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Sample records for blocker ro 40-5967

  1. Novel mode of action of the calcium antagonist mibefradil (Ro 40-5967): potent immunosuppression by inhibition of T-cell infiltration through allogeneic endothelium.

    PubMed Central

    Blaheta, R A; Hailer, N P; Brude, N; Wittig, B; Oppermann, E; Leckel, K; Harder, S; Scholz, M; Weber, S; Encke, A; Markus, B H

    1998-01-01

    Cyclosporin A reduces the mitotic activity of allosensitized lymphocytes, but fails to limit emigration of these cells into the donor organ. However, the modulation of both lymphocyte proliferation and infiltration are desirable characteristics of immunosuppressive therapy. The calcium-channel blocker, verapamil, has recently been shown to effectively prevent the transmigration of CD4+ and CD8+ T cells through allogeneic endothelium. Mibefradil (Ro 40-5967) represents a new generation of calcium antagonists with high potency and long-term activity. To evaluate the immunosuppressive potential of this drug, the influence of mibefradil on lymphocyte adhesion to, horizontal locomotion along, and penetration through allogeneic endothelium (HUVEC) was performed. When lymphocytes were prestimulated for 24 hr with mibefradil, adhesion and penetration were dose-dependently reduced. The adhesion ID50 values were 3.4 microM (CD4+ T cells) versus 9.2 microM (CD8+ T cells) and 2.1 microM (CD4+ T cells) versus 3.9 microM (CD8+ T cells) with regard to penetration. Mibefradil also effectively blocked horizontal locomotion. Specific down-regulation of T-cell binding to the P-selection receptor (ID50: CD4+ T cells, 0.8 microM: CD8+ T cells, 1.2 microM) and to the intracellular adhesion molecule-1 (ICAM-1) receptor (ID50: CD4+ T cells, 1.9 microM; CD8+ T cells, 1.5 microM) by mibefradil seems to be responsible for the decreased adhesion and penetration rates. Reduction of intracellular F-actin in T lymphocytes could diminish cell locomotion. In conclusion, the potent suppressive properties of mibefradil support its use as a co-medication in cyclosporin A-based immunosuppressive therapy. PMID:9741343

  2. Alpha Blockers

    MedlinePlus

    ... conditions such as high blood pressure and benign prostatic hyperplasia. Find out more about this class of medication. ... these conditions: High blood pressure Enlarged prostate (benign prostatic hyperplasia) Though alpha blockers are commonly used to treat ...

  3. Beta Blockers

    MedlinePlus

    Diseases and Conditions High blood pressure (hypertension) Beta blockers, also called beta-adrenergic blocking agents, treat a variety of conditions, such as high blood pressure and migraines. Find out more about this ...

  4. H2 blockers

    MedlinePlus

    ... ulcer disease - H2 blockers; PUD - H2 blockers; Gastroesophageal reflux - H2 blockers ... blockers are used to: Relieve symptoms of acid reflux, or gastroesophageal reflux disease (GERD). This is a ...

  5. β-Adrenergic blockers.

    PubMed

    Frishman, William H; Saunders, Elijah

    2011-09-01

    KEY POINTS AND PRACTICAL RECOMMENDATIONS: •  β-Blockers are appropriate treatment for patients with hypertension and those who have concomitant ischemic heart disease, heart failure, obstructive cardiomyopathy, or certain arrhythmias. •  β-Blockers can be used in combination with other antihypertensive drugs to achieve maximal blood pressure control. Labetalol can be used in hypertensive emergencies and urgencies. •  β-Blockers may be useful in patients having hyperkinetic circulation (palpitations, tachycardia, hypertension, and anxiety), migraine headache, and essential tremor. •  β-Blockers are highly heterogeneous with respect to various pharmacologic effects: degree of intrinsic sympathomimetic activity, membrane-stabilizing activity, β(1) selectivity, α(1) -adrenergic-blocking effect, tissue solubility, routes of systemic elimination, potencies and duration of action, and specific effects may be important in the selection of a drug for clinical use. •  β-Blocker usage to reduce perioperative ischemia and cardiovascular complications may not benefit as many patients as was once hoped and may actually cause harm in some individuals. Currently the best evidence supports β-blocker use in two patient groups: patients undergoing vascular surgery with known ischemic heart disease or multiple risk factors for it and for patients already receiving β-blockers for known cardiovascular conditions.

  6. Beta blockers in hypertension.

    PubMed

    Thadani, U

    1983-11-10

    Beta-adrenoceptor antagonists are effective in the management of patients with mild-to-moderate hypertension. Noncardioselective agents, cardioselective agents and beta blockers with intrinsic sympathomimetic activity (ISA) are equally effective, provided they are used in equipotent doses. Beta blockers can be used as first-line therapy in the management of hypertension and can be safely combined with diuretics, vasodilators, or both, for a better control of blood pressure. The exact mechanism by which beta blockers decrease blood pressure remains speculative, but they all reduce cardiac output during long-term therapy; drugs with ISA lower cardiac output and heart rate less than do drugs without ISA. Pharmacokinetic properties of beta blockers differ widely; drugs metabolized by the liver have shorter plasma half-lives than drugs primarily excreted by the kidneys. Although many of the side effects of various beta blockers are similar, differences in water and lipid solubility account for a higher incidence of central nervous system side effects with lipid-soluble drugs (such as propranolol and metoprolol) than with hydrophilic drugs (such as atenolol and timolol). The incidence of cold extremities has been reported to be less with drugs with ISA, and the incidence of bronchospasm less with cardioselective drugs. In the management of uncomplicated mild-to-moderate hypertension, all beta blockers are equally effective and produce less troublesome side effects than alternative antihypertensive agents. For effective therapy beta blockers can be used in 2 divided daily doses or even once daily.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. 46 CFR 111.105-40 - Additional requirements for RO/RO vessels.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... RO/RO vessels. (a) Each RO/RO vessel must meet ABS Steel Vessel Rules (incorporated by reference; see... 1 hazardous location. (c) Where the ventilation requirement of ABS Steel Vessel Rules section...

  8. Pharmacogenetics of beta-blockers.

    PubMed

    Shin, Jaekyu; Johnson, Julie A

    2007-06-01

    Beta-blockers are an important cardiovascular drug class, recommended as first-line treatment of numerous diseases such as heart failure, hypertension, and angina, as well as treatment after myocardial infarction. However, responses to a beta-blocker are variable among patients. Results of numerous studies now suggest that genetic polymorphisms may contribute to variability in responses to beta-blockers. This review summarizes the pharmacogenetic data for beta-blockers in patients with various diseases and discusses the potential implications of beta-blocker pharmacogenetics in clinical practice.

  9. CoRoTlog

    NASA Astrophysics Data System (ADS)

    Plasson, Ph.

    2006-11-01

    LESIA, in close cooperation with CNES, DLR and IWF, is responsible for the tests and validation of the CoRoT instrument digital process unit which is made up of the BEX and DPU assembly. The main part of the work has consisted in validating the DPU software and in testing the BEX/DPU coupling. This work took more than two years due to the central role of the software tested and its technical complexity. The first task, in the validation process, was to carry out the acceptance tests of the DPU software. These tests consisted in checking each of the 325 requirements identified in the URD (User Requirements Document) and were played in a configuration using the DPU coupled to a BEX simulator. During the acceptance tests, all the transversal functionalities of the DPU software, like the TC/TM management, the state machine management, the BEX driving, the system monitoring or the maintenance functionalities were checked in depth. The functionalities associated with the seismology and exoplanetology processing, like the loading of window and mask descriptors or the configuration of the service execution parameters, were also exhaustively tested. After having validated the DPU software against the user requirements using a BEX simulator, the following step consisted in coupling the DPU and the BEX in order to check that the formed unit worked correctly and met the performance requirements. These tests were conducted in two phases: the first one was devoted to the functional aspects and the tests of interface, the second one to the performance aspects. The performance tests were based on the use of the DPU software scientific services and on the use of full images representative of a realistic sky as inputs. These tests were also based on the use of a reference set of windows and parameters, which was provided by the scientific team and was representative, in terms of load and complexity, of the one that could be used during the observation mode of the CoRoT instrument

  10. Beta-Blockers and Calcium Channel Blockers: First Line Agents.

    PubMed

    Pascual, Isaac; Moris, Cesar; Avanzas, Pablo

    2016-08-01

    Beta-blockers and calcium channel blockers (CCB) are milestones in the treatment of stable coronary ischaemic disease. Their main effects are particularly suited for the management of effort-induced angina because of the reduction of oxygen demand they achieve. The clinical benefits of these drugs are highly reproducible and have been shown to improve overall clinical outcomes. Despite the availability of other, and newer antianginal drugs, treatment guidelines continue to recommend the use of beta-blockers and calcium channel blockers as first line therapies.

  11. Beta-blockers in hypertension.

    PubMed

    Ram, C Venkata S

    2010-12-15

    Beta blockers have been used in the treatment of cardiovascular conditions for decades. Despite a long history and status as a guideline-recommended treatment option for hypertension, recent meta-analyses have brought into question whether β blockers are still an appropriate therapy given outcomes data from other antihypertensive drug classes. However, β blockers are a heterogenous class of agents with diverse pharmacologic and physiologic properties. Much of the unfavorable data revealed in the recent meta-analyses were gleaned from studies involving nonvasodilating, traditional β blockers, such as atenolol. However, findings with traditional β blockers may not be extrapolated to other members of the class, particularly those agents with vasodilatory activity. Vasodilatory β blockers (i.e., carvedilol and nebivolol) reduce blood pressure in large part through reducing systemic vascular resistance rather than by decreasing cardiac output, as is observed with traditional β blockers. Vasodilating ability may also ameliorate some of the concerns associated with traditional β blockade, such as the adverse effects on metabolic and lipid parameters, including an increased risk for new-onset diabetes. Furthermore, vasodilating ability is physiologically relevant and important in treating a condition with common co-morbidities involving metabolic and lipid abnormalities such as hypertension. In patients with hypertension and diabetes or coronary artery disease, vasodilating β blockers provide effective blood pressure control with neutral or beneficial effects on important parameters for the co-morbid disease. In conclusion, it is time for a reexamination of the clinical evidence for the use of β blockers in hypertension, recognizing that there are patients for whom β blockers, particularly those with vasodilatory actions, are an appropriate treatment option.

  12. Tuning Photochromic Ion Channel Blockers

    PubMed Central

    2011-01-01

    Photochromic channel blockers provide a conceptually simple and convenient way to modulate neuronal activity with light. We have recently described a family of azobenzenes that function as tonic blockers of Kv channels but require UV-A light to unblock and need to be actively switched by toggling between two different wavelengths. We now introduce red-shifted compounds that fully operate in the visible region of the spectrum and quickly turn themselves off in the dark. Furthermore, we have developed a version that does not block effectively in the dark-adapted state, can be switched to a blocking state with blue light, and reverts to the inactive state automatically. Photochromic blockers of this type could be useful for the photopharmacological control of neuronal activity under mild conditions. PMID:22860175

  13. How Do Beta Blocker Drugs Affect Exercise?

    MedlinePlus

    ... Aneurysm More How do beta blocker drugs affect exercise? Updated:Aug 5,2015 Beta blockers are a ... about them: Do they affect your ability to exercise? The answer can vary a great deal, depending ...

  14. Can Beta Blockers Cause Weight Gain?

    MedlinePlus

    Diseases and Conditions High blood pressure (hypertension) Can beta blockers cause weight gain? Answers from Sheldon G. Sheps, ... can occur as a side effect of some beta blockers, especially the older ones, such as atenolol (Tenormin) ...

  15. Ozonation of reverse osmosis concentrate: kinetics and efficiency of beta blocker oxidation.

    PubMed

    Benner, Jessica; Salhi, Elisabeth; Ternes, Thomas; von Gunten, Urs

    2008-06-01

    Reverse osmosis (RO) concentrate samples were obtained from a RO-membrane system that uses effluents of wastewater treatment plants (WWTP) as feed water for the production of drinking water. A number of different pharmaceuticals (e.g. antibiotics, contrast media, beta blockers) were found in the WWTP effluent as well as in the RO-concentrate. Overall, a concentration factor (feed:concentrate) of approximately 3-4 was measured. Beta blockers (acebutolol, atenolol, bisoprolol, celiprolol, metoprolol, propranolol, timolol) were found in the range of low ng/L to low microg/L. Because metoprolol and propranolol are classified as potentially toxic to aquatic organisms and all beta blocker molecules have moieties, which are reactive towards ozone (amine groups, activated aromatic rings), it was tested whether ozonation can be applied for their mitigation. Rate constants for the reaction of acebutolol, atenolol, metoprolol and propranolol with ozone and OH radicals were determined. At pH 7 acebutolol, atenolol and metoprolol react with ozone with an apparent second-order rate constant k(O)(3) of about 2,000 M(-1)s(-1), whereas propranolol reacts with approximately 10(5)M(-1)s(-1). The rate constants for the reaction of the selected compounds with OH radicals were determined to be 0.5-1.0 x 10(10)M(-1)s(-1). Experiments with RO concentrate showed that an ozone dose of only 5mg/L resulted in a quantitative removal of propranolol in 0.8s and 10mg O(3)/L oxidized 70% of metoprolol in only 1.2s. Tests with chlorinated and non-chlorinated WWTP effluent showed an increase of ozone stability but a decrease of hydroxyl radical exposure in the samples after chlorination. This may shift the oxidation processes towards direct ozone reactions and favor the degradation of compounds with high k(O)(3).

  16. [Applications for bronchial blockers in thoracic surgery].

    PubMed

    García-Guasch, R; Campos, J H; Granell, M; Peña, J J

    2007-11-01

    One-lung ventilation is commonly used to facilitate visualization of the field during thoracic surgery. New devices for performing this technique that have become available over the past 2 decades include the Univent bronchial blocker incorporated in a single-lumen tube, the Arndt endobronchial blocker, and the Cohen endobronchial blocker. Although insertion of a double-lumen tube is still the method used most often to isolate the lung, bronchial blockade is an increasingly common technique and, in certain clinical settings, provides advantages over the double-lumen tube. This review provides an update on new concepts in the use of bronchial blockers as a technique for lung isolation and one-lung ventilation. The literature search was performed on MEDLINE through PubMed using the keywords bronchial blockers and thoracic surgery. The search span started with 1982-the year the first modern bronchial blocker was described - and ended with February 2006.

  17. Characterisation of RO fouling in an integrated MBR/RO system for wastewater reuse.

    PubMed

    Moreno, J; Monclús, H; Stefani, M; Cortada, E; Aumatell, J; Adroer, N; De Lamo-Castellví, S; Comas, J

    2013-01-01

    Membrane filtration has gradually gained acceptance as the preferred pre-treatment for reverse osmosis (RO). In this paper, an integrated membrane bioreactor (MBR)/RO system for wastewater reuse treating real sewage water has been evaluated and the RO fouling has been characterised. The MBR achieved low values of organic matter, total nitrogen, PO(4)(3-), total organic carbon, turbidity and conductivity. Filtration with two different RO commercial membranes was performed after the MBR pre-treatment and the same average fouling rate (0.08 bar day(-1)) was noted. These results gained from the characterisation of the high quality MBR/RO permeate show its potential for water reuse. Inorganic precipitation appears to be the predominant form of fouling in the RO membranes. Calcium phosphate and alumino-silicates were identified by a scanning electron microscope combined with an energy dispersive X-ray and polysaccharides, amide and aliphatic structures were detected with attenuated total reflection infrared microspectroscopy.

  18. Effects of (−)-RO363 at human atrial β-adrenoceptor subtypes, the human cloned β3-adrenoceptor and rodent intestinal β3-adrenoceptors

    PubMed Central

    Molenaar, Peter; Sarsero, Doreen; Arch, Jonathan R S; Kelly, John; Henson, Sian M; Kaumann, Alberto J

    1997-01-01

    Chronic treatment of patients with β-blockers causes atrial inotropic hyperresponsiveness through β2-adrenoceptors, 5-HT4 receptors and H2-receptors but apparently not through β1-adrenoceptors despite data claiming an increased β1-adrenoceptor density from homogenate binding studies. We have addressed the question of β1-adrenoceptor sensitivity by determining the inotropic potency and intrinsic activity of the β1-adrenoceptor selective partial agonist (−)-RO363 and by carrying out both homogenate binding and quantitative β-adrenoceptor autoradiography in atria obtained from patients treated or not treated with β-blockers. In the course of the experiments it became apparent that (−)-RO363 also may cause agonistic effects through the third atrial β-adrenoceptor. To assess whether (−)-RO363 also caused agonistic effects through β3-adrenoceptors we studied its relaxant effects in rat colon and guinea-pig ileum, as well as receptor binding and adenylyl cyclase stimulation of chinese hamster ovary (CHO) cells expressing human β3-adrenoceptors. β-Adrenoceptors were labelled with (−)-[125I]-cyanopindolol. The density of both β1- and β2-adrenoceptors was unchanged in the 2 groups, as assessed with both quantitative receptor autoradiography and homogenate binding. The affinities of (−)-RO363 for β1-adrenoceptors (pKi=8.0–7.7) and β2-adrenoceptors (pKi=6.1–5.8) were not significantly different in the two groups. (−)-RO363 increased atrial force with a pEC50 of 8.2 (β-blocker treated) and 8.0 (non-β-blocker treated) and intrinsic activity with respect to (−)-isoprenaline of 0.80 (β-blocker treated) and 0.54 (non-β-blocker treated) (P<0.001) and with respect to Ca2+ (7 mM) of 0.65 (β-blocker treated) and 0.45 (non-β-blocker treated) (P<0.01). The effects of (−)-RO363 were resistant to antagonism by the β2-adrenoceptor antagonist, ICI 118,551 (50 nM). The effects of 0.3–10 nM (−)-RO363 were antagonized by 3–10 nM of the

  19. Removal of emerging contaminants from municipal wastewater with an integrated membrane system, MBR-RO.

    PubMed

    Dolar, Davor; Gros, Meritxell; Rodriguez-Mozaz, Sara; Moreno, Jordi; Comas, Joaquim; Rodriguez-Roda, Ignasi; Barceló, Damià

    2012-11-15

    The presence of emerging contaminants in the aquatic environment and their potential effects on living organisms has become an issue of growing concern. Among emerging contaminants, pharmaceuticals may enter the aquatic environment due to their high consumption and their incomplete removal in conventional municipal wastewater treatment plants (WWTPs). The main goal of this study was the assessment of the removal efficiency of pharmaceuticals found in municipal wastewater of a coastal WWTP (Castell-Platja d'Aro, Spain) using an integrated pilot scale membrane system (MBR-RO). Twenty multiple-class pharmaceuticals (including psychiatric drugs, macrolide antibiotics, β-blockers, sulfonamide and fluoroquinolone antibiotics, histamine H2 receptor antagonists, anti-inflammatories, nitroimidazole, β-agonist and antiplatelet agent) were measured in real influent with the lowest average concentration for psychiatric drugs (0.017 μg L(-1)) to the highest for macrolide antibiotics (2.02 μg L(-1)). Although some contaminants were in relatively high concentrations (even up to 2.90 μg L(-1) in the case of ofloxacin). The combination of MBR and RO treatment showed excellent overall removal of target emerging contaminants with removal rates above 99% for all of them. For some compounds (metronidazole, hydrocodone, codein, ranitidine) MBR provided high removal efficiency (up to 95%). Additionally RO membrane showed removal rates always higher than 99%.

  20. Effects of (-)-RO363 at human atrial beta-adrenoceptor subtypes, the human cloned beta 3-adrenoceptor and rodent intestinal beta 3-adrenoceptors.

    PubMed

    Molenaar, P; Sarsero, D; Arch, J R; Kelly, J; Henson, S M; Kaumann, A J

    1997-01-01

    1. Chronic treatment of patients with beta-blockers causes atrial inotropic hyperresponsiveness through beta 2-adrenoceptors, 5-HT4 receptors and H2-receptors but apparently not through beta 1-adrenoceptors despite data claiming an increased beta 1-adrenoceptor density from homogenate binding studies. We have addressed the question of beta 1-adrenoceptor sensitivity by determining the inotropic potency and intrinsic activity of the beta 1-adrenoceptor selective partial agonist (-)-RO363 and by carrying out both homogenate binding and quantitative beta-adrenoceptor autoradiography in atria obtained from patients treated or not treated with beta-blockers. In the course of the experiments it became apparent that (-)-RO363 also may cause agonistic effects through the third atrial beta-adrenoceptor. To assess whether (-)-RO363 also caused agonistic effects through beta 3-adrenoceptors we studied its relaxant effects in rat colon and guinea-pig ileum, as well as receptor binding and adenylyl cyclase stimulation of chinese hamster ovary (CHO) cells expressing human beta 3-adrenoceptors. 2. beta-Adrenoceptors were labelled with (-)-[125I]-cyanopindolol. The density of both beta 1- and beta 2-adrenoceptors was unchanged in the 2 groups, as assessed with both quantitative receptor autoradiography and homogenate binding. The affinities of (-)-RO363 for beta 1-adrenoceptors (pKi = 8.0-7.7) and beta 2-adrenoceptors (pKi = 6.1-5.8) were not significantly different in the two groups. 3. (-)-RO363 increased atrial force with a pEC50 of 8.2 (beta-blocker treated) and 8.0 (non-beta-blocker treated) and intrinsic activity with respect to (-)-isoprenaline of 0.80 (beta-blocker treated) and 0.54 (non-beta-blocker treated) (P < 0.001) and with respect to Ca2+ (7 mM) of 0.65 (beta-blocker treated) and 0.45 (non-beta-blocker treated) (P < 0.01). The effects of (-)-RO363 were resistant to antagonism by the beta 2-adrenoceptor antagonist, ICI 118,551 (50 nM). The effects of 0.3-10 nM (-)-RO

  1. Ro(SS-A) and anti-Ro(SS-A): an update.

    PubMed

    Sibilia, J

    1998-01-01

    Anti-Ro/SSA antibodies are the antinuclear antibodies most commonly found in everyday clinical practice and are closely associated with Sjögren's syndrome, systemic lupus erythematosus and neonatal lupus. They play a pathogenic role in a variety of clinical manifestations, including skin lesions and neonatal lupus heart block. Autoantibodies to Ro(SS-A) recognize a ribonucleoprotein complex composed of small single-stranded RNAs (hYRNAs) and of one or more peptides. Four molecular forms of this complex have been differentiated based on the nature of the peptide: a lymphocyte and an erythrocyte Ro with a 60 kDa peptide, a lymphocyte Ro with a 52 kDa peptide and an erythrocyte Ro with a 54 kDa peptide. The Ro complex is found in most tissues and cells (erythrocytes, platelets), with differences in structure and quantity across tissues, species and embryonic development stages. Although its function remains unknown, its ability to bind nucleic acids and the fact that it shares homologies with gene regulation proteins suggest that it may participate in RNA transcription processes. A number of environmental factors (exposure to ultraviolet radiation, viral infections) may cause translocation of the Ro complex to nucleocytoplasmic and membrane sites where it is not normally found, thereby leading to the development of autoimmunity. The structure of the Ro(SS-A)-hYRNA complex and the development of autoimmunity are currently the focus of active research efforts that can be expected to improve our understanding of the clinical manifestations directly related to anti-Ro(SS-A) antibodies.

  2. Misperceptions About β-Blockers and Diuretics

    PubMed Central

    Ubel, Peter A; Jepson, Christopher; Asch, David A

    2003-01-01

    BACKGROUND Based on a series of clinical trials showing no difference in the effectiveness or tolerability of most major classes of antihypertensive medications, the Joint National Commission on High Blood Pressure Treatment recommends that physicians prescribe β-blockers or diuretics as initial hypertensive therapy unless there are compelling indications for another type of medication. Nevertheless, many physicians continue to favor more expensive medications like angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers as first line agents. The persistent use of these agents raises questions as to whether physicians perceive ACE inhibitors and calcium channel blockers to be better than β-blockers and diuretics. METHODS We surveyed 1,200 primary care physicians in 1997, and another 500 primary care physicians in 2000, and asked them to estimate the relative effectiveness and side effects of 4 classes of medication in treating a hypothetical patient with uncomplicated hypertension: ACE inhibitors, β-blockers, calcium channel blockers, and diuretics. In addition, we asked them to indicate whether they ever provided free samples of hypertension medications to their patients. RESULTS Perceptions of the relative effectiveness and side effects of the 4 classes of hypertension medications did not significantly change over the 3 years, nor did prescription recommendations. Physicians perceive that diuretics are less effective at lowering blood pressure than the other 3 classes (P < .001). They also perceive that β-blockers are less tolerated than the other 3 classes (P < .001). In a multivariate model, perceptions of effectiveness and tolerability displayed significant associations with prescription preference independent of background variables. The only other variable to contribute significantly to the model was provision of free medication samples to patients. CONCLUSIONS Despite numerous clinical trials showing no difference in the effectiveness

  3. Adsorption of beta blockers to environmental surfaces.

    PubMed

    Kibbey, Tohren C G; Paruchuri, Rajiv; Sabatini, David A; Chen, Lixia

    2007-08-01

    Beta-adrenergic blocking agents (beta blockers) are widely used pharmaceuticals which have been detected in the environment. Predicting the transport and ultimate fate of beta blockers in the environment requires understanding their adsorption to soils and sediments, something for which little information is currently available. The objective of this work was to examine the adsorption of three beta blockers, propranolol, metoprolol and nadolol, to a natural alluvial material, as well as to six minerals present as components of the alluvial material. Batch adsorption experiments indicate that, for most of the minerals studied, compound hydrophobicity is an important predictor of adsorption, with propranolol,the most hydrophobic compound studied, adsorbing to the greatest extent. Results further suggest that, for the minerals studied, electrostatic effects are not a good predictor of adsorption; adsorption extent was not well-predicted by either surface zeta potential or by the difference between experiment pH and point of zero charge, despite the cationic nature af the three beta blockers at experiment pH values. Experiments were conducted to examine the effect of an anionic surfactant, sodium dodecyl benzene sulfonate (SDBS), on adsorption. Results indicate that SDBS significantly increases the adsorption of propranolol to two different sorbents. This result is potentially important because surfactants such as SDBS are likely to be present in wastewater effluents with beta blockers and could influence their mobility in the environment.

  4. AstRoMap European Astrobiology Roadmap.

    PubMed

    Horneck, Gerda; Walter, Nicolas; Westall, Frances; Grenfell, John Lee; Martin, William F; Gomez, Felipe; Leuko, Stefan; Lee, Natuschka; Onofri, Silvano; Tsiganis, Kleomenis; Saladino, Raffaele; Pilat-Lohinger, Elke; Palomba, Ernesto; Harrison, Jesse; Rull, Fernando; Muller, Christian; Strazzulla, Giovanni; Brucato, John R; Rettberg, Petra; Capria, Maria Teresa

    2016-03-01

    The European AstRoMap project (supported by the European Commission Seventh Framework Programme) surveyed the state of the art of astrobiology in Europe and beyond and produced the first European roadmap for astrobiology research. In the context of this roadmap, astrobiology is understood as the study of the origin, evolution, and distribution of life in the context of cosmic evolution; this includes habitability in the Solar System and beyond. The AstRoMap Roadmap identifies five research topics, specifies several key scientific objectives for each topic, and suggests ways to achieve all the objectives. The five AstRoMap Research Topics are • Research Topic 1: Origin and Evolution of Planetary Systems • Research Topic 2: Origins of Organic Compounds in Space • Research Topic 3: Rock-Water-Carbon Interactions, Organic Synthesis on Earth, and Steps to Life • Research Topic 4: Life and Habitability • Research Topic 5: Biosignatures as Facilitating Life Detection It is strongly recommended that steps be taken towards the definition and implementation of a European Astrobiology Platform (or Institute) to streamline and optimize the scientific return by using a coordinated infrastructure and funding system.

