

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

    Science.gov (United States)

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

    2018-01-30

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

  5. Ultrafast proton shuttling in Psammocora cyan fluorescent protein.

    Science.gov (United States)

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

    2013-09-26

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

  6. Pumps and pump facilities. 2. ed.

    International Nuclear Information System (INIS)

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

    1981-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Wolfgang W Bolten

    2010-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Imad M Tleyjeh

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

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

    Directory of Open Access Journals (Sweden)

    Gross M

    2010-03-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Arpana Sali

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

  13. Green proteorhodopsin reconstituted into nanoscale phospholipid bilayers (nanodiscs) as photoactive monomers.

    Science.gov (United States)

    Ranaghan, Matthew J; Schwall, Christine T; Alder, Nathan N; Birge, Robert R

    2011-11-16

    Over 4000 putative proteorhodopsins (PRs) have been identified throughout the oceans and seas of the Earth. The first of these eubacterial rhodopsins was discovered in 2000 and has expanded the family of microbial proton pumps to all three domains of life. With photophysical properties similar to those of bacteriorhodopsin, an archaeal proton pump, PRs are also generating interest for their potential use in various photonic applications. We perform here the first reconstitution of the minimal photoactive PR structure into nanoscale phospholipid bilayers (nanodiscs) to better understand how protein-protein and protein-lipid interactions influence the photophysical properties of PR. Spectral (steady-state and time-resolved UV-visible spectroscopy) and physical (size-exclusion chromatography and electron microscopy) characterization of these complexes confirms the preparation of a photoactive PR monomer within nanodiscs. Specifically, when embedded within a nanodisc, monomeric PR exhibits a titratable pK(a) (6.5-7.1) and photocycle lifetime (∼100-200 ms) that are comparable to the detergent-solubilized protein. These ndPRs also produce a photoactive blue-shifted absorbance, centered at 377 or 416 nm, that indicates that protein-protein interactions from a PR oligomer are required for a fast photocycle. Moreover, we demonstrate how these model membrane systems allow modulation of the PR photocycle by variation of the discoidal diameter (i.e., 10 or 12 nm), bilayer thickness (i.e., 23 or 26.5 Å), and degree of saturation of the lipid acyl chain. Nanodiscs also offer a highly stable environment of relevance to potential device applications.

  14. Effect of a pH Gradient on the Protonation States of Cytochrome c Oxidase: A Continuum Electrostatics Study.

    Science.gov (United States)

    Magalhães, Pedro R; Oliveira, A Sofia F; Campos, Sara R R; Soares, Cláudio M; Baptista, António M

    2017-02-27

    Cytochrome c oxidase (CcO) couples the reduction of dioxygen to water with transmembrane proton pumping, which leads to the generation of an electrochemical gradient. In this study we analyze how one of the components of the electrochemical gradient, the difference in pH across the membrane, or ΔpH, influences the protonation states of residues in CcO. We modified our continuum electrostatics/Monte Carlo (CE/MC) method in order to include the ΔpH and applied it to the study of CcO, in what is, to our best knowledge, the first CE/MC study of CcO in the presence of a pH gradient. The inclusion of a transmembrane pH gradient allows for the identification of residues whose titration behavior depends on the pH on both sides of the membrane. Among the several residues with unusual titration profiles, three are well-known key residues in the proton transfer process of CcO: E286 I , Y288 I , and K362 I . All three residues have been previously identified as being critical for the catalytic or proton pumping functions of CcO. Our results suggest that when the pH gradient increases, these residues may be part of a regulatory mechanism to stem the proton flow.

  15. The mechanism of electron gating in proton pumping cytochrome c oxidase: the effect of pH and temperature on internal electron transfer.

    Science.gov (United States)

    Brzezinski, P; Malmström, B G

    1987-10-29

    Electron-transfer reactions following flash photolysis of the mixed-valence cytochrome oxidase-CO complex have been measured at 445, 598 and 830 nm between pH 5.2 and 9.0 in the temperature range of 0-25 degrees C. There is a rapid electron transfer from the cytochrome a3-CuB pair to CuA (time constant: 14200 s-1), which is followed by a slower electron transfer to cytochrome a. Both the rate and the amplitude of the rapid phase are independent of pH, and the rate in the direction from CuA to cytochrome a3-CuB is practically independent of temperature. The second phase depends strongly on pH due to the titration of an acid-base group with pKa = 7.6. The equilibrium at pH 7.4 corresponds to reduction potentials of 225 and 345 mV for cytochrome a and a3, respectively, from which it is concluded that the enzyme is in a different conformation compared to the fully oxidized form. The results have been used to suggest a series of reaction steps in a cycle of the oxidase as a proton pump. Application of the electron-transfer theory to the temperature-dependence data suggests a mechanism for electron gating in the pump. Reduction of both cytochrome a and CuA leads to a conformational change, which changes the structure of cytochrome a3-CuB in such a way that the reorganizational barrier for electron transfer is removed and the driving force is increased.

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

    Science.gov (United States)

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

    2016-12-01

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

  17. Root bacterial endophytes confer drought resistance and enhance expression and activity of a vacuolar H+ -pumping pyrophosphatase in pepper plants.

    Science.gov (United States)

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

    2018-05-22

    It has been previously shown that the transgenic overexpression of the plant root vacuolar proton pumps H + -ATPase (V-ATPase) and H + -PPase (V-PPase) confer tolerance to drought. Since plant-root endophytic bacteria can also promote drought tolerance, we hypothesize that such promotion can be associated to the enhancement of the host vacuolar proton pumps expression and activity. To test this hypothesis, we selected two endophytic bacteria endowed with an array of in vitro plant growth promoting traits. Their genome sequences confirmed the presence of traits previously shown to confer drought resistance to plants, such as the synthesis of nitric oxide and of organic volatile organic compounds. We used the two strains on pepper (Capsicuum annuum L.) because of its high sensitivity to drought. Under drought conditions, both strains stimulated a larger root system and enhanced the leaves' photosynthetic activity. By testing the expression and activity of the vacuolar proton pumps, H + -ATPase (V-ATPase) and H + -PPase (V-PPase), we found that bacterial colonization enhanced V-PPase only. We conclude that the enhanced expression and activity of V-PPase can be favoured by the colonization of drought-tolerance-inducing bacterial endophytes. This article is protected by copyright. All rights reserved. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

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

    International Nuclear Information System (INIS)

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

    2001-01-01

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

  19. Pumping behavior of sputter ion pumps

    International Nuclear Information System (INIS)

    Chou, T.S.; McCafferty, D.

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

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

    Science.gov (United States)

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

    2016-11-01

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

  1. The AcrB efflux pump: conformational cycling and peristalsis lead to multidrug resistance.

    Science.gov (United States)

    Seeger, Markus A; Diederichs, Kay; Eicher, Thomas; Brandstätter, Lorenz; Schiefner, André; Verrey, François; Pos, Klaas M

    2008-09-01

    Antimicrobial resistance of human pathogenic bacteria is an emerging problem for global public health. This resistance is often associated with the overproduction of membrane transport proteins that are capable to pump chemotherapeutics, antibiotics, detergents, dyes and organic solvents out of the cell. In Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa, tripartite multidrug efflux systems extrude a large variety of cytotoxic substances from the cell membrane directly into the medium bypassing the periplasm and the outer membrane. In E. coli, the tripartite efflux system AcrA/AcrB/TolC is the pump in charge of the efflux of multiple antibiotics, dyes, bile salts and detergents. The trimeric outer membrane factor (OMF) TolC forms a beta-barrel pore in the outer membrane and exhibits a long periplasmic alpha-helical conduit. The periplasmic membrane fusion protein (MFP) AcrA serves as a linker between TolC and the trimeric resistance nodulation cell division (RND) pump AcrB, located in the inner membrane acting as a proton/drug antiporter. The newly elucidated asymmetric structure of trimeric AcrB reveals three different monomer conformations representing consecutive states in a transport cycle. The monomers show tunnels with occlusions at different sites leading from the lateral side through the periplasmic porter (pore) domains towards the funnel of the trimer and TolC. The structural changes create a hydrophobic pocket in one monomer, which is not present in the other two monomers. Minocyclin and doxorubicin, both AcrB substrates, specifically bind to this pocket substantiating its role as drug binding pocket. The energy transduction from the proton motive force into drug efflux includes proton binding in (and release from) the transmembrane part. The conformational changes observed within a triad of essential, titratable residues (Asp407/Asp408/Lys940) residing in the hydrophobic transmembrane domain appear to be transduced by

  2. Imaging an optogenetic pH sensor reveals that protons mediate lateral inhibition in the retina.

    Science.gov (United States)

    Wang, Tzu-Ming; Holzhausen, Lars C; Kramer, Richard H

    2014-02-01

    The reciprocal synapse between photoreceptors and horizontal cells underlies lateral inhibition and establishes the antagonistic center-surround receptive fields of retinal neurons to enhance visual contrast. Despite decades of study, the signal mediating the negative feedback from horizontal cells to cones has remained under debate because the small, invaginated synaptic cleft has precluded measurement. Using zebrafish retinas, we show that light elicits a change in synaptic proton concentration with the correct magnitude, kinetics and spatial dependence to account for lateral inhibition. Light, which hyperpolarizes horizontal cells, causes synaptic alkalinization, whereas activating an exogenously expressed ligand-gated Na(+) channel, which depolarizes horizontal cells, causes synaptic acidification. Whereas acidification was prevented by blocking a proton pump, re-alkalinization was prevented by blocking proton-permeant ion channels, suggesting that distinct mechanisms underlie proton efflux and influx. These findings reveal that protons mediate lateral inhibition in the retina, raising the possibility that protons are unrecognized retrograde messengers elsewhere in the nervous system.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-07-01

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

  4. Redshift of the purple membrane absorption band and the deprotonation of tyrosine residues at high pH: Origin of the parallel photocycles of trans-bacteriorhodopsin

    OpenAIRE

    Balashov, S. P.; Govindjee, R.; Ebrey, T. G.

    1991-01-01

    At high pH (> 8) the 570 nm absorption band of all-trans bacteriorhodopsin (bR) in purple membrane undergoes a small (1.5 nm) shift to longer wavelengths, which causes a maximal increase in absorption at 615 nm. The pK of the shift is 9.0 in the presence of 167 mM KCl, and its intrinsic pK is ∼8.3. The red shift of the trans-bR absorption spectrum correlates with the appearance of the fast component in the light-induced L to M transition, and absorption increases at 238 and 297 nm which are a...

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

    Science.gov (United States)

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

    2014-07-01

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

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

    Science.gov (United States)

    Odaka, Takeo; Yamato, Shigeru; Yokosuka, Osamu

    2017-01-01

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

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

    Science.gov (United States)

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

    2011-05-01

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

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

    Science.gov (United States)

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

    2015-06-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ana María Pello Lázaro

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

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Science.gov (United States)

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

    2012-07-01

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

  13. Operational experience with the TRIUMF optically pumped polarized H- ion source

    International Nuclear Information System (INIS)

    Schmor, P.W.; Buchmann, L.; Jayamanna, K.; Levy, C.D.P.; McDonald, M.; Ruegg, R.