  5. AstRoMap European Astrobiology Roadmap

    PubMed Central

    Horneck, Gerda; Westall, Frances; Grenfell, John Lee; Martin, William F.; Gomez, Felipe; Leuko, Stefan; Lee, Natuschka; Onofri, Silvano; Tsiganis, Kleomenis; Saladino, Raffaele; Pilat-Lohinger, Elke; Palomba, Ernesto; Harrison, Jesse; Rull, Fernando; Muller, Christian; Strazzulla, Giovanni; Brucato, John R.; Rettberg, Petra; Capria, Maria Teresa

    2016-01-01

    Abstract The European AstRoMap project (supported by the European Commission Seventh Framework Programme) surveyed the state of the art of astrobiology in Europe and beyond and produced the first European roadmap for astrobiology research. In the context of this roadmap, astrobiology is understood as the study of the origin, evolution, and distribution of life in the context of cosmic evolution; this includes habitability in the Solar System and beyond. The AstRoMap Roadmap identifies five research topics, specifies several key scientific objectives for each topic, and suggests ways to achieve all the objectives. The five AstRoMap Research Topics are • Research Topic 1: Origin and Evolution of Planetary Systems• Research Topic 2: Origins of Organic Compounds in Space• Research Topic 3: Rock-Water-Carbon Interactions, Organic Synthesis on Earth, and Steps to Life• Research Topic 4: Life and Habitability• Research Topic 5: Biosignatures as Facilitating Life Detection It is strongly recommended that steps be taken towards the definition and implementation of a European Astrobiology Platform (or Institute) to streamline and optimize the scientific return by using a coordinated infrastructure and funding system. Key Words: Astrobiology roadmap—Europe—Origin and evolution of life—Habitability—Life detection—Life in extreme environments. Astrobiology 16, 201–243. PMID:27003862

  6. Calcium channel blockers, beta-blockers and digitalis poisoning: management in the emergency room.

    PubMed

    Ojetti, V; Migneco, A; Bononi, F; De Lorenzo, A; Gentiloni Silveri, N

    2005-01-01

    Calcium channel blockers and beta-blockers intoxications account for up to 65% of deaths for cardiovascular drugs, causing severe clinical symptoms refractory to standard medications. The most serious poisonings are those resulting from verapamil and propanolol ingestion. Both support and antidotic therapy are necessary for these potentially unstable patients. Supportive measures and the use of digoxin-specific antibody fragments are first line treatment for digitalis glycoside poisoning.

  7. Optimal Use of Beta-Blockers for Congestive Heart Failure.

    PubMed

    Lee, Hae-Young; Baek, Sang Hong

    2016-01-01

    Beta-blockers are the cornerstone treatment for congestive heart failure (HF). Current HF guidelines commonly recommend β-blockers for the treatment of HF with reduced left ventricular ejection fraction (LVEF). The effect of β-blockers, however, is less clear for HF patients with preserved LVEF, unstable severe acute HF, or right ventricular failure. This review summarizes the effect of β-blockers in various clinical situations and suggests a strategy for optimal use. (Circ J 2016; 80: 565-571).

  8. [Beta-blockers and chronic obstructive pulmonary disease].

    PubMed

    Sova, Milan; Kamasová, Monika; Václavík, Jan; Sovová, Eliška; Hajdová, Lenka; Kolek, Vítězslav

    2016-04-01

    This general article discusses the problems of beta-blockers use in patients with chronic obstructive pulmonary disease (COPD). Its aim is to refute exaggerated concerns of physicians over possible undesirable effects of beta-blockers on the patient respiratory functions and present new data on the effects of beta-blockers on the extent of COPD exacerbations, bronchial reactivity and mortality of patients.

  9. Beta-blockers in anxiety disorders.

    PubMed

    Hayes, P E; Schulz, S C

    1987-01-01

    Studies evaluating the antianxiety and antipanic properties of beta-blockers do not support their routine use in treating either generalized anxiety disorder or panic disorder. The use of propranolol for anxiety disorders accompanied by physical symptoms, especially cardiovascular complaints, may be effective in some patients when combined with benzodiazepines or perhaps in some non-responders to conventional treatment. Better designed studies are needed to evaluate the exact role of beta-blocking agents in treating anxiety. The efficacy of propranolol in patients with panic disorder has not been widely researched, but preliminary results have not been encouraging. Propranolol may provide symptomatic relief in some patients with residual somatic complaints (i.e., palpitations and tachycardia), when combined with the patient's ongoing drug regimen. Because beta-blockers may induce depression, they should be used cautiously--if at all--in panic patients with concurrent depressive illness.

  10. Anti-ENA profiles related with anti-SS-A/Ro. The detection of Ro52 and Ro60 according to the presence of SS-B/La, and ANA pattern and titer.

    PubMed

    González, D Almeida; Rodríguez, C Casañas; Armas, L Magdalena; Varela, A Roces; Rodríguez, I Marcelino; Duarte, M Troche; de León, A Cabrera

    2014-09-01

    Anti-Ro52 (Ro52) and anti-Ro60 (Ro60) antibodies are associated with different clinical entities. We investigated their relationship with the presence of anti-SS-B/La (SSB) antibody, the pattern and titer of antinuclear antibody (ANA), and the variations in antibody profiles related with anti-SS-A/Ro (SSA) positivity. Our aim was to develop a strategy to increase the efficiency of anti-extractable nuclear antigen (ENA) determinations. Statistical analyses were based on the Chi-squared test for categorical variables, the Mann-Whitney U test to compare profiles, and the odds ratio (OR) and 95% confidence interval (95% CI) to estimate the risk of variability. We analyzed 800 SSA-positive samples with Ro52 or Ro60 reactivity. The most frequent profiles were Ro52+Ro60+SSB (n=349, 43.6%); Ro52+Ro60 (n=126, 15.8%); Ro52 (n=121, 15.1%) and Ro60 (n=71, 8.9%). In samples positive only for SSA and an ANA titer ≤1:640, the most likely profile was positivity for either Ro52 or Ro60, whereas when the ANA titer was >1:640, positivity for both Ro52 and Ro60 simultaneously was more likely (p<0.001). In samples positive for both SSA and SSB, the most likely profile was Ro52+Ro60+SSB regardless of the ANA titer (p=0.001). When only SSA was positive and the ANA staining pattern was nucleolar, centromeric or cytoplasmic, Ro52 positivity was most likely (p<0.001). When both SSA and SSB were positive, both Ro52 and Ro60 were likely to be positive regardless of the ANA staining pattern. In 28.7% of the patients the profile was variable. Variability was significantly greater in those with the SSA profile (23/67) than with the SSA+SSB profile (15/105; OR=1.9, 95% CI=1.1-3.3; p=0.025), and the difference in variability was greatest between the Ro52+Ro60 profile (8/23) and the Ro52+Ro60+SSB profile (8/68; OR=4.2, 95% CI=1.9-9.5; p<0.001). We conclude that to increase efficiency in the immunology laboratory, positivity for Ro52 and Ro60 individually or simultaneously can be deduced from SSB

  11. An Introduction to the RoLI[TM

    ERIC Educational Resources Information Center

    Meyer, Jan H. F.

    2004-01-01

    The Reflections on Learning Inventory (RoLI) is an instrument designed to capture variation in students' engagement of learning--typically in a given disciplinary context or topic-specific 'episode'. Although the RoLI has been employed as a research instrument in a number of published studies on the modelling of student learning in higher…

  12. RoMPS concept review automatic control of space robot

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The Robot operated Material Processing in Space (RoMPS) experiment is being performed to explore the marriage of two emerging space commercialization technologies: materials processing in microgravity and robotics. This concept review presents engineering drawings and limited technical descriptions of the RoMPS programs' electrical and software systems.

  13. 29 CFR 1918.86 - Roll-on roll-off (Ro-Ro) operations (see also § 1918.2, Ro-Ro operations, and § 1918.25).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... their cargo capacities and shall not be overloaded. (h) Cargo weights. Cargo to be handled via a Ro-Ro ramp shall be plainly marked with its weight in pounds (kilograms). Alternatively, the cargo stow plan or equivalent record containing the actual gross weight of the load may be used to determine...

  14. 29 CFR 1918.86 - Roll-on roll-off (Ro-Ro) operations (see also § 1918.2, Ro-Ro operations, and § 1918.25).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... their cargo capacities and shall not be overloaded. (h) Cargo weights. Cargo to be handled via a Ro-Ro ramp shall be plainly marked with its weight in pounds (kilograms). Alternatively, the cargo stow plan or equivalent record containing the actual gross weight of the load may be used to determine...

  15. Recent standardization activities on radio on fiber (RoF)

    NASA Astrophysics Data System (ADS)

    Ogawa, Hiroyo; Kuri, Toshiaki; Kanno, Atsushi; Kawanishi, Tetsuya

    2013-12-01

    The Radio on Fiber (RoF) technologies are unique transmission means of radio analog signals through optical fiber cables. These technologies are currently discussed at international standard organizations such as ITU-T, IEC, APT and IEEE802. This invited paper summarizes RoF standardization activities at those standard organizations.

  16. SyRoTek--Distance Teaching of Mobile Robotics

    ERIC Educational Resources Information Center

    Kulich, M.; Chudoba, J.; Kosnar, K.; Krajnik, T.; Faigl, J.; Preucil, L.

    2013-01-01

    E-learning is a modern and effective approach for training in various areas and at different levels of education. This paper gives an overview of SyRoTek, an e-learning platform for mobile robotics, artificial intelligence, control engineering, and related domains. SyRoTek provides remote access to a set of fully autonomous mobile robots placed in…

  17. 9 years of existence of the site astronomy.ro

    NASA Astrophysics Data System (ADS)

    Haus, Marian

    2013-06-01

    The article represents a history of the Astronomical site: http://www.astronomy.ro and its forum http://www.astronomy.ro/forum/. To the actual moment about 1700 members - amateur astronomers from every where in Romania and outside - contribute to this site and forum. The main areas of interst are: Astronomical Instruments, Astrophotography, Eclipses, Solar Astronomy, Comets, Asteroids and Meteors, Optics.

  18. 29 CFR 1918.86 - Roll-on roll-off (Ro-Ro) operations (see also § 1918.2, Ro-Ro operations, and § 1918.25).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., Ro-Ro operations, and § 1918.25). 9 (a) Traffic control system. An organized system of vehicular and pedestrian traffic control shall be established and maintained at each entrance/exit ramp and on ramps within... their cargo capacities and shall not be overloaded. (h) Cargo weights. Cargo to be handled via a...

  19. 29 CFR 1918.86 - Roll-on roll-off (Ro-Ro) operations (see also § 1918.2, Ro-Ro operations, and § 1918.25).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., Ro-Ro operations, and § 1918.25). 9 (a) Traffic control system. An organized system of vehicular and pedestrian traffic control shall be established and maintained at each entrance/exit ramp and on ramps within... their cargo capacities and shall not be overloaded. (h) Cargo weights. Cargo to be handled via a...

  20. Cesáro partial sums of concave univalent functions

    NASA Astrophysics Data System (ADS)

    Aldawish, Ibtisam; Darus, Maslina

    2014-06-01

    In this article, we consider the Cesáro partial sums of certain concave univalent functions. We studied geometric properties of the Cesáro partial sums of certain concave univalent functions in the open unit disk. Examples are illustrated.

  1. Redefining beta-blocker use in hypertension: selecting the right beta-blocker and the right patient.

    PubMed

    Mann, Samuel J

    2017-01-01

    Randomized controlled trials have concluded that the cardiovascular outcome of first-step treatment of hypertension with traditional vasoconstricting beta-blockers is inferior to treatment with other antihypertensive drug classes. Beta-blocker use is also associated with undesirable side effects. Consequently, some recent guidelines consider beta-blockers an inferior option for first-step treatment of hypertension. Despite this, beta-blockers are still widely prescribed, and likely overused, in the management of hypertension. It is the contention of this perspective that beta-blockers do have an important role in treating hypertension, but their use needs to be much better targeted, by better identification of both the right patient and the right beta-blocker. Identifying the right patient involves consideration of underlying mechanisms of hypertension. In the absence of comorbidities for which a beta-blocker is indicated, beta-blockers would not seem to be the preferred treatment for patients with either sodium/volume-mediated hypertension, for which they are usually ineffective, or for those with renin-angiotensin system-mediated hypertension, for which angiotensin-converting enzyme inhibitors and angiotensin receptor blockers provide equal antihypertensive efficacy with evidence of better outcome and fewer adverse effects. Beta-blockers would instead appear to be best suited for patients with sympathetically driven, that is, neurogenic, hypertension, whether as a first-step drug, such as in patients with hypertension in the acute post-stroke period, in so-called "hyperkinetic" patients, and in patients with labile hypertension, or as an add-on drug in patients with resistant hypertension. In choosing among the beta-blockers, combined alpha/beta-blockade offers advantages over beta-blocker monotherapy and merits greater clinical and research attention. Finally, unreliable bioavailability greatly interferes with the effectiveness of lipophilic, but not

  2. Highlights on Novel Technologies for the Detection of Antibodies to Ro60, Ro52, and SS-B

    PubMed Central

    Infantino, M.; Bentow, C.; Seaman, A.; Benucci, M.; Atzeni, F.; Sarzi-Puttini, P.; Olivito, B.; Meacci, F.; Manfredi, M.; Mahler, M.

    2013-01-01

    Objective. We aimed to compare a chemiluminescent immunoassay (CIA, QUANTA Flash) on BIO-FLASH with a multiplex flow immunoassay (MFI) on BioPlex 2200 for the detection of antibodies to Ro60, Ro52, and SS-B. Methods. The study included 241 samples, from patients suffering from systemic autoimmune diseases (n = 108) as well as disease controls (n = 133). All samples were tested for anti-Ro52, anti-Ro60, and anti-SS-B (La) antibodies on QUANTA Flash (INOVA Diagnostics, San Diego, USA) and BioPlex 2200 (Bio-Rad Laboratories Inc., Hercules, USA). Discrepant samples were tested by two independent methods: BlueDot/ANA and QUANTRIX Microarray (both D-tek, Belgium). Results. The overall qualitative agreements were 95.4% (95% confidence interval, CI 92.0–97.7%) for anti-Ro52, 98.8% (95% CI 96.4–99.7%) for anti-Ro60, and 91.7% (95% CI 87.5–94.9%) for anti-SS-B antibodies. There were 34 discrepant samples among all assays (20 anti-SS-B, 11 anti-Ro52, 3 anti-Ro60). 30/33 of retested samples (by D-tek dot blot) agreed with the QUANTA Flash results. Similar findings were obtained with QUANTRIX Microarray kit. Conclusion. QUANTA Flash and BioPlex 2200 show good qualitative agreement. The clinical performances were similar for anti-Ro52 and anti-Ro60 autoantibodies while differences were observed for anti-SS-B (La) antibodies. PMID:24376466

  3. Correction to Clark and Ro (2014).

    PubMed

    2015-01-01

    Reports an error in "Three-pronged assessment and diagnosis of personality disorder and its consequences: Personality functioning, pathological traits, and psychosocial disability" by Lee Anna Clark and Eunyoe Ro (Personality Disorders: Theory, Research, and Treatment, 2014[Jan], Vol 5[1], 55-69). There was an error in the results. Under the subheading, Personality Traits-Functioning Relations, on page 63, the second, third, and fourth paragraph have been revised. The revisions are included in the erratum. (The following abstract of the original article appeared in record 2014-07188-003.) The alternative dimensional model of personality disorder (PD) in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5; American Psychiatric Association, 2013), Section III, has two main criteria: impairment in personality functioning and one or more pathological personality traits. The former is defined as disturbances in self-functioning (viz., identity, self-direction), and/or interpersonal functioning (viz., empathy, intimacy). Distinguishing personality functioning and traits is important conceptually, because simply having extreme traits is not necessarily pathological. However, adding personality functioning to PD diagnosis represents an empirical challenge, because the constructs overlap conceptually. Further, there is debate regarding whether diagnosis of mental disorder requires either distress or disability, concepts that also overlap with maladaptive-range personality traits and personality dysfunction. We investigated interrelations among these constructs using multiple self-report measures of each domain in a mixed community-patient sample (N = 402). We examined the structures of functioning (psychosocial disability and personality) and personality traits, first independently, then jointly. The disability/functioning measures yielded the 3 dimensions we have found previously (Ro & Clark, 2013). Trait measures had a hierarchical structure

  4. Sodium channel blockers in neuropathic pain.

    PubMed

    Kalso, Eija

    2005-01-01

    Subtypes of tetrodotoxin resistant voltage-gated sodium channels are involved in the development of certain types of neuropathic pains. After nerve injury hyperexcitability and spontaneous firing develop at the site of injury and also in the dorsal root ganglion cell bodies. This hyperexcitability results at least partly from accumulation of sodium channels at the site of injury. The facts that these sodium channels seem to exist in peripheral nerves only and that they can be blocked at the resting state (use-dependent block) offer the possibility to develop drugs, which selectively block these damaged, overexcited nerves. At the moment no such drugs are available. However, some of the most potent drugs that are currently used to manage neuropathic pain e.g. amitriptyline and other tricyclic antidepressants, also block these channels in addition to having several other mechanisms of action. Also most anticonvulsants that are used to alleviate neuropathic pain are sodium channel blockers. Lidocaine, the prototype drug, has been shown to be effective in peripheral neuropathic pain. Its use is limited by the fact that it cannot be administered orally. An oral local anesthetic type sodium channel blocker, mexiletine is an antiarrhythmic agent that is effective in neuropathic pain. However, effective doses may be difficult to achieve because of adverse effects.

  5. H2-blocker modulates heart rate variability.

    PubMed

    Ooie, T; Saikawa, T; Hara, M; Ono, H; Seike, M; Sakata, T

    1999-01-01

    The use of H2-blockers in the treatment of patients with peptic ulcer has become popular. However, this treatment has adverse cardiovascular effects. The aim of this study was to investigate proarrhythmic rhythm and autonomic nervous activity by analyzing heart rate variability in patients treated with omeprazole, ranitidine, and plaunotol. Nineteen patients (mean age 67.5 +/- 2.7 years) with active gastric ulcer were treated with omeprazole (20 mg/day) for 8 weeks, then ranitidine (300 mg/day) for the next 4 months, and finally plaunotol (240 mg/day). At each stage of the treatment, Holter electrocardiography was performed, and heart rate variability and arrhythmias analyzed. Heart rate variability yielded power in the low- (0.04-0.15 Hz) and high-frequency components (0.15-0.4 Hz). Although both ranitidine and omeprazole induced little change in cardiac rhythm, the high-frequency power was higher (10.3 +/- 0.8 vs 8.6 +/- 0.6 ms, P < 0.05) and the ratio of low-to-high frequency power was lower (1.41 +/-0.10 vs 1.59 +/- 0.09. P < 0.05) during ranitidine than during plaunotol treatment. Cosinor analysis of heart rate variability revealed a decreased amplitude of low-frequency power during omeprazole compared with during ranitidine and plaunotol treatment. Ranitidine modulated high-frequency power which may be related to the adverse cardiovascular effects of H2-blocker.

  6. Assuring the Legacy of the CoRoT Planets

    NASA Astrophysics Data System (ADS)

    Deeg, H. J.; Klagyivik, P.; Alonso, R.; Hoyer, S.

    2015-09-01

    For the long-lasting impact of CoRoT's planet findings, precise knowledge of the times of their transits is of vital importance for any future observing campaigns. Here we give the motivation and first results of a systematic revisit of the transits of most CoRoT planets to refine their ephemeris. As secondary objectives, more precise planet characterisations, from period or transit shape variations on/and from use of a well-defined passband may be obtained.

  7. VizieR Online Data Catalog: CoRoT/Exoplanet fields with MATISSE (Gazzano+, 2010)

    NASA Astrophysics Data System (ADS)

    Gazzano, J.-C.; de Laverny, P.; Deleuil, M.; Recio-Blanco, A.; Bouchy, F.; Moutou, C.; Bijaoui, A.; Ordenovic, C.; Gandoli, D.; Loeillet, B.

    2010-11-01

    Atomic data modifications from VALD initial request, atmospheric parameters for 1227 CoRoT targets, radial velocity for 1534 CoRoT targets, and Vsini for 1604 CoRoT targets in three CoRoT/Exoplanet fields LRa01, LRc01, and SRc01. The reported uncertainties are only internal errors. (6 data files).

  8. Higher order multi-dimensional extensions of Cesàro theorem

    NASA Astrophysics Data System (ADS)

    Accardi, Luigi; Ji, Un Cig; Saitô, Kimiaki

    2015-12-01

    The Cesàro theorem is extended to the cases: (1) higher order Cesàro mean for sequence (discrete case); and (2) higher order, multi-dimensional and continuous Cesàro mean for functions. Also, we study the Cesàro theorem for the case of positive-order.

  9. Proteinase inhibitor homologues as potassium channel blockers.

    PubMed

    Lancelin, J M; Foray, M F; Poncin, M; Hollecker, M; Marion, D

    1994-04-01

    We report here the NMR structure of dendrotoxin I, a powerful potassium channel blocker from the venom of the African Elapidae snake Dendroaspis polylepis polylepis (black mamba), calculated from an experimentally-derived set of 719 geometric restraints. The backbone of the toxin superimposes on bovine pancreatic trypsin inhibitor (BPTI) with a root-mean-square deviation of < 1.7 A. The surface electrostatic potential calculated for dendrotoxin I and BPTI, reveal an important difference which might account for the differences in function of the two proteins. These proteins may provide examples of adaptation for specific and diverse biological functions while at the same time maintaining the overall three-dimensional structure of a common ancestor.

  10. Antibody to dihydropyridine calcium entry blockers

    SciTech Connect

    Thayer, S.; Minaskanian, G.; Fairhurst, A.

    1986-03-05

    Antibodies that recognize dihydropyridine calcium entry blockers were elicited from rabbits. A sensitive and specific radioimmunoassay for dihydropyridines was developed and its specificity compared to the DHP binding site in skeletal muscle membranes. The antibody bound (/sup 3/H)nitrendipine with a higher affinity (K/sub D/ = 0.155 nM) than did the DHP receptor of skeletal muscle (K/sub D/ = 1-3 nM). However, in contrast to the DHP receptor, the antibody recognized only those DHP drugs with meta-nitrophenyl substituents at the 4-position on the DHP ring, and thus reflected the meta position of the nitro group on the DHP hapten used as an antigen. Both the antibody and the receptor exhibited stereospecificity, with each site recognizing the (+) isomer of nicardipine as the more potent. This antibody should prove useful in the studies of some potentially irreversible DHP molecules and for use in the production of anti-idotype antibodies.

  11. Beta-Adrenergic Receptor Blockers in Hypertension: Alive and Well.

    PubMed

    Frishman, William H

    2016-10-27

    βeta-Adrenergic receptor blockers (β-blockers) are an appropriate treatment for patients having systemic hypertension (HTN) who have concomitant ischemic heart disease (IHD), heart failure, obstructive cardiomyopathy, aortic dissection or certain cardiac arrhythmias. β-blockers can be used in combination with other antiHTN drugs to achieve maximal blood pressure control. Labetalol can be used in HTN emergencies and urgencies. β-blockers may be useful in HTN patients having a hyperkinetic circulation (palpitations, tachycardia, HTN, and anxiety), migraine headache, and essential tremor. β-blockers are highly heterogeneous with respect to various pharmacologic properties: degree of intrinsic sympathomimetic activity , membrane stabilizing activity , β1 selectivity, α1-adrenergic blocking effects, tissue solubility, routes of systemic elimination, potencies and duration of action, and specific properties may be important in the selection of a drug for clinical use. β-blocker usage to reduce perioperative myocardial ischemia and cardiovascular (CV) complications may not benefit as many patients as was once hoped, and may actually cause harm in some individuals. Currently the best evidence supports perioperative β-blocker use in two patient groups: patients undergoing vascular surgery with known IHD or multiple risk factors for it, and for those patients already receiving β-blockers for known CV conditions.

  12. Calcium channel blockers in cardiovascular pharmacotherapy.

    PubMed

    Godfraind, Theophile

    2014-11-01

    This paper summarizes the pharmacological properties of calcium channel blockers (CCBs), their established therapeutic uses for cardiovascular disorders and the current improvement of their clinical effects through drug combinations. Their identification resulted from study of small molecules including coronary dilators, which were named calcium antagonists. Further experiments showed that they reduced contraction of arteries by inhibiting calcium entry and by interacting with binding sites identified on voltage-dependent calcium channels. This led to the denomination calcium channel blockers. In short-term studies, by decreasing total peripheral resistance, CCBs lower arterial pressure. By unloading the heart and increasing coronary blood flow, CCBs improve myocardial oxygenation. In long-term treatment, the decrease in blood pressure is more pronounced in hypertensive than in normotensive patients. A controversy on the safety of CCBs ended after a large antihypertensive trial (ALLHAT) sponsored by the National Heart, Lung, and Blood Institute. There are two main types of CCBs: dihydopyridine and non-dihydropyridine; the first type is vascular selective. Dihydropyrines are indicated for hypertension, chronic, stable and vasospastic angina. Non-dihydropyridines have the same indications plus antiarrythmic effects in atrial fibrillation or flutter and paroxysmal supraventricular tachycardia. In addition, CCBs reduced newly formed coronary lesions in atherosclerosis. In order to reach recommended blood pressure goals, there is a recent therapeutic move by combination of CCBs with other antihypertensive agents particularly with inhibitors acting at the level of the renin-angiotensin system. They are also combined with statins. Prevention of dementia has been reported in hypertensive patients treated with nitrendipine, opening a way for further studies on CCBs' beneficial effect in cognitive deterioration associated with aging.

  13. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning.

    PubMed

    Engebretsen, Kristin M; Kaczmarek, Kathleen M; Morgan, Jenifer; Holger, Joel S

    2011-04-01

    INTRODUCTION. High-dose insulin therapy, along with glucose supplementation, has emerged as an effective treatment for severe beta-blocker and calcium channel-blocker poisoning. We review the experimental data and clinical experience that suggests high-dose insulin is superior to conventional therapies for these poisonings. PRESENTATION AND GENERAL MANAGEMENT. Hypotension, bradycardia, decreased systemic vascular resistance (SVR), and cardiogenic shock are characteristic features of beta-blocker and calcium-channel blocker poisoning. Initial treatment is primarily supportive and includes saline fluid resuscitation which is essential to correct vasodilation and low cardiac filling pressures. Conventional therapies such as atropine, glucagon and calcium often fail to improve hemodynamic status in severely poisoned patients. Catecholamines can increase blood pressure and heart rate, but they also increase SVR which may result in decreases in cardiac output and perfusion of vascular beds. The increased myocardial oxygen demand that results from catecholamines and vasopressors may be deleterious in the setting of hypotension and decreased coronary perfusion. METHODS. The Medline, Embase, Toxnet, and Google Scholar databases were searched for the years 1975-2010 using the terms: high-dose insulin, hyperinsulinemia-euglycemia, beta-blocker, calcium-channel blocker, toxicology, poisoning, antidote, toxin-induced cardiovascular shock, and overdose. In addition, a manual search of the Abstracts of the North American Congress of Clinical Toxicology and the Congress of the European Association of Poisons Centres and Clinical Toxicologists published in Clinical Toxicology for the years 1996-2010 was undertaken. These searches identified 485 articles of which 72 were considered relevant. MECHANISMS OF HIGH-DOSE INSULIN BENEFIT. There are three main mechanisms of benefit: increased inotropy, increased intracellular glucose transport, and vascular dilatation. EFFICACY OF HIGH

  14. Beta-blockers in COPD: time for reappraisal.

    PubMed

    Lipworth, Brian; Wedzicha, Jadwiga; Devereux, Graham; Vestbo, Jørgen; Dransfield, Mark T

    2016-09-01

    The combined effects on the heart of smoking and hypoxaemia may contribute to an increased cardiovascular burden in chronic obstructive pulmonary disease (COPD). The use of beta-blockers in COPD has been proposed because of their known cardioprotective effects as well as reducing heart rate and improving systolic function. Despite the proven cardiac benefits of beta-blockers post-myocardial infarction and in heart failure they remain underused due to concerns regarding potential bronchoconstriction, even with cardioselective drugs. Initiating treatment with beta-blockers requires dose titration and monitoring over a period of weeks, and beta-blockers may be less well tolerated in older patients with COPD who have other comorbidities. Medium-term prospective placebo-controlled safety studies in COPD are warranted to reassure prescribers regarding the pulmonary and cardiac tolerability of beta-blockers as well as evaluating their potential interaction with concomitant inhaled long-acting bronchodilator therapy. Several retrospective observational studies have shown impressive reductions in mortality and exacerbations conferred by beta-blockers in COPD. However, this requires confirmation from long-term prospective placebo-controlled randomised controlled trials. The real challenge is to establish whether beta-blockers confer benefits on mortality and exacerbations in all patients with COPD, including those with silent cardiovascular disease where the situation is less clear.

  15. CoRoT: Harvest of the exoplanet program

    NASA Astrophysics Data System (ADS)

    Moutou, Claire; Deleuil, Magali; Guillot, Tristan; Baglin, Annie; Bordé, Pascal; Bouchy, Francois; Cabrera, Juan; Csizmadia, Szilárd; Deeg, Hans J.

    2013-11-01

    One of the objectives of the CoRoT mission is the search for transiting extrasolar planets using high-precision photometry, and the accurate characterization of their fundamental parameters. The CoRoT satellite consecutively observes crowded stellar fields since February 2007, in high-cadence precise photometry; periodic eclipses are detected and analyzed in the stellar light curves. Then complementary observations using ground-based facilities allows establishing the nature of the transiting body and its mass. CoRoT has acquired more than 163,000 light curves and detected about 500 planet candidates. A fraction of them (5%) are confirmed planets whose masses are independently measured. Main highlights of the CoRoT discoveries are: (i) the variety of internal structures in close-in giant planets, (ii) the characterization of the first known transiting rocky planet, CoRoT-7b, and (iii) multiple constraints on the formation, evolution, role of tides in planetary systems.

  16. Type 2 Diabetes and ADP Receptor Blocker Therapy

    PubMed Central

    Samoš, Matej; Fedor, Marián; Kovář, František; Mokáň, Michal; Bolek, Tomáš; Galajda, Peter; Kubisz, Peter; Mokáň, Marián

    2016-01-01

    Type 2 diabetes (T2D) is associated with several abnormalities in haemostasis predisposing to thrombosis. Moreover, T2D was recently connected with a failure in antiplatelet response to clopidogrel, the most commonly used ADP receptor blocker in clinical practice. Clopidogrel high on-treatment platelet reactivity (HTPR) was repeatedly associated with the risk of ischemic adverse events. Patients with T2D show significantly higher residual platelet reactivity on ADP receptor blocker therapy and are more frequently represented in the group of patients with HTPR. This paper reviews the current knowledge about possible interactions between T2D and ADP receptor blocker therapy. PMID:26824047

  17. Beta-Blockers: Current State of Knowledge and Perspectives.

    PubMed

    Ogrodowczyk, Magdalena; Dettlaff, Katarzyna; Jelinska, Anna

    2016-01-01

    It has been over half a century since propranolol, the first beta-blocker, was developed for medical treatment. Since that time a large number of compounds from this group have been synthesised and many are now in clinical use. The structure, function, pharmacokinetics, and mechanism of beta-blockers have been established. The possibilities for their use in treating different conditions continue to evolve. Since the discovery of later generation beta-blockers, such as carvedilol and nebivolol, the search for new compounds continues, and may include known substances with beta-blocking properties which could extend their therapeutic potential.

  18. Anxiolytics not acting at the benzodiazepine receptor: beta blockers.

    PubMed

    Tyrer, P

    1992-01-01

    1. Although there is clear evidence for many controlled trials in the past 25 years that beta blockers are effective in anxiety disorders clear indications for their use are lacking. 2. The balance of evidence suggests that the mechanism of action of beta-blocking drugs is through peripheral blockade of beta-mediated symptoms. 3. Most evidence to the efficacy of beta-blockers comes from study of their use in generalized anxiety and in acute stress. 4. Because beta-blockers carry no risks of pharmacological dependence they may be preferred to many other anti-anxiety drugs.

  19. Evaluation of RO modules for the SSP ETC/LSS.

    NASA Technical Reports Server (NTRS)

    Jasionowski, W. J.; Bambenek, R. A.

    1973-01-01

    During the past eight years the NASA Manned Spacecraft Center has supported the development of an Integrated Water and Waste Management System for use in the Space Station Prototype (SSP) Environmental Thermal Control/Life-Support System (ETC/LSS). This system includes the reverse osmosis (RO) process for recycling wash water and the compression distillation process for recovering useable water from urine, urinal flush water, humidity condensate, commode flush water and the wash water concentrated by RO. This paper summarizes the experimental work performed during the past four years to select the best commercially available RO module for this system and to also define which surfactants and germicides are most compatible with the selected module.

  20. Marine Bivalve Cellular Responses to Beta Blocker Exposures

    EPA Science Inventory

    β blockers are prescription drugs used for medical treatment of hypertension and arrhythmias. They prevent binding of agonists such as catecholamines to β adrenoceptors. In the absence of agonist induced activation of the receptor, adenylate cyclase is not activated whi...

  1. Renal vascular effects of calcium channel blockers in hypertension.

    PubMed

    Benstein, J A; Dworkin, L D

    1990-12-01

    Recent evidence suggests that calcium channel blockers have specific effects on renal hemodynamics in patients with hypertension and may also slow the progression of chronic renal failure. When these agents are studied in vitro, their predominant effect is to reverse afferent arteriolar vasoconstriction induced by catecholamines or angiotensin II. Because efferent resistance may remain high, glomerular filtration rate rises while renal blood flow remains low. The effects in vivo are less consistent. In human hypertension, calcium channel blockers lower renal resistance and may raise both renal blood flow and glomerular filtration rate. In experimental models of chronic renal disease, calcium channel blockers slow the progression of renal damage; however, variable effects on renal hemodynamics have been found. Other factors implicated in the progression of renal damage, including compensatory renal hypertrophy, platelet aggregation, and calcium deposition, may also be favorably influenced by these agents. Recent studies suggest that calcium channel blockers may have similar protective effects in patients with hypertension and chronic renal disease.

  2. [Takotsubo cardiomyopathy: a novel beta-adrenergic blocker withdrawal syndrome].

    PubMed

    Tomcsányi, János; Jávor, Kinga; Arabadzisz, Hrisula; Zsoldos, András; Wagner, Vince; Sármán, Balázs

    2013-02-17

    The authors describe two cases of takotsubo cardiomyopathy developing after an abrupt withdrawal of carvedilol and bisoprolol. Takotsubo or stress cardiomyopathy is characterized by acute and reversible cardiac dysfunction without coronary artery disease. It is triggered by acute emotional or physical stress, drugs or drug withdrawal. The immediate discontinuation of the long acting vasodilator beta-blocker, carvedilol has not yet been described to cause takotsubo cardiomyopathy. The authors recommend cautious withdrawal of beta-blockers.

  3. [40 years beta-adrenoceptor blockers in psychiatry].

    PubMed

    Kornischka, J; Cordes, J; Agelink, M W

    2007-04-01

    Beta-adrenoceptor blockers belong to the most successful drug classes of medicine. Mainly they are used in internal medicine. 40 years ago beta-adrenoceptor blockers have occasionally been used in psychiatry for the treatment of anxiety disorders. Over the past four decades, the effects of beta-adrenoceptor blockers in the treatment of schizophrenic and manic psychoses, withdrawal syndromes and aggressive behaviour with temper outbursts has been investigated. Beta-adrenoceptor blockers are also used in the treatment of side-effects of psychopharmacological agents like neuroleptic or antidepressant-induced tachycardias, lithium-induced tremor, antipsychotic-induced akathisia or tardive dyskinesia as well. Since the mid-nineties it has been attempted to improve the efficacy of antidepressant agents by means of the 5-HT-(1a)-receptorantagonist pindolol. Presumedly memory consolidation of traumatic events can be enhanced by adrenergic activation. Therefore some open clinical trials investigated the effects of propranolol, a lipid soluble drug, which crosses the blood-brain barrier easily, to reduce the manifestation of PTSD. The present review presents the results of the literature with respect to the indications for beta-blockers in psychiatry. Considering evidence-based-medicine criteria beta-blockers are indicated to treat lithium-induced tremor, antipsychotic-induced akathisia and to reduce aggressive behavior of patients with brain-injuries.

  4. Asteroseismology of OB stars with CoRoT

    NASA Astrophysics Data System (ADS)

    Degroote, P.; Aerts, C.; Samadi, R.; Miglio, A.; Briquet, M.; Auvergne, M.; Baglin, A.; Baudin, F.; Catala, C.; Michel, E.

    2010-12-01

    The CoRoT satellite is revolutionizing the photometric study of massive O-type and B-type stars. During its long runs, CoRoT observed the entire main sequence B star domain, from typical hot β Cep stars, via cooler hybrid p- and g-mode pulsators to the SPB stars near the edge of the instability strip. CoRoT lowers the sensitivity barrier from the typical mmag-precision reached from the ground, to the μmag-level reached from space. Within the wealth of detected and identified pulsation modes, relations have been found in the form of multiplets, combination of frequencies, and frequency- and period spacings. This wealth of observational evidence is finally providing strong constraints to test current models of the internal structure and pulsations of hot stars. Aside from the expected opacity driven modes with infinite lifetime, other unexpected types of variability are detected in massive stars, such as modes of stochastic nature. The simultaneous observation of all these light curve characteristics implies a challenge for both observational asteroseismology and stellar modelling. The CoRoT space mission was developed and is operated by the French space agency CNES, with participation of ESA's RSSD and Science Programmes, Austria, Belgium, Brazil, Germany, and Spain.

  5. StRoBe: A Classroom-on-Task Measure.

    ERIC Educational Resources Information Center

    Marchant, Gregory J.

    Researchers as well as others evaluating teachers or programs are often interested in the verbal and non-verbal behaviors related to the learning of students in classrooms. The Student Record of Behavior (StRoBe) is a classroom observation instrument designed to provide simple low inference information concerning student behaviors related to…

  6. Removing Arsenic with a Softening/RO Combo

    EPA Science Inventory

    This paper provides a very short summary of the arsenic demonstration program and the limited test results from the point-of-use (POU), reverse osmosis (RO) project in Homedale, ID. Preformance data is presented on the effectiveness of the POU treatment system to remove arseni...

  7. AmeriFlux US-Ro1 Rosemount- G21

    DOE Data Explorer

    Baker, John [USDA-ARS; Griffis, Tim [University of Minnesota; Griffis, Timothy [University of Minnesota

    2016-01-01

    This is the AmeriFlux version of the carbon flux data for the site US-Ro1 Rosemount- G21. Site Description - This tower is located in a farm field farmed in accordance with the dominant farming practice in the region: a corn/soybean rotation with chisel plow tillage in the fall following corn harvest and in the spring following soybeans.

  8. AmeriFlux US-Ro3 Rosemount- G19

    DOE Data Explorer

    Baker, John [USDA-ARS; Griffis, Tim [University of Minnesota

    2016-01-01

    This is the AmeriFlux version of the carbon flux data for the site US-Ro3 Rosemount- G19. Site Description - This tower is located in a farm field farmed in accordance with the cominant farming practice in the region: a corn/soybean rotation with chisel plow tillage in the fall following corn harvest and in the spring following soybeans.

  9. Isotretinoin (Ro-Accutane) teratogenesis. A case report.

    PubMed

    Giannoulis, C H; Papathanasiou, K; Tantanasis, T H; Vaitsi, V; Tzafettas, I

    2005-01-01

    A case of teratogenesis in a 16-year-old pregnant patient is described. She had been using 60 mg Ro-Accutane daily till the 16th week of gestation. Sonography showed no cephalic skull up to the frontal bone of the fetus. A central lagostroma was also detected.

  10. Empirical Error Analysis of GPS RO Atmospheric Profiles

    NASA Astrophysics Data System (ADS)

    Scherllin-Pirscher, B.; Steiner, A. K.; Foelsche, U.; Kirchengast, G.; Kuo, Y.

    2010-12-01

    In the upper troposphere and lower stratosphere (UTLS) region the radio occultation (RO) technique provides accurate profiles of atmospheric parameters. These profiles can be used in operational meteorology (i.e., numerical weather prediction), atmospheric and climate research. We present results of an empirical error analysis of GPS RO data retrieved at UCAR and at WEGC and compare data characteristics of CHAMP, GRACE-A, and Formosat-3/COSMIC. Retrieved atmospheric profiles of bending angle, refractivity, dry pressure, dry geopotential height, and dry temperature are compared to reference profiles extracted from ECMWF analysis fields. This statistical error characterization yields a combined (RO observational plus ECMWF model) error. We restrict our analysis to the years 2007 to 2009 due to known ECMWF deficiencies prior to 2007 (e.g., deficiencies in the representation of the austral polar vortex or the weak representation of tropopause height variability). The GPS RO observational error is determined by subtracting the estimated ECMWF error from the combined error in terms of variances. Our results indicate that the estimated ECMWF error and the GPS RO observational error are approximately of the same order of magnitude. Differences between different satellites are small below 35 km. The GPS RO observational error features latitudinal and seasonal variations, which are most pronounced at stratospheric altitudes at high latitudes. We present simplified models for the observational error, which depend on a few parameters only (Steiner and Kirchengast, JGR 110, D15307, 2005). These global error models are derived from fitting simple analytical functions to the GPS RO observational error. From the lower troposphere up to the tropopause, the model error decreases closely proportional to an inverse height law. Within a core "tropopause region" of the upper troposphere/lower stratosphere the model error is constant and above this region it increases exponentially with

  11. Cesàro operators on Hardy spaces in the unit ball

    NASA Astrophysics Data System (ADS)

    Guo, Xiaoqin; Ren, Guangbin

    2008-03-01

    This article establishes the boundedness of the generalized Cesàro operator on holomorphic Hardy spaces in the unit ball. The approach consists in writing the generalized Cesàro operator as a composition of certain integral operators.

  12. Comparison of antibody assays for detection of autoantibodies to Ro 52, Ro 60 and La associated with primary Sjögren's syndrome.

    PubMed

    Trier, Nicole Hartwig; Nielsen, Inger Ødum; Friis, Tina; Houen, Gunnar; Theander, Elke

    2016-06-01

    Anti-Ro(52/60) and anti-La constitute the hallmark autoantibodies in primary Sjögren's syndrome, being present in 40-70% of sera. Several anti-Ro/La assays exist, but antibody detection appears to be assay-specific, thus the aim of this study was to compare several anti-Ro/La assays. In total, 96 sera from individuals with primary Sjögren's syndrome and 114 healthy controls were tested for anti-Ro 52/60 and anti-La in 17 immunoassays. Especially the immunoassays used for detection of anti-Ro 52 differed in their sensitivity (48-79%), while only small differences in sensitivities were observed for the anti-Ro 60 (69-77%) anti-La (39-44%) assays. Concordances of 65%, 79% and 73% for the anti-Ro 52, anti-Ro 60 and anti-La assays were found, respectively. The majority of the assays yielded high specificities, primarily ranging from 97 to 100%, except from a single anti-Ro 60 assay, which yielded a specificity of 79%. Occasionally, reactivity levels were increased in a few assays, indicating that false-positive results can be obtained when applying assays of reduced specificity. In general, the commercial assays appeared to perform better than the in-house analyses. When correcting the in-house assays for background reactivity, sensitivities were reduced by approximately 7%, 17%, and 19% for anti-Ro 52, anti-Ro 60 and anti-La assays, respectively, illustrating the pitfalls when applying immunoassays for detection of autoantibodies, which in theory may apply to commercial assays as well. Finally, increased total sensitivities were obtained when combining assays. These studies contribute to clarify the clinical utility of immunoassays for detection of autoantibodies of Ro 52, Ro 60 and La and illustrate that the most efficient strategy to maximize antibody sensitivity is to combine several assays.

  13. Gene encoding human Ro-associated autoantigen Y5 RNA.

    PubMed Central

    Maraia, R; Sakulich, A L; Brinkmann, E; Green, E D

    1996-01-01

    Ro ribonucleoproteins are composed of Y RNAs and the Ro 60 kDa protein. While the Ro 60 kDa protein is implicated in an RNA discard pathway that recognizes 3'-extended 5S rRNAs, the function of Y RNAs remains unknown [O'Brien,C.A. and Wolin,S.L. (1995) Genes Dev. 8,2891-2903]. Y5 RNA occupies a large fraction of Ro 60 kDa protein in human Ro RNPs, contains an atypical 3'-extension not found on other Y RNAs, and constitutes an RNA antigen in certain autoimmune patients [Boulanger et al. (1995) Clin. Exp. Immunol. 99, 29-36]. An overabundance of Y RNA retroposed pseudogenes has previously complicated the isolation of mammalian Y RNA genes. The source gene for Y5 RNA was isolated from human DNA as well as from Galago senegalis DNA. Authenticity of the hY5 RNA gene was demonstrated in vivo and its activity was compared with the hY4 RNA gene that also uses a type 3 promoter for RNA polymerase III. The hY5 RNA gene was subsequently found to reside within a few hundred thousand base pairs of other Y RNA genes and the linear order of the four human Y RNA genes on chromosome 7q36 was determined. Phylogenetic comparative analyses of promoter and RNA structure indicate that the Y5 RNA gene has been subjected to positive selection during primate evolution. Consistent with the proposal of O'Brien and Harley [O'Brian,C.A. and Wolin,S.L. (1992) Gene 116, 285-289], analysis of flanking sequences suggest that the hY5 RNA gene may have originated as a retroposon. PMID:8836182

  14. Formulary considerations in selection of beta-blockers.

    PubMed

    Yedinak, K C

    1993-08-01

    Selection of beta-adrenergic blockers for formulary addition can be a difficult task, especially with the increasing availability of new beta-blockers, as well as the numerous differences in pharmacodynamic and pharmacokinetic properties of currently available agents. Nevertheless, appropriate evaluation of the important characteristics of beta-blockers should allow selection of the most cost-effective agents for formulary addition. Most importantly, differences in efficacy, product formulation and cost should be carefully considered when making formulary decisions. Notably, evidence from clinical trials indicates differences in efficacy among beta-blockers for post-myocardial infarction prophylaxis, situational anxiety, essential tremor, thyrotoxicosis, migraine prophylaxis and prevention of bleeding associated with oesophageal varices. For many clinical situations, it is also important to select an effective agent that is available in both an oral and intravenous formulation, especially for cardioprotection after acute myocardial infarction and for use in supraventricular arrhythmias. In addition, availability of sustained release products and generic formulations should be considered for their potential to increase compliance and decrease cost, respectively. Comparative drug costs, as well as costs associated with decreased compliance, should also be carefully evaluated. Differences in beta-receptor selectivity, duration of action and presence of intrinsic sympathomimetic activity (ISA) are also important considerations in the selection of beta-blockers for formulary consideration. Although degree of selectivity is relative, beta 1-selective agents may be less likely to induce bronchospasm in patients with chronic obstructive pulmonary disease (COPD) and may be less likely to affect glucose homeostasis in patients with diabetes mellitus. Duration of action of a beta-blocker is an important consideration for evaluation of efficacy throughout the recommended

  15. Voltage-gated sodium channel blockers as immunomodulators.

    PubMed

    Roselli, Francesco; Livrea, Paolo; Jirillo, Emilio

    2006-01-01

    Several Voltage-Gated Sodium Channels (VGSC) are widely expressed on lymphocytes and macrophages but their role in immune function is still debated. Nevertheless, Na(+) influx through VGSC is required for lymphocytes activation and proliferation, since these responses are blocked by Na(+)-free medium or by VGSC blockers. These effects may be mediated by the reduced intracellular Na(+) levels, which in turn may impair the activity of Na(+)/Ca(++) exchanger resulting in reduced intracellular Ca(++) levels during lymphocyte activation. Furthermore, in Jurkat cell line VGSC appear to be involved in cell volume regulation, migration in artificial matrix and cell death by apoptosis. VGSC play a role in macrophage function as well, and VGSC blockers impair both phagocytosis and inflammatory responses. Several VGSC blockers have shown immunomodulatory properties in mice models, skewing the immune response toward a Th2-mediated response, while suppressing Th1-mediated responses, and VGSC already used in clinical practice are known to modulate immunoglobulin (Ig) levels both in mice and in humans. These effects suggest that VGSC blockers may find clinical application in the treatment of autoimmune and inflammatory disease. However, many of these drugs induce a number of severe side effects. The relevance of VGSC function in immune regulation suggest that the testing of newly patented VGSC blockers for their effect on immunity may be worthwhile.

  16. Beta-blocker therapy and the risk of anaphylaxis.

    PubMed Central

    Toogood, J H

    1987-01-01

    Beta-blocker therapy is associated with an increase in the severity and, possibly, the incidence of acute anaphylaxis. The population at risk consists of people with allergic conditions who are given a beta-blocker for an unrelated condition. Anaphylaxis under these conditions may be severe, protracted and resistant to conventional treatment because of the beta-adrenergic blockade. Severe or fatal attacks have been triggered by insect stings, the ingestion of allergenic foods or drugs, and injections of radiocontrast media, antisera or immunotherapy antigens. These occurrences are probably infrequent, but their incidence is unknown. At least two fatal cases have recently occurred in Canada. Clinical allergists, internists and family practitioners in particular should be aware of the need for aggressive and prolonged support in patients who experience anaphylaxis while receiving beta-blocker therapy and should report all such occurrences to the federal registry of adverse drug reactions. Allergy skin testing or immunotherapy is inadvisable in patients who take a beta-blocker orally or in the form of ophthalmic eyedrops. The list of relative contraindications to beta-blocker use should be extended to include susceptibility to recurrent anaphylaxis, whether it is idiopathic or due to an identifiable cause. PMID:2882832

  17. T-type Calcium Channel Blockers as Neuroprotective Agents

    PubMed Central

    Kopecky, Benjamin J.; Liang, Ruqiang; Bao, Jianxin

    2014-01-01

    T-type calcium channels are expressed in many diverse tissues, including neuronal, cardiovascular, and endocrine. T-type calcium channels are known to play roles in the development, maintenance, and repair of these tissues but have also been implicated in disease when not properly regulated. Calcium channel blockers have been developed to treat various diseases and their use clinically is widespread due to both their efficacy as well as their safety. Aside from their established clinical applications, recent studies have suggested neuroprotective effects of T-type calcium channels blockers. Many of the current T-type calcium channel blockers could act on other molecular targets besides T-type calcium channels making it uncertain whether their neuroprotective effects are solely due to blocking of T-type calcium channels. In this review, we discuss these drugs as well as newly developed chemical compounds that are designed to be more selective for T-type calcium channels. We review in vitro and in vivo evidence of neuroprotective effects by these T-type calcium channel blockers. We conclude by discussing possible molecular mechanisms underlying neuroprotective effects by T-type calcium channel blockers. PMID:24563219

  18. HPLC Enantioseparation of β-Blockers on Ovomucoid Stationary Phase.

    PubMed

    Imre, Silvia; Ormenişan, Anca; Tero-Vescan, Amelia; Muntean, Daniela-Lucia; Vari, Camil-Eugen

    2016-07-07

    The purpose of this study was to separate single and multiple pairs of six β-blockers enantiomers by high performance liquid chromatography on ovomucoid (OM) column in optimal conditions. The separation was performed isocratically or in gradient elution at 25°C, flow rate of 1 mL/min and 220 nm. The mobile phase consisted of phosphate buffer/acetonitrile or methanol. The effect of the organic modifier, the influence of pH and the percentage of the aqueous phase on resolution were investigated. The elution order of propranolol (PRP) enantiomers was established as well as the detection and quantification limits. The results show that OM was suitable for enantiomeric separation of the nonselective β-blockers carvedilol, PRP, pindolol and oxprenolol, and not for the two β-1 selective blockers, atenolol and metoprolol. A hypothesis regarding a possible correlation between structure-pharmacological activity-chromatographic behavior is proposed.

  19. Influence of alpha stimulants and beta blockers on yohimbine toxicity.

    PubMed

    Bourin, M; Malinge, M; Colombel, M C; Larousse, C

    1988-01-01

    1. Potentiation of yohimbine-induced sublethality has been largely used to predict antidepressant action. 2. Several products were tested in order to understand the mechanism of this toxicity better: an alpha-1 central stimulant (adrafinil); an alpha-2 central stimulant (clonidine); and 4 beta-blockers (propranolol, atenolol, penbutolol and metoprolol). 3. It was found that atenolol and adrafinil could not antagonize toxicity, whereas clonidine and the other 3 beta-blockers could. 4. It is suggested that a central beta-origin toxicity exists since only beta-blockers which cross the blood-brain barrier are capable of antagonizing this activity. 5. The fact that clonidine also antagonized this toxicity may be explained by the beta-antagonist action of this substance at the high doses used.

  20. Interaction of grapefruit juice and calcium channel blockers.

    PubMed

    Sica, Domenic A

    2006-07-01

    Drug-drug interactions are commonly recognized occurrences in the hypertensive population. Drug-nutrient interactions, however, are less well appreciated. The grapefruit juice-calcium channel blocker interaction is one that has been known since 1989. The basis for this interaction has been diligently explored and appears to relate to both flavanoid and nonflavanoid components of grapefruit juice interfering with enterocyte CYP3A4 activity. In the process, presystemic clearance of susceptible drugs decreases and bioavailability increases. A number of calcium channel blockers are prone to this interaction, with the most prominent interaction occurring with felodipine. The calcium channel blocker and grapefruit juice interaction should be incorporated into the knowledge base of rational therapeutics for the prescribing physician.

  1. Stellar classification of CoRoT targets

    NASA Astrophysics Data System (ADS)

    Damiani, C.; Meunier, J.-C.; Moutou, C.; Deleuil, M.; Ysard, N.; Baudin, F.; Deeg, H.