    1991-05-01

    The initial goal of a polarized proton beam extracted from the TRIUMF cyclotron, having a current of 5 μA with 60% polarization, has been achieved with the development of the optically pumped polarized H - ion source. This beam is now being used to produce an intense secondary beam of polarized neutrons for the TRIUMF experimental program. Much of the recent development effort has addressed the reliability requirements for routine operation. This paper describes the results with emphasis on the laser stabilization subsystem, the modifications to the electron cyclotron resonance proton ion source (ECRIS), the sodium charge exchange cells and the development of a low energy polarimeter. Also discussed are the developments which should lead to a higher polarization. (Author) 7 refs

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

    Science.gov (United States)

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

    2014-08-14

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

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

    Science.gov (United States)

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

    2017-07-17

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

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

    Science.gov (United States)

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

    2014-11-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Shiro Fujii

    2012-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Shin S

    2015-04-01

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

  1. Calcium uptake and proton transport by acidocalcisomes of Toxoplasma gondii.

    Directory of Open Access Journals (Sweden)

    Peter Rohloff

    Full Text Available Acidocalcisomes are acidic calcium stores found in diverse organisms, being conserved from bacteria to humans. They possess an acidic matrix that contains several cations bound to phosphates, which are mainly present in the form of short and long polyphosphate chains. Their matrix is acidified through the action of proton pumps such as a vacuolar proton ATPase and a vacuolar proton pyrophosphatase. Calcium uptake occurs through a Ca(2+/H(+ countertransporting ATPase located in the membrane of the organelle. Acidocalcisomes have been identified in a variety of microorganisms, including Apicomplexan parasites such as Plasmodium and Eimeria species, and in Toxoplasma gondii. We report the purification and characterization of an acidocalcisome fraction from T. gondii tachyzoites after subcellular fractionation and further discontinuous iodixanol gradient purification. Proton and calcium transport activities in the fraction were characterized by fluorescence microscopy and spectrophotometric methods using acridine orange and arsenazo III, respectively. This work will facilitate the understanding of the function of acidocalcisomes in Apicomplexan parasites, as we can now isolate highly purified fractions that could be used for proteomic analysis to find proteins that may clarify the biogenesis of these organelles.

  2. Adsorption pump for helium pumping out

    International Nuclear Information System (INIS)

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

    1981-01-01

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

  3. Proton-air and proton-proton cross sections

    Directory of Open Access Journals (Sweden)

    Ulrich Ralf

    2013-06-01

    Full Text Available Different attempts to measure hadronic cross sections with cosmic ray data are reviewed. The major results are compared to each other and the differences in the corresponding analyses are discussed. Besides some important differences, it is crucial to see that all analyses are based on the same fundamental relation of longitudinal air shower development to the observed fluctuation of experimental observables. Furthermore, the relation of the measured proton-air to the more fundamental proton-proton cross section is discussed. The current global picture combines hadronic proton-proton cross section data from accelerator and cosmic ray measurements and indicates a good consistency with predictions of models up to the highest energies.

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

    Science.gov (United States)

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

    2016-09-01

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

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

    International Nuclear Information System (INIS)

    Welch, K.M.

    1991-01-01

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

  6. An Observation of Diamond-Shaped Particle Structure in a Soya Phosphatidylcohline and Bacteriorhodopsin Composite Langmuir Blodgett Film Fabricated by Multilayer Molecular Thin Film Method

    Science.gov (United States)

    Tsujiuchi, Y.; Makino, Y.

    A composite film of soya phosphatidylcohline (soya PC) and bacteriorhodopsin (BR) was fabricated by the multilayer molecular thin film method using fatty acid and lipid on a quartz substrate. Direct Force Microscopy (DFM), UV absorption spectra and IR absorption spectra of the film were characterized on the detail of surface structure of the film. The DFM data revealed that many rhombus (diamond-shaped) particles were observed in the film. The spectroscopic data exhibited the yield of M-intermediate of BR in the film. On our modelling of molecular configuration indicate that the coexistence of the strong inter-molecular interaction and the strong inter-molecular interaction between BR trimmers attributed to form the particles.

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

    International Nuclear Information System (INIS)

    Welch, K.M.

    1991-01-01

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

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

    Science.gov (United States)

    Armstrong, David; Nakhla, Nardine

    2016-01-01

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

  9. The TRIUMF optically-pumped polarized H- ion source

    International Nuclear Information System (INIS)

    Levy, C.D.P.; Jayamanna, K.; McDonald, M.; Schmor, P.W.; Van Oers, W.T.H.; Welz, J.; Wight, G.W.; Dutto, G.; Zelenski, A.N.; Sakae, T.

    1995-09-01

    The TRIUMF dc optically-pumped polarized H - ion source (OPPIS) produces 200 μA dc H - current at 85% polarization within a normalized emittance (90%) of 0.8 π mm mrad, for operations at the TRIUMF cyclotron. As a result of development of the ECR primary proton source, 1.6 mA dc polarized H - current is produced within a normalized emittance of 2 π mm mrad, suitable for high energy accelerators. The OPPIS has also been developed for use in a parity non-conservation experiment which has very severe limits on permissible helicity-correlated changes in beam current and energy. (author)

  10. The TRIUMF optically-pumped polarized H- ion source

    International Nuclear Information System (INIS)

    Levy, C.D.P.; Jayamanna, K.; McDonald, M.

    1995-09-01

    The TRIUMF dc optically-pumped polarized H - ion source (OPPIS) produces 200 microA dc H - current at 85% polarization within a normalized emittance (90%) of 0.8 π mm mrad, for operations at the TRIUMF cyclotron. As a result of development of the ECR primary proton source, 1.6 mA dc polarized H - current is produced within a normalized emittance of 2 π mm mrad, suitable for high energy accelerators. The OPPIS has also been developed for use in a parity non-conservation experiment which has very severe limits on permissible helicity-correlated changes in beam current and energy

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

    Science.gov (United States)

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

    2017-01-01

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

  12. Proton-proton bremsstrahlung

    International Nuclear Information System (INIS)

    Fearing, H.W.

    1990-01-01

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

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

    Science.gov (United States)

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

    2017-10-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

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

    Science.gov (United States)

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

    2013-07-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2017-06-01

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

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

    Science.gov (United States)

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

    1995-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  20. Lansoprazole induces apoptosis of breast cancer cells through inhibition of intracellular proton extrusion

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shangrong; Wang, Yifan; Li, Shu Jie, E-mail: shujieli@nankai.edu.cn

    2014-06-13

    Highlights: • Lansoprazole (LPZ) induces cell apoptosis in breast cancer cells. • LPZ markedly inhibits intracellular proton extrusion. • LPZ induces an increase in intracellular ATP level, lysosomal alkalinization and ROS accumulation. - Abstract: The increased glycolysis and proton secretion in tumors is proposed to contribute to the proliferation and invasion of cancer cells during the process of tumorigenesis and metastasis. Here, treatment of human breast cancer cells with proton pump inhibitor (PPI) lansoprazole (LPZ) induces cell apoptosis in a dose-dependent manner. In the implantation of the MDA-MB-231 xenografts in nude mice, administration of LPZ significantly inhibits tumorigenesis and induces large-scale apopotosis of tumor cells. LPZ markedly inhibits intracellular proton extrusion, induces an increase in intracellular ATP level, lysosomal alkalinization and accumulation of reactive oxygen species (ROS) in breast cancer cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and diphenyleneiodonium (DPI), a specific pharmacological inhibitor of NADPH oxidases (NOX), significantly abolish LPZ-induced ROS accumulation in breast cancer cells. Our results suggested that LPZ may be used as a new therapeutic drug for breast tumor.

  1. Lansoprazole induces apoptosis of breast cancer cells through inhibition of intracellular proton extrusion

    International Nuclear Information System (INIS)

    Zhang, Shangrong; Wang, Yifan; Li, Shu Jie

    2014-01-01

    Highlights: • Lansoprazole (LPZ) induces cell apoptosis in breast cancer cells. • LPZ markedly inhibits intracellular proton extrusion. • LPZ induces an increase in intracellular ATP level, lysosomal alkalinization and ROS accumulation. - Abstract: The increased glycolysis and proton secretion in tumors is proposed to contribute to the proliferation and invasion of cancer cells during the process of tumorigenesis and metastasis. Here, treatment of human breast cancer cells with proton pump inhibitor (PPI) lansoprazole (LPZ) induces cell apoptosis in a dose-dependent manner. In the implantation of the MDA-MB-231 xenografts in nude mice, administration of LPZ significantly inhibits tumorigenesis and induces large-scale apopotosis of tumor cells. LPZ markedly inhibits intracellular proton extrusion, induces an increase in intracellular ATP level, lysosomal alkalinization and accumulation of reactive oxygen species (ROS) in breast cancer cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and diphenyleneiodonium (DPI), a specific pharmacological inhibitor of NADPH oxidases (NOX), significantly abolish LPZ-induced ROS accumulation in breast cancer cells. Our results suggested that LPZ may be used as a new therapeutic drug for breast tumor

  2. Centrifugal pumps

    CERN Document Server

    Anderson, HH

    1981-01-01

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

  3. Photoluminescence of radiation-induced color centers in lithium fluoride thin films for advanced diagnostics of proton beams

    Science.gov (United States)

    Piccinini, M.; Ambrosini, F.; Ampollini, A.; Picardi, L.; Ronsivalle, C.; Bonfigli, F.; Libera, S.; Nichelatti, E.; Vincenti, M. A.; Montereali, R. M.

    2015-06-01

    Systematic irradiation of thermally evaporated 0.8 μm thick polycrystalline lithium fluoride films on glass was performed by proton beams of 3 and 7 MeV energies, produced by a linear accelerator, in a fluence range from 1011 to 1015 protons/cm2. The visible photoluminescence spectra of radiation-induced F2 and F3+ laser active color centers, which possess almost overlapping absorption bands at about 450 nm, were measured under laser pumping at 458 nm. On the basis of simulations of the linear energy transfer with proton penetration depth in LiF, it was possible to obtain the behavior of the measured integrated photoluminescence intensity of proton irradiated LiF films as a function of the deposited dose. The photoluminescence signal is linearly dependent on the deposited dose in the interval from 103 to about 106 Gy, independently from the used proton energies. This behavior is very encouraging for the development of advanced solid state radiation detectors based on optically transparent LiF thin films for proton beam diagnostics and two-dimensional dose mapping.

  4. Protein proton-proton dynamics from amide proton spin flip rates

    International Nuclear Information System (INIS)

    Weaver, Daniel S.; Zuiderweg, Erik R. P.

    2009-01-01

    Residue-specific amide proton spin-flip rates K were measured for peptide-free and peptide-bound calmodulin. K approximates the sum of NOE build-up rates between the amide proton and all other protons. This work outlines the theory of multi-proton relaxation, cross relaxation and cross correlation, and how to approximate it with a simple model based on a variable number of equidistant protons. This model is used to extract the sums of K-rates from the experimental data. Error in K is estimated using bootstrap methodology. We define a parameter Q as the ratio of experimental K-rates to theoretical K-rates, where the theoretical K-rates are computed from atomic coordinates. Q is 1 in the case of no local motion, but decreases to values as low as 0.5 with increasing domination of sidechain protons of the same residue to the amide proton flips. This establishes Q as a monotonous measure of local dynamics of the proton network surrounding the amide protons. The method is applied to the study of proton dynamics in Ca 2+ -saturated calmodulin, both free in solution and bound to smMLCK peptide. The mean Q is 0.81 ± 0.02 for free calmodulin and 0.88 ± 0.02 for peptide-bound calmodulin. This novel methodology thus reveals the presence of significant interproton disorder in this protein, while the increase in Q indicates rigidification of the proton network upon peptide binding, confirming the known high entropic cost of this process

  5. Correlated photon-pair generation in a periodically poled MgO doped stoichiometric lithium tantalate reverse proton exchanged waveguide

    NARCIS (Netherlands)

    Lobino, M.; Marshall, G.D.; Xiong, C.; Clark, A.S.; Bonneau, D.; Natarajan, C.M.; Tanner, M.G.; Hadfield, R.H.; Dorenbos, S.N.; Zijlstra, T.; Zwiller, V.; Marangoni, M.; Ramponi, R.; Thompson, M.G.; Eggleton, B.J.; O'Brien, J.L.

    2011-01-01

    We demonstrate photon-pair generation in a reverse proton exchanged waveguide fabricated on a periodically poled magnesium doped stoichiometric lithium tantalate substrate. Detected pairs are generated via a cascaded second order nonlinear process where a pump laser at wavelength of 1.55 ?m is first

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

    Science.gov (United States)

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

    2014-10-01

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

  7. LMFBR with booster pump in pumping loop

    International Nuclear Information System (INIS)

    Rubinstein, H.J.

    1975-01-01

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

  8. Exploring the entrance of proton pathways in cytochrome c oxidase from Paracoccus denitrificans: surface charge, buffer capacity and redox-dependent polarity changes at the internal surface.