    2016-11-01

    Context. The CoRoT mission was the first dedicated to the search for exoplanets from space. The CoRoT exoplanet channel observed about 163 600 targets to detect transiting planetary companions. In addition to the search for exoplanets, the extremely precise photometric time series provided by CoRoT for this vast number of stars is an invaluable resource for stellar studies. Because CoRoT targets are faint (11 ≤ r ≤ 16) and close to the galactic plane, only a small subsample has been observed spectroscopically. Consequently, the stellar classification of CoRoT targets required the design of a classification method suited for the needs and time frame of the mission. Aims: We describe the latest classification scheme used to derive the spectral type of CoRoT targets, which is based on broadband multi-colour photometry. We assess the accuracy of this spectral classification for the first time. Methods: We validated the method on simulated data. This allows the quantification of the effect of different sources of uncertainty on the spectral type. Using galaxy population synthesis models, we produced a synthetic catalogue that has the same properties as the CoRoT targets. In this way, we are able to predict typical errors depending on the estimated luminosity class and spectral type. We also compared our results with independent estimates of the spectral type. Cross-checking those results allows us to identify the systematics of the method and to characterise the stellar populations observed by CoRoT. Results: We find that the classification method performs better for stars that were observed during the mission-dedicated photometric ground-based campaigns.The luminosity class is wrong for less than 7% of the targets. Generally, the effective temperature of stars classified as early type (O, B, and A) is overestimated. Conversely, the temperature of stars classified as later type tends to be underestimated. This is mainly due to the adverse effect of interstellar

  2. THE MASS OF CoRoT-7b

    SciTech Connect

    Hatzes, Artie P.; Wuchterl, Guenther; Fridlund, Malcolm; Gandolfi, Davide; Nachmani, Gil; Mazeh, Tsevi; Valencia, Diana; Hebrard, Guillaume; Borde, Pascal; Carone, Ludmila; Paetzold, Martin; Udry, Stephane; Bouchy, Francois; Deleuil, Magali; Moutou, Claire; Barge, Pierre; Deeg, Hans; Tingley, Brandon; Dvorak, Rudolf; Ferraz-Mello, Sylvio E-mail: malcolm.fridlund@esa.int; and others

    2011-12-10

    The mass of CoRoT-7b, the first transiting super-Earth exoplanet, is still a subject of debate. A wide range of masses have been reported in the literature ranging from as high as 8 M{sub Circled-Plus} to as low as 2.3 M{sub Circled-Plus }. This range in mass is largely due to the activity level of the star that contributes a significant amount of radial velocity (RV) 'jitter' and how the various methods correct this jitter. Although most mass determinations give a density consistent with a rocky planet, the lower value permits a bulk composition that can be up to 50% water. We present an analysis of the CoRoT-7b RV measurements that uses very few and simple assumptions in treating the activity signal. By analyzing those RV data for which multiple measurements were made in a given night, we remove the activity related RV contribution without any a priori model. We argue that the contribution of activity to the final RV curve is negligible and that the K-amplitude due to the planet is well constrained. This yields a mass of 7.42 {+-} 1.21 M{sub Circled-Plus} and a mean density of {rho} = 10.4 {+-} 1.8 gm cm{sup -3}. CoRoT-7b is similar in mass and radius to the second rocky planet to be discovered, Kepler-10b, and within the errors they have identical bulk densities-they are virtual twins. These bulk densities lie close to the density-radius relationship for terrestrial planets similar to what is seen for Mercury. CoRoT-7b and Kepler-10b may have an internal structure more like Mercury than the Earth.

  3. Climate Change detection using GPS RO and CMIP5 data

    NASA Astrophysics Data System (ADS)

    Molodtsov, S.; Kirilenko, A.; Olsen, D.

    2013-12-01

    General circulation models' (GCMs) response to the increase of atmospheric concentration of greenhouse gases (GHG) due to anthropogenic emissions is evident under variety of forcing scenarios. However the investigation of the anthropogenic signal in the real climate system is challenging as it requires long term high accuracy global coverage data. GPS Radio Occultation (GPS RO) technique becomes close to meeting all of these requirements, becoming the benchmark for climate data. We implemented the analysis for upper troposphere - lower stratosphere (UTLS) region between 50°N and 50°S latitudes, where the GPS RO data has higher quality. For observations, we used vertical profiles of temperature and/or geopotential heights from 2001-2008 CHAMP and 2006-2011 COSMIC occultation. GCM trends of the response patterns to the external forcings of respective climate variables were extracted from CMIP 5 GCM runs under representative concentration pathways (RCP) 8.5 and historical climate scenarios, for the same period. Natural variability was calculated using CMIP 5 GCM runs under preindustrial control scenario. The GPS RO data was downloaded from CDAAC website, GCM CMIP 5 data was obtained from Earth System Grid web page. We used optimal fingerprinting method which is generalized multivariate regression adjusted for climate change detection studies. Optimal fingerprinting allows estimating of the climate signal separately from natural climate variability. Following this methodology we applied Empirical Orthogonal Functions to filter observed and modeled data in order to decrease impact of natural variability and maximize the signal to noise ratio. Temperature and geopotential height trends in the simulated and observed climate datasets show similar features of warming of the upper troposphere and cooling of the lower stratosphere in the tropics region. Using optimal fingerprinting we found that the anthropogenic signal emerges from natural variability in GPS RO temperature

  4. On the geometric properties of Cesàro spaces

    NASA Astrophysics Data System (ADS)

    Astashkin, Sergey V.

    2012-04-01

    It is proved that the Cesàro space \\operatorname{Ces}_{p} \\lbrack 0,1 \\rbrack , 1\\le p<\\infty, contains a complemented subspace isomorphic to l^q if and only if either q=1 or q=p. A class of subspaces of this space that contain complemented copies of the space l^p is distinguished. Bibliography: 16 titles.

  5. High performance RO membranes for desalination and wastewater reclamation and their operation results.

    PubMed

    Henmi, M; Fusaoka, Y; Tomioka, H; Kurihara, M

    2010-01-01

    Reverse osmosis (RO) membrane is one of the most powerful tools for solving the global water crisis, and is used in a variety of water treatment scenes such as drinking water purification, waste-water treatment, boiler feed water production, ultra pure water production for semiconductor industry, etc. The desired performance of RO membrane varies according to quality of feed water being treated, and Toray has been developing RO membranes with suitable characteristic for each operating condition. RO membranes for seawater desalination and wastewater reclamation are especially regarded as most promising targets. Recently, high boron removal and energy saving RO membrane for seawater desalination and low fouling RO membrane for wastewater reclamation have been developed. In this paper, the prospect of attaining these renovative RO membrane, and furthermore, job references will be discussed.

  6. Sensitization by SR-2508 plus Ro 03-8799

    SciTech Connect

    Stone, H.B.; Luu, Y.H.; Lam, K.N.

    1986-07-01

    The primary toxicity of Ro 03-8799 is a central nervous system toxicity, whereas that of SR-2508 is a peripheral neuropathy. The feasibility of reducing overall toxicity while maintaining maximal radiosensitization by using the two sensitizers together was tested. The LD50/2 of Ro 03-8799 was 0.68 mg/g body wt (mg/gbw) after intravenous (i.v.) administration, and that of SR-2508 was 4.4 mg/gbw after i.v. administration. When both drugs were given together in equitoxic proportions, the LD50/2 was 0.45 mg of Ro 03-8799 plus 2.9 mg of SR-2508/gbw. These doses are 66% of the respective LD50/2 values of the drugs when given separately. Radiosensitization was evaluated using in vivo-in vitro assays with EMT6/SF tumors in BALB/c mice. At drug doses between 10 and 60% of the LD50/2, sensitization was generally maximal and similar to that from misonidazole, but there was less sensitization below this dose, both with the drugs given separately and together. If chronic toxicities of these drugs overlap as do the acute toxicities there will be little or no additional benefit from using these drugs in combination, compared to using them separately.

  7. Cellular Responses to Beta Blocker Exposures in Marine Bivalves

    EPA Science Inventory

    β blockers are prescription drugs used for medical treatment of hypertension and arrhythmias. They prevent activation of adenylate cyclase and increases in blood pressure by limiting cAMP production and protein kinase A activation. After being taken therapeutically, β b...

  8. The safety of H(2)-blockers use during pregnancy.

    PubMed

    Matok, Ilan; Gorodischer, Rafael; Koren, Gideon; Sheiner, Eyal; Wiznitzer, Arnon; Uziel, Elia; Levy, Amalia

    2010-01-01

    Little data exist on the safety of H(2)-blockers during pregnancy. A computerized database of medications dispensed from 1998 to 2007 to all women registered in the "Clalit" health maintenance organization, in the Southern District of Israel, was linked with computerized databases containing maternal and infant hospitalization records from the district hospital. The following confounders were controlled for: parity, maternal age, ethnic group, maternal diabetes, smoking, and peripartum fever. Also, therapeutic pregnancy termination data were analyzed. A total of 117 960 infants were born during the study period, 84 823 of them (72%) to women registered at Clalit; 1148 of the latter were exposed to H(2)-blockers during the first trimester of pregnancy. Exposure to H(2)-blockers was not associated with an increased risk for congenital malformations (adjusted odds ratio [OR] = 1.03, 95% confidence interval [CI]: 0.80-1.32); also, no such association was found when therapeutic pregnancy terminations were included in the analysis (adjusted OR = 1.17, 95% CI: 0.93-1.46). Exposure to H(2)-blockers was not associated with perinatal mortality, premature delivery, low birth weight, or low Apgar scores.

  9. Diabetes mellitus reduces the antiarrhythmic effect of ion channel blockers.

    PubMed

    Ito, Isao; Hayashi, Yukio; Kawai, Yusuke; Iwasaki, Mitsuo; Takada, Koji; Kamibayashi, Takahiko; Yamatodani, Atsushi; Mashimo, Takashi

    2006-09-01

    We designed the present study to examine whether diabetes mellitus affects the antiarrhythmic effect of flecainide, a sodium channel blocker, E-4031, a potassium channel blocker, and verapamil, a calcium channel blocker, in diabetic rats. The experiments were performed in intact and diabetic rats 2, 4, and 6 wk after administration of streptozotocin. Rats were anesthetized with halothane and monitored continuously for arterial blood pressure and premature ventricular contractions. The arrhythmogenic dose of epinephrine was defined as the smallest dose producing 3 or more premature ventricular contractions within a 15-s period. The arrhythmogenic doses of epinephrine in the presence of flecainide were 8.2 +/- 2.2 (mean +/- sd), 7.4 +/- 6.1, 5.5 +/- 2.8, and 2.0 +/- 0.5 microg/kg in intact and diabetic rats 2, 4, and 6 wk after streptozotocin administration, respectively. Similarly, the arrhythmogenic doses of epinephrine in the presence of E-4031 were 7.7 +/- 2.6, 2.3 +/- 0.7, 2.0 +/- 0.7, and 1.2 +/- 0.5 microg/kg, and those in the presence of verapamil were 8.2 +/- 2.1, 3.1 +/- 1.2, 2.3 +/- 0.9, and 1.5 +/- 0.5 microg/kg. Insulin partially recovered the antiarrhythmic effect of the blockers. We concluded that diabetes mellitus reduces the antiarrhythmic effects of flecainide, E-4031, and verapamil.

  10. Peptide toxins and small-molecule blockers of BK channels

    PubMed Central

    Yu, Mu; Liu, San-ling; Sun, Pei-bei; Pan, Hao; Tian, Chang-lin; Zhang, Long-hua

    2016-01-01

    Large conductance, Ca2+-activated potassium (BK) channels play important roles in the regulation of neuronal excitability and the control of smooth muscle contractions. BK channels can be activated by changes in both the membrane potential and intracellular Ca2+ concentrations. Here, we provide an overview of the structural and pharmacological properties of BK channel blockers. First, the properties of different venom peptide toxins from scorpions and snakes are described, with a focus on their characteristic structural motifs, including their disulfide bond formation pattern, the binding interface between the toxin and BK channel, and the functional consequence of the blockage of BK channels by these toxins. Then, some representative non-peptide blockers of BK channels are also described, including their molecular formula and pharmacological effects on BK channels. The detailed categorization and descriptions of these BK channel blockers will provide mechanistic insights into the blockade of BK channels. The structures of peptide toxins and non-peptide compounds could provide templates for the design of new channel blockers, and facilitate the optimization of lead compounds for further therapeutic applications in neurological disorders or cardiovascular diseases. PMID:26725735

  11. Beta-Blockers and Nitrates: Pharmacotherapy and Indications.

    PubMed

    Facchini, Emanuela; Degiovanni, Anna; Cavallino, Chiara; Lupi, Alessandro; Rognoni, Andrea; Bongo, Angelo S

    2015-01-01

    Many clinically important differences exist between beta blockers. B1-selectivity is of clinical interest because at clinically used doses, b1- selective agents block cardiac b-receptors while having minor effects on bronchial and vascular b-receptors. Beta-adrenergic blocking agents significantly decrease the frequency and duration of angina pectoris, instead the prognostic benefit of beta-blockers in stable angina has been extrapolated from studies of post myocardial infarction but has not yet been documented without left ventricular disfunction or previous myocardial infarction. Organic nitrates are among the oldest drugs, but they still remain a widely used adjuvant in the treatment of symptomatic coronary artery disease. While their efficacy in relieving angina pectoris symptoms in acute settings and in preventing angina before physical or emotional stress is undisputed, the chronic use of nitrates has been associated with potentially important side effects such as tolerance and endothelial dysfunction. B-blockers are the firstline anti-anginal therapy in stable stable angina patients without contraindications, while nitrates are the secondline anti-anginal therapy. Despite 150 years of clinical practice, they remain fascinating drugs, which in a chronic setting still deserve investigation. This review evaluated pharmacotherapy and indications of Beta-blockers and nitrates in stable angina.

  12. Bio-inspired voltage-dependent calcium channel blockers.

    PubMed

    Yang, Tingting; He, Lin-Ling; Chen, Ming; Fang, Kun; Colecraft, Henry M

    2013-01-01

    Ca(2+) influx via voltage-dependent CaV1/CaV2 channels couples electrical signals to biological responses in excitable cells. CaV1/CaV2 channel blockers have broad biotechnological and therapeutic applications. Here we report a general method for developing novel genetically encoded calcium channel blockers inspired by Rem, a small G-protein that constitutively inhibits CaV1/CaV2 channels. We show that diverse cytosolic proteins (CaVβ, 14-3-3, calmodulin and CaMKII) that bind pore-forming α1-subunits can be converted into calcium channel blockers with tunable selectivity, kinetics and potency, simply by anchoring them to the plasma membrane. We term this method 'channel inactivation induced by membrane-tethering of an associated protein' (ChIMP). ChIMP is potentially extendable to small-molecule drug discovery, as engineering FK506-binding protein into intracellular sites within CaV1.2-α1C permits heterodimerization-initiated channel inhibition with rapamycin. The results reveal a universal method for developing novel calcium channel blockers that may be extended to develop probes for a broad cohort of unrelated ion channels.

  13. [Obtaining antibodies to 1,4-dihydropyridine calcium channel blockers].

    PubMed

    Burkin, A A; Murkin, M A

    2008-01-01

    Immunization of rabbits with amlodipine conjugated with horseradish peroxidase resulted in raising polyclonal antibodies that allowed group determination of 1,4-dihydropyridine calcium channel blockers in aqueous solutions by ELISA with a sensitivity of 0.1 to 1.0 ng/ml for amlodipine, felodipine, nifedipine, and isradipine.

  14. SS-A/Ro52 promotes apoptosis by regulating Bcl-2 production

    SciTech Connect

    Jauharoh, Siti Nur Aisyah; Saegusa, Jun; Sugimoto, Takeshi; Ardianto, Bambang; Kasagi, Shimpei; Sugiyama, Daisuke; Kurimoto, Chiyo; Tokuno, Osamu; Nakamachi, Yuji; Kumagai, Shunichi; Kawano, Seiji

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Ro52{sup low} HeLa cells are resistant to apoptosis upon various stimulations. Black-Right-Pointing-Pointer Ro52 is upregulated by IFN-{alpha}, etoposide, or IFN-{gamma} and anti-Fas Ab. Black-Right-Pointing-Pointer Ro52-mediated apoptosis is independent of p53. Black-Right-Pointing-Pointer Ro52 selectively regulates Bcl-2 expression. -- Abstract: SS-A/Ro52 (Ro52), an autoantigen in systemic autoimmune diseases such as systemic lupus erythematosus and Sjoegren's syndrome, has E3 ligase activity to ubiquitinate proteins that protect against viral infection. To investigate Ro52's role during stress, we transiently knocked it down in HeLa cells by siRo52 transfection. We found that Ro52{sup low} HeLa cells were significantly more resistant to apoptosis than wild-type HeLa cells when stimulated by H{sub 2}O{sub 2}- or diamide-induced oxidative stress, IFN-{alpha}, IFN-{gamma} and anti-Fas antibody, etoposide, or {gamma}-irradiation. Furthermore, Ro52-mediated apoptosis was not influenced by p53 protein level in HeLa cells. Depleting Ro52 in HeLa cells caused Bcl-2, but not other Bcl-2 family molecules, to be upregulated. Taken together, our data showed that Ro52 is a universal proapoptotic molecule, and that its proapoptotic effect does not depend on p53, but is exerted through negative regulation of the anti-apoptotic protein Bcl-2. These findings shed light on a new physiological role for Ro52 that is important to intracellular immunity.

  15. Dispersion and nonlinear effects in OFDM-RoF system

    NASA Astrophysics Data System (ADS)

    Alhasson, Bader H.; Bloul, Albe M.; Matin, M.

    2010-08-01

    The radio-over-fiber (RoF) network has been a proven technology to be the best candidate for the wireless-access technology, and the orthogonal frequency division multiplexing (OFDM) technique has been established as the core technology in the physical layer of next generation wireless communication system, as a result OFDM-RoF has drawn attentions worldwide and raised many new research topics recently. At the present time, the trend of information industry is towards mobile, wireless, digital and broadband. The next generation network (NGN) has motivated researchers to study higher-speed wider-band multimedia communication to transmit (voice, data, and all sorts of media such as video) at a higher speed. The NGN would offer services that would necessitate broadband networks with bandwidth higher than 2Mbit/s per radio channel. Many new services emerged, such as Internet Protocol TV (IPTV), High Definition TV (HDTV), mobile multimedia and video stream media. Both speed and capacity have been the key objectives in transmission. In the meantime, the demand for transmission bandwidth increased at a very quick pace. The coming of 4G and 5G era will provide faster data transmission and higher bit rate and bandwidth. Taking advantages of both optical communication and wireless communication, OFDM Radio over Fiber (OFDM-RoF) system is characterized by its high speed, large capacity and high spectral efficiency. However, up to the present there are some problems to be solved, such as dispersion and nonlinearity effects. In this paper we will study the dispersion and nonlinearity effects and their elimination in OFDM-radio-over-fiber system.

  16. Potential prodrugs of 6-acetylmethylenepenicillanic acid (Ro 15-1903).

    PubMed

    Adam, S; Then, R; Angehrn, P

    1986-06-01

    The synthesis and biological activities of a series of non-classical penicillins are described. These compounds were synthesized by treating the pivaloyloxymethyl ester of 6-acetylmethylenepenicillanic acid (Ro 15-1903) with various nucleophiles. They were found to be less active against the beta-lactamases from Proteus vulgaris 1028, Escherichia coli 1024, Klebsiella pneumoniae NCTC 418 and E. coli RTEM than the parent compound. Nevertheless, synergy with ampicillin against whole bacterial cells producing beta-lactamases was evident, although the single compounds did not exhibit antibacterial properties. With the compounds 2a and 2b, synergistic interaction with ampicillin could also be demonstrated in mice.

  17. Conversion of tunneled hemodialysis catheter into HeRO device can provide immediate access for hemodialysis.

    PubMed

    Vasquez, Julio C; DeLaRosa, Jacob; Rahim, Fahim; Rahim, Naeem

    2010-11-01

    Patients with central venous occlusion who are ''tunneled catheter dependent'' are a challenge for hemodialysis access. A relatively new option for them is the hemodialysis reliable outflow (HeRO) device that can be totally implanted subcutaneously. However, patients still require a tunneled hemodialysis catheter that is used until the HeRO device is mature, 4 to 6 weeks later. Here, we describe a conversion of an existing tunneled hemodialysis catheter into a HeRO device, which was combined with a ''self-sealing'' Flixene graft. This allowed almost immediate use of the HeRO device without the need for placement of a catheter.

  18. Removal of organic contaminants by RO and NF membranes

    NASA Technical Reports Server (NTRS)

    Yoon, Yeomin; Lueptow, Richard M.

    2005-01-01

    Rejection characteristics of organic and inorganic compounds were examined for six reverse osmosis (RO) membranes and two nanofiltration (NF) membranes that are commercially available. A batch stirred-cell was employed to determine the membrane flux and the solute rejection for solutions at various concentrations and different pH conditions. The results show that for ionic solutes the degree of separation is influenced mainly by electrostatic exclusion, while for organic solutes the removal depends mainly upon the solute radius and molecular structure. In order to provide a better understanding of rejection mechanisms for the RO and NF membranes, the ratio of solute radius (r(i,s)) to effective membrane pore radius (r(p)) was employed to compare rejections. An empirical relation for the dependence of the rejection of organic compounds on the ratio r(i,s)/r(p) is presented. The rejection for organic compounds is over 75% when r(i,s)/r(p) is greater than 0.8. In addition, the rejection of organic compounds is examined using the extended Nernst-Planck equation coupled with a steric hindrance model. The transport of organic solutes is controlled mainly by diffusion for the compounds that have a high r(i,s)/r(p) ratio, while convection is dominant for compounds that have a small r(i,s)/r(p) ratio. c2005 Elsevier B.V. All rights reserved.

  19. [Beta-blockers in septic shock: a review].

    PubMed

    Vela-Vásquez, R S; Grigorov-Tzenkov, I; Aguilar, J L

    2015-02-01

    In septic shock, high adrenergic stress is associated with cardiovascular and systemic adverse effects, which can negatively affect the results. Beta-adrenergic receptor block has been shown to be effective in controlling the disproportionate increase in heart rate, maintaining a favorable hemodynamic profile and apparently improving the efficiency of the cardiovascular system in order to maintain tissue perfusion. They have also been shown to modulate favorably catecholamine-induced immunosuppression and to decrease insulin resistance, protein catabolism, and proinflammatory cytokine expression associated with cardiovascular dysfunction. Selective beta-1 blockers appear to provide better results than non-selective blockers, even suggesting a positive impact on mortality. Future clinical trials are still needed to confirm these findings and define the scope of their benefits.

  20. Use of β-Blockers in Pulmonary Hypertension.

    PubMed

    Perros, Frédéric; de Man, Frances S; Bogaard, Harm J; Antigny, Fabrice; Simonneau, Gérald; Bonnet, Sébastien; Provencher, Steeve; Galiè, Nazzareno; Humbert, Marc

    2017-04-01

    Contrasting with the major attention that left heart failure has received, right heart failure remains understudied both at the preclinical and clinical levels. However, right ventricle failure is a major predictor of outcomes in patients with precapillary pulmonary hypertension because of pulmonary arterial hypertension, and in patients with postcapillary pulmonary hypertension because of left heart disease. In pulmonary hypertension, the status of the right ventricle is one of the most important predictors of both morbidity and mortality. Paradoxically, there are currently no approved therapies targeting the right ventricle in pulmonary hypertension. By analogy with the key role of β-blockers in the management of left heart failure, some authors have proposed to use these agents to support the right ventricle function in pulmonary hypertension. In this review, we summarize the current knowledge on the use of β-blockers in pulmonary hypertension.

  1. Influence of calcium blockers on the SPR of erythrocytes

    NASA Astrophysics Data System (ADS)

    Shynkarenko, Olena V.; Tril, Orest; Wojnarowska, Renata; Prohorenko, Sergiy; Shergii, E. M.

    2016-12-01

    One of the promising areas of research is the impact of calcium channel blockers (CB) of biological fluids. This paper shows that the CB impact on a biological fluid can be efficiently combine with the surface plasmon resonance (SPR). It is shown that the addition of CB at the SPR measurements affect the stability of membranes and acts differently on the kinetics of erythrocytes ligament in the different groups of people.

  2. Dark and bright blocker soliton interaction in defocusing waveguide arrays.

    PubMed

    Smirnov, Eugene; Rüter, Christian E; Stepić, Milutin; Shandarov, Vladimir; Kip, Detlef

    2006-11-13

    We experimentally demonstrate the interaction of an optical probe beam with both bright and dark blocker solitons formed with low optical light power in a saturable defocusing waveguide array in photorefractive lithium niobate. A phase insensitive interaction of the beams is achieved by means of counterpropagating light waves. Partial and full reflection (blocking) of the probe beam on the positive or negative light-induced defect is obtained, respectively, in good agreement with numerical simulations.

  3. Cellular Responses to Beta Blocker Exposures in Marine ...

    EPA Pesticide Factsheets

    β blockers are prescription drugs used for medical treatment of hypertension and arrhythmias. They prevent activation of adenylate cyclase and increases in blood pressure by limiting cAMP production and protein kinase A activation. After being taken therapeutically, β blockers may make their way to coastal habitats via discharge from waste water treatment plants, posing a potential risk to aquatic organisms. The aim of our research is to evaluate cellular biomarkers of β blocker exposure using two drugs, propranolol and metoprolol, in three commercially important marine bivalves -Crassostrea virginica, Mytilus edulis and Mercenaria mercenaria. Bivalves were obtained from Narragansett Bay (Rhode Island, USA) and acclimated in the laboratory. Following acclimation, gills and hepatopancreas tissues were harvested and separately exposed to 0, 1, 10, 100 and 1000 ng/l of each drug for 24 hours. Samples were preserved for cellular biomarker assays. Elevated cellular damage and changes in enzymatic activities were noted at environmentally relevant concentrations, and M. mercenaria was found to be the most sensitive bivalve out of the three species tested. These studies enhance our understanding of the potential impacts of commonly used prescription medication on organisms in coastal ecosystems, and demonstrate that filter feeders such as marine bivalves may serve as good model organisms to examine the effects of water soluble drugs. Evaluating a suite of biomarkers

  4. Marine Bivalve Cellular Responses to Beta Blocker Exposures ...

    EPA Pesticide Factsheets

    β blockers are prescription drugs used for medical treatment of hypertension and arrhythmias. They prevent binding of agonists such as catecholamines to β adrenoceptors. In the absence of agonist induced activation of the receptor, adenylate cyclase is not activated which in turn limits cAMP production and protein kinase A activation, preventing increases in blood pressure and arrhythmias. After being taken therapeutically, commonly prescribed β blockers may make their way to coastal habitats via discharge from waste water treatment plants (WWTP) posing a potential risk to aquatic organisms. The aim of our research is to evaluate cellular responses of three commercially important marine bivalves - Eastern oysters, blue mussels and hard clams - upon exposure to two β blocker drugs, propranolol and metoprolol, and to find molecular initiating events (MIEs) indicative of the exposure. Bivalves were obtained from Narragansett Bay (Rhode Island, USA) and acclimated in the laboratory. Following acclimation, gills and hepatopancreas (HP) tissues were harvested and separately exposed to 0, 1, 10, 100 and 1000 ng/l of each drug. Tissues were bathed in 30 parts per thousand (ppt) filtered seawater, antibiotic mix, Leibovitz nutrient media, and the test drug. Exposures were conducted for 24 hours and samples were saved for cellular biomarker assays. A lysosomal destabilization assay, which is a marker of membrane damage, was also performed at the end of each exposure.

  5. The Clinical Relevance of Beta Blockers in Ovarian Carcinoma

    PubMed Central

    Hefner, J.; Csef, H.

    2016-01-01

    The last ten years have seen hardly any improvement in the prognosis of ovarian carcinoma. There is a great need for new treatment strategies, and a recent retrospective study showing a survival advantage with the use of beta blockers met with a very positive response. This systematic review summarizes the current state of knowledge and research on the topic: A database analysis identified six clinical studies showing inconsistent results with respect to the administration of beta blockers and disease course. The 13 preclinical studies identified showed almost without exception both that catecholamines had detrimental effects on tumour progression, and that these effects could be influenced by pharmacological blockade. Overall the available evidence does not justify the use of beta blockers in clinical practice for ovarian carcinoma at the present time. This article also outlines details of research design required for further studies needed on the subject. Preclinical research findings are however very impressive: They not only form an important basis for the development of future clinical studies but also, through revealing new pathomechanisms, they already make an important contribution towards the development of new treatment strategies for ovarian carcinoma. PMID:27761025

  6. Photolysis of beta-blockers in environmental waters.

    PubMed

    Piram, Anne; Salvador, Arnaud; Verne, Cécilia; Herbreteau, Bernard; Faure, René

    2008-11-01

    Many drugs such as beta-blockers have been shown to occur in aquatic environments. Even if adequate ecotoxicity data are not available, it is of primary importance to get informations about their fate in environmental waters, particularly about their photofate in sewage treatment plant effluents (STP). The main difficulties when studying pharmaceutical photochemical behaviour in environmental waters, are linked to the very low environmentally relevant concentrations (ng L(-1) to microg L(-1)) which can generate problems in terms of analytical sensitivity. Moreover, the complexity of environmental matrices can modify micropollutants degradation kinetics. The photodegradation of beta-blockers has been compared at two concentration levels (10 microg L(-1) and 10 mg L(-1)) and in two different matrices (pure water and STP effluent). It has been shown that the concentration does not influence beta-blockers degradation pathways, thus allowing the identification of degradation compounds using the 10 mg L(-1) solutions. Although environmental waters speed up the degradation process, the same photoproducts were appeared in both matrices. Using LC-MS/MS, hydroxyl radical additions have been identified as an important degradation pathway for especially pindolol, propranolol and timolol, leading to several positional isomers, corresponding to mono-, di- or tri-hydroxylations. Kinetics of appearance/disappearance of these photoproducts have been studied in STP effluents.

  7. Treatment for calcium channel blocker poisoning: A systematic review

    PubMed Central

    Dubé, P.-A.; Gosselin, S.; Guimont, C.; Godwin, J.; Archambault, P. M.; Chauny, J.-M.; Frenette, A. J.; Darveau, M.; Le sage, N.; Poitras, J.; Provencher, J.; Juurlink, D. N.; Blais, R.

    2014-01-01

    Context Calcium channel blocker poisoning is a common and sometimes life-threatening ingestion. Objective To evaluate the reported effects of treatments for calcium channel blocker poisoning. The primary outcomes of interest were mortality and hemodynamic parameters. The secondary outcomes included length of stay in hospital, length of stay in intensive care unit, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. Methods Medline/Ovid, PubMed, EMBASE, Cochrane Library, TOXLINE, International pharmaceutical abstracts, Google Scholar, and the gray literature up to December 31, 2013 were searched without time restriction to identify all types of studies that examined effects of various treatments for calcium channel blocker poisoning for the outcomes of interest. The search strategy included the following Keywords: [calcium channel blockers OR calcium channel antagonist OR calcium channel blocking agent OR (amlodipine or bencyclane or bepridil or cinnarizine or felodipine or fendiline or flunarizine or gallopamil or isradipine or lidoflazine or mibefradil or nicardipine or nifedipine or nimodipine or nisoldipine or nitrendipine or prenylamine or verapamil or diltiazem)] AND [overdose OR medication errors OR poisoning OR intoxication OR toxicity OR adverse effect]. Two reviewers independently selected studies and a group of reviewers abstracted all relevant data using a pilot-tested form. A second group analyzed the risk of bias and overall quality using the STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) checklist and the Thomas tool for observational studies, the Institute of Health Economics tool for Quality of Case Series, the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines, and the modified NRCNA (National Research Council for the National Academies) list for animal studies. Qualitative synthesis was used to summarize the evidence. Of 15,577 citations identified in

  8. Gas-Phase Ozonolysis of Cycloalkenes: Formation of Highly Oxidized RO2 Radicals and Their Reactions with NO, NO2, SO2, and Other RO2 Radicals.

    PubMed

    Berndt, Torsten; Richters, Stefanie; Kaethner, Ralf; Voigtländer, Jens; Stratmann, Frank; Sipilä, Mikko; Kulmala, Markku; Herrmann, Hartmut

    2015-10-15

    The gas-phase reaction of ozone with C5-C8 cycloalkenes has been investigated in a free-jet flow system at atmospheric pressure and a temperature of 297 ± 1 K. Highly oxidized RO2 radicals bearing at least 5 O atoms in the molecule and their subsequent reaction products were detected in most cases by means of nitrate-CI-APi-TOF mass spectrometry. Starting from a Criegee intermediate after splitting-off an OH-radical, the formation of these RO2 radicals can be explained via an autoxidation mechanism, meaning RO2 isomerization (ROO → QOOH) and subsequently O2 addition (QOOH + O2 → R'OO). Time-dependent RO2 radical measurements concerning the ozonolysis of cyclohexene indicate rate coefficients of the intramolecular H-shifts, ROO → QOOH, higher than 1 s(-1). The total molar yield of highly oxidized products (predominantly RO2 radicals) from C5-C8 cycloalkenes in air is 4.8-6.0% affected with a calibration uncertainty by a factor of about two. For the most abundant RO2 radical from cyclohexene ozonolysis, O,O-C6H7(OOH)2O2 ("O,O" stands for two O atoms arising from the ozone attack), the determination of the rate coefficients of the reaction with NO2, NO, and SO2 yielded (1.6 ± 0.5) × 10(-12), (3.4 ± 0.9) × 10(-11), and <10(-14) cm(3) molecule(-1) s(-1), respectively. The reaction of highly oxidized RO2 radicals with other peroxy radicals (R'O2) leads to detectable accretion products, RO2 + R'O2 → ROOR' + O2, which allows to acquire information on peroxy radicals not directly measurable with the nitrate ionization technique applied here. Additional experiments using acetate as the charger ion confirm conclusively the existence of highly oxidized RO2 radicals and closed-shell products. Other reaction products, detectable with this ionization technique, give a deeper insight in the reaction mechanism of cyclohexene ozonolysis.

  9. In vitro activity of RO363, a beta1-adrenoceptor selective agonist.

    PubMed Central

    Iakovidis, D.; Malta, E.; McPherson, G. A.; Raper, C.

    1980-01-01

    1 The beta-adrenoceptor stimulant effects of RO363 and (--)-isoprenaline have been compared in a variety of isolated tissue preparations. 2 RO363 is approximately half as potent as (--)-isoprenaline in tissues where actions are due to beta1-receptor activation (guinea-pig atrial and ileal preparations and ventricular strips from the rabbit, rat and guinea-pig. 3 In uterine and lung strip preparations from the guinea-pig, where responses are due to beta2-receptor stimulation. RO363 is 100 to 350 times less active than (--)-isoprenaline and has a low intrinsic activity. 4 In spontaneously contracted tracheal preparations from the guinea-pig, RO363 is a full agonist and is approximately half as potent as (--)-isoprenaline. These effects of RO363 are due to the activation of a population of beta1-receptors in the tissue since RO363 and (--)-isoprenaline have the same relative potencies in trachea, cardiac and ileal preparations. In addition the Kb values for practolol are similar in all these preparations when RO363 is used as the agonist. 5 The results show that RO363 is a potent and highly selective beta1-receptor agonist. PMID:6103722

  10. Emerging roles for the Ro 60 kDa autoantigen in noncoding RNA metabolism

    PubMed Central

    Sim, Soyeong; Wolin, Sandra L.

    2011-01-01

    All cells contain an enormous variety of ribonucleoprotein complexes that function in diverse processes. Although the mechanisms by which many of these RNPs contribute to cell metabolism are well understood, the roles of others are only now beginning to be revealed. A member of this latter category, the Ro 60 kDa protein and its associated noncoding Y RNAs, was discovered because the protein component is a frequent target of the autoimmune response in patients with the rheumatic diseases systemic lupus erythematosus and Sjögren’s syndrome. Recent studies have shown that Ro is ring-shaped, binds the single-stranded ends of misfolded noncoding RNAs in its central cavity, and may function in noncoding RNA quality control. Although Ro is not present in yeast, many bacterial genomes contain potential Ro orthologs. In the radiation-resistant eubacterium Deinococcus radiodurans, the Ro ortholog functions with exoribonucleases during stress-induced changes in RNA metabolism. Moreover, in both D. radiodurans and animal cells, Ro is involved in the response to multiple types of environmental stress. Finally, Y RNAs can influence the subcellular location of Ro, inhibit access of the central cavity to other RNAs and may also act as binding sites for proteins that influence Ro function. PMID:21823229

  11. TU-CD-BRD-00: Incident Learning / RO-ILS

    SciTech Connect

    2015-06-15

    It has long been standard practice in radiation oncology to report internally when a patient’s treatment has not gone as planned and to report events to regulatory agencies when legally required. Most potential errors are caught early and never affect the patient. Quality assurance steps routinely prevent errors from reaching the patient, and these “near misses” are much more frequent than treatment errors. A growing number of radiation oncology facilities have implemented incident learning systems to report and analyze both errors and near misses. Using the term “incident learning” instead of “event reporting” emphasizes the need to use these experiences to change the practice and make future errors less likely and promote an educational, non-punitive environment. There are challenges in making such a system practical and effective. Speakers from institutions of different sizes and practice environments will share their experiences on how to make such a system work and what benefits their clinics have accrued. Questions that will be addressed include: How to create a system that is easy for front line staff to access How to motivate staff to report How to promote the system as positive and educational and not punitive or demeaning How to organize the team for reviewing and responding to reports How to prioritize which reports to discuss in depth How not to dismiss the rest How to identify underlying causes How to design corrective actions and implement change How to develop useful statistics and analysis tools How to coordinate a departmental system with a larger risk management system How to do this without a dedicated quality manager Some speakers’ experience is with in-house systems and some will share experience with the AAPM/ASTRO national Radiation Oncology Incident Learning System (RO-ILS). Reports intended to be of value nationally need to be comprehensible to outsiders; examples of useful reports will be shown. There will be ample time set

  12. High Flux, Fouling Resistant Membranes for RO Pretreatment

    DTIC Science & Technology

    2010-07-30

    hollow-fiber, ultrafiltration membrane. Activities in the second 3 months of the project included: 1. completing the set up of production and lab...develop a fouling resistant, hollow‐fiber,  ultrafiltration  membrane.  Activities in the second 3 months of the project included:  1. completing the set up...of the RO.  However, current commercial  ultrafiltration  and microfiltration  membranes used for RO pre‐treatment are inadequate and subject to fouling

  13. Clinical review of beta-blockers in anxiety.

    PubMed

    Kelly, D

    1980-09-01

    Anxiety has three essential elements: the subjective experience, autonomic symptoms and avoidance behaviour. Various theories are considered which highlight the psychic and somatic aspects of anxiety. Beta-adrenergic receptor blocking drugs have been used with advantage to treat everyday stresses. These include the anxiety produced by the civil disturbances in Northern Ireland, performing surgery, dentistry, musical instruments or speaking in public, as well as examination nerves. The profile of symptoms such as tachycardia, palpitations and tremor which are most likely to respond to beta-blockers are discussed as well as their side-effects. Their mode of action is different from other anxiolytics, with which they can be combined.

  14. [Effects of H2-blockers on alcohol dehydrogenase (ADH) activity].

    PubMed

    Jelski, Wojciech; Orywal, Karolina; Szmitkowski, Maciej

    2008-12-01

    First-pass metabolism (FPM) of alcohol is demonstrated by lower blood alcohol concentrations after oral than intravenous administration of the same dose. FPM occurs predominantly in the stomach and has been attributed to class IV of alcohol dehydrogenase (ADH) isoenzyme localizated in the gastric mucosa. A number of factors that influence on gastric ADH activity and thereby modulate FPM have been identified. These include age, sex, ethnicity, concentrations and amounts of alcohol consumed and drugs. Several H2-receptor antagonists, including cimetidine and ranitidine, inhibit gastric ADH activity and reduce FPM, resulting in higher blood alcohol concentrations after H2-blockers administration.

  15. VizieR Online Data Catalog: CoRoT observation log (N2-4.4) (CoRoT 2016)

    NASA Astrophysics Data System (ADS)

    COROT Team

    2014-03-01

    CoRoT, a space astronomy mission, has measured photometric micro-variability of stars from minutes to months (up to 150 days) with a high duty cycle (more than 90%). The mission was led by CNES in association with four French laboratories and 7 participating countries and agencies (Austria, Belgium, Brazil, Germany, Spain, and the ESA Science Programme). The satellite was composed of a PROTEUS platform (the 3rd in the series) and a unique instrument: a stellar rapid photometer. It was launched on December 27th 2006 by a Soyuz Rocket, from Bakonour. The mission has lasted almost 6 years (the nominal 3-year duration and a 3-year extension) and has observed more than 160 000 stars. It stopped sending data on November 2nd 2012. Two regions of the sky were accessible for long period of time: circles of 10 degrees centered on the equator around alpha=06:50 and alpha=18:50. They were called the CoRoT eyes: the "anticenter" and the "center eye" (as they are approximately in these directions). Each pointing covers 1.4x2.8 square degrees within one of those CoRoT eyes. The original scientific objectives were focussed on the study of stellar pulsations (asteroseismology) to probe the internal structure of stars, and the detection of small exoplanets through their "transiting in front of their host star, and the measurement of their size. This lead to introduce two modes of observations, working simultaneously: - The "bright star" mode dedicated to very precise seismology of a small sample of bright and closeby stars - The "faint star" mode, observing a very large number of stars at the same time, to detect transits, which are rare events, as they imply the alignment of the star, the planet and the observer. The large amount of data gathered in this mode turned out to be extremely fruitful for many topics of stellar physics. Beyond these two initial objectives, CoRoT data revealed stellar variability associated with various other phenomena: granulation, rotational modulation

  16. Rapid field assessment of RO desalination of brackish agricultural drainage water.

    PubMed

    Thompson, John; Rahardianto, Anditya; Gu, Han; Uchymiak, Michal; Bartman, Alex; Hedrick, Marcos; Lara, David; Cooper, Jim; Faria, Jose; Christofides, Panagiotis D; Cohen, Yoram

    2013-05-15

    Rapid field evaluation of RO feed filtration requirements, selection of effective antiscalant type and dose, and estimation of suitable scale-free RO recovery level were demonstrated using a novel approach based on direct observation of mineral scaling and flux decline measurements, utilizing an automated Membrane Monitor (MeMo). The MeMo, operated in a stand-alone single-pass desalting mode, enabled rapid assessment of the adequacy of feed filtration by enabling direct observation of particulate deposition on the membrane surface. The diagnostic field study with RO feed water of high mineral scaling propensity revealed (via direct MeMo observation) that suspended particulates (even for feed water of turbidity <1 NTU) could serve as seeds for promoting surface crystal nucleation. With feed filtration optimized, a suitable maximum RO water recovery, with complete mineral scale suppression facilitated by an effective antiscalant dose, can be systematically and directly identified (via MeMo) in the field for a given feed water quality. Scale-free operating conditions, determined via standalone MeMo rapid diagnostic tests, were shown to be applicable to spiral-would RO system as validated via both flux decline measurements and ex-situ RO plant membrane scale monitoring. It was shown that the present approach is suitable for rapid field assessment of RO operability and it is particularly advantageous when evaluating water sources of composition that may vary both temporally and across the regions of interest.

  17. New Insight into Effects of β-Blockers on Arterial Functions

    PubMed Central

    Eguchi, Kazuo

    2016-01-01

    The effects of β-blockers on arterial properties are not well investigated. In our recent study, we compared the effects of the two β-blockers celiprolol and bisoprolol on blood pressure, baroreflex sensitivity (BRS), flow-mediated vasodilatation, and vascular stiffness. We found that bisoprolol achieved a greater reduction in the pulse rate and improved BRS and vascular stiffness, whereas celiprolol reduced the central blood pressure level. In this review, the mechanisms of different types of β-blockers and their effects on arteries are discussed, and the appropriate use of β-blockers in hypertensive subjects will be proposed. PMID:27195240

  18. New Insight into Effects of β-Blockers on Arterial Functions.

    PubMed

    Eguchi, Kazuo

    2016-04-01

    The effects of β-blockers on arterial properties are not well investigated. In our recent study, we compared the effects of the two β-blockers celiprolol and bisoprolol on blood pressure, baroreflex sensitivity (BRS), flow-mediated vasodilatation, and vascular stiffness. We found that bisoprolol achieved a greater reduction in the pulse rate and improved BRS and vascular stiffness, whereas celiprolol reduced the central blood pressure level. In this review, the mechanisms of different types of β-blockers and their effects on arteries are discussed, and the appropriate use of β-blockers in hypertensive subjects will be proposed.

  19. β-Blockers and Vascular Hemodynamics in Patients With Peripheral Arterial Disease.

    PubMed

    Schlager, Oliver; Gajdosova Kovacicova, Ludmila; Senn, Oliver; Amann-Vesti, Beatrice; Wilkinson, Ian B; Jacomella, Vincenzo; Husmann, Marc

    2016-12-01

    Aortic augmentation index (AIx) is a marker of central aortic pressure burden and is modulated by antihypertensive drugs. In patients with peripheral arterial disease (PAD) undergoing antihypertensive treatment, aortic pressures parameters, heart rate-adjusted augmentation index (AIx75), and unadjusted AIx were determined. The (aortic) systolic and diastolic blood pressure did not differ between PAD patients who were taking β-blockers (n=61) and those who were not taking β-blockers (n=80). In patients taking β-blockers, augmentation pressure and pulse pressure were higher than in patients who did not take β-blockers (augmentation pressure, P=.02; pulse pressure, P=.005). AIx75 was lower in PAD patients taking β-blockers than in patients not taking β-blockers (P=.04), while the AIx did not differ between PAD patients taking and not taking β-blockers. The present study demonstrates that β-blockers potentially affect markers of vascular hemodynamics in patients with PAD. Because these markers are surrogates of cardiovascular risk, further studies are warranted to clarify the impact of selective β-blocker treatment on clinical outcome in patients with PAD.

  20. Model studies of the function of blockers on the small conductance potassium ion channel.

    PubMed

    Ciechanowicz-Rutkowska, M; Lewinski, K; Oleksyn, B; Stec, B

    2003-09-01

    A correlation between KI (equilibrium dissociation constants) and IC50 (concentration at 50% inhibition) inhibitors for the family of blockers of the small conductance potassium ion channels and their intrinsic characteristics like molecular mass and volume have been investigated. Most of the blockers in the family are not selective, in contrast to apamin - an 18 amino acid bee venom toxin - that is known to be a highly potent and selective blocker of these channels. Differences and similarities between the blockers have been analyzed, pointing toward the origin of their selectivity and relative potency. In conclusion, an ion channel blocking is a process controlled mainly by diffusion, in accordance with previous experimental results.

  1. Kinetic Hairpin Oligonucleotide Blockers for Selective Amplification of Rare Mutations

    PubMed Central

    Jia, Yanwei; Sanchez, J. Aquiles; Wangh, Lawrence J.

    2014-01-01

    Detection of rare mutant alleles in an excess of wild type alleles is increasingly important in cancer diagnosis. Several methods for selective amplification of a mutant allele via the polymerase chain reaction (PCR) have been reported, but each of these methods has its own limitations. A common problem is that Taq DNA polymerase errors early during amplification generate false positive mutations which also accumulate exponentially. In this paper, we described a novel method using hairpin oligonucleotide blockers that can selectively inhibit the amplification of wild type DNA during LATE-PCR amplification. LATE-PCR generates double-stranded DNA exponentially followed by linear amplification of single-stranded DNA. The efficiency of the blocker is optimized by adjusting the LATE-PCR temperature cycling profile. We also demonstrate that it is possible to minimize false positive signals caused by Taq DNA polymerase errors by using a mismatched excess primer plus a modified PCR profile to preferentially enrich for mutant target sequences prior to the start of the exponential phase of LATE-PCR amplification. In combination these procedures permit amplification of specific KRAS mutations in the presence of more than 10,000 fold excess of wild type DNA without false positive signals. PMID:25082368

  2. Angiotensin receptor blockers & endothelial dysfunction: Possible correlation & therapeutic implications

    PubMed Central

    Radenković, Miroslav; Stojanović, Marko; Nešić, Ivana Milićević; Prostran, Milica

    2016-01-01

    The endothelium is one of the most important constituents of vascular homeostasis, which is achieved through continual and balanced production of different relaxing and contractile factors. When there is a pathological disturbance in release of these products, endothelial dysfunction (ED) will probably occur. ED is considered to be the initial step in the development of atherosclerosis. This pathological activation and inadequate functioning of endothelial cells was shown to be to some extent a reversible process, which all together resulted in increased interest in investigation of different beneficial treatment options. To this point, the pharmacological approach, including for example, the use of angiotensin-converting enzyme inhibitors or statins, was clearly shown to be effective in the improvement of ED. One of many critical issues underlying ED represents instability in the balance between nitric oxide and angiotensin II (Ang II) production. Considering that Ang II was confirmed to be important for the development of ED, the aim of this review article was to summarize the findings of up to date clinical studies associated with therapeutic application of angiotensin receptor blockers and improvement in ED. In addition, it was of interest to review the pleiotropic actions of angiotensin receptor blockers linked to the improvement of ED. The prospective, randomized, double-blind, placebo or active-controlled clinical trials were identified and selected for the final evaluation. PMID:27934794

  3. Role of β-blocker therapy in pediatric heart failure.

    PubMed

    Patel, Akash R; Shaddy, Robert E

    2010-01-01

    Heart failure is becoming an increasingly common and significant problem in the field of pediatric cardiology. The numerous types of cardiomyopathies, and more recently, long-term survival of patients with congenital heart disease, have added to a growing patient population. Over the last several decades, our knowledge base regarding mechanisms of disease and therapeutic intervention in adult patients with heart failure has drastically changed. The most recent and important breakthrough in the pharmacologic treatment of heart failure has been the particular role of β-blocker therapy. This medication has led to significant improvements in survival and symptoms in adults, with less convincing findings in limited studies in pediatrics. The ability to study the benefits of this therapy in patients has been challenging owing to the heterogeneity of the patient population and lack of large sample sizes. However, as we investigate the mechanisms behind the disease process, the differences that exist between disease conditions and ages, and the significant alterations that may exist at the molecular and genetic level, our understanding of β-blocker therapy in pediatric heart failure will improve, and ultimately may lead to patient-specific therapy.

  4. Metaflumizone is a novel sodium channel blocker insecticide.

    PubMed

    Salgado, V L; Hayashi, J H

    2007-12-15

    Metaflumizone is a novel semicarbazone insecticide, derived chemically from the pyrazoline sodium channel blocker insecticides (SCBIs) discovered at Philips-Duphar in the early 1970s, but with greatly improved mammalian safety. This paper describes studies confirming that the insecticidal action of metaflumizone is due to the state-dependent blockage of sodium channels. Larvae of the moth Spodoptera eridania injected with metaflumizone became paralyzed, concomitant with blockage of all nerve activity. Furthermore, tonic firing of abdominal stretch receptor organs from Spodoptera frugiperda was blocked by metaflumizone applied in the bath, consistent with the block of voltage-dependent sodium channels. Studies on native sodium channels, in primary-cultured neurons isolated from the CNS of the larvae of the moth Manduca sexta and on Para/TipE sodium channels heterologously expressed in Xenopus (African clawed frog) oocytes, confirmed that metaflumizone blocks sodium channels by binding selectively to the slow-inactivated state, which is characteristic of the SCBIs. The results confirm that metaflumizone is a novel sodium channel blocker insecticide.

  5. WARM SPITZER PHOTOMETRY OF THE TRANSITING EXOPLANETS CoRoT-1 AND CoRoT-2 AT SECONDARY ECLIPSE

    SciTech Connect

    Deming, Drake; Knutson, Heather; Agol, Eric; Cowan, Nicolas B.; Desert, Jean-Michel; Charbonneau, David; Burrows, Adam; Fortney, Jonathan J.; Laughlin, Gregory; Langton, Jonathan; Showman, Adam P.; Lewis, Nikole K.

    2011-01-10

    We measure secondary eclipses of the hot giant exoplanets CoRoT-1 at 3.6 and 4.5 {mu}m, and CoRoT-2 at 3.6 {mu}m, both using Warm Spitzer. We find that the Warm Spitzer mission is working very well for exoplanet science. For consistency of our analysis we also re-analyze archival cryogenic Spitzer data for secondary eclipses of CoRoT-2 at 4.5 and 8 {mu}m. We compare the total data for both planets, including optical eclipse measurements by the CoRoT mission, and ground-based eclipse measurements at 2 {mu}m, to existing models. Both planets exhibit stronger eclipses at 4.5 than at 3.6 {mu}m, which is often indicative of an atmospheric temperature inversion. The spectrum of CoRoT-1 is best reproduced by a 2460 K blackbody, due either to a high altitude layer that strongly absorbs stellar irradiance, or an isothermal region in the planetary atmosphere. The spectrum of CoRoT-2 is unusual because the 8 {mu}m contrast is anomalously low. Non-inverted atmospheres could potentially produce the CoRoT-2 spectrum if the planet exhibits line emission from CO at 4.5 {mu}m, caused by tidal-induced mass loss. However, the viability of that hypothesis is questionable because the emitting region cannot be more than about 30% larger than the planet's transit radius, based on the ingress and egress times at eclipse. An alternative possibility to account for the spectrum of CoRoT-2 is an additional opacity source that acts strongly at wavelengths less than 5 {mu}m, heating the upper atmosphere while allowing the deeper atmosphere seen at 8 {mu}m to remain cooler. We obtain a similar result as Gillon et al. for the phase of the secondary eclipse of CoRoT-2, implying an eccentric orbit with e cos({omega}) = -0.0030 {+-} 0.0004.

  6. Gibberellins regulate the transcription of the continuous flowering regulator, RoKSN, a rose TFL1 homologue

    PubMed Central

    Foucher, Fabrice

    2012-01-01

    The role of gibberellins (GAs) during floral induction has been widely studied in the annual plant Arabidopsis thaliana. Less is known about this control in perennials. It is thought that GA is a major regulator of flowering in rose. In spring, low GA content may be necessary for floral initiation. GA inhibited flowering in once-flowering roses, whereas GA did not block blooming in continuous-flowering roses. Recently, RoKSN, a homologue of TFL1, was shown to control continuous flowering. The loss of RoKSN function led to continuous flowering behaviour. The objective of this study was to understand the molecular control of flowering by GA and the involvement of RoKSN in this inhibition. In once-flowering rose, the exogenous application of GA3 in spring inhibited floral initiation. Application of GA3 during a short period of 1 month, corresponding to the floral transition, was sufficient to inhibit flowering. At the molecular level, RoKSN transcripts were accumulated after GA3 treatment. In spring, this accumulation is correlated with floral inhibition. Other floral genes such as RoFT, RoSOC1, and RoAP1 were repressed in a RoKSN-dependent pathway, whereas RoLFY and RoFD repression was RoKSN independent. The RoKSN promoter contained GA-responsive cis-elements, whose deletion suppressed the response to GA in a heterologous system. In summer, once-flowering roses did not flower even after exogenous application of a GA synthesis inhibitor that failed to repress RoKSN. A model is presented for the GA inhibition of flowering in spring mediated by the induction of RoKSN. In summer, factors other than GA may control RoKSN. PMID:23175671

  7. Ceftriaxone (Ro 13-9904) therapy of serious infection.

    PubMed Central

    Bradsher, R W

    1982-01-01

    Ceftriaxone (Ro 13-9904), a newly developed cephalosporin with a long half-life, was evaluated for efficacy and safety in 19 patients with serious infections. Underlying illnesses were present in 16 patients. Ceftriaxone was given intravenously every 12 h. Infections treated included gram-negative bacillary pneumonias (two cases), staphylococcal and streptococcal soft tissue-skeletal infections (six cases), spontaneous peritonitis (two cases), and complicated urinary tract infections (nine cases). Bacteremia was present in three patients. Microbiological and clinical cures were achieved in all but one case, although three patients with urinary infection had recurrences 6 weeks posttherapy. The only failure occurred in a patient with pneumonia who had a Pseudomonas aeruginosa isolated from sputum with an initial minimal inhibitory concentration of 4 micrograms/ml, but after 9 days of therapy, a repeat isolate had a minimal inhibitory concentration of 32 micrograms/ml. The minimal inhibitory concentrations for the other isolates ranged from less than or equal to 0.6 to 8.0 micrograms/ml. The mean peak plasma level of ceftriaxone was 99.9 micrograms/ml. The only side effects noted were drug fever in one patient, phlebitis in two patients, and thrombocytosis in four patients. PMID:6289739

  8. Transiting exoplanets from the CoRoT space mission. VII. The ``hot-Jupiter''-type planet CoRoT-5b

    NASA Astrophysics Data System (ADS)

    Rauer, H.; Queloz, D.; Csizmadia, Sz.; Deleuil, M.; Alonso, R.; Aigrain, S.; Almenara, J. M.; Auvergne, M.; Baglin, A.; Barge, P.; Bordé, P.; Bouchy, F.; Bruntt, H.; Cabrera, J.; Carone, L.; Carpano, S.; de La Reza, R.; Deeg, H. J.; Dvorak, R.; Erikson, A.; Fridlund, M.; Gandolfi, D.; Gillon, M.; Guillot, T.; Guenther, E.; Hatzes, A.; Hébrard, G.; Kabath, P.; Jorda, L.; Lammer, H.; Léger, A.; Llebaria, A.; Magain, P.; Mazeh, T.; Moutou, C.; Ollivier, M.; Pätzold, M.; Pont, F.; Rabus, M.; Renner, S.; Rouan, D.; Shporer, A.; Samuel, B.; Schneider, J.; Triaud, A. H. M. J.; Wuchterl, G.