    Science.gov (United States)

    Kirchberg, Kristina; Michel, Hartmut; Alexiev, Ulrike

    2013-03-01

    Cytochrome c oxidase (CcO), the terminal oxidase of cellular respiration, reduces molecular oxygen to water. The mechanism of proton pumping as well as the coupling of proton and electron transfer is still not understood in this redox-linked proton pump. Eleven residues at the aqueous-exposed surfaces of CcO from Paracoccus denitrificans have been exchanged to cysteines in a two-subunit base variant to yield single reactive cysteine variants. These variants are designed to provide unique labeling sites for probes to be used in spectroscopic experiments investigating the mechanism of proton pumping in CcO. To this end we have shown that all cysteine variants are enzymatically active. Cysteine positions at the negative (N-) side of the membrane are located close to the entrance of the D- and K-proton transfer pathways that connect the N-side with the catalytic oxygen reduction site. Labeling of the pH-indicator dye fluorescein to these sites allowed us to determine the surface potential at the cytoplasmic CcO surface, which corresponds to a surface charge density of -0.5 elementary charge/1000Å(2). In addition, acid-base titrations revealed values of CcO buffer capacity. Polarity measurements of the label environment at the N-side provided (i) site-specific values indicative of a hydrophilic and a more hydrophobic environment dependent on the label position, and (ii) information on a global change to a more apolar environment upon reduction of the enzyme. Thus, the redox state of the copper and heme centers inside the hydrophobic interior of CcO affect the properties at the cytoplasmic surface. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Proton-transfer lasers based on solid copolymers of modified 2-(2'-hydroxyphenyl)benzimidazoles with methacrylate monomers

    Science.gov (United States)

    Costela, A.; García-Moreno, I.; Mallavia, Ricardo; Amat-Guerri, F.; Barroso, J.; Sastre, R.

    1998-06-01

    We report on the lasing action of two newly synthesized 2-(2'-hydroxyphenyl) benzimidazole derivatives copolymerized with methyl methacrylate. The laser samples were transversely pumped with a N 2 laser at 337 nm. The influence on the proton-transfer laser performance of the distance between the chromophore group and the polymeric main chain and of the rigidity of the polymeric host matrix, were studied. Significant increases in lasing efficiency and photostability are demonstrated for some of the new materials, as compared to those previously obtained with related proton-transfer dyes also covalently bound to methacrylic monomers.

  10. The pumping of hydrogen and helium by sputter-ion pumps

    International Nuclear Information System (INIS)

    Welch, K.M.; Pate, D.J.; Todd, R.J.

    1992-01-01

    The pumping of hydrogen in diode and triode sputter-ion pumps is 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 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 or titanium alloy anodes is also shown to measurably impact on the speed of these pumps at.very low pressures. This stems from the fact that hydrogen is x10 6 more soluble in titanium than in stainless steel. Hydrogen becomes resident in the anodes because of fast neutral burial. Lastly, quantitative data are given for the He speeds and capacities of both noble and conventional diode and triode pumps. The effectiveness of various pump regeneration procedures, subsequent to the pumping of He, is reported.These included bakeout and N 2 glow discharge cleaning. The comparative desorption of He with the subsequent pumping of N 2 is reported on. The N 2 speed of these pumps was used as the benchmark for defining the size of the pumps vs. their respective He speeds

  11. Proton microprobe analysis of pancreatic. beta. cells

    Energy Technology Data Exchange (ETDEWEB)

    Lindh, U [Uppsala Univ. (Sweden). Gustaf Werner Inst.; Juntti-Berggren, L; Berggren, P O; Hellman, B [Uppsala Univ. (Sweden)

    1985-01-01

    Freeze-dried pancreas sections from obese hyperglycemic mice were subjected to proton bombardment and the elemental contents in the ..beta.. cells and the exocrine part were obtained from the characteristic X-rays emitted. Quantitative data were provided for 18 different elements. The mole ratio between K and Na exceeded 10, implying that neither the sample preparation nor the irradiation had induced significant diffuse changes. With the demonstration of this high K/Na ratio it seems likely that also the ..beta.. cells are equipped with an efficient Na/sup +//K/sup +/ pump. The ..beta.. cells contained about 70 mmoles Cl per litre cell water. Observed amounts of Ca and Mg were equivalent to those previously recorded by electrothermal atomic absorption spectroscopy. The significant role of Zn for the storage of insulin was emphasized by the demonstration of 3 times as much of this element in the ..beta.. cells as compared with the exocrine pancreas. In addition, the sensitivity of the proton microprobe enabled measurements of various trace elements such as Rb, Cr, Cu, Al and Pb not previously demonstrated in the pancreatic ..beta.. cells.

  12. Theoretical study of annealed proton-exchanged Nd $LiNbO_{3}$ channel waveguide lasers with variational method

    CERN Document Server

    De Long Zhang; Yuan Guo Xie; Guilan, Ding; Yuming, Cui; Cai He Chen

    2001-01-01

    The controllable fabrication parameters, including anneal time, initial exchange time, channel width, dependences of TM/sub 00/ mode size, corresponding effective refractive index, effective pump area, and coupling efficiency between pump and laser modes in z-cut annealed proton-exchanged (APE) Nd:LiNbO/sub 3/ channel waveguide lasers were studied by using variational method. The effect of channel width on the surface index increment and the waveguide depth was taken into account. The features of mode size and effective refractive index were summarized, discussed, and compared with previously published experimental results. The effective pump area, which is directly proportional to threshold pump power, increases strongly, slightly, and very slightly with the increase of anneal time, channel width, and initial exchange time, respectively. However, the coupling efficiency, which is directly proportional to slope efficiency, remains constant (around 0.82) no matter what changes made to these parameters. The var...

  13. Liquid metals pumping

    International Nuclear Information System (INIS)

    Le Frere, J.P.

    1984-01-01

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

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

    Science.gov (United States)

    Kushner, Pamela R; Peura, David A

    2011-05-01

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

  15. A structural overview of the plasma membrane Na+,K+-ATPase and H+-ATPase ion pumps

    DEFF Research Database (Denmark)

    Morth, Jens Preben; Pedersen, Bjørn Panella; Buch-Pedersen, Morten Jeppe

    2011-01-01

    transport systems that are responsible for uptake and extrusion of metabolites and other ions. The ion gradients are also both directly and indirectly used to control pH homeostasis and to regulate cell volume. The plasma membrane H(+)-ATPase maintains a proton gradient in plants and fungi and the Na......Plasma membrane ATPases are primary active transporters of cations that maintain steep concentration gradients. The ion gradients and membrane potentials derived from them form the basis for a range of essential cellular processes, in particular Na(+)-dependent and proton-dependent secondary......(+),K(+)-ATPase maintains a Na(+) and K(+) gradient in animal cells. Structural information provides insight into the function of these two distinct but related P-type pumps....

  16. A structural overview of the plasma membrane Na+,K+-ATPase and H+-ATPase ion pumps

    DEFF Research Database (Denmark)

    Morth, Jens Preben; Pedersen, Bjørn Panella; Buch-Pedersen, Morten Jeppe

    2011-01-01

    transport systems that are responsible for uptake and extrusion of metabolites and other ions. The ion gradients are also both directly and indirectly used to control pH homeostasis and to regulate cell volume. The plasma membrane H(+)-ATPase maintains a proton gradient in plants and fungi and the Na(+),K(+)-ATPase...... maintains a Na(+) and K(+) gradient in animal cells. Structural information provides insight into the function of these two distinct but related P-type pumps.......Plasma membrane ATPases are primary active transporters of cations that maintain steep concentration gradients. The ion gradients and membrane potentials derived from them form the basis for a range of essential cellular processes, in particular Na(+)-dependent and proton-dependent secondary...

  17. Continuously pumping and reactivating gas pump

    International Nuclear Information System (INIS)

    Batzer, T.H.; Call, W.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

  18. Continuously pumping and reactivating gas pump

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2016-02-01

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

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

    Science.gov (United States)

    Liu, Fang; Shokrollahi, Honaz

    2015-05-15

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

  1. Effect of pump limiter throat on pumping efficiency

    International Nuclear Information System (INIS)

    Ghendrih, P.; Grosman, A.; Samain, A.; Capes, H.; Morera, J.P.

    1988-01-01

    The necessary control of plasma edge density has led to the development of pump limiters to achieve this task. On Tore Supra, where a large part of the program is devoted to plasma edge studies, two types of such density control apparatus have been implemented, a set of pump limiters and the pumps associated to the ergodic divertor (magnetically assisted pump limiters). Generally two different kinds of pump limiters can be used, those with a throat which drives the plasma from the open edge plasma (SOL) to the neutralizer plate, and those without or with a very short throat. We are interested here in this aspect of the pump limiter concept, i.e. on the throat effect on neutral density build-up in the vicinity of the pumping plates (and hence on pumping efficieny). The underlying idea of this throat effect can be readily understood; indeed while the neutral capture in pump limiters without throats is only a ballistic effect, on expects the plasma to improve the efficiency of pump-limiters via plasma-neutral-sidewall interactions in the throat. This problem has been studied both numerically and analytically. The paper is divided as follows. In section 2, we describe the basic features of pump-limiters which are modelized by the numerical code Cezanne. Section 3 is devoted to the throat length effect considering in particular the neutral density profile in the throat and the neutral density buil-up as a function of the throat lenght. In section 4, we show that the plugging effect occurs for reasonnable values of throat lengths. An analytical value of the plugging length is discussed and compared to the values obtained numerically

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-11-01

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

  4. Partial purification of the ATP-driven calcium pump of Streptococcus sanguis

    International Nuclear Information System (INIS)

    Lynn, A.R.; Rosen, B.P.

    1986-01-01

    ATP-dependent transport of calcium has been observed in several species of streptococci as uptake of 45 Ca 2+ into everted membrane vesicles. Membranes from Streptococcus sanguis and Streptococcus faecalis were solubilized with octyl-β-D-glucoside or Triton X-100, and the extracts reconstituted into proteoliposomes containing Escherichia coli or soybean phospholipid. Calcium transport in reconstituted proteoliposomes was insensitive to the ionophores nigericin and valinomycin and was unaffected by the F 0 F 1 inhibitor N,N'-dicyclohexylcarbodiimide. Uptake was inhibited by ortho-vanadate with a K/sub i/ in the micromolar range. These results demonstrate that the reconstituted transport activities are not the result of ATP-driven proton pumping via the F 0 F 1 coupled to a calcium/proton antiporter and suggest that existence of a calcium translocating ATPase. Partial purification of the transport activity from Streptococcus sanguis has been achieved using density gradient centrifugation and FPLC

  5. Study of Hydrogen Pumping through Condensed Argon in Cryogenic pump

    International Nuclear Information System (INIS)

    Jadeja, K A; Bhatt, S B

    2012-01-01

    In ultra high vacuum (UHV) range, hydrogen is a dominant residual gas in vacuum chamber. Hydrogen, being light gas, pumping of hydrogen in this vacuum range is limited with widely used UHV pumps, viz. turbo molecular pump and cryogenic pump. Pre condensed argon layers in cryogenic pump create porous structure on the surface of the pump, which traps hydrogen gas at a temperature less than 20° K. Additional argon gas injection in the cryogenic pump, at lowest temperature, generates multiple layers of condensed argon as a porous frost with 10 to 100 A° diameters pores, which increase the pumping capacity of hydrogen gas. This pumping mechanism of hydrogen is more effective, to pump more hydrogen gas in UHV range applicable in accelerator, space simulation etc. and where hydrogen is used as fuel gas like tokamak. For this experiment, the cryogenic pump with a closed loop refrigerator using helium gas is used to produce the minimum cryogenic temperature as ∼ 14° K. In this paper, effect of cryosorption of hydrogen is presented with different levels of argon gas and hydrogen gas in cryogenic pump chamber.

  6. Peculiar properties of photoinduced hydroxylaminolysis in different bacteriorhodopsin-based media using O-substituted hydroxylamines.