    2009-10-01

    Aims: The CoRoT space mission continues to photometrically monitor about 12 000 stars in its field-of-view for a series of target fields to search for transiting extrasolar planets ever since 2007. Deep transit signals can be detected quickly in the “alarm-mode” in parallel to the ongoing target field monitoring. CoRoT's first planets have been detected in this mode. Methods: The CoRoT raw lightcurves are filtered for orbital residuals, outliers, and low-frequency stellar signals. The phase folded lightcurve is used to fit the transit signal and derive the main planetary parameters. Radial velocity follow-up observations were initiated to secure the detection and to derive the planet mass. Results: We report the detection of CoRoT-5b, detected during observations of the LRa01 field, the first long-duration field in the galactic anti-center direction. CoRoT-5b is a “hot Jupiter-type” planet with a radius of 1.388+0.046-0.047 R_Jup, a mass of 0.467+0.047-0.024 M_Jup, and therefore, a mean density of 0.217+0.031-0.025 g cm-3. The planet orbits an F9V star of 14.0 mag in 4.0378962 ± 0.0000019 days at an orbital distance of 0.04947+0.00026-0.00029 AU. Observations made with SOPHIE spectrograph at the Observatoire de Haute Provence (07B.PNP.MOUT), France, and HARPS spectrograph at ESO La Silla Observatory (072.C-0488(E), 082.C-0312(A)), and partly based on observations made at the Anglo-Australian Telescope. The CoRoT space mission, launched on December 27, 2006, was developed and is operated by CNES, with the contribution of Austria, Belgium, Brasil, ESA, Germany, and Spain.

  9. Roll-On/Roll-Off (RO/RO) Discharge Facility Tests with MV CYGNUS and SS ATLANTIC BEAR (COTS CNO Project 299, DT-IIF-1).

    DTIC Science & Technology

    1983-11-01

    AD-R139 346 ROLL-ON/ROLL-OFF (RO/RO) DISCHARGE FACILITY TESTS NITH 1/1 MY CYGNUS AND SS A..(U) DAVID N TAYLOR NAVAL SHIP RESEARCH AND DEVELOPMENT...MICROCOPY RESOLUTION TEST CHART NATIONA. DUEAU OF STANOAD$S-1963-A •-’ ,jh DAVID W. TAYLOR NAVAL SHIP RMSEARCH AND DEVELOPMENT CENTER ROLL-ON/ROLL...by the David W. Taylor Naval Ship Research and Development Center (DTNSRDC), Mobile Support Systems Office, Code 1190, Task Area Y0816.002 and Work

  10. Transiting exoplanets from the CoRoT space mission. XXV. CoRoT-27b: a massive and dense planet on a short-period orbit

    NASA Astrophysics Data System (ADS)

    Parviainen, H.; Gandolfi, D.; Deleuil, M.; Moutou, C.; Deeg, H. J.; Ferraz-Mello, S.; Samuel, B.; Csizmadia, Sz.; Pasternacki, T.; Wuchterl, G.; Havel, M.; Fridlund, M.; Angus, R.; Tingley, B.; Grziwa, S.; Korth, J.; Aigrain, S.; Almenara, J. M.; Alonso, R.; Baglin, A.; Barros, S. C. C.; Bordé, P.; Bouchy, F.; Cabrera, J.; Díaz, R. F.; Dvorak, R.; Erikson, A.; Guillot, T.; Hatzes, A.; Hébrard, G.; Mazeh, T.; Montagnier, G.; Ofir, A.; Ollivier, M.; Pätzold, M.; Rauer, H.; Rouan, D.; Santerne, A.; Schneider, J.

    2014-02-01

    Aims: We report the discovery of a massive and dense transiting planet CoRoT-27b on a 3.58-day orbit around a 4.2 Gyr-old G2 star. The planet candidate was identified from the CoRoT photometry, and was confirmed as a planet with ground-based spectroscopy. Methods: The confirmation of the planet candidate is based on radial velocity observations combined with imaging to rule out blends. The characterisation of the planet and its host star was carried out using a Bayesian approach where all the data (CoRoT photometry, radial velocities, and spectroscopic characterisation of the star) are used jointly. The Bayesian analysis included a study whether the assumption of white normally distributed noise holds for the CoRoT photometry and whether the use of a non-normal noise distribution offers advantages in parameter estimation and model selection. Results: CoRoT-27b has a mass of 10.39 ± 0.55MJup, a radius of 1.01 ± 0.04RJup, a mean density of 12.6-1.67+1.92g cm-3, and an effective temperature of 1500 ± 130 K. The planet orbits around its host star, a 4.2 Gyr-old G2-star with a mass M⋆ = 1.06M⊙ and a radius R⋆ = 1.05R⊙, on a 0.048 ± 0.007 AU orbit of 3.58 days. The radial velocity observations allow us to exclude highly eccentric orbits, namely, e < 0.065 with 99% confidence. Given its high mass and density, theoretical modelling of CoRoT-27b is demanding. We identify two solutions with heavy element mass fractions of 0.11 ± 0.08M⊕ and 0.07 ± 0.06M⊕, but even solutions void of heavy elements cannot be excluded. We carry out a secondary eclipse search from the CoRoT photometry using a method based on Bayesian model selection, but conclude that the noise level is too high to detect eclipses shallower than 9% of the transit depth. Using a non-normal noise model was shown not to affect the parameter estimation results, but led to significant improvement in the sensitivity of the model selection process. The CoRoT space mission, launched on December 27, 2006

  11. Quality of life in functional rhinoplasty: rhinoplasty outcomes evaluation German version (ROE-D).

    PubMed

    Bulut, Olcay Cem; Plinkert, Peter K; Wallner, Frank; Baumann, Ingo

    2016-09-01

    The aim of this study was to validate a German version of the rhinoplasty outcomes evaluation (ROE) questionnaire. A prospective study was conducted and a German translated ROE (ROE-D) questionnaire administered to 100 patients preoperatively, 6 and 12 months postoperatively. The translation was performed according to internationally accepted guidelines. To validate this instrument, we evaluated its reliability, validity and sensitivity. ROE-D was completed by 54 patients after 6 months and by 69 patients 1 year after functional rhinoplasty. Cronbach's α indicated good internal consistency. Reliability was tested with a split-half-reliability, showing significant correlation. Discrimination validity was demonstrated by a comparison with healthy controls. Sensitivity to change showed medium to large effects. ROE-D is a reliable, validated and sensitive German instrument for measuring health-related quality of life in patients after rhinoplasty. The ROE-D focuses mainly on the aesthetic aspects of the rhinoplasty surgery.

  12. Clinical Profile of Eprosartan: A Different Angiotensin II Receptor Blocker

    PubMed Central

    Blankestijn, P. J; Rupp, H

    2008-01-01

    Rationale. The goal of antihypertensive treatment is to reduce risk of cardiovascular morbidity and mortality. Apart from blood pressure lowering per se, also reducing the activities of the renin-angiotensin system and sympathetic nervous system appears to be important. Angiotensin II receptor blocker drugs (ARBs) have provided a useful class of anti-hypertensive drugs. Eprosartan is a relatively new ARB which is chemically distinct (non-biphenyl, non-tetrazole) from all other ARBs (biphenyl tetrazoles). An analysis has been made on available experimental and clinical data on eprosartan which not only is an effective and well tolerated antihypertensive agent, but also lowers the activities of the renin-angiotensin system and sympathetic nervous system. Experimental and pharmacokinetic studies on eprosartan have shown differences with the other ARBs. The distinct properties of this non-biphenyl, non-tetrazole ARB might be relevant in the effort to reduce cardiovascular risk, also beyond its blood pressure lowering capacity. PMID:18855637

  13. Combination ACE inhibitor and angiotensin receptor blocker therapy - future considerations.

    PubMed

    Sica, Domenic A

    2007-01-01

    Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are regularly prescribed for the management of hypertension. Each of these drug classes has also been shown to provide survival benefits for patients with heart failure, proteinuric chronic kidney disease, and/or a high cardiac risk profile. The individual gains seen with each of these drug classes have led to speculation that their combination might offer additive if not synergistic outcome benefits. The foundation of this hypothesis, although biologically possible, has thus far not been sufficiently well proven to support the everyday use of these 2 drug classes in combination. Additional outcomes trials, which are currently proceeding to their conclusion, may provide the necessary proof to support an expanded use of these 2 drug classes in combination.

  14. Effects of Beta-blockers on Punished Responding and on Heart Rate in Pigeons

    DTIC Science & Technology

    1986-06-17

    previous behavioral and/or pharmacological history. Heart rate increases during punished responding were decreased by the beta - blockers . Propranolol and...higher doses. With the beta - blockers , larger increases in punished responding were generally associated with greater heart rate decreases.

  15. Beta-Adrenergic blockers as antiarrhythmic and antifibrillatory compounds: an overview.

    PubMed

    Singh, Bramah N

    2005-06-01

    Beta-Adrenergic blockers have a wide spectrum of action for controlling cardiac arrhythmias that is larger than initially thought. Data from the past several decades indicate that, as an antiarrhythmic class, beta-blockers remain among the very few pharmacologic agents that reduce the incidence of sudden cardiac death, prolong survival, and ameliorate symptoms caused by arrhythmias in patients with cardiac disease. As a class of compounds, beta-blockers have a fundamental pharmacologic property that attenuates the effects of competitive adrenergic receptors. However, the net clinical effects of the different beta-receptor blockers may vary quantitatively because of variations in associated intrinsic sympathomimetic agonism and in their intrinsic potency for binding to beta-receptors. These individual compounds also differ in their selectivity for beta(1)- and beta(2)-receptors. Metoprolol is a beta(1)-selective blocker, whereas carvedilol is a nonselective beta(1)- and beta(2)-blocker, an antioxidant, and has a propensity to inhibit alpha(1)-receptors and endothelin. Evolving data from controlled and uncontrolled clinical trials suggest that there are clinically significant differences among this class of drugs. Recent evidence also suggests that the antiarrhythmic actions of certain beta-receptor blockers such as carvedilol and metoprolol extend beyond the ventricular tissue to encompass atrial cells and help maintain sinus rhythm in patients with atrial fibrillation, especially in combination with potent antifibrillatory agents such as amiodarone. This introduction provides a current perspective on these newer developments in the understanding of the antiarrhythmic and antifibrillatory actions of beta-blockers.

  16. Prediction and experimental validation of acute toxicity of beta-blockers in Ceriodaphnia dubia.

    PubMed

    Fraysse, Benoit; Garric, Jeanne

    2005-10-01

    Acute toxicity of beta-adrenoceptor blockers (beta-blockers) was studied with beta-blockers as single compounds or in mixture using the standardized acute 2-d Ceriodaphnia dubia immobility test. The tested compounds were selected according to their selectivity for the beta1-adrenoceptor, with three beta1-selective blockers (acebutolol, atenolol, and metoprolol) and three non-beta1-selective blockers (nadolol, oxprenolol, and propranolol). The acute toxicity (median effective concentration) of the six single compounds ranged from 1.4 mg/L for propranolol to 163 mg/L for nadolol. According to European Union directive 93/67EEC, these values range from toxic for aquatic organisms to nonclassified. The more toxic compounds, propranolol and oxprenolol, are both characterized by a membrane-stabilizing activity, a strong affinity for the beta1-adrenoceptor, and a high octanol-water partition coefficient (log Kow). The property of beta-receptor selectivity seems not to be involved in the observed acute toxicity of the single compounds for C. dubia. Nevertheless, the toxicity of the selected compounds in mixture can be defined according to the beta1-selectivity. Two main joint effects have been detected: An independent action for the beta1-selective blockers, and an additive effect when either the nonselective beta1-selective blockers or the six compounds are tested together. The concentration addition model seems to be appropriate, providing a reasonable worst-case estimation of beta-blocker mixture toxicity for regulatory purposes.

  17. Clinical significance of antibodies to Ro52/TRIM21 in systemic sclerosis

    PubMed Central

    2012-01-01

    Introduction Autoantibodies to Ro52 recently identified as TRIM21 are among the most common autoantibodies in systemic autoimmune rheumatic diseases, but their clinical association remains poorly understood. We undertook this study to determine the clinical and serologic associations of anti-Ro52/TRIM21 antibodies in patients with systemic sclerosis (SSc). Methods Detailed clinical data and sera from 963 patients with SSc enrolled in a multicenter cohort study were collected and entered into a central database. Antibodies to Ro52/TRIM21 and other autoantibodies were detected with an addressable laser-bead immunoassay and different enzyme-linked immunosorbent assay (ELISA) systems. Associations between anti-Ro52/TRIM21 antibodies and clinical and other serologic manifestations of SSc were investigated. Results Anti-Ro52/TRIM21 antibodies were present in 20% of SSc patients and overlapped with other main SSc-related antibodies, including anti-centromere (by immunofluorescence and centromere protein (CENP)-A and CENP-B ELISA), anti-topoisomerase I, anti-RNA polymerase III, and anti-Pm/Scl antibodies. Anti-Ro52/TRIM21 antibodies were strongly associated with interstitial lung disease (odds ratio (OR), 1.53; 95% confidence interval (CI), 1.11 to 2.12; P = 0.0091) and overlap syndrome (OR, 2.06; 95% CI, 1.01 to 4.19; P = 0.0059). Conclusions Anti-Ro52/TRIM21 antibodies were the second most common autoantibodies in this SSc cohort. In SSc, anti-Ro52/TRIM21 antibodies may be a marker of interstitial lung disease and overlap syndrome. PMID:22394602

  18. Percutaneous endovascular management of occluded HeRO dialysis access device.

    PubMed

    Vasquez, Julio C; DeLaRosa, Jacob; Leon, Juan J; Rahim, Naeem; Rahim, Fahim

    2010-01-01

    The Hemodialysis Reliable Outflow (HeRO) device is a novel alternative for dialysis access in patients with no suitable veins in the upper extremities. We placed a HeRO device in a 67-year-old woman with end-stage renal disease and 2 months later, it was being used for hemodialysis. After 1 month of uneventful use, the device thrombosed and it was rescued with a percutaneous endovascular approach. The device remains patent 6 months after the intervention.

  19. The influence of antiscalants on biofouling of RO membranes in seawater desalination.

    PubMed

    Sweity, Amer; Oren, Yoram; Ronen, Zeev; Herzberg, Moshe

    2013-06-15

    Antiscalants are surface active polyelectrolyte compounds commonly used in reverse osmosis (RO) desalination processes to avoid membrane scaling. In spite of the significant roles of antiscalants in preventing membrane scaling, they are prone to enhance biofilm growth on RO membranes by either altering membrane surface properties or by serving as nutritional source for microorganisms. In this study, the contribution of antiscalants to membrane biofouling in seawater desalination was investigated. The effects of two commonly used antiscalants, polyphosphonate- and polyacrylate-based, were tested. The effects of RO membrane (DOW-Filmtec SW30 HRLE-400) exposure to antiscalants on its physico-chemical properties were studied, including the consequent effects on initial deposition and growth of the sessile microorganisms on the RO membrane surface. The effects of antiscalants on membrane physico-chemical properties were investigated by filtration of seawater supplemented with the antiscalants through flat-sheet RO membrane and changes in surface zeta potential and hydrophobicity were delineated. Adsorption of antiscalants to polyamide surfaces simulating RO membrane's polyamide layer and their effects on the consequent bacterial adhesion was tested using a quartz crystal microbalance with dissipation monitoring technology (QCM-D) and direct fluorescent microscopy. A significant increase in biofilm formation rate on RO membranes surface was observed in the presence of both types of antiscalants. Polyacrylate-based antiscalant was shown to enhance initial cell attachment as observed with the QCM-D and a parallel plate flow cell, due to rendering the polyamide surface more hydrophobic. Polyphosphonate-based antiscalants also increased biofilm formation rate, most likely by serving as an additional source of phosphorous to the seawater microbial population. A thicker biofilm layer was formed on the RO membrane when the polyacrylate-based antiscalant was used. Following

  20. Alpha-adrenergic blocker mediated osteoblastic stem cell differentiation

    SciTech Connect

    Choi, Yoon Jung; Lee, Jue Yeon; Lee, Seung Jin; Chung, Chong-Pyoung; Park, Yoon Jeong

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer Doxazocin directly up-regulated bone metabolism at a low dose. Black-Right-Pointing-Pointer Doxazocin induced osteoblastic stem cell differentiation without affecting cell proliferation. Black-Right-Pointing-Pointer This osteogenic stem cell differentiation is mediated by ERK-signal dependent pathway. -- Abstract: Recent researches have indicated a role for antihypertensive drugs including alpha- or beta-blockers in the prevention of bone loss. Some epidemiological studies reported the protective effects of those agents on fracture risk. However, there is limited information on the association with those agents especially at the mechanism of action. In the present study, we investigated the effects of doxazosin, an alpha-blocker that is clinically used for the treatment of benign prostatic hyperplasia (BPH) along with antihypertensive medication, on the osteogenic stem cell differentiation. We found that doxazosin increased osteogenic differentiation of human mesenchymal stem cells, detected by Alizarin red S staining and calcein. Doxazosin not only induced expression of alkaline phosphatase, type I collagen, osteopontin, and osteocalcin, it also resulted in increased phosphorylation of extracellular signal-regulated kinase (ERK1/2), a MAP kinase involved in osteoblastic differentiation. Treatment with U0126, a MAP kinase inhibitor, significantly blocked doxazosin-induced osteoblastic differentiation. Unrelated to activation of osteogenic differentiation by doxazosin, we found that there were no significant changes in adipogenic differentiation or in the expression of adipose-specific genes, including peroxisome proliferator-activated receptor {gamma}, aP2, or LPL. In this report, we suggest that doxazosin has the ability to increase osteogenic cell differentiation via ERK1/2 activation in osteogenic differentiation of adult stem cells, which supports the protective effects of antihypertensive drug on fracture risk and

  1. Planets and Stellar Activity: Hide and Seek in the CoRoT-7 system

    NASA Astrophysics Data System (ADS)

    Haywood, R. D.; Cameron, A. C.; Queloz, D.; Barros, S. C. C.; Deleuil, M.; Fares, R.; Gillon, M.; Hatzes, A.; Lanza, A. F.; Lovis, C.; Moutou, C.; Pepe, F.; Pollacco, D.; Santerne, A.; Ségransan, D.; Unruh, Y.

    2014-01-01

    Since the discovery of the transiting Super-Earth CoRoT-7b, several investigations have been made of the number and precise masses of planets present in the system, but they all yield different results, owing to the star's high level of activity. Radial velocity (RV) variations induced by stellar activity therefore need to be modelled and removed to allow a reliable detection of all planets in the system. We re-observed CoRoT-7 in January 2012 with both HARPS and the CoRoT satellite, so that we now have the benefit of simultaneous RV and photometric data. We fitted the off-transit variations in the CoRoT lightcurve using a harmonic decomposition similar to that implemented in Queloz et al. (2009). This fit was then used to model the stellar RV contribution, according to the methods described by Aigrain et al. (2011). This model was incorporated into a Monte Carlo Markov Chain in order to make a precise determination of the orbits of CoRoT-7b and CoRoT-7c. We also assess the evidence for the presence of one or two additional planetary companions.

  2. Expression of CD45RO on circulating CD19+ B-cells in Crohn's disease.

    PubMed Central

    Yacyshyn, B R; Pilarski, L M

    1993-01-01

    Crohn's disease is an immunoregulatory disorder of the intestine that can be associated with systemic manifestations. This study analysed B-cell differentiation antigens to identify B-cell subpopulations unique to patients with Crohn's disease. CD45 isoform expression was used as an indicator of B-cell differentiation stage. This work shows that B-cells in blood and gut of patients with Crohn's disease are at an advanced stage of differentiation based on their unusual presentation of transitional (RA+ RO+) and late stage (RO+)CD45 isoforms on lamina propria lymphocytes, whereas normal intestinal lamina propria lymphocytes B-cells express primarily CD45RA. Crohn's disease patients had heightened expression of the CD45RO isoform on CD19+ lamina propria lymphocytes, and was found in a statistically significant proportion of Crohn's peripheral blood mononuclear cells (PBMC) where CD19+ PBMC had an expression pattern affecting an unexpectedly high proportion of these differentiated or late stage CD45RO+ B-cells. The expression of CD45RO varied greatly among CD19+ PBMC from patients with Crohn's disease, so multiple regression analysis was performed between these CD45 isoforms and several clinical parameters. After grouping high and low CD45RO expression on CD19+ B-cells, a significant statistical difference was found between high Crohn's disease activity index (CDAI) and low CDAI Crohn's disease patients respectively. PMID:7506695

  3. Characterisation of residual ionospheric errors in bending angles using GNSS RO end-to-end simulations

    NASA Astrophysics Data System (ADS)

    Liu, C. L.; Kirchengast, G.; Zhang, K. F.; Norman, R.; Li, Y.; Zhang, S. C.; Carter, B.; Fritzer, J.; Schwaerz, M.; Choy, S. L.; Wu, S. Q.; Tan, Z. X.

    2013-09-01

    Global Navigation Satellite System (GNSS) radio occultation (RO) is an innovative meteorological remote sensing technique for measuring atmospheric parameters such as refractivity, temperature, water vapour and pressure for the improvement of numerical weather prediction (NWP) and global climate monitoring (GCM). GNSS RO has many unique characteristics including global coverage, long-term stability of observations, as well as high accuracy and high vertical resolution of the derived atmospheric profiles. One of the main error sources in GNSS RO observations that significantly affect the accuracy of the derived atmospheric parameters in the stratosphere is the ionospheric error. In order to mitigate the effect of this error, the linear ionospheric correction approach for dual-frequency GNSS RO observations is commonly used. However, the residual ionospheric errors (RIEs) can be still significant, especially when large ionospheric disturbances occur and prevail such as during the periods of active space weather. In this study, the RIEs were investigated under different local time, propagation direction and solar activity conditions and their effects on RO bending angles are characterised using end-to-end simulations. A three-step simulation study was designed to investigate the characteristics of the RIEs through comparing the bending angles with and without the effects of the RIEs. This research forms an important step forward in improving the accuracy of the atmospheric profiles derived from the GNSS RO technique.

  4. Effects of the 5-HT(6) receptor antagonist Ro 04-6790 on learning consolidation.

    PubMed

    Meneses, A

    2001-01-08

    The 5-HT(6) receptor antagonist Ro-04-6790 or 8-OH-DPAT injection improved learning consolidation on an autoshaping task, while mCPP, scopolamine and dizocilpine decreased the performance. The effect induced by scopolamine, but not that induced by mCPP, was reversed completely by Ro-04-6790, while dizocilpine effect was antagonized partially. Nevertheless, ritanserin or WAY 100635, but not Ro 04-6790, antagonized the 8-OH-DPAT facilitatory effects on learning consolidation. As WAY 100635 did not modify the Ro 04-6790 facilitatory effect, hence 5-HT(1A), and/or 5-HT(7), but not 5-HT(6), receptors might mediate the 8-OH-DPAT facilitatory effect on learning consolidation. Since, the Ro 04-6790 facilitatory effect was unaffected by 5-HT(1A), 5-HT(2A)/(2B)/(2C), 5-HT(3) or 5-HT(4) receptor blockade, thereby, the facilitatory effect induced by Ro 04-6790 involved specifically 5-HT(6) receptors. Indeed, the present data provide further support to the notion that, 5-HT(6) receptors play a significant part in the learning consolidation under normal and dysfunctional memory conditions.

  5. Shortening baroreflex delay in hypertrophic cardiomyopathy patients – an unknown effect of β-blockers

    PubMed Central

    Katarzynska-Szymanska, Agnieszka; Ochotny, Romuald; Oko-Sarnowska, Zofia; Wachowiak-Baszynska, Hanna; Krauze, Tomasz; Piskorski, Jaroslaw; Gwizdala, Adrian; Mitkowski, Przemyslaw; Guzik, Przemyslaw

    2013-01-01

    Aims Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy and impaired diastolic and systolic function. Abnormal sympathetic–parasympathetic balance is a potential stimulus for left ventricular hypertrophy in HCM patients. β-Blockers are routinely used in HCM for their strong negative inotropic effect; however, these drugs also influence the sympathetic–parasympathetic balance. This study aimed to determine the autonomic control of the cardiovascular system and the autonomic effects of β-blockers in HCM patients treated or untreated with β-blockers. Methods Among 51 HCM outpatients (18–70 years old; 29 men) there were 19 individuals with no medication and 32 subjects treated with a β-blocker. Fourteen age- and gender-matched (23–70 years old; nine men) healthy volunteers were enrolled in the control group. Continuous, non-invasive finger blood pressure was recorded during supine rest for 30 min. Autonomic regulation of the cardiovascular system was measured by heart rate variability and spontaneous baroreflex function (cross-correlation sequence method). Results The mean pulse interval, time domain and spectral measures of heart rate variability and baroreflex sensitivity were comparable between HCM patients, treated or not with β-blockers, and the control group. However, the delay of the baroreflex was significantly longer in HCM patients who were not treated with β-blockers [2.0 (1.6–2.3) s] in comparison with HCM patients receiving β-blockers [1.4 (1.1–1.8) s; P = 0.0072] or control subjects [1.2 (0.8–1.8) s; P = 0.0025]. This delay did not differ between HCM patients treated with β-blockers and the control group. Conclusions Hypertrophic cardiomyopathy not treated with β-blockers is accompanied by prolonged baroreflex delay. The use of β-blockers normalizes this delay. PMID:23126403

  6. Increased infections with β-blocker use in ischemic stroke, a β2-receptor mediated process?

    PubMed

    Starr, Jordan B; Tirschwell, David L; Becker, Kyra J

    2017-03-03

    Strokes promote immunosuppression, partially from increased sympathetic activity. Altering sympathetic drive with β-blockers has variably been shown to improve stroke outcomes. This study adds to this literature using propensity score matching to limit confounding and by examining the effects of selective and non-selective β-blockers. Prospective data from acute ischemic stroke admissions at a single center from July 2010-June 2015 were analyzed. Outcomes included infection (urinary tract infection [UTI], pneumonia, or bacteremia), discharge modified Rankin Score (mRS), and in-hospital death. Any selective and non-selective β-blocker use during the first 3 days of admission were investigated with propensity score matching. A sensitivity analysis was also performed. This study included 1431 admissions. Any β-blocker use was associated with increased infections (16.4 vs. 10.7%, p = 0.030). Non-selective β-blocker use was associated with increased infections (18.9 vs. 9.7%, p = 0.005) and UTIs (13.0 vs. 5.5%, p = 0.009). Selective β-blocker use was not associated with infection. There were no associations between β-blocker use and in-hospital death or discharge mRS. In the sensitivity analysis, the association between non-selective β-blocker use and urinary tract infections persisted (12.5 vs. 4.2%, p = 0.044). No associations with death or mRS were found. Early β-blocker use after ischemic stroke may increase the risk of infection but did not change disability or mortality risk. The mechanism may be mediated by β2-adrenergic receptor antagonism given the different effects seen with selective versus non-selective β-blocker use.

  7. Uptitration of renin-angiotensin system blocker and beta-blocker therapy in patients hospitalized for heart failure with reduced versus preserved left ventricular ejection fractions.