    Science.gov (United States)

    Dyukova, Tatyana V; Druzhko, Anna B

    2010-01-01

    The process of photoinduced hydroxylaminolysis has been re-examined in different bacteriorhodopsin (BR)-based media using O-substituted hydroxylamines, in particular, O-(4-nitrobenzyl) hydroxylamine hydrochloride (NBHA), O-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine hydrochloride (FBHA) and O-(t-butyl) hydroxylamine hydrochloride (BHA). Both wild type (WT) and D96N BR-based gelatine films and gels were studied. The expected increase in the bleaching rate of BR in gelatin films by using O-substituted hydroxylamines in place of HA was not achieved. On the other hand, it was shown that in gels HA derivatives NBHA and FBHA (as against HA itself) do provide about three- to four-fold higher bleaching rate. By contrast to that in films, D96N BR in gels demonstrates more effective bleaching as compared to WT BR. The plausible interpretation for the results is discussed in frames of reduced mobilities of large-sized molecules of O-substituted hydroxylamines in dehydrated media. FBHA- or NBHA-modified gels possess higher photosensitivity both with D96N and WT BR (as compared with that for HA-modified gels) and offer a potentiality for application as an irreversible-recording medium. As anticipated, it is specifically D96N BR gel modified with FBHA that may present a promising medium suitable for write-once recording thus extending the range of recording materials in the optical processing field. © 2010 The Authors. Journal Compilation. The American Society of Photobiology.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

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

    Science.gov (United States)

    Gigante, Antonio; Tagarro, Ignacio

    2012-04-01

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

  10. Photoluminescence of radiation-induced color centers in lithium fluoride thin films for advanced diagnostics of proton beams

    Energy Technology Data Exchange (ETDEWEB)

    Piccinini, M., E-mail: massimo.piccinini@enea.it; Ampollini, A.; Picardi, L.; Ronsivalle, C.; Bonfigli, F.; Libera, S.; Vincenti, M. A.; Montereali, R. M. [ENEA, C.R. Frascati, UTAPRAD, Technical Unit for Development and Applications of Radiations, Via E. Fermi 45, 00044 Frascati (Rome) (Italy); Ambrosini, F. [University Sapienza-Roma I, Piazzale Aldo Moro 5, 00185 Rome (Italy); Nichelatti, E. [ENEA, C.R. Casaccia, UTTMAT, Technical Unit for Materials Technologies, Via Anguillarese 301, 00123 S. Maria di Galeria (Rome) (Italy)

    2015-06-29

    Systematic irradiation of thermally evaporated 0.8 μm thick polycrystalline lithium fluoride films on glass was performed by proton beams of 3 and 7 MeV energies, produced by a linear accelerator, in a fluence range from 10{sup 11} to 10{sup 15} protons/cm{sup 2}. The visible photoluminescence spectra of radiation-induced F{sub 2} and F{sub 3}{sup +} laser active color centers, which possess almost overlapping absorption bands at about 450 nm, were measured under laser pumping at 458 nm. On the basis of simulations of the linear energy transfer with proton penetration depth in LiF, it was possible to obtain the behavior of the measured integrated photoluminescence intensity of proton irradiated LiF films as a function of the deposited dose. The photoluminescence signal is linearly dependent on the deposited dose in the interval from 10{sup 3} to about 10{sup 6 }Gy, independently from the used proton energies. This behavior is very encouraging for the development of advanced solid state radiation detectors based on optically transparent LiF thin films for proton beam diagnostics and two-dimensional dose mapping.

  11. Structural and functional aspects of the multidrug efflux pump AcrB.

    Science.gov (United States)

    Eicher, Thomas; Brandstätter, Lorenz; Pos, Klaas M

    2009-08-01

    The tripartite efflux system AcrA/AcrB/TolC is the main pump in Escherichia coli for the efflux of multiple antibiotics, dyes, bile salts and detergents. The inner membrane component AcrB is central to substrate recognition and energy transduction and acts as a proton/drug antiporter. Recent structural studies show that homotrimeric AcrB can adopt different monomer conformations representing consecutive states in an allosteric functional rotation transport cycle. The conformational changes create an alternate access drug transport tunnel including a hydrophobic substrate binding pocket in one of the cycle intermediates.

  12. Dry vacuum pumps

    International Nuclear Information System (INIS)

    Sibuet, R

    2008-01-01

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

  13. Off-Pump Versus On-Pump Coronary Artery Bypass Grafting

    DEFF Research Database (Denmark)

    Møller, Christian H; Steinbrüchel, Daniel A

    2014-01-01

    Coronary artery bypass grafting (CABG) remains the preferred treatment in patients with complex coronary artery disease. However, whether the procedure should be performed with or without the use of cardiopulmonary bypass, referred to as off-pump and on-pump CABG, is still up for debate....... Intuitively, avoidance of cardiopulmonary bypass seems beneficial as the systemic inflammatory response from extracorporeal circulation is omitted, but no single randomized trial has been able to prove off-pump CABG superior to on-pump CABG as regards the hard outcomes death, stroke or myocardial infarction....... In contrast, off-pump CABG is technically more challenging and may be associated with increased risk of incomplete revascularization. The purpose of the review is to summarize the current literature comparing outcomes of off-pump versus on-pump coronary artery bypass surgery....

  14. Heat pump technology

    CERN Document Server

    Von Cube, Hans Ludwig; Goodall, E G A

    2013-01-01

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

  15. Liquid metal pump

    Science.gov (United States)

    Pennell, William E.

    1982-01-01

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

  16. Liquid metal pump

    International Nuclear Information System (INIS)

    Pennell, W.E.

    1982-01-01

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

  17. Heat pumps

    CERN Document Server

    Brodowicz, Kazimierz; Wyszynski, M L; Wyszynski

    2013-01-01

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

  18. Proton radiography to improve proton therapy treatment

    NARCIS (Netherlands)

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

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

  19. Proton radioactivity from proton-rich nuclei

    International Nuclear Information System (INIS)

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

    1999-03-01

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

  20. Experimental Study on Series Operation of Sliding Vane Pump and Centrifugal Pump

    OpenAIRE

    Li, Tao; Zhang, Weiming; Jiang, Ming; Li, Zhengyang

    2013-01-01

    A platform for sliding vane pump and centrifugal pump tests is installed to study the series operation of them under different characteristics of pipeline. Firstly, the sliding vane pump and the centrifugal pump work independently, and the performance is recorded. Then, the two types of pumps are combined together, with the sliding vane pump acting as the feeding pump. Comparison is made between the performance of the independently working pump and the performance of series operation pump. Re...

  1. Centrifugal pump handbook

    CERN Document Server

    Pumps, Sulzer

    2010-01-01

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

  2. Recent Advances in the Field of Bionanotechnology: An Insight into Optoelectric Bacteriorhodopsin, Quantum Dots, and Noble Metal Nanoclusters

    Directory of Open Access Journals (Sweden)

    Christopher Knoblauch

    2014-10-01

    Full Text Available Molecular sensors and molecular electronics are a major component of a recent research area known as bionanotechnology, which merges biology with nanotechnology. This new class of biosensors and bioelectronics has been a subject of intense research over the past decade and has found application in a wide variety of fields. The unique characteristics of these biomolecular transduction systems has been utilized in applications ranging from solar cells and single-electron transistors (SETs to fluorescent sensors capable of sensitive and selective detection of a wide variety of targets, both organic and inorganic. This review will discuss three major systems in the area of molecular sensors and electronics and their application in unique technological innovations. Firstly, the synthesis of optoelectric bacteriorhodopsin (bR and its application in the field of molecular sensors and electronics will be discussed. Next, this article will discuss recent advances in the synthesis and application of semiconductor quantum dots (QDs. Finally, this article will conclude with a review of the new and exciting field of noble metal nanoclusters and their application in the creation of a new class of fluorescent sensors.

  3. Proton Radiography to Improve Proton Radiotherapy : Simulation Study at Different Proton Beam Energies

    NARCIS (Netherlands)

    Biegun, Aleksandra; Takatsu, Jun; van Goethem, Marc-Jan; van der Graaf, Emiel; van Beuzekom, Martin; Visser, Jan; Brandenburg, Sijtze

    To improve the quality of cancer treatment with protons, a translation of X-ray Computed Tomography (CT) images into a map of the proton stopping powers needs to be more accurate. Proton stopping powers determined from CT images have systematic uncertainties in the calculated proton range in a

  4. Penis Pump

    Science.gov (United States)

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

  5. Pumping characteristics of sputter ion pump (SIP) and titanium sublimation pump (TSP) combination

    International Nuclear Information System (INIS)

    Ratnakala, K.C.; Patel, R.J.; Bhavsar, S.T.; Pandiyar, M.L.; Ramamurthi, S.S.

    1995-01-01

    For achieving hydrocarbon free, clean ultra high vacuum, SIP-TSP combination is one of the ideal choice for pumping. For the SRS facility in Centre for Advanced Technology (CAT), we are utilising this combination, enmass. For this purpose, two modules of these combination set-ups are assembled, one with the TSP as an integral part of SIP and the other, with TSP as a separate pump mounted on the top of SIP. The pump bodies were vacuum degassed at 700 degC at 10 -5 mbar for 3 hrs. An ultimate vacuum of 3 x 10 -11 mbar was achieved, after a bake-out at 250 degC for 4 hrs, followed by continuous SIP pumping for 48 hrs, with two TSP flashing at approximately 10 hrs interval. The pump-down patterns as well as the pressure-rise patterns are studied. (author). 2 refs., 5 figs

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

    Science.gov (United States)

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

    2013-01-01

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

  7. Proton solvation and proton transfer in chemical and electrochemical processes

    International Nuclear Information System (INIS)

    Lengyel, S.; Conway, B.E.

    1983-01-01

    This chapter examines the proton solvation and characterization of the H 3 O + ion, proton transfer in chemical ionization processes in solution, continuous proton transfer in conductance processes, and proton transfer in electrode processes. Topics considered include the condition of the proton in solution, the molecular structure of the H 3 O + ion, thermodynamics of proton solvation, overall hydration energy of the proton, hydration of H 3 O + , deuteron solvation, partial molal entropy and volume and the entropy of proton hydration, proton solvation in alcoholic solutions, analogies to electrons in semiconductors, continuous proton transfer in conductance, definition and phenomenology of the unusual mobility of the proton in solution, solvent structure changes in relation to anomalous proton mobility, the kinetics of the proton-transfer event, theories of abnormal proton conductance, and the general theory of the contribution of transfer reactions to overall transport processes

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

    Science.gov (United States)

    Vardar, Rukiye; Keskin, Muharrem

    2017-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Agus D. Susanto

    2008-09-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Emma Mares-García

    2017-06-01

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

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

    Science.gov (United States)

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

    2018-05-22

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

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

    Science.gov (United States)

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

    2017-02-01

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

  14. Protein-Based Three-Dimensional Memories and Associative Processors

    Science.gov (United States)

    Birge, Robert

    2008-03-01

    The field of bioelectronics has benefited from the fact that nature has often solved problems of a similar nature to those which must be solved to create molecular electronic or photonic devices that operate with efficiency and reliability. Retinal proteins show great promise in bioelectronic devices because they operate with high efficiency (˜0.65%), high cyclicity (>10^7), operate over an extended wavelength range (360 -- 630 nm) and can convert light into changes in voltage, pH, absorption or refractive index. This talk will focus on a retinal protein called bacteriorhodopsin, the proton pump of the organism Halobacterium salinarum. Two memories based on this protein will be described. The first is an optical three-dimensional memory. This memory stores information using volume elements (voxels), and provides as much as a thousand-fold improvement in effective capacity over current technology. A unique branching reaction of a variant of bacteriorhodopsin is used to turn each protein into an optically addressed latched AND gate. Although three working prototypes have been developed, a number of cost/performance and architectural issues must be resolved prior to commercialization. The major issue is that the native protein provides a very inefficient branching reaction. Genetic engineering has improved performance by nearly 500-fold, but a further order of magnitude improvement is needed. Protein-based holographic associative memories will also be discussed. The human brain stores and retrieves information via association, and human intelligence is intimately connected to the nature and enormous capacity of this associative search and retrieval process. To a first order approximation, creativity can be viewed as the association of two seemingly disparate concepts to form a totally new construct. Thus, artificial intelligence requires large scale associative memories. Current computer hardware does not provide an optimal environment for creating artificial

  15. Centrifugal pumps

    CERN Document Server

    Gülich, Johann Friedrich

    2014-01-01

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

  16. Characterization of channel waveguides and tunable microlasers in SU8 doped with rhodamine B fabricated using proton beam writing

    International Nuclear Information System (INIS)

    Rao, S Venugopal; Bettiol, A A; Watt, F

    2008-01-01

    We present our results on the fabrication and characterization of buried channel waveguides and tunable microlasers in SU8 doped with rhodamine B achieved using direct writing with a 2.0 MeV proton beam. The channel waveguides, fabricated in single exposure, had an optical propagation loss of -1 at 532 nm measured using the scattering technique while the microlasers with dimensions of 250 x 250 μm 2 had a threshold of ∼150 μJ mm -2 when pumped with 532 nm nanosecond pulses. The emitted wavelength from the microlasers was tunable to an extent of ∼15 nm with increasing pump intensity and different pumping angles. The advantages of such micro-photonic components for the realization of a lab-on-a-chip device are discussed briefly. (fast track communication)

  17. Pumping characteristics of roots blower pumps for light element gases

    International Nuclear Information System (INIS)

    Hiroki, Seiji; Abe, Tetsuya; Tanzawa, Sadamitsu; Nakamura, Jun-ichi; Ohbayashi, Tetsuro

    2002-07-01

    The pumping speed and compression ratio of the two-stage roots blower pumping system were measured for light element gases (H 2 , D 2 and He) and for N 2 , in order to assess validity of the ITER torus roughing system as an ITER R and D task (T234). The pumping system of an Edwards EH1200 (nominal pumping speed of 1200 m 3 /s), two EH250s (ibid. 250 m 3 /s) and a backing pump (ibid. 100 m 3 /s) in series connection was tested under PNEUROP standards. The maximum pumping speeds of the two-stage system for D 2 and N 2 were 1200 and 1300 m 3 /h, respectively at 60 Hz, which satisfied the nominal pumping speed. These experimental data support the design validity of the ITER torus roughing system. (author)

  18. PUMPS

    Science.gov (United States)

    Thornton, J.D.

    1959-03-24

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

  19. Pump characteristics and applications

    CERN Document Server

    Volk, Michael

    2013-01-01

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

  20. Pump element for a tube pump

    DEFF Research Database (Denmark)

    2011-01-01

    The invention relates to a tube pump comprising a tube and a pump element inserted in the tube, where the pump element comprises a rod element and a first and a second non-return valve member positioned a distance apart on the rod element. The valve members are oriented in the same direction...... relative to the rod element so as to allow for a fluid flow in the tube through the first valve member, along the rod element, and through the second valve member. The tube comprises an at least partly flexible tube portion between the valve members such that a repeated deformation of the flexible tube...... portion acts to alternately close and open the valve members thereby generating a fluid flow through the tube. The invention further relates to a pump element comprising at least two non-return valve members connected by a rod element, and for insertion in an at least partly flexible tube in such tube...

  1. Pumping behavior of sputtering ion pump

    Energy Technology Data Exchange (ETDEWEB)

    Chou, T.S.; Bittner, J.; Schuchman, J.

    1991-12-31

    To optimize the design of a distributed ion pump (DIP) for the Superconducting X-Ray Lithography Source (SXLS) the stability of the rotating electron cloud at very high magnetic field beyond transition, must be re-examined. In this work the pumping speed and frequency spectrum of a DIP at various voltages (1 to 10 KV) and various magnetic fields (0.1 to 4 Tesla) are measured. Three cell diameters 10 mm, 5 mm and 2.5 mm, each 8 mm long, and with 3 or 4 mm gaps between anode and cathode are investigated. In this study both the titanium cathodes and the stainless steel anode plates are perforated with holes comparable in size to the anode cell diameters. Only the partially saturated pumping behavior is under investigation. The ultimate pressure and conditioning of the pump will be investigated at a later date when the stability criterion for the electron cloud is better understood.

  2. Pumping behavior of sputtering ion pump

    Energy Technology Data Exchange (ETDEWEB)

    Chou, T.S.; Bittner, J.; Schuchman, J.

    1991-01-01

    To optimize the design of a distributed ion pump (DIP) for the Superconducting X-Ray Lithography Source (SXLS) the stability of the rotating electron cloud at very high magnetic field beyond transition, must be re-examined. In this work the pumping speed and frequency spectrum of a DIP at various voltages (1 to 10 KV) and various magnetic fields (0.1 to 4 Tesla) are measured. Three cell diameters 10 mm, 5 mm and 2.5 mm, each 8 mm long, and with 3 or 4 mm gaps between anode and cathode are investigated. In this study both the titanium cathodes and the stainless steel anode plates are perforated with holes comparable in size to the anode cell diameters. Only the partially saturated pumping behavior is under investigation. The ultimate pressure and conditioning of the pump will be investigated at a later date when the stability criterion for the electron cloud is better understood.

  3. Multiple pump housing

    Science.gov (United States)

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

    2010-03-23

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

  4. Assessing the energy efficiency of pumps and pump units background and methodology

    CERN Document Server

    Bernd Stoffel, em Dr-Ing

    2015-01-01

    Assessing the Energy Efficiency of Pumps and Pump Units, developed in cooperation with Europump, is the first book available providing the background, methodology, and assessment tools for understanding and calculating energy efficiency for pumps and extended products (pumps+motors+drives). Responding to new EU requirements for pump efficiency, and US DOE exploratory work in setting pump energy efficiency guidelines, this book provides explanation, derivation, and illustration of PA and EPA methods for assessing energy efficiency. It surveys legislation related to pump energy eff

  5. Effect of Non-linear Velocity Loss Changes in Pumping Stage of Hydraulic Ram Pumps on Pumping Discharge Rate

    Directory of Open Access Journals (Sweden)

    Reza Fatahialkouhi

    2018-03-01

    Full Text Available The ram pump is a device which pumps a portion of input discharge to the pumping system in a significant height by using renewable energy of water hammer. The complexities of flow hydraulic on one hand and on the other hand the use of simplifying assumptions in ram pumps have caused errors in submitted analytical models for analyzing running cycle of these pumps. In this study it has been tried to modify the governing analytical model on hydraulic performance of these pumps in pumping stage. In this study by creating a logical division, the cycle of the ram pump was divided into three stages of acceleration, pumping and recoil and the governing equations on each stage of cycling are presented by using method of characteristics. Since the closing of impulse valve is nonlinear, velocity loss in pumping stage is considered nonlinearly. Also the governing equations in pumping stage were modified by considering disc elasticity of impulse valve and changing volume of the pump body when the water hammer phenomenon is occurred. In order to evaluate results and determine empirical factors of the proposed analytical model, a physical model of the ram pump is made with internal diameter of 51 mm. Results of this study are divided into several parts. In the first part, loss coefficients of the impulse valve were measured experimentally and empirical equations of drag coefficient and friction coefficient of the impulse valve were submitted by using nonlinear regression. In the second part, results were evaluated by using experimental data taken from this study. Evaluation of statistical error functions showed that the proposed model has good accuracy for predicting experimental observations. In the third part, in order to validate the results in pumping stage, the analytical models of Lansford and Dugan (1941 and Tacke (1988 were used and the error functions resulted from prediction of experimental observations were investigated through analytical models of

  6. Performance Analysis Of Single-Pumped And Dual-Pumped Parametric Optical Amplifier

    Directory of Open Access Journals (Sweden)

    Sandar Myint

    2015-06-01

    Full Text Available Abstract In this study we present a performance analysis of single-pumped and dual- pumped parametric optical amplifier and present the analysis of gain flatness in dual- pumped Fiber Optical Parametric Amplifier FOPA based on four-wave mixing FWM. Result shows that changing the signal power and pump power give the various gains in FOPA. It is also found out that the parametric gain increase with increase in pump power and decrease in signal power. .Moreover in this paper the phase matching condition in FWM plays a vital role in predicting the gain profile of the FOPAbecause the parametric gain is maximum when the total phase mismatch is zero.In this paper single-pumped parametric amplification over a 50nm gain bandwidth is demonstrated using 500 nm highly nonlinear fiber HNLF and signal achieves about 31dB gain. For dual-pumped parametric amplification signal achieves 26.5dB gains over a 50nm gain bandwidth. Therefore dual-pumped parametric amplifier can provide relatively flat gain over a much wider bandwidth than the single-pumped FOPA.

  7. Proton decay: spectroscopic probe beyond the proton drip line

    International Nuclear Information System (INIS)

    Seweryniak, D; Davids, C N; Robinson, A; Woods, P J; Blank, B; Carpenter, M P; Davinson, T; Freeman, S J; Hammond, N; Hoteling, N; Janssens, R V F; Khoo, T L; Liu, Z; Mukherjee, G; Shergur, J; Sinha, S; Sonzogni, A A; Walters, W B; Woehr, A

    2005-01-01

    Proton decay has been transformed in recent years from an exotic phenomenon into a powerful spectroscopic tool. The frontiers of experimental and theoretical proton-decay studies will be reviewed. Different aspects of proton decay will be illustrated with recent results on the deformed proton emitter 135 Tb, the odd-odd deformed proton emitter 130 Eu, the complex fine structure in the odd-odd 146 Tm nucleus and on excited states in the transitional proton emitter 145 Tm

  8. Residual heat removal pump and low pressure safety injection pump retrofit program

    International Nuclear Information System (INIS)

    Dudiak, J.G.; McKenna, J.M.

    1992-01-01

    Residual Heat Removal (RHR) and low pressure safety injection (LPSI) pumps installed in pressurized water-to-reactor power plants are used to provide low-head safety injection in the event of loss of coolant in the reactor coolant system. Because these pumps are subjected to rather severe temperature and pressure transients, the majority of pumps installed in the RHR service are vertical pumps with a single stage impeller. Typically the pump impeller is mounted on an extended motor shaft (close-coupled configuration) and a mechanical seal is employed at the pump end of the shaft. Traditionally RHR and LPSI pumps have been a significant maintenance item for many utilities. Periodic mechanical seal of motor bearing replacement often is considered routine maintenance. The closed-coupled pump design requires disassembly of the casing cover from the lower pump casing while performing these routine maintenance tasks. This paper introduces a design modification developed to convert the close-coupled RHR and LPSI pumps to a coupled configuration

  9. Is the Ca2+-ATPase from sarcoplasmic reticulum also a heat pump?

    Science.gov (United States)

    Kjelstrup, Signe; de Meis, Leopoldo; Bedeaux, Dick; Simon, Jean-Marc

    2008-11-01

    We calculate, using the first law of thermodynamics, the membrane heat fluxes during active transport of Ca(2+) in the Ca(2+)-ATPase in leaky and intact vesicles, during ATP hydrolysis or synthesis conditions. The results show that the vesicle interior may cool down during hydrolysis and Ca(2+)-uptake, and heat up during ATP synthesis and Ca(2+)-efflux. The heat flux varies with the SERCA isoform. Electroneutral processes and rapid equilibration of water were assumed. The results are consistent with the second law of thermodynamics for the overall processes. The expression for the heat flux and experimental data, show that important contributions come from the enthalpy of hydrolysis for the medium in question, and from proton transport between the vesicle interior and exterior. The analysis give quantitative support to earlier proposals that certain, but not all, Ca(2+)-ATPases, not only act as Ca(2+)-pumps, but also as heat pumps. It can thus help explain why SERCA 1 type enzymes dominate in tissues where thermal regulation is important, while SERCA 2 type enzymes, with their lower activity and better ability to use the energy from the reaction to pump ions, dominate in tissues where this is not an issue.

  10. Proton imaging apparatus for proton therapy application

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  11. Pump Application as Hydraulic Turbine – Pump as Turbine (PaT)

    OpenAIRE

    Rusovs, D

    2009-01-01

    The paper considers pump operation as hydraulic turbine with purpose to produce mechanical power from liquid flow. The Francis hydraulic turbine was selected for comparison with centrifugal pump in reverse operation. Turbine and centrifugal pump velocity triangles were considered with purpose to evaluate PaT efficiency. Shape of impeller blades for turbine and pumps was analysed. Specific speed calculation is carried out with purpose to obtain similarity in pump and turbine description. For ...