    PubMed

    Verbrugge, Frederik H; Duchenne, Jürgen; Bertrand, Philippe B; Dupont, Matthias; Tang, W H Wilson; Mullens, Wilfried

    2013-12-15

    In ambulatory patients with heart failure (HF) and reduced ejection fraction (rEF), renin-angiotensin system (RAS) and β-blockers at guideline-recommended target dose reduce all-cause mortality and readmissions. Benefits in HF with preserved ejection fraction (pEF), as well as uptitration after a hospitalization, remain uncertain. This study assesses the impact of RAS- and β-blocker uptitrations in patients with HFrEF versus HFpEF during and immediately after a hospital admission. In consecutive patients (209 HFrEF with left ventricular ejection fraction <40% and 108 HFpEF with left ventricular ejection fraction ≥40%), RAS- and β-blocker dose changes were followed during 6 months after an index HF hospitalization. Patients with a RAS- and β-blocker dose increase of ≥10% of the recommended target dose were compared with patients without uptitration. Patients who received uptitration were significantly younger, with a higher heart rate and better renal function, and received spironolactone more often. Both RAS- and β-blocker uptitrations were associated with significant reductions in the composite end-point of all-cause mortality or HF readmissions in HFrEF (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.22 to 0.60 and HR 0.51, 95% CI 0.32 to 0.81, respectively). After correction for age, heart rate, blood pressure, renal function, and spironolactone use, this association remained significant for RAS blockers (HR 0.54, 95% CI 0.31 to 0.93, p = 0.027) but not for β-blockers (HR 0.65, 95% CI 0.39 to 1.09, p = 0.101). No benefit of RAS- or β-blocker uptitration was observed in HFpEF. In conclusion, uptitration of neurohumoral blockers after an HF hospitalization is more frequently performed in younger patients with low co-morbidity burden. RAS-blocker uptitration independently predicts clinical outcome in patients with HFrEF but not in those with HFpEF.

  8. Increasing RO efficiency by chemical-free ion-exchange and Donnan dialysis: Principles and practical implications.

    PubMed

    Vanoppen, Marjolein; Stoffels, Griet; Demuytere, Célestin; Bleyaert, Wouter; Verliefde, Arne R D

    2015-09-01

    Ion-exchange (IEX) and Donnan dialysis (DD) are techniques which can selectively remove cations, limiting scaling in reverse osmosis (RO). If the RO concentrate could be recycled for regeneration of these pre-treatment techniques, RO recovery could be largely increased without the need for chemical addition or additional technologies. In this study, two different RO feed streams (treated industrial waste water and simple tap water) were tested in the envisioned IEX-RO and DD-RO hybrids including RO concentrate recycling. The efficiency of multivalent cation removal depends mainly on the ratio of monovalent to multivalent cations in the feed stream, influencing the ion-exchange efficiency in both IEX and DD. Since the mono-to-multivalent ratio was very high in the waste water, the RO recovery could potentially be increased to 92%. For the tap water, these high RO recoveries could only be reached by adding additional NaCl, because of the low initial monovalent to multivalent ratio in the feed. In both cases, the IEX-RO hybrid proved to be most cost-efficient, due to the high current cost of the membranes used in DD. The membrane cost would have to decrease from ±300 €/m² to 10-30 €/m² - comparable to current reverse osmosis membranes - to achieve a comparable cost. In conclusion, the recycling of RO concentrate to regenerate ion exchange pre-treatment techniques for RO is an interesting option to increase RO recovery without addition of chemicals, but only at high monovalent/multivalent cation-ratios in the feed stream.

  9. Transiting exoplanets from the CoRoT space mission. VIII. CoRoT-7b: the first super-Earth with measured radius

    NASA Astrophysics Data System (ADS)

    Léger, A.; Rouan, D.; Schneider, J.; Barge, P.; Fridlund, M.; Samuel, B.; Ollivier, M.; Guenther, E.; Deleuil, M.; Deeg, H. J.; Auvergne, M.; Alonso, R.; Aigrain, S.; Alapini, A.; Almenara, J. M.; Baglin, A.; Barbieri, M.; Bruntt, H.; Bordé, P.; Bouchy, F.; Cabrera, J.; Catala, C.; Carone, L.; Carpano, S.; Csizmadia, Sz.; Dvorak, R.; Erikson, A.; Ferraz-Mello, S.; Foing, B.; Fressin, F.; Gandolfi, D.; Gillon, M.; Gondoin, Ph.; Grasset, O.; Guillot, T.; Hatzes, A.; Hébrard, G.; Jorda, L.; Lammer, H.; Llebaria, A.; Loeillet, B.; Mayor, M.; Mazeh, T.; Moutou, C.; Pätzold, M.; Pont, F.; Queloz, D.; Rauer, H.; Renner, S.; Samadi, R.; Shporer, A.; Sotin, Ch.; Tingley, B.; Wuchterl, G.; Adda, M.; Agogu, P.; Appourchaux, T.; Ballans, H.; Baron, P.; Beaufort, T.; Bellenger, R.; Berlin, R.; Bernardi, P.; Blouin, D.; Baudin, F.; Bodin, P.; Boisnard, L.; Boit, L.; Bonneau, F.; Borzeix, S.; Briet, R.; Buey, J.-T.; Butler, B.; Cailleau, D.; Cautain, R.; Chabaud, P.-Y.; Chaintreuil, S.; Chiavassa, F.; Costes, V.; Cuna Parrho, V.; de Oliveira Fialho, F.; Decaudin, M.; Defise, J.-M.; Djalal, S.; Epstein, G.; Exil, G.-E.; Fauré, C.; Fenouillet, T.; Gaboriaud, A.; Gallic, A.; Gamet, P.; Gavalda, P.; Grolleau, E.; Gruneisen, R.; Gueguen, L.; Guis, V.; Guivarc'h, V.; Guterman, P.; Hallouard, D.; Hasiba, J.; Heuripeau, F.; Huntzinger, G.; Hustaix, H.; Imad, C.; Imbert, C.; Johlander, B.; Jouret, M.; Journoud, P.; Karioty, F.; Kerjean, L.; Lafaille, V.; Lafond, L.; Lam-Trong, T.; Landiech, P.; Lapeyrere, V.; Larqué, T.; Laudet, P.; Lautier, N.; Lecann, H.; Lefevre, L.; Leruyet, B.; Levacher, P.; Magnan, A.; Mazy, E.; Mertens, F.; Mesnager, J.-M.; Meunier, J.-C.; Michel, J.-P.; Monjoin, W.; Naudet, D.; Nguyen-Kim, K.; Orcesi, J.-L.; Ottacher, H.; Perez, R.; Peter, G.; Plasson, P.; Plesseria, J.-Y.; Pontet, B.; Pradines, A.; Quentin, C.; Reynaud, J.-L.; Rolland, G.; Rollenhagen, F.; Romagnan, R.; Russ, N.; Schmidt, R.; Schwartz, N.; Sebbag, I.; Sedes, G.; Smit, H.; Steller, M. B.; Sunter, W.; Surace, C.; Tello, M.; Tiphène, D.; Toulouse, P.; Ulmer, B.; Vandermarcq, O.; Vergnault, E.; Vuillemin, A.; Zanatta, P.

    2009-10-01

    Aims: We report the discovery of very shallow (Δ F/F ≈ 3.4× 10-4), periodic dips in the light curve of an active V = 11.7 G9V star observed by the CoRoT satellite, which we interpret as caused by a transiting companion. We describe the 3-colour CoRoT data and complementary ground-based observations that support the planetary nature of the companion. Methods: We used CoRoT colours information, good angular resolution ground-based photometric observations in- and out- of transit, adaptive optics imaging, near-infrared spectroscopy, and preliminary results from radial velocity measurements, to test the diluted eclipsing binary scenarios. The parameters of the host star were derived from optical spectra, which were then combined with the CoRoT light curve to derive parameters of the companion. Results: We examined all conceivable cases of false positives carefully, and all the tests support the planetary hypothesis. Blends with separation >0.40´´or triple systems are almost excluded with a 8 × 10-4 risk left. We conclude that, inasmuch we have been exhaustive, we have discovered a planetary companion, named CoRoT-7b, for which we derive a period of 0.853 59 ± 3 × 10-5 day and a radius of Rp = 1.68 ± 0.09 R_Earth. Analysis of preliminary radial velocity data yields an upper limit of 21 M_Earth for the companion mass, supporting the finding. Conclusions: CoRoT-7b is very likely the first Super-Earth with a measured radius. This object illustrates what will probably become a common situation with missions such as Kepler, namely the need to establish the planetary origin of transits in the absence of a firm radial velocity detection and mass measurement. The composition of CoRoT-7b remains loosely constrained without a precise mass. A very high surface temperature on its irradiated face, ≈1800-2600 K at the substellar point, and a very low one, ≈50 K, on its dark face assuming no atmosphere, have been derived. The CoRoT space mission, launched on 27

  10. RoBlock: a prototype autonomous manufacturing cell

    NASA Astrophysics Data System (ADS)

    Baekdal, Lars K.; Balslev, Ivar; Eriksen, Rene D.; Jensen, Soren P.; Jorgensen, Bo N.; Kirstein, Brian; Kristensen, Bent B.; Olsen, Martin M.; Perram, John W.; Petersen, Henrik G.; Petersen, Morten L.; Ruhoff, Peter T.; Skjolstrup, Carl E.; Sorensen, Anders S.; Wagenaar, Jeroen M.

    2000-10-01

    RoBlock is the first phase of an internally financed project at the Institute aimed at building a system in which two industrial robots suspended from a gantry, as shown below, cooperate to perform a task specified by an external user, in this case, assembling an unstructured collection of colored wooden blocks into a specified 3D pattern. The blocks are identified and localized using computer vision and grasped with a suction cup mechanism. Future phases of the project will involve other processes such as grasping and lifting, as well as other types of robot such as autonomous vehicles or variable geometry trusses. Innovative features of the control software system include: The use of an advanced trajectory planning system which ensures collision avoidance based on a generalization of the method of artificial potential fields, the use of a generic model-based controller which learns the values of parameters, including static and kinetic friction, of a detailed mechanical model of itself by comparing actual with planned movements, the use of fast, flexible, and robust pattern recognition and 3D-interpretation strategies, integration of trajectory planning and control with the sensor systems in a distributed Java application running on a network of PC's attached to the individual physical components. In designing this first stage, the aim was to build in the minimum complexity necessary to make the system non-trivially autonomous and to minimize the technological risks. The aims of this project, which is planned to be operational during 2000, are as follows: To provide a platform for carrying out experimental research in multi-agent systems and autonomous manufacturing systems, to test the interdisciplinary cooperation architecture of the Maersk Institute, in which researchers in the fields of applied mathematics (modeling the physical world), software engineering (modeling the system) and sensor/actuator technology (relating the virtual and real worlds) could

  11. MBR/RO/ozone processes for TFT-LCD industrial wastewater treatment and recycling.

    PubMed

    Chen, T K; Ni, C H; Chan, Y C; Lu, M C

    2005-01-01

    This research is mainly to explore the treatment capacity for TFT-LCD industrial wastewater recycling by the processes combined with membrane bioreactor (MBR), reverse osmosis (RO) and ozone(O3). The organic wastewater from the TFT-LCD industry was selected as the target. MBR, RO and ozone plants were established for evaluation. An MBR plant consisted of a 2-stage anoxic/aerobic bioreactor and an immersed UF membrane unit was employed. The effluent of MBR was conducted into the RO system then into the ozone system. The RO system consisted of a spiral membrane in the vessel. One bubble column, 75 cm high and diameter 5 cm, were used as the ozonation reactor. On the bottom of ozonation reactor is a porous diffuser for releasing gas, with an aperture of 100 microm (0.1 cm). Over the whole experimental period, the MBR process achieved a satisfactory organic removal. The COD could be removed with an average of over 98.5%. For the TOC item, the average removal efficiency was 97.4%. The stable effluent quality and satisfactory removal performance were ensured by the efficient interception performance of an immersed UF membrane device incorporated with the biological reactor. Moreover, the MBR effluent did not contain any suspended solids and the SDI value was under 3. After the treatment of RO, excellent water quality was found. The water quality of permeate was under 5 mg/I, 2 mg/l and 50 micros/cm for COD, TOC and conductivity respectively. The treated water can be recycled and reused for the cooling tower make-up water or other purposes. After the treatment of ozone, the treated water quality was under 5 mg/l and 0.852 mg/l for COD and TOC respectively. The test results of MBR, MBR/RO and MBR/RO/ozone processes were compared as possible appropriate treatment technologies applied in TFT-LCD industrial wastewater reuse and recycling.

  12. Does the benzodiazepine antagonist Ro 15-1788 antagonize the action of ethanol?

    PubMed

    Klotz, U; Ziegler, G; Rosenkranz, B; Mikus, G

    1986-11-01

    Ethanol aggravates benzodiazepine-induced central nervous depression by pharmacokinetic and/or pharmacodynamic interactions and Ro 15-1788 reverses promptly the hypnotic effects of benzodiazepines. We therefore studied the acute effects of Ro 15-1788 on the ethanol-induced sedation in six healthy male subjects. Subsequently to an oral loading dose (0.54 g ethanol kg-1) ethanol was infused for 4 h (0.15 g ethanol kg-1 h-1) and steady state blood levels between 0.9 to 1.2 g l-1 were reached within 2 h. At steady state and during the elimination phase of ethanol an intravenous bolus of 0.5 mg Ro 15-1788 or placebo was administered in a randomized, double-blind crossover fashion. The marked sedative effects of ethanol as assessed by visual analogue scales (2 to 6 fold increase in the sedation index), and choice reaction time (25 to 40% prolongation) were not affected by Ro 15-1788. However, the pharmaco-EEG indicated that Ro 15-1788 seems to reverse transiently the ethanol-induced changes in total alpha, delta, and slow alpha bands. There was no pharmacokinetic interaction between both agents since elimination of Ro 15-1788 (t1/2 = 1.2 +/- 0.7 h) and of ethanol (0.17 +/- 0.02 g l-1 h-1) were in good agreement with control values. Thus, it could be concluded that Ro 15-1788 might affect for a short while the action of ethanol by interfering with the benzodiazepine receptors.

  13. Regulation of intraocular pressure and pupil size by beta-blockers and epinephrine.

    PubMed

    Ohrström, A; Pandolfi, M

    1980-12-01

    The interaction of adrenergic beta-receptor blockers and epinephrine on intraocular pressure and pupil size was investigated in healthy volunteers. Oral (atenolol and propranolol) and local (timolol) beta-blockers were studied. The experiment was carried out under double-blind randomized crossover conditions. The results showed that the combination of oral beta-blockers with topical epinephrine had an additive hypotensive effect on IOP, while timolol and epinephrine eyedrops both reduced the IOP used alone, but combined had an antagonistic effect, resulting in the disappearance of the epinephrine-mediated IOP reduction.

  14. Reappraisal of role of angiotensin receptor blockers in cardiovascular protection.

    PubMed

    Ram, C Venkata S

    2011-01-01

    Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have shown cardioprotective and renoprotective properties. These agents are recommended as first-line therapy for the treatment of hypertension and the reduction of cardiovascular risk. Early studies pointed to the cardioprotective and renoprotective effects of ARBs in high-risk patients. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) established the clinical equivalence of the cardioprotective and renoprotective effects of telmisartan and ramipril, but did not find an added benefit of the combination over ramipril alone. Similar findings were observed in the Telmisartan Randomized AssessmeNt Study in aCE INtolerant subjects with cardiovascular Disease (TRANSCEND) trial conducted in ACEI-intolerant patients. In ONTARGET, telmisartan had a better tolerability profile with similar renoprotective properties compared with ramipril, suggesting a potential clinical benefit over ramipril. The recently completed Olmesartan Reducing Incidence of Endstage Renal Disease in Diabetic Nephropathy Trial (ORIENT) and Olmesartan and Calcium Antagonists Randomized (OSCAR) studies will further define the role of ARBs in cardioprotection and renoprotection for high-risk patients.

  15. Safety and tolerability of beta-blockers: prejudices & reality.

    PubMed

    Erdmann, Erland

    2010-01-01

    Beta-blockers (BB) substantially improve survival in chronic heart failure and after myocardial infarction. However, concern about side-effects may deter clinicians from prescribing these life-saving drugs. In reality, absolute contraindications are rare. Only 3-5% of patients are intolerant because of hypotension or bradycardia. Data from randomized controlled trials and retrospective studies show that most patients eligible to receive BB tolerate them well. BB are not contraindicated in chronic obstructive pulmonary disease (COPD); in fact, these patients also benefit because of their high cardiovascular risk. In patients with COPD, as in the elderly, BB should be started at a low dose and uptitrated slowly. Monitoring of lung function during initiation is important, as undiagnosed coexistent asthma could be revealed. When patients are unaware of the drug in use, erectile dysfunction (ED) is reported no more often with BB than with any other drug prescribed for heart failure or hypertension. However, when patients are aware of the potential side-effects of BB, the resultant anxiety may cause ED. Patients should be reassured that BB prolong life and in the great majority are not the cause of ED, which may rather be related to the underlying disease (diabetes, hypertension, and atherosclerosis).

  16. Free radical destruction of beta-blockers in aqueous solution.

    PubMed

    Song, Weihua; Cooper, William J; Mezyk, Stephen P; Greaves, John; Peake, Barrie M

    2008-02-15

    Many pharmaceutical compounds and metabolites are currently found in surface and ground waters which indicates their ineffective removal by conventional water treatment technologies. Advanced oxidation/reduction processes (AO/ RPs) are alternatives to traditional water treatment, which utilize free radical reactions to directly degrade chemical contaminants. This study reports the absolute rate constants for reaction of three beta-blockers (atenolol, metoprolol, and propranolol) with the two major AO/RP radicals; the hydroxyl radical (*OH) and hydrated electron ((e-)aq). The bimolecular reaction rate constants for *OH are (7.05 +/- 0.27) x 10(9), (8.39 +/- 0.06) x 10(9), and (1.07 +/- 0.02) x 10(10), and for (e-)aq they are (5.91 +/- 0.21) x 10(8), (1.73 +/- 0.03) x 10(8), and (1.26 +/- 0.02) x 10(10), respectively. Transient spectra were observed for the intermediate radicals produced by hydroxyl radical reactions. In addition, preliminary degradation mechanisms and major products were elucidated using 60Co gamma-irradiation and LC-MS. These data are required for both evaluating the potential use of AO/RPs for the destruction of these compounds and for studies of their fate and transport in surface waters where radical chemistry may be important in assessing their lifetime.

  17. Speckle Imaging of Kepler and CoRoT Exo-planet Transit Candidate Stars

    NASA Astrophysics Data System (ADS)

    Howell, Steve B.; Horch, Elliott; Sherry, William; Ciardi, David

    2010-08-01

    Kepler and CoRoT are complementary space missions dedicated to the detection of exoplanets. The primary science goal of CoRoT is to find Neptune-sized (>3 Earth radii) planets in intermediate orbits, while the prime science goal of Kepler is to find Earth-sized planets (<3 Earth radii) in year-long orbits. Both missions employ the photometric transit method and both spacecraft are performing well with nominal operation of the spacecraft, telescopes, electronics, and instruments. As with ground-based surveys, Kepler and CoRoT candidates need to be screened for background eclipsing binary stars which, when photometrically blended with the primary target, can mimic exo-planetary transits. The list of candidate transiting planets found by Kepler/CoRoT requires follow-up to ascertain probable or certain exo- planet detection. While Earth-sized (and Neptune-sized in long orbital periods) exo-planets can not currently (easily) be confirmed from the ground, many of the false positive eliminations steps can be performed by ground-based observations. Follow-up for Kepler exo-planet candidates is now aimed at Neptune-size and smaller planets in longer period orbits. This proposal aims to obtain high resolution speckle imaging to observe Kepler/CoRoT exo-planet transit candidates in order to eliminate the largest false positive contributor in any transit search - background eclipsing binary stars or faint companion stars.

  18. Abnormal clinical pharmacokinetics of the developmental radiosensitizers pimonidazole (Ro 03-8799) and etanidazole (SR 2508)

    SciTech Connect

    Maughan, T.S.; Newman, H.F.; Bleehen, N.M.; Ward, R.; Workman, P. )

    1990-05-01

    The hypoxic cell radiosensitizers Ro 03-8799 (pimonidazole) and SR 2508 (etanidazole) are under evaluation as single agents (Phase III) and in combination (Phase I). Ro 03-8799 produces an acute, transient central nervous system syndrome, whereas SR 2508 causes cumulative, peripheral neurotoxicity; both effects are dose-limiting. Pharmacokinetic studies have shown the importance of area under the plasma drug concentration versus time curve (AUC) in predicting the risk of peripheral neuropathy. Most patients have very similar pharmacokinetic parameters. This study reports 2/25 patients receiving 0.75 g/m2 Ro 03-8799 plus 2.0 g/m2 SR 2508 who showed significant discrepancies in drug handling. One patient exhibited a markedly elevated AUC and prolonged t1/2 beta for SR 2508 and this was associated with an unusually rapid onset of peripheral neuropathy. A second patient showed normal handling of SR 2508 but prolonged values for both t1/2 alpha and t1/2 beta for Ro 03-8799 and unusually low levels of its N-oxide metabolite. In addition a low peak Ro 03-8799 concentration combined with a very high volume of distribution was found in this patient, leading to a normal AUC value and toxicity profile. Both patients exhibited a relatively low creatinine clearance. The mechanisms which may underlie these findings are discussed, and the importance of pharmacokinetic monitoring in the use of these agents is emphasized.

  19. Data Analysis Provenance: Use Case for Exoplanet Search in CoRoT Database

    NASA Astrophysics Data System (ADS)

    de Souza, L.; Salete Marcon Gomes Vaz, M.; Emílio, M.; Ferreira da Rocha, J. C.; Janot Pacheco, E.; Carlos Boufleur, R.

    2012-09-01

    CoRoT (COnvection Rotation and Planetary Transits) is a mission led by the French national space agency CNES, in collaboration with Austria, Spain, Germany, Belgium and Brazil. The mission priority is dedicated to exoplanet search and stellar seismology. CoRoT light curves database became public after one year of their delivery to the CoRoT Co-Is, following the CoRoT data policy. The CoRoT archive contains thousands of light curves in FITS format. Several exoplanet search algorithms require detrend algorithms to remove both stellar and instrumental signal, improving the chance to detect a transit. Different detrend and transit detection algorithms can be applied to the same database. Tracking the origin of the information and how the data was derived in each level in the data analysis process is essential to allow sharing, reuse, reprocessing and further analysis. This work aims at applying a formalized and codified knowledge model by means of domain ontology. It allows to enrich the data analysis with semantic and standardization. It holds the provenance information in the database for a posteriori recovers by humans or software agents.

  20. Transiting exoplanets from the CoRoT space mission. XXVII. CoRoT-28b, a planet orbiting an evolved star, and CoRoT-29b, a planet showing an asymmetric transit

    NASA Astrophysics Data System (ADS)

    Cabrera, J.; Csizmadia, Sz.; Montagnier, G.; Fridlund, M.; Ammler-von Eiff, M.; Chaintreuil, S.; Damiani, C.; Deleuil, M.; Ferraz-Mello, S.; Ferrigno, A.; Gandolfi, D.; Guillot, T.; Guenther, E. W.; Hatzes, A.; Hébrard, G.; Klagyivik, P.; Parviainen, H.; Pasternacki, Th.; Pätzold, M.; Sebastian, D.; Tadeu dos Santos, M.; Wuchterl, G.; Aigrain, S.; Alonso, R.; Almenara, J.-M.; Armstrong, J. D.; Auvergne, M.; Baglin, A.; Barge, P.; Barros, S. C. C.; Bonomo, A. S.; Bordé, P.; Bouchy, F.; Carpano, S.; Chaffey, C.; Deeg, H. J.; Díaz, R. F.; Dvorak, R.; Erikson, A.; Grziwa, S.; Korth, J.; Lammer, H.; Lindsay, C.; Mazeh, T.; Moutou, C.; Ofir, A.; Ollivier, M.; Pallé, E.; Rauer, H.; Rouan, D.; Samuel, B.; Santerne, A.; Schneider, J.

    2015-07-01

    Context. We present the discovery of two transiting extrasolar planets by the satellite CoRoT. Aims: We aim at a characterization of the planetary bulk parameters, which allow us to further investigate the formation and evolution of the planetary systems and the main properties of the host stars. Methods: We used the transit light curve to characterize the planetary parameters relative to the stellar parameters. The analysis of HARPS spectra established the planetary nature of the detections, providing their masses. Further photometric and spectroscopic ground-based observations provided stellar parameters (log g, Teff, v sin i) to characterize the host stars. Our model takes the geometry of the transit to constrain the stellar density into account, which when linked to stellar evolutionary models, determines the bulk parameters of the star. Because of the asymmetric shape of the light curve of one of the planets, we had to include the possibility in our model that the stellar surface was not strictly spherical. Results: We present the planetary parameters of CoRoT-28b, a Jupiter-sized planet (mass 0.484 ± 0.087 MJup; radius 0.955 ± 0.066 RJup) orbiting an evolved star with an orbital period of 5.208 51 ± 0.000 38 days, and CoRoT-29b, another Jupiter-sized planet (mass 0.85 ± 0.20 MJup; radius 0.90 ± 0.16 RJup) orbiting an oblate star with an orbital period of 2.850 570 ± 0.000 006 days. The reason behind the asymmetry of the transit shape is not understood at this point. Conclusions: These two new planetary systems have very interesting properties and deserve further study, particularly in the case of the star CoRoT-29. The CoRoT space mission, launched on December 27th 2006, was developed and is operated by CNES, with the contribution of Austria, Belgium, Brazil, ESA (RSSD and Science Programme), Germany, and Spain. Based on observations obtained with the Nordic Optical Telescope, operated on the island of La Palma jointly by Denmark, Finland, Iceland

  1. Beta-blockers in the treatment of neurological and psychiatric disorders.

    PubMed

    Peet, M; Yates, R A

    1981-09-01

    Beta-blockers, originally introduced into clinical practice for the treatment of cardiovascular disorders, are being increasingly advocated in the treatment of diverse neurological and psychiatric conditions. Thus, propranolol and certain other beta-blockers have been shown to be effective, and may be the drugs of choice, in the treatment of benign essential tremor and the prevention of recurrent migraine attacks. These drugs also have a useful role to play in the treatment of anxiety and alcohol withdrawal states, although beta-blockers have not come into general use in these conditions. The action of propranolol and related drugs in these neurological and psychiatric conditions is generally considered to be mediated by blockade of peripheral beta-adrenergic receptors, although other effects, either central or peripheral, may also be involved. The use of beta-blockers in the treatment of psychosis remains controversial. Current evidence does not support the use of propranolol in schizophrenia, but further studies in mania are warranted.

  2. The current status of beta blockers' use in the management of hypertension.

    PubMed

    Akbar, Shahid; Alorainy, Mohammad S

    2014-11-01

    The invention of beta (β)-blockers culminated in a new era in the treatment of cardiovascular diseases (CD), and changed the course of pharmacology research for years to come. Since the introduction of propranolol into clinical practice in 1964, β-blockers enjoyed a special place in the clinicians' armamentarium against CDs, especially for patients with ischemic heart diseases, and are still one of the most extensively used therapeutic drugs in both cardiac and non-cardiac ailments. Current uses of β-blockers in CDs include ischemic heart diseases, hypertension, cardiac arrhythmias, and heart failure. Other substantial non-cardiac uses include glaucoma, migraine, situational anxiety, benign essential tremors, and cardiac symptoms of thyrotoxicosis. This review covers some of the evolutionary changes of clinical uses of β-blockers, the rationale for their use, some recent controversies surrounding their use for treatment of hypertension, and advantages of newer additions to the group. 