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2012-03-01

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

  14. Heat pumps

    CERN Document Server

    Macmichael, DBA

    1988-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Satoshi Takasugi

    2016-10-01

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

  16. Measurement of small-angle antiproton-proton and proton-proton elastic scattering at the CERN intersecting storage rings

    NARCIS (Netherlands)

    Amos, N.; Block, M.M.; Bobbink, G.J.; Botje, M.A.J.; Favart, D.; Leroy, C.; Linde, F.; Lipnik, P.; Matheys, J-P.; Miller, D.

    1985-01-01

    Antiproton-proton and proton-proton small-angle elastic scattering was measured for centre-of-mass energies at the CERN Intersectung Storage Rings. In addition, proton-proton elastic scattering was measured at . Using the optical theorem, total cross sections are obtained with an accuracy of about

  17. Transient Resonance Raman Spectroscopy of a Light-Driven Sodium-Ion-Pump Rhodopsin from Indibacter alkaliphilus.

    Science.gov (United States)

    Kajimoto, Kousuke; Kikukawa, Takashi; Nakashima, Hiroki; Yamaryo, Haruki; Saito, Yuta; Fujisawa, Tomotsumi; Demura, Makoto; Unno, Masashi

    2017-05-04

    Sodium-ion-pump rhodopsin (NaR) is a microbial rhodopsin that transports Na + during its photocycle. Here we explore the photocycle mechanism of NaR from Indibacter alkaliphilus with transient absorption and transient resonance Raman spectroscopy. The transient absorption data indicate that the photocycle of NaR is K (545 nm) → L (490 nm)/M (420 nm) → O 1 (590 nm) → O 2 (560 nm) → NaR, where the L and M are formed as equilibrium states. The presence of K, L, M, and O intermediates was confirmed by the resonance Raman spectra with 442 and 532 nm excitation. The main component of the transient resonance Raman spectra was due to L which contains a 13-cis retinal protonated Schiff base. The presence of an enhanced hydrogen out-of-plane band as well as its sensitivity to the H/D exchange indicate that the retinal chromophore is distorted near the Schiff base region in L. Moreover, the retinal Schiff base of the L state forms a hydrogen bond that is stronger than that of the dark state. These observations are consistent with a Na + pumping mechanism that involves a proton transfer from the retinal Schiff base to a key aspartate residue (Asp116 in Krokinobacter eikastus rhodopsin 2) in the L/M states.

  18. Numerical simulation for nuclear pumped laser

    Energy Technology Data Exchange (ETDEWEB)

    Sakasai, Kaoru [Japan Atomic Energy Research Inst., Tokyo (Japan)

    1998-07-01

    To apply nuclear pumped laser of {sup 3}He-Ne-Ar gas to detect neutron, the optimum gas mixture was investigated by numerical simulation. When {sup 3}He-Ne-Ar mixture gas are irradiated by neutron, proton and triton with high velocity are produced by {sup 3}He(np)T and two charge particles ionized {sup 3}He, Ne and Ar which reacted each other and attained to 3p`(1/2){sub 0}-3S`(1/2). The calculation method is constructed by defining the rate equations of each ion and exited atom and the electron energy balance equation and by time integrating the simultaneous differential equations of the above two equations and the law of conservation of charge. Penning ionization and energy transport by elastic collision of neutral atom were considered in the transport process of electron energy direct ionization by secondary charge particle. Calculation time was 1 msec. The optimum component was shown 3 atm He, 24 Torr He and 8 Torr Ar by simulation. Laser oscilation was generated under the conditions 3.3 x 10{sup 14} (N/cm{sup 2}/5) thermal neutron flux at 50 cm laser cell length and 99% coefficient of reflection of mirror. After laser oscilation, laser output was proportional to neutron flux. These results showed nuclear pumped laser of {sup 3}He-Ne-Ar was able to detect optically neutron. (S.Y)

  19. Reactor coolant purification system circulation pumps (CUW pumps)

    International Nuclear Information System (INIS)

    Tsutsui, Toshiaki

    1979-01-01

    Coolant purification equipments for BWRs have been improved, and the high pressure purifying system has become the main type. The quantity of purifying treatment also changed to 2% of the flow rate of reactor feed water. As for the circulation pumps, canned motor pumps are adopted recently, and the improvements of reliability and safety are attempted. The impurities carried in by reactor feed water and the corrosion products generated in reactors and auxiliary equipments are activated by neutron irradiation or affect heat transfer adversely, adhering to fuel claddings are core structures. Therefore, a part of reactor coolant is led to the purification equipments, and returned to reactors after the impurities are eliminated perfectly. At the time of starting and stopping reactors, excess reactor water and the contaminated water from reactors are transferred to main condenser hot wells or waste treatment systems. Thus the prescribed water quality is maintained. The operational modes of and the requirements for the CUW pumps, the construction and the features of the canned motor type CUW pumps are explained. Recently, a pump operated for 11 months without any maintenance has been disassembled and inspected, but the wear of bearings has not been observed, and the high reliability of the pump has been proved. (Kako, I.)

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

    Science.gov (United States)

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

    2012-01-01

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

  1. Work plan, AP-102 mixer pump removal and pump replacement

    International Nuclear Information System (INIS)

    Jimenez, R.F.

    1994-01-01

    The objective of this work plan is to plan the steps and estimate the costs required to remove the failed AP-102 mixer pump, and to plan and estimate the cost of the necessary design and specification work required to order a new, but modified, mixer pump including the pump and pump pit energy absorbing design. The main hardware required for the removal of the mixer is as follows: a flexible receiver and blast shield; a metal container for the pulled mixer pump; and a trailer and strongback to haul and manipulate the container. Additionally: a gamma scanning device will be needed to detect the radioactivity emanating from the mixer as it is pulled from the tank; a water spray system will be required to remove tank waste from the surface of the mixer as it is pulled from the AP-102 tank; and a lifting yoke to lift the mixer from the pump pit (the SY-101 Mixer Lifting Yoke will be used). A ''green house'' will have to be erected over the AP-102 pump pit and an experienced Hoisting and Rigging crew must be assembled and trained in mixer pump removal methods before the actual removal is undertaken

  2. On proton CT reconstruction using MVCT-converted virtual proton projections

    Energy Technology Data Exchange (ETDEWEB)

    Wang Dongxu; Mackie, T. Rockwell; Tome, Wolfgang A. [Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53705 and Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242 (United States); Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53705 and Morgridge Institute of Research, University of Wisconsin, Madison, Wisconsin 53715 (United States); Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53705 and Oncophysics Institute, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York 10461 (United States)

    2012-06-15

    Purpose: To describe a novel methodology of converting megavoltage x-ray projections into virtual proton projections that are otherwise missing due to the proton range limit. These converted virtual proton projections can be used in the reconstruction of proton computed tomography (pCT). Methods: Relations exist between proton projections and multispectral megavoltage x-ray projections for human tissue. Based on these relations, these tissues can be categorized into: (a) adipose tissue; (b) nonadipose soft tissues; and (c) bone. These three tissue categories can be visibly identified on a regular megavoltage x-ray computed tomography (MVCT) image. With an MVCT image and its projection data available, the x-ray projections through heterogeneous anatomy can be converted to the corresponding proton projections using predetermined calibration curves for individual materials, aided by a coarse segmentation on the x-ray CT image. To show the feasibility of this approach, mathematical simulations were carried out. The converted proton projections, plotted on a proton sinogram, were compared to the simulated ground truth. Proton stopping power images were reconstructed using either the virtual proton projections only or a blend of physically available proton projections and virtual proton projections that make up for those missing due to the range limit. These images were compared to a reference image reconstructed from theoretically calculated proton projections. Results: The converted virtual projections had an uncertainty of {+-}0.8% compared to the calculated ground truth. Proton stopping power images reconstructed using a blend of converted virtual projections (48%) and physically available projections (52%) had an uncertainty of {+-}0.86% compared with that reconstructed from theoretically calculated projections. Reconstruction solely from converted virtual proton projections had an uncertainty of {+-}1.1% compared with that reconstructed from theoretical projections

  3. On proton CT reconstruction using MVCT-converted virtual proton projections

    International Nuclear Information System (INIS)

    Wang Dongxu; Mackie, T. Rockwell; Tomé, Wolfgang A.

    2012-01-01

    Purpose: To describe a novel methodology of converting megavoltage x-ray projections into virtual proton projections that are otherwise missing due to the proton range limit. These converted virtual proton projections can be used in the reconstruction of proton computed tomography (pCT). Methods: Relations exist between proton projections and multispectral megavoltage x-ray projections for human tissue. Based on these relations, these tissues can be categorized into: (a) adipose tissue; (b) nonadipose soft tissues; and (c) bone. These three tissue categories can be visibly identified on a regular megavoltage x-ray computed tomography (MVCT) image. With an MVCT image and its projection data available, the x-ray projections through heterogeneous anatomy can be converted to the corresponding proton projections using predetermined calibration curves for individual materials, aided by a coarse segmentation on the x-ray CT image. To show the feasibility of this approach, mathematical simulations were carried out. The converted proton projections, plotted on a proton sinogram, were compared to the simulated ground truth. Proton stopping power images were reconstructed using either the virtual proton projections only or a blend of physically available proton projections and virtual proton projections that make up for those missing due to the range limit. These images were compared to a reference image reconstructed from theoretically calculated proton projections. Results: The converted virtual projections had an uncertainty of ±0.8% compared to the calculated ground truth. Proton stopping power images reconstructed using a blend of converted virtual projections (48%) and physically available projections (52%) had an uncertainty of ±0.86% compared with that reconstructed from theoretically calculated projections. Reconstruction solely from converted virtual proton projections had an uncertainty of ±1.1% compared with that reconstructed from theoretical projections. If

  4. An analytical method for defining the pump`s power optimum of a water-to-water heat pump heating system using COP

    Directory of Open Access Journals (Sweden)

    Nyers Jozsef

    2017-01-01

    Full Text Available This paper analyzes the energy efficiency of the heat pump and the complete heat pump heating system. Essentially, the maximum of the coefficient of performance of the heat pump and the heat pump heating system are investigated and determined by applying a new analytical optimization procedure. The analyzed physical system consists of the water-to-water heat pump, circulation and well pump. In the analytical optimization procedure the "first derivative equal to zero" mathematical method is applied. The objective function is the coefficient of performance of the heat pump, and the heat pump heating system. By using the analytical optimization procedure and the objective function, as the result, the local and the total energy optimum conditions with respect to the mass flow rate of hot and cold water i. e. the power of circulation or well pump are defined.

  5. Optical Properties Of Polymeric Films Of Bacteriorhodopsin And Its Functional Variants: New Materials For Optical Information Processing

    Science.gov (United States)

    Hampp, Norbert; Braeuchle, Christoph R.; Oesterhelt, Dieter

    1990-01-01

    Purple membrane (PM) from Halobacterium halobium consists of a two-dimensional crystal of the photochromic retinal protein bacteriorhodopsin (BR). Purple membrane embedded in inert polymer matrices can be used as reversible recording medium in holography. The thermal and photochemical stability (at least 100.000 recording cycles at room temperature), the high quantum yield (70%), the high resolution (~ 5000 lines/mm) and the wide spectral range (400-680 nm) of these films are promising features for any possible technical application. The variability of this material was restricted to chemical modifications of the chromophoric group for a long time. new class of BR based recording media is introduced by the availability of variants of BR with a modified amino acid sequence. After generation of a mutant strain PM variants can be easily produced by the same cultivation and purification procedures as the PM of the wildtype and therefore are available in virtually unlimited amounts, too. As an example the properties of PM-films containing the variant BR-326, which differs from the wildtype by a single amino acid, are reported here. The improved diffraction efficiency (~ 2-fold) and increased sensitivity (~ 50%) of films containing BR-326 give an impression of the new possibilities for optimizing reversible recording media by biochemical and gentechnological methods as an alternative or an addition to conventional chemical methods.

  6. Electromagnetic pump technology

    International Nuclear Information System (INIS)

    Prabhakar, R.

    1994-01-01

    Fast Breeder Reactors have an important role to play in our nuclear power programme. Liquid metal sodium is used as the coolant for removing fission heat generated in fast reactors and a distinctive physical property of sodium is its high electrical conductivity. This enables application of electromagnetic (EM) pumps, working on same principle as electric motors, for pumping liquid sodium. Due to its lower efficiency as compared to centrifugal pumps, use of EM pumps has been restricted to reactor auxiliary circuits and experimental facilities. As part of our efforts to manufacture fast reactor components indigenously, work on the development of two types of EM pumps namely flat linear induction pump (FLIP) and annular linear induction pump (ALIP) has been undertaken. Design procedures based on an equivalent circuit approach have been established and results from testing a 5.6 x 10E-3 Cum/s (20 Cum/h) FLIP in a sodium loop were used to validate the procedure. (author). 7 refs., 6 figs

  7. Pumping life

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  8. Champagne Heat Pump

    Science.gov (United States)

    Jones, Jack A.

    2004-01-01

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

  9. Pumping of methane by an ionization assisted Zr/Al getter pump

    International Nuclear Information System (INIS)

    Shen, G.L.

    1987-01-01

    The pumping of methane by an ionization assisted Zr/Al getter pump has been investigated. This pump consists of 12 pieces of ring getters. A spiral shape W filament is located within the ring getters. A bias voltage is applied across the filament and the getter itself. The experiments have shown that (1) when the bias voltage is turned off, the pumping speed of the getter pump for methane increases exponentially with the filament temperature; (2) when the filament temperature is held constant, its pumping speed varies directly with the ionization electron current; (3) when the filament temperature is 2063 0 C and the electron current is 57 mA, the pumping speed of the Zr/Al getter pump is 475 ml/s, and the specific speed is 16.8 ml/s cm 2 ; and (4) an activation energy and critical temperature measured for methane molecules decomposition are, respectively, 47.4 kcal/mol and about 1700 0 C. Analysis of the results indicates that methane is pumped by an ionization assisted Zr/Al getter pump not because of the adsorption and the diffusion of methane molecules directly, but because methane molecules are decomposed as C and H 2 through a catalysis of the hot W filament, carbon is adsorbed on the surface of the W filament, and is diffused into the interior of the W lattice. H 2 is immediately absorbed by the Zr/Al getters. Besides, electron impact with CH 4 would result in the additional decomposition and ionization, then the effect of electron bombardment enhances methane pumping by the Zr/Al getters

  10. Breastfeeding FAQs: Pumping

    Science.gov (United States)

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

  11. Development and evaluation of cryosorption pump and cryotrapping pump for CTR applications

    International Nuclear Information System (INIS)

    Kuribayashi, S.; Ota, H.; Sato, H.

    1986-01-01

    In order to obtain the engineering data to design compound cryopump for CTR, the authors tested the cryosorption pump and cryotrapping pump. The cryosorption panel was consisted of coconut charcoal metallically bonded to 4.2K cryopanel by brazing. The initial pumping speed of helium of cryosorption pump was found to be ≅2.2 iota/scm/sup 2/. The speed dropped off with loading (about 8 Torr iota/cm/sup 2/) to 1.5 iota/scm/sup 2/. The initial helium pumping speed of the 4.2K cryotrapping pump by argon spray was found to be ≅6 iota/scm/sup 2/. The speed, however, dropped off with loading (≅0.3 Torr iota/cm/sup 2/) to less than 5%. These results indicate that the cryosorption pump by coconut charcoal is superior to the cryotrapping pump, because the capacity of the former is larger than the latter

  12. Efficiency and threshold pump intensity of CW solar-pumped solid-state lasers

    Science.gov (United States)

    Hwang, In H.; Lee, Ja H.

    1991-01-01

    The authors consider the relation between the threshold pumping intensity, the material properties, the resonator parameters, and the ultimate slope efficiencies of various solid-state laser materials for solar pumping. They clarify the relation between the threshold pump intensity and the material parameters and the relation between the ultimate slope efficiency and the laser resonator parameters such that a design criterion for the solar-pumped solid-state laser can be established. Among the laser materials evaluated, alexandrite has the highest slope efficiency of about 12.6 percent; however, it does not seem to be practical for a solar-pumped laser application because of its high threshold pump intensity. Cr:Nd:GSGG is the most promising for solar-pumped lasing. Its threshold pump intensity is about 100 air-mass-zero (AM0) solar constants and its slope efficiency is about 12 percent when thermal deformation is completely prevented.

  13. Pumping station design for a pumped-storage wind-hydro power plant

    International Nuclear Information System (INIS)

    Anagnostopoulos, John S.; Papantonis, Dimitris E.

    2007-01-01

    This work presents a numerical study of the optimum sizing and design of a pumping station unit in a hybrid wind-hydro plant. The standard design that consists of a number of identical pumps operating in parallel is examined in comparison with two other configurations, using one variable-speed pump or an additional set of smaller jockey pumps. The aim is to reduce the amount of the wind generated energy that cannot be transformed to hydraulic energy due to power operation limits of the pumps and the resulting step-wise operation of the pumping station. The plant operation for a period of one year is simulated by a comprehensive evaluation algorithm, which also performs a detailed economic analysis of the plant using dynamic evaluation methods. A preliminary study of the entire plant sizing is carried out at first using an optimization tool based on evolutionary algorithms. The performance of the three examined pumping station units is then computed and analyzed in a comparative study. The results reveal that the use of a variable-speed pump constitutes the most effective and profitable solution, and its superiority is more pronounced for less dispersed wind power potential

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

    Science.gov (United States)

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

    2016-05-01

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

  15. Reaction pathways of photoexcited retinal in proteorhodopsin studied by pump-dump-probe spectroscopy.

    Science.gov (United States)

    Rupenyan, Alisa; van Stokkum, Ivo H M; Arents, Jos C; van Grondelle, Rienk; Hellingwerf, Klaas J; Groot, Marie Louise

    2009-12-17

    Proteorhodopsin (pR) is a membrane-embedded proton pump from the microbial rhodopsin family. Light absorption by its retinal chromophore initiates a photocycle, driven by trans/cis isomerization on the femtosecond to picosecond time scales. Here, we report a study on the photoisomerization dynamics of the retinal chromophore of pR, using dispersed ultrafast pump-dump-probe spectroscopy. The application of a pump pulse initiates the photocycle, and with an appropriately tuned dump pulse applied at a time delay after the dump, the molecules in the initial stages of the photochemical process can be de-excited and driven back to the ground state. In this way, we were able to resolve an intermediate on the electronic ground state that represents chromophores that are unsuccessful in isomerization. In particular, the fractions of molecules that undergo slow isomerization (20 ps) have a high probability to enter this state rather than the isomerized K-state. On the ground state reaction surface, return to the stable ground state conformation via a structural or vibrational relaxation occurs in 2-3 ps. Inclusion of this intermediate in the kinetic scheme led to more consistent spectra of the retinal-excited state, and to a more accurate estimation of the quantum yield of isomerization (Phi = 0.4 at pH 6).

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

    Science.gov (United States)

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

    2018-01-15

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

  17. Vibrational Spectroscopy of Cation and Anion Channelrhodopsins

    Science.gov (United States)

    Yi, Adrian S.

    Optogenetics is a technique to control and monitor cell activity with light by expression of specific microbial rhodopsins. Cation channelrhodopsins (CCRs) and anion channelrhodopsins (ACRs) have been demonstrated to activate and silence cell activity, respectively. In this dissertation, the molecular mechanisms of two channelrhodopsins are studied: a CCR from Chlamydomonas augustae (CaChR1) and an ACR from Guillardia theta (GtACR1). The recently discovered GtACR1is especially interesting, as it achieves neural silencing with 1/1000th of the light intensity compared to previous microbial rhodopsin silencing ion pumps. Static and time-resolved resonance Raman, FTIR difference, and UV-visible spectroscopies were utilized in addition to various biochemical and genetic techniques to explore the molecular mechanisms of these channelrhodopsins. In CaChR1, Glu169 and Asp299 residues are located nearby the Schiff base (SB) similar to the homologous residues Asp85 and Asp212, which exist in an ionized state in unphotolyzed bacteriorhodopsin (BR) and play a key role in proton pumping. We observe significant changes in the protonation states of the SB, Glu169, and Asp299 of CaChR1 leading up to the open-channel P2 state, where all three groups exist in a charge neutral state. This unusual charge neutrality along with the position of these groups in the CaChR1 ion channel suggests that charge neutrality plays an important role in cation gating and selectivity in these low efficiency CCRs. Significant differences exist in the photocycle and protonation/hydrogen bonding states of key residues inGtACR1compared to BR and CaChR1. Resonance Raman studies reveal that in the unphotolyzed state of GtACR1, residues Glu68, Ser97 (BR Asp85 homolog), and Asp234 (BR Asp212 homolog) located near the SB exist in charge neutral states. Furthermore, upon K formation, these residues do not change their protonation states. At room temperature, a slow decay of the red-shifted K intermediate is

  18. BWR series pump recirculation system

    International Nuclear Information System (INIS)

    Dillmann, C.W.

    1992-01-01

    This patent describes a recirculation system for driving reactor coolant water contained in an annular downcomer defined between a boiling water reactor vessel and a reactor core spaced radially inwardly therefrom. It comprises a plurality of circumferentially spaced second pumps disposed in the downcomer, each including an inlet for receiving from the downcomer a portion of the coolant water as pump inlet flow, and an outlet for discharging the pump inlet flow pressurized in the second pump as pump outlet flow; and means for increasing pressure of the pump inlet flow at the pump inlet including a first pump disposed in series flow with the second pump for first receiving the pump inlet flow from the downcomer and discharging to the second pump inlet flow pressurized in the first pump

  19. Early outcome of off-pump versus on-pump coronary revascularization

    African Journals Online (AJOL)

    Introduction: The use of coronary artery bypass surgery (CABG) with cardiopulmonary bypass (CPB) or without CPB technique (off-pump) can be associated with different mortality and morbidity and their outcomes remain uncertain. The goal of this study was to evaluate the early outcome of on-pump versus off-pump CABG.

  20. Pumps in wearable ultrafiltration devices: pumps in wuf devices.

    Science.gov (United States)

    Armignacco, Paolo; Garzotto, Francesco; Bellini, Corrado; Neri, Mauro; Lorenzin, Anna; Sartori, Marco; Ronco, Claudio

    2015-01-01

    The wearable artificial kidney (WAK) is a device that is supposed to operate like a real kidney, which permits prolonged, frequent, and continuous dialysis treatments for patients with end-stage renal disease (ESRD). Its functioning is mainly related to its pumping system, as well as to its dialysate-generating and alarm/shutoff ones. A pump is defined as a device that moves fluids by mechanical action. In such a context, blood pumps pull blood from the access side of the dialysis catheter and return the blood at the same rate of flow. The main aim of this paper is to review the current literature on blood pumps, describing the way they have been functioning thus far and how they are being engineered, giving details about the most important parameters that define their quality, thus allowing the production of a radar comparative graph, and listing ideal pumps' features. © 2015 S. Karger AG, Basel.

  1. Specificity of anion-binding in the substrate-pocket ofbacteriorhodopsin

    Energy Technology Data Exchange (ETDEWEB)

    Facciotti, Marc T.; Cheung, Vincent S.; Lunde, Christopher S.; Rouhani, Shahab; Baliga, Nitin S.; Glaeser, Robert M.

    2003-08-30

    The structure of the D85S mutant of bacteriorhodopsin with a nitrate anion bound in the Schiff-base binding site, and the structure of the anion-free protein have been obtained in the same crystal form. Together with the previously solved structures of this anion pump, in both the anion-free state and bromide-bound state, these new structures provide insight into how this mutant of bacteriorhodopsin is able to bind a variety of different anions in the same binding pocket. The structural analysis reveals that the main structural change that accommodates different anions is the repositioning of the polar side-chain of S85. On the basis of these x-ray crystal structures, the prediction is then made that the D85S/D212N double mutant might bind similar anions and do so over a broader pH range than does the single mutant. Experimental comparison of the dissociation constants, K{sub d}, for a variety of anions confirms this prediction and demonstrates, in addition, that the binding affinity is dramatically improved by the D212N substitution.

  2. TFTR ultrahigh-vacuum pumping system incorporating mercury diffusion pumps

    International Nuclear Information System (INIS)

    Sink, D.A.; Sniderman, M.

    1976-06-01

    The TFTR vacuum vessel will have a system of four 61 cm diameter mercury diffusion pumps to provide a base pressure in the 10 -8 to 10 -9 Torr range as well as a low impurity level within the vessel. The system, called the Torus Vacuum Pumping System (TVPS), will be employed with the aid of an occasional 250 0 C bakeout in situ as well as periodic applications of aggressive discharge cleaning. The TVPS is an ultrahigh-vacuum (UHV) system using no elastomers as well as being a closed system with respect to tritium or any tritiated gases. The backing system employing approximately 75 all-metal isolation valves is designed with the features of redundancy and flexibility employed in a variety of ways to meet the fundamental requirements and functions enumerated for the TVPS. Since the design, is one which is a modification of the conceptual design of the TVPS, those features which have changed are discussed. Calculations are presented for the major performance parameters anticipated for the TVPS and include conductances, effective pumping speeds, base pressures, operating parameters, getter pump parameters, and calculations of time constants associated with leak checking. Modifications in the vacuum pumping system for the guard regions on the twelve bellows sections are presented so that it is compatible with the main TVPS. The bellows pumping system consists of a mechanical pump unit, a zirconium aluminum getter pump unit and a residual gas analyzer. The control and management of the TVPS is described with particular attention given to providing both manual and automatic control at a local station and at the TFTR Central Control. Such operations as testing, maintenance, leak checking, startup, bakeout, and various other operations are considered in some detail. Various aspects related to normal pulsing, discharge cleaning, non-tritium operations and tritium operations are also taken into consideration. A cost estimate is presented

  3. Photovoltaic pump systems

    Science.gov (United States)

    Klockgether, J.; Kiessling, K. P.

    1983-09-01

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

  4. Damages on pumps and systems the handbook for the operation of centrifugal pumps

    CERN Document Server

    Merkle, Thomas

    2014-01-01

    Damage on Pumps and Systems. The Handbook for the Operation of Centrifugal Pumps offers a combination of the theoretical basics and practical experience for the operation of circulation pumps in the engineering industry. Centrifugal pumps and systems are extremely vulnerable to damage from a variety of causes, but the resulting breakdown can be prevented by ensuring that these pumps and systems are operated properly. This book provides a total overview of operating centrifugal pumps, including condition monitoring, preventive maintenance, life cycle costs, energy savings and economic aspects. Extra emphasis is given to the potential damage to these pumps and systems, and what can be done to prevent breakdown. Addresses specific issues about pumping of metal chips, sand, abrasive dust and other solids in fluidsEmphasis on economic and efficiency aspects of predictive maintenance and condition monitoring Uses life cycle costs (LCC) to evaluate and calculate the costs of pumping systems

  5. Electrokinetic pump

    Science.gov (United States)

    Patel, Kamlesh D.

    2007-11-20

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

  6. Proton therapy

    International Nuclear Information System (INIS)

    Smith, Alfred R

    2006-01-01

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

  7. Pumping behavior of ion pump elements at high and misaligned magnetic fields

    Energy Technology Data Exchange (ETDEWEB)

    Hseuh, H. C.; Jiang, W. S.; Mapes, M.

    1994-11-01

    The pumping speeds of several diode type ion pump elements with cell radii of 5 mm, 5.5 mm, 6 mm, 9 mm and 12 mm were measured while being subjected to a magnetic field B, ranging from 500 Gauss up to 15 KG, and misalignment angles (angles between the direction of B and the anode axis) from 0 to 13 degrees. The pumping speeds of elements with the 9 mm and 12 mm cells peaked around 1--2 KG, then dropped off rapidly with an increasing magnetic field. The pumping speeds of the smaller cell elements remained constant with an increasing magnetic field. The pumping speeds of all the elements decreased with increasing misalignment. The measured pumping speeds from this study are 3--4 times lower than the calculated pumping, speeds using previously reported empirical formulae.

  8. Pumping behavior of ion pump elements at high and misaligned magnetic fields

    International Nuclear Information System (INIS)

    Hseuh, H.C.; Jiang, W.S.; Mapes, M.

    1994-01-01

    The pumping speeds of several diode type ion pump elements with cell radii of 5 mm, 5.5 mm, 6 mm, 9 mm and 12 mm were measured while being subjected to a magnetic field B, ranging from 500 Gauss up to 15 KG, and misalignment angles (angles between the direction of B and the anode axis) from 0 to 13 degrees. The pumping speeds of elements with the 9 mm and 12 mm cells peaked around 1--2 KG, then dropped off rapidly with an increasing magnetic field. The pumping speeds of the smaller cell elements remained constant with an increasing magnetic field. The pumping speeds of all the elements decreased with increasing misalignment. The measured pumping speeds from this study are 3--4 times lower than the calculated pumping, speeds using previously reported empirical formulae

  9. Proton-proton bremsstrahlung in a relativistic covariant model

    NARCIS (Netherlands)

    Martinus, Gerard Henk

    1998-01-01

    Proton-proton bremsstrahlung is one of the simplest processes involving the half off-shell NN interaction. Since protons are equally-charged particles with the same mass, electric-dipole radiation is suppressed and higher-order effects play an important role. Thus it is possible to get information

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

    Science.gov (United States)

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

    2016-04-01

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

  11. Liquid metal pump

    International Nuclear Information System (INIS)

    Pennell, W.E.

    1981-01-01

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

  12. Proton-Proton and Proton-Antiproton Colliders

    CERN Document Server

    Scandale, Walter

    2014-01-01

    In the last five decades, proton–proton and proton–antiproton colliders have been the most powerful tools for high energy physics investigations. They have also deeply catalyzed innovation in accelerator physics and technology. Among the large number of proposed colliders, only four have really succeeded in becoming operational: the ISR, the SppbarS, the Tevatron and the LHC. Another hadron collider, RHIC, originally conceived for ion–ion collisions, has also been operated part-time with polarized protons. Although a vast literature documenting them is available, this paper is intended to provide a quick synthesis of their main features and key performance.

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

    Science.gov (United States)

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

    2016-08-01

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

  14. Dynamics of Anti-Proton -- Protons and Anti-Proton -- Nucleus Reactions

    CERN Document Server

    Galoyan, A; Uzhinsky, V

    2016-01-01

    A short review of simulation results of anti-proton-proton and anti-proton-nucleus interactions within the framework of Geant4 FTF (Fritiof) model is presented. The model uses the main assumptions of the Quark-Gluon-String Model or Dual Parton Model. The model assumes production and fragmentation of quark-anti-quark and diquark-anti-diquark strings in the mentioned interactions. Key ingredients of the model are cross sections of string creation processes and an usage of the LUND string fragmentation algorithm. They allow one to satisfactory describe a large set of experimental data, especially, a strange particle production, Lambda hyperons and K mesons.

  15. High-vacuum plasma pump

    International Nuclear Information System (INIS)

    Dorodnov, A.M.; Minajchev, V.E.; Miroshkin, S.I.

    1980-01-01

    The action of an electric-arc high-vacuum pump intended for evacuating the volumes in which the operation processes are followed by a high gas evolution is considered. The operation of the pump is based on the principle of controlling the getter feed according to the gas load and effect of plasma sorbtion pumping. The pump performances are given. The starting pressure is about 5 Pa, the limiting residual pressure is about 5x10 -6 Pa, the pumping out rate of nitrogen in the pressure range 5x10 -5 -5x10 -3 Pa accounts for about 4000 l/s, the power consumption comes to 6 kW. Analyzing the results of the test operation of the pump, it has been concluded that its principal advantages are the high starting pressure, controlled getter feed rate and possibility of pumping out the gases which are usually pumped out with difficulty. The operation reliability of the pump is defined mainly by reliable operation of the ignition system of the vacuum arc [ru

  16. Pumping machinery theory and practice

    CERN Document Server

    Badr, Hassan M

    2014-01-01

    Pumping Machinery Theory and Practice comprehensively covers the theoretical foundation and applications of pumping machinery. Key features: Covers characteristics of centrifugal pumps, axial flow pumps and displacement pumpsConsiders pumping machinery performance and operational-type problemsCovers advanced topics in pumping machinery including multiphase flow principles, and two and three-phase flow pumping systemsCovers different methods of flow rate control and relevance to machine efficiency and energy consumptionCovers different methods of flow rate control and relevance to machine effi

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

    Science.gov (United States)

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

    2018-04-01

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

  18. Theoretical Analysis of Proton Relays in Electrochemical Proton-Coupled Electron Transfer

    International Nuclear Information System (INIS)

    Auer, Benjamin; Fernandez, Laura; Hammes-Schiffer, Sharon

    2011-01-01

    The coupling of long-range electron transfer to proton transport over multiple sites plays a vital role in many biological and chemical processes. Recently a molecule with a hydrogen-bond relay inserted between the proton donor and acceptor sites in a proton-coupled electron transfer (PCET) system was studied electrochemically. The standard rate constants and kinetic isotope effects (KIEs) were measured experimentally for this system and a related single proton transfer system. In the present paper, these systems are studied theoretically using vibronically nonadiabatic rate constant expressions for electrochemical PCET. Application of this approach to proton relays requires the calculation of multidimensional proton vibrational wavefunctions and incorporation of multiple proton donor-acceptor motions. The calculated KIEs and relative standard rate constants for the single and double proton transfer systems are in agreement with the experimental data. The calculations indicate that the standard rate constant is lower for the double proton transfer system because of the smaller overlap integral between the ground state reduced and oxidized proton vibrational wavefunctions for this system, resulting in greater contributions from excited electron-proton vibronic states with higher free energy barriers. The decrease in proton donor-acceptor distances due to thermal fluctuations and the contributions from excited electron-proton vibronic states play important roles in proton relay systems. The theory suggests that the PCET rate constant may be increased by decreasing the equilibrium proton donor-acceptor distances or modifying the thermal motions of the molecule to facilitate the concurrent decrease of these distances. The submission of this journal article in ERIA is a requirement of the EFRC subcontract with Pennsylvania State University collaborators to get publications to OSTI.

  19. Hydraulic optimization of 'S' characteristics of the pump-turbine for Xianju pumped storage plant

    International Nuclear Information System (INIS)

    Liu, W C; Zheng, J S; Cheng, J; Shi, Q H

    2012-01-01

    The pump-turbine with a rated power capacity of 375MW each at Xianju pumped storage plant is the most powerful one under construction in China. In order to avoid the instability near no-load conditions, the hydraulic design of the pump-turbine has been optimized to improving the 'S' characteristic in the development of the model pump-turbine. This paper presents the cause of 'S' characteristic of a pump-turbine by CFD simulation of the internal flow. Based on the CFD analysis, the hydraulic design optimization of the pump-turbine was carried out to eliminate the 'S' characteristics of the machine at Xianju pumped storage plant and a big step for removing the 'S' characteristic of a pump-turbine has been obtained. The model test results demonstrate that the pump-turbine designed for Xianju pumped storage plant can smoothly operate near no-load conditions without an addition of misaligned guide vanes.

  20. Halophilic archaea on Earth and in space: growth and survival under extreme conditions.

    Science.gov (United States)

    Oren, Aharon

    2014-12-13

    Salts are abundant on Mars, and any liquid water that is present or may have been present on the planet is expected to be hypersaline. Halophilic archaea (family Halobacteriaceae) are the microorganisms best adapted to life at extremes of salinity on Earth. This paper reviews the properties of the Halobacteriaceae that may make the group good candidates for life also on Mars. Many species resist high UV and gamma radiation levels; one species has survived exposure to vacuum and radiation during a space flight; and there is at least one psychrotolerant species. Halophilic archaea may survive for millions of years within brine inclusions in salt crystals. Many species have different modes of anaerobic metabolism, and some can use light as an energy source using the light-driven proton pump bacteriorhodopsin. They are also highly tolerant to perchlorate, recently shown to be present in Martian soils, and some species can even use perchlorate as an electron acceptor to support anaerobic growth. The presence of characteristic carotenoid pigments (α-bacterioruberin and derivatives) makes the Halobacteriaceae easy to identify by Raman spectroscopy. Thus, if present on Mars, such organisms may be detected by Raman instrumentation planned to explore Mars during the upcoming ExoMars mission. © 2014 The Author(s) Published by the Royal Society. All rights reserved.