  3. Modeling of the Binding of Peptide Blockers to Voltage-Gated Potassium Channels: Approaches and Evidence

    PubMed Central

    Novoseletsky, V. N.; Volyntseva, A. D.; Shaitan, K. V.; Kirpichnikov, M. P.; Feofanov, A. V.

    2016-01-01

    Modeling of the structure of voltage-gated potassium (KV) channels bound to peptide blockers aims to identify the key amino acid residues dictating affinity and provide insights into the toxin-channel interface. Computational approaches open up possibilities for in silico rational design of selective blockers, new molecular tools to study the cellular distribution and functional roles of potassium channels. It is anticipated that optimized blockers will advance the development of drugs that reduce over activation of potassium channels and attenuate the associated malfunction. Starting with an overview of the recent advances in computational simulation strategies to predict the bound state orientations of peptide pore blockers relative to KV-channels, we go on to review algorithms for the analysis of intermolecular interactions, and then take a look at the results of their application. PMID:27437138

  4. Research and development of Ro-boat: an autonomous river cleaning robot

    NASA Astrophysics Data System (ADS)

    Sinha, Aakash; Bhardwaj, Prashant; Vaibhav, Bipul; Mohommad, Noor

    2013-12-01

    Ro-Boat is an autonomous river cleaning intelligent robot incorporating mechanical design and computer vision algorithm to achieve autonomous river cleaning and provide a sustainable environment. Ro-boat is designed in a modular fashion with design details such as mechanical structural design, hydrodynamic design and vibrational analysis. It is incorporated with a stable mechanical system with air and water propulsion, robotic arms and solar energy source and it is proceed to become autonomous by using computer vision. Both "HSV Color Space" and "SURF" are proposed to use for measurements in Kalman Filter resulting in extremely robust pollutant tracking. The system has been tested with successful results in the Yamuna River in New Delhi. We foresee that a system of Ro-boats working autonomously 24x7 can clean a major river in a city on about six months time, which is unmatched by alternative methods of river cleaning.

  5. WE-B-Exhibit Hall-01: Ask the RO-ILS Experts

    SciTech Connect

    Ezzell, G; Sanscrainte, E; Tomlinson, C

    2015-06-15

    Have a question about RO-ILS: Radiation Oncology Incident Learning System™, or interested in learning more? Sponsored by the American Society for Radiation Oncology (ASTRO) and AAPM, RO-ILS is the only medical specialty society-sponsored incident learning system for radiation oncology. It facilitates safer and higher quality care in radiation oncology by providing a mechanism for shared learning in a secure and non-punitive environment. Please join our RO-ILS experts for a question and answer session on Wednesday, July 15th at 8:30 in the Partners in Solutions Room in Exhibit Hall C. Our experts include: Gary Ezzell, PhD, Mayo Clinic Arizona, [Brett Miller, Phillip Beron, and Derek Brown], Emily Sanscrainte from Clarity PSO and Cindy Tomlinson, MPP, ASTRO.

  6. Removal of bisphenol A (BPA) from water by various nanofiltration (NF) and reverse osmosis (RO) membranes.

    PubMed

    Yüksel, Suna; Kabay, Nalan; Yüksel, Mithat

    2013-12-15

    The removal of an endocrine disrupting compound, bisphenol A (BPA), from model solutions by selected nanofiltration (NF) and reverse osmosis (RO) membranes was studied. The commercially available membranes NF 90, NF 270, XLE BWRO, BW 30 (Dow FilmTech), CE BWRO and AD SWRO (GE Osmonics) were used to compare their performances for BPA removal. The water permeability coefficients, rejection of BPA and permeate flux values were calculated for all membranes used. No significant changes in their BPA removal were observed for all tight polyamide based NF and RO membranes tested except for loose NF 270 membrane. The polyamide based membranes exhibited much better performance than cellulose acetate membrane for BPA removal. Almost a complete rejection (≥ 98%) for BPA was obtained with three polyamide based RO membranes (BW 30, XLE BWRO and AD SWRO). But cellulose acetate based CE BWRO membrane offered a low and variable (10-40%) rejection for BPA.

  7. Local rotundity structure of Cesàro-Orlicz sequence spaces

    NASA Astrophysics Data System (ADS)

    Foralewski, Pawel; Hudzik, Henryk; Szymaszkiewicz, Alicja

    2008-09-01

    Some criteria for extreme points and strong U-points in Cesàro-Orlicz spaces are given. In consequence we find a Cesàro-Orlicz sequence space different from c0 which has no extreme points. Some examples show that in these spaces the notion of the strong U-point is essentially stronger than the notion of the extreme point. Various examples presented in this paper show that there are some differences between criteria for extreme points and strong U-points in Orlicz spaces and in Cesàro-Orlicz spaces. We also show that the uniqueness of the local best approximation needs the notion of SU-point, that is, the notion of the extreme point is not strong enough here.

  8. On the spectrum of the Cesàro operator on spaces of analytic functions

    NASA Astrophysics Data System (ADS)

    Persson, Anna-Maria

    2008-04-01

    This paper concerns the Cesàro operator acting on various spaces of analytic functions on the unit disc. The remarkable fact that this operator is subnormal when acting on the Hardy space H2 has lead to extensive studies of its spectral picture on other spaces of this type. We present some of the methods that have been used to obtain information about the spectrum of the Cesàro operator acting on Hardy and Bergman spaces and give a unified approach to these problems which also yields new results in this direction. In particular, we prove that the Cesàro operator is subdecomposable on H1 and on the standard weighted Bergman spaces , [alpha][greater-or-equal, slanted]0.

  9. The study of Be stars with the CoRoT satellite

    NASA Astrophysics Data System (ADS)

    Diago, P. D.; Gutierrez-Soto, J.; Fabregat, J.; Suso, J.; COROT Be Team

    2011-11-01

    The CoRoT space mission, launched in December 2006, is a spacecraft devoted to the study of the stellar interiors and the exo-planet search. Concerning the seismology of the Be stars, the presence of pulsations in late-type Be stars is still a matter of controversy. It constitutes an important issue to establish the relationship between non-radial pulsations and the mass-loss mechanism in Be stars. In this field, the CoRoT satellite is providing data with an unprecedent quality and precision that is confirming non-radial pulsations in Be stars. The CoRoT Be Team is an international collaboration composed by members from France, Spain, Brazil and Belgium and is in charge of the exploitation and analysis of the Be stars data. In this work we present the highlighted results of the observed Be stars by CoRoT and the future prospects of the CoRoT Be Team. These results include the detection of the Be star HD 49 330 during an outburst phase and the measurement of the change in the oscillation spectrum during this rare event. These observations gave insight into the nature of the explosion. It will help to solve a question that has been pending for years: are oscillations the cause of the outbursts? Moreover, for the first time, the CoRoT satellite has detected simultaneously the rotational and the pulsational frequencies for the Be star HD 50 209, which constitutes a proof of the presence of pulsations in the Be stars. %J Highlights of Spanish Astrophysics VI, Proceedings of the IX Scientific Meeting of the Spanish Astronomical Society (SEA), held in Madrid, September 13 - 17, 2010, Eds.: M. R. Zapatero Osorio, J. Gorgas, J. Maiz Apellaniz, J. R. Pardo, and A. Gil de Paz., p. 531-531

  10. Planetary transit candidates in the CoRoT-SRc01 field

    NASA Astrophysics Data System (ADS)

    Erikson, A.; Santerne, A.; Renner, S.; Barge, P.; Aigrain, S.; Alapini, A.; Almenara, J.-M.; Alonso, R.; Auvergne, M.; Baglin, A.; Benz, W.; Bonomo, A. S.; Bordé, P.; Bouchy, F.; Bruntt, H.; Cabrera, J.; Carone, L.; Carpano, S.; Csizmadia, Sz.; Deleuil, M.; Deeg, H. J.; Díaz, R. F.; Dvorak, R.; Ferraz-Mello, S.; Fridlund, M.; Gandolfi, D.; Gazzano, J.-C.; Gillon, M.; Guenther, E. W.; Guillot, T.; Hatzes, A.; Hébrard, G.; Jorda, L.; Lammer, H.; Léger, A.; Llebaria, A.; Mayor, M.; Mazeh, T.; Moutou, C.; Ollivier, M.; Ofir, A.; Pätzold, M.; Pepe, F.; Pont, F.; Queloz, D.; Rabus, M.; Rauer, H.; Régulo, C.; Rouan, D.; Samuel, B.; Schneider, J.; Shporer, A.; Tingley, B.; Udry, S.; Wuchterl, G.

    2012-03-01

    Context. The space mission CoRoT is devoted to the analysis of stellar variability and the photometric detection of extrasolar planets. Aims: We present the list of planetary transit candidates detected in the first short run observed by CoRoT that targeted SRc01, towards the Galactic center in the direction of Aquila, which lasted from April to May 2007. Methods: Among the acquired data, we analyzed those for 1269 sources in the chromatic bands and 5705 in the monochromatic band. Instrumental noise and the stellar variability were treated with several detrending tools, to which several transit-search algorithms were subsequently applied. Results: Fifty-one sources were classified as planetary transit candidates and 26 were followed up with ground-based observations. Until now, no planet has been detected in the CoRoT data from the SRc01 field. The CoRoT space mission, launched on December 27th 2006, has been developed and is operated by CNES, with contributions from Austria, Belgium, Brazil, ESA, Germany, and Spain. The CoRoT data are available to the community from the CoRoT archive: http://idoc-corot.ias.u-psud.frBased in part on observations made with the 1.93-m telescope at Observatoire de Haute Provence (CNRS), France (SOPHIE Program 08A.PNP.MOUT).Based in part on observations made with the ESO-3.60-m telescope at La Silla Observatory (ESO), Chile (HARPS Program ESO - 081.C-0388) and with the ESO-VLT telescope at Paranal Observatory (ESO), Chile (FLAMES Program ESO - 081.C-0413).

  11. EXO-DAT: AN INFORMATION SYSTEM IN SUPPORT OF THE CoRoT/EXOPLANET SCIENCE

    SciTech Connect

    Deleuil, M.; Meunier, J. C.; Moutou, C.; Surace, C.; Barbieri, M.; Agneray, F.; Granet, Y.; Guterman, P.; Deeg, H. J.; Almenara, J. M.; Hodgkin, S.

    2009-08-15

    Exo-Dat is a database and an information system created primarily in support of the exoplanet program of the COnvection ROtation and planetary Transits (CoRoT) mission. In the directions of CoRoT pointings, it provides a united interface to several sets of data: stellar published catalogs, photometric and spectroscopic data obtained during the mission preparation, results from the mission and from follow-up observations, and several mission-specific technical parameters. The new photometric data constitute the subcatalog Exo-Cat, and give consistent 4-color photometry of 14.0 million stars with a completeness to 19th magnitude in the r-filter. It covers several zones in the galactic plane around CoRoT pointings, with a total area of 209 deg{sup 2}. This Exo-Dat information system provides essential technical support to the ongoing CoRoT light-curve analyses and ground-based follow-up by supplying additional complementary information such as the prior knowledge of the star's fundamental parameters or its contamination level inside the large CoRoT photometric mask. The database is fully interfaced with VO tools and thus benefits from existing visualization and analysis tools like TOPCAT or ALADIN. It is accessible to the CoRoT community through the Web, and will be gradually opened to the public. It is the ideal tool to prepare the foreseen statistical studies of the properties of the exoplanetary systems. As a VO-compliant system, such analyses could thus benefit from the most up-to-date classifier tools.

  12. A meta-analysis of the effects of β-adrenergic blockers in chronic heart failure.

    PubMed

    Zhang, Xiaojian; Shen, Chengwu; Zhai, Shujun; Liu, Yukun; Yue, Wen-Wei; Han, Li

    2016-10-01

    Adrenergic β-blockers are drugs that bind to, but do not activate β-adrenergic receptors. Instead they block the actions of β-adrenergic agonists and are used for the treatment of various diseases such as cardiac arrhythmias, angina pectoris, myocardial infarction, hypertension, headache, migraines, stress, anxiety, prostate cancer, and heart failure. Several meta-analysis studies have shown that β-blockers improve the heart function and reduce the risks of cardiovascular events, rate of mortality, and sudden death through chronic heart failure (CHF) of patients. The present study identified results from recent meta-analyses of β-adrenergic blockers and their usefulness in CHF. Databases including Medline/Embase/Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed were searched for the periods May, 1985 to March, 2011 and June, 2013 to August, 2015, and a number of studies identified. Results of those studies showed that use of β-blockers was associated with decreased sudden cardiac death in patients with heart failure. However, contradictory results have also been reported. The present meta-analysis aimed to determine the efficacy of β-blockers on mortality and morbidity in patients with heart failure. The results showed that mortality was significantly reduced by β-blocker treatment prior to the surgery of heart failure patients. The results from the meta-analysis studies showed that β-blocker treatment in heart failure patients correlated with a significant decrease in long-term mortality, even in patients that meet one or more exclusion criteria of the MERIT-HF study. In summary, the findings of the current meta-analysis revealed beneficial effects different β-blockers have on patients with heart failure or related heart disease.

  13. Effects of Beta-Blocker Withdrawal in Acute Decompensated Heart Failure

    PubMed Central

    Prins, Kurt W.; Neill, John M.; Tyler, John O.; Eckman, Peter M.; Duval, Sue

    2015-01-01

    OBJECTIVES This study sought to evaluate the effects of beta-blocker withdrawal in acute decompensated heart failure (ADHF). BACKGROUND Published reports showed trends for either no harm or increased risk of in-hospital mortality, short-term mortality, and rehospitalization rates in patients admitted for ADHF that discontinued beta-blockers; however, a comprehensive analysis has not been conducted. METHODS Relevant studies from January 2000 through January 2015 were identified in the PubMed, EMBASE, and COCHRANE electronic databases. Where appropriate data were available, weighted relative risks were estimated using random-effects meta-analysis techniques. RESULTS Five observational studies and 1 randomized clinical trial (n = 2,704 patients who continued beta-blocker therapy and n = 439 patients who discontinued beta-blocker therapy) that reported the short-term effects of beta-blocker withdrawal in ADHF were included in the analyses. In 2 studies, beta-blocker withdrawal significantly increased risk of in-hospital mortality (risk ratio: 3.72; 95% confidence interval [CI]: 1.51 to 9.14). Short-term mortality (relative risk: 1.61; 95% CI: 1.04 to 2.49; 4 studies) and combined short-term rehospitalization or death (relative risk: 1.59; 95% CI: 1.03 to 2.45; 4 studies) were also significantly increased. CONCLUSIONS Discontinuation of beta-blockers in patients admitted with ADHF was associated with significantly increased in-hospital mortality, short-term mortality, and the combined endpoint of short-term rehospitalization or mortality. These data suggest beta-blockers should be continued in ADHF patients if their clinical picture allows. PMID:26251094

  14. Dihydropyridine type calcium channel blocker-induced turbid dialysate in patients undergoing peritoneal dialysis.

    PubMed

    Yoshimoto, K; Saima, S; Nakamura, Y; Nakayama, M; Kubo, H; Kawaguchi, Y; Nishitani, H; Nakamura, Y; Yasui, A; Yokoyama, K; Kuriyama, S; Shirai, D; Kugiyama, A; Hayano, K; Fukui, H; Horigome, I; Amagasaki, Y; Tsubakihara, Y; Kamekawa, T; Ando, R; Tomura, S; Okamoto, R; Miwa, S; Koyama, T; Echizen, H

    1998-08-01

    We previously reported that manidipine, a new dihydropyridine type calcium channel blocker, produced chylous peritoneal dialysate being visually indistinguishable from infective peritonitis in 5 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) [Yoshimoto et al. 1993]. To study whether such an adverse drug reaction would also be elicited by other commonly prescribed calcium channel blockers in CAPD patients, we have conducted postal inquiry to 15 collaborating hospitals and an institutional survey in International Medical Center of Japan as to the possible occurrence of calcium channel blocker-associated non-infective, turbid peritoneal dialysate in CAPD patients. Our diagnostic criteria for drug-induced turbidity of dialysate as a) it developed within 48 h after the administration of a newly introduced calcium channel blocker to the therapeutic regimen, b) absence of clinical symptoms of peritoneal inflammation (i.e., pyrexia, abdominal pain, nausea or vomiting), c) the fluid containing normal leukocyte counts and being negative for bacterial and fungal culture of the fluid, and d) it disappeared shortly after the withdrawal of the assumed causative agent. Results showed that 19 out of 251 CAPD patients given one of the calcium channel blockers developed non-infective turbid peritoneal dialysis that fulfilled all the above criteria. Four calcium channel blockers were suspected to be associated with the events: benidipine [2 out of 2 (100%) patients given the drug], manidipine [15 out of 36 (42%) patients], nisoldipine [1 out of 11 (9%) patients] and nifedipine [1 out of 159 (0.6%)] in descending order of frequency. None of the patients who received nicardipine, nilvadipine, nitrendipine, barnidipine and diltiazem (25, 7, 2, 1 and 8 patients, respectively) exhibited turbid dialysate. In conclusion, we consider that certain dihydropyridine type calcium channel blockers would cause turbid peritoneal dialysate being similar to that observed in

  15. Transiting exoplanets from the CoRoT space mission. XX. CoRoT-20b: A very high density, high eccentricity transiting giant planet

    NASA Astrophysics Data System (ADS)

    Deleuil, M.; Bonomo, A. S.; Ferraz-Mello, S.; Erikson, A.; Bouchy, F.; Havel, M.; Aigrain, S.; Almenara, J.-M.; Alonso, R.; Auvergne, M.; Baglin, A.; Barge, P.; Bordé, P.; Bruntt, H.; Cabrera, J.; Carpano, S.; Cavarroc, C.; Csizmadia, Sz.; Damiani, C.; Deeg, H. J.; Dvorak, R.; Fridlund, M.; Hébrard, G.; Gandolfi, D.; Gillon, M.; Guenther, E.; Guillot, T.; Hatzes, A.; Jorda, L.; Léger, A.; Lammer, H.; Mazeh, T.; Moutou, C.; Ollivier, M.; Ofir, A.; Parviainen, H.; Queloz, D.; Rauer, H.; Rodríguez, A.; Rouan, D.; Santerne, A.; Schneider, J.; Tal-Or, L.; Tingley, B.; Weingrill, J.; Wuchterl, G.

    2012-02-01

    We report the discovery by the CoRoT space mission of a new giant planet, CoRoT-20b. The planet has a mass of 4.24 ± 0.23 MJup and a radius of 0.84 ± 0.04 RJup. With a mean density of 8.87 ± 1.10 g cm-3, it is among the most compact planets known so far. Evolutionary models for the planet suggest a mass of heavy elements of the order of 800 M⊕ if embedded in a central core, requiring a revision either of the planet formation models or both planet evolution and structure models. We note however that smaller amounts of heavy elements are expected by more realistic models in which they are mixed throughout the envelope. The planet orbits a G-type star with an orbital period of 9.24 days and an eccentricity of 0.56.The star's projected rotational velocity is vsini = 4.5 ± 1.0 km s-1, corresponding to a spin period of 11.5 ± 3.1 days if its axis of rotation is perpendicular to the orbital plane. In the framework of Darwinian theories and neglecting stellar magnetic breaking, we calculate the tidal evolution of the system and show that CoRoT-20b is presently one of the very few Darwin-stable planets that is evolving toward a triple synchronous state with equality of the orbital, planetary and stellar spin periods. The CoRoT space mission, launched on December 27th 2006, has been developed and is operated by CNES, with the contribution of Austria, Belgium, Brazil, ESA (RSSD and Science Programme), Germany, and Spain.

  16. Transiting exoplanets from the CoRoT space mission. V. CoRoT-Exo-4b: stellar and planetary parameters

    NASA Astrophysics Data System (ADS)

    Moutou, C.; Bruntt, H.; Guillot, T.; Shporer, A.; Guenther, E.; Aigrain, S.; Almenara, J. M.; Alonso, R.; Auvergne, M.; Baglin, A.; Barbieri, M.; Barge, P.; Benz, W.; Bordé, P.; Bouchy, F.; Deeg, H. J.; de La Reza, R.; Deleuil, M.; Dvorak, R.; Erikson, A.; Fridlund, M.; Gillon, M.; Gondoin, P.; Hatzes, A.; Hébrard, G.; Jorda, L.; Kabath, P.; Lammer, H.; Léger, A.; Llebaria, A.; Loeillet, B.; Magain, P.; Mayor, M.; Mazeh, T.; Ollivier, M.; Pätzold, M.; Pepe, F.; Pont, F.; Queloz, D.; Rabus, M.; Rauer, H.; Rouan, D.; Schneider, J.; Udry, S.; Wuchterl, G.

    2008-09-01

    Aims: The CoRoT satellite has announced its fourth transiting planet (Aigrain et al. 2008, A&A, 488, L43) with space photometry. We describe and analyse complementary observations of this system performed to establish the planetary nature of the transiting body and to estimate the fundamental parameters of the planet and its parent star. Methods: We have analysed high precision radial-velocity data, ground-based photometry, and high signal-to-noise ratio spectroscopy. Results: The parent star CoRoT-Exo-4 (2MASS 06484671-0040219) is a late F-type star of mass of 1.16 M⊙ and radius of 1.17 R⊙. The planet has a circular orbit with a period of 9.20205 d. The planet radius is 1.19 R_Jup and the mass is 0.72 M_Jup. It is a gas-giant planet with a “normal” internal structure of mainly H and He. CoRoT-Exo-4b has the second longest period of the known transiting planets. It is an important discovery since it occupies an empty area in the mass-period diagram of transiting exoplanets. Based on observations obtained with CoRoT, a space project operated by the French Space Agency, CNES, with participation of the Science Programme of ESA, ESTEC/RSSD, Austria, Belgium, Brazil, Germany and Spain; and on observations made with the SOPHIE spectrograph at Observatoire de Haute Provence, France (PNP.07B.MOUT), and the HARPS spectrograph at ESO La Silla Observatory (079.C-0127/F). Table 2 and Fig. 5 are only available in electronic form at http://www.aanda.org

  17. Ziconotide: neuronal calcium channel blocker for treating severe chronic pain.

    PubMed

    Miljanich, G P

    2004-12-01

    Ziconotide (PRIALT) is a neuroactive peptide in the final stages of clinical development as a novel non-opioid treatment for severe chronic pain. It is the synthetic equivalent of omega-MVIIA, a component of the venom of the marine snail, Conus magus. The mechanism of action underlying ziconotide's therapeutic profile derives from its potent and selective blockade of neuronal N-type voltage-sensitive calcium channels (N-VSCCs). Direct blockade of N-VSCCs inhibits the activity of a subset of neurons, including pain-sensing primary nociceptors. This mechanism of action distinguishes ziconotide from all other analgesics, including opioid analgesics. In fact, ziconotide is potently anti-nociceptive in animal models of pain in which morphine exhibits poor anti-nociceptive activity. Moreover, in contrast to opiates, tolerance to ziconotide is not observed. Clinical studies of ziconotide in more than 2,000 patients reveal important correlations to ziconotide's non-clinical pharmacology. For example, ziconotide provides significant pain relief to severe chronic pain sufferers who have failed to obtain relief from opiate therapy and no evidence of tolerance to ziconotide is seen in these patients. Contingent on regulatory approval, ziconotide will be the first in a new class of neurological drugs: the N-type calcium channel blockers, or NCCBs. Its novel mechanism of action as a non-opioid analgesic suggests ziconotide has the potential to play a valuable role in treatment regimens for severe chronic pain. If approved for clinical use, ziconotide will further validate the neuroactive venom peptides as a source of new and useful medicines.

  18. Attenuation of thermal nociception and hyperalgesia by VR1 blockers

    PubMed Central

    García-Martínez, Carolina; Humet, Marc; Planells-Cases, Rosa; Gomis, Ana; Caprini, Marco; Viana, Felix; De la Peña, Elvira; Sanchez-Baeza, Francisco; Carbonell, Teresa; De Felipe, Carmen; Pérez-Payá, Enrique; Belmonte, Carlos; Messeguer, Angel; Ferrer-Montiel, Antonio

    2002-01-01

    Vanilloid receptor subunit 1 (VR1) appears to play a critical role in the transduction of noxious chemical and thermal stimuli by sensory nerve endings in peripheral tissues. Thus, VR1 antagonists are useful compounds to unravel the contribution of this receptor to pain perception, as well as to induce analgesia. We have used a combinatorial approach to identify new, nonpeptidic channel blockers of VR1. Screening of a library of trimers of N-alkylglycines resulted in the identification of two molecules referred to as DD161515 {N-[2-(2-(N-methylpyrrolidinyl)ethyl]glycyl]-[N-[2,4-dichlorophenethyl]glycyl]-N-(2,4-dichlorophenethyl)glycinamide} and DD191515 {[N-[3-(N,N-diethylamino)propyl]glycyl]-[N-[2,4-dichlorophenethyl]glycyl]-N-(2,4-dichlorophenethyl)glycinamide} that selectively block VR1 channel activity with micromolar efficacy, rivaling that characteristic of vanilloid-related inhibitors. These compounds appear to be noncompetitive VR1 antagonists that recognize a receptor site distinct from that of capsaicin. Intraperitoneal administration of both trialkylglycines into mice significantly attenuated thermal nociception as measured in the hot plate test. It is noteworthy that these compounds eliminated pain and neurogenic inflammation evoked by intradermal injection of capsaicin into the animal hindpaw, as well as the thermal hyperalgesia induced by tissue irritation with nitrogen mustard. In contrast, responses to mechanical stimuli were not modified by either compound. Modulation of sensory nerve fibers excitability appears to underlie the peptoid analgesic activity. Collectively, these results indicate that blockade of VR1 activity attenuates chemical and thermal nociception and hyperalgesia, supporting the tenet that this ionotropic receptor contributes to chemical and thermal sensitivity and pain perception in vivo. These trialkylglycine-based, noncompetitive VR1 antagonists may likely be developed into analgesics to treat inflammatory pain. PMID:11854530

  19. CoRoT archive as a treasury of variable stars

    NASA Astrophysics Data System (ADS)

    Benko, Jozsef M.; Paparo, Margit

    2015-08-01

    The CoRoT satellite supported the scientific community by a huge data base of variable stars. The investigation of RR Lyrae stars (radially pulsating classical variable stars of high amplitude), especially benefit the continuous space data, due to long periodicity. The CoRoT RR Lyrae stars were intensively discussed in numerous papers in the last few years, but the latest runs have not been checked for finding RR Lyrae stars up to now. We found eight new RR Lyrae stars that we investigated for the lately localized characteristics of Blazhko RR Lyrae stars: the period doubling and additional modes. We present the preliminary results here.

  20. Fetal manifestations of maternal anti‐Ro and La antibodies – more than complete heart block

    PubMed Central

    2015-01-01

    Abstract Complete heart block (CHB) is a potentially fatal condition occurring in approximately 1:10000 fetuses. Whilst it is well recognised that maternal anti‐Ro and La antibodies are associated with fetal CHB, there are multiple other manifestations of fetal exposure to these autoantibodies which are not widely appreciated and rarely diagnosed. The importance of identifying affected fetuses lies in the significantly increased risk of recurrence in future pregnancies, and the potential for treatments which may modify this risk. This paper presents several cases to highlight the varying fetal presentations of maternal anti‐Ro and La antibodies. PMID:28191254

  1. Multiple star systems observed with CoRoT and Kepler

    NASA Astrophysics Data System (ADS)

    Southworth, John

    2015-09-01

    The CoRoT and Kepler satellites were the first space platforms designed to perform high-precision photometry for a large number of stars. Multiple systems display a wide variety of photometric variability, making them natural benefactors of these missions. I review the work arising from CoRoT and Kepler observations of multiple systems, with particular emphasis on eclipsing binaries containing giant stars, pulsators, triple eclipses and/or low-mass stars. Many more results remain untapped in the data archives of these missions, and the future holds the promise of K2, TESS and PLATO.

  2. Renin-angiotensin system blockers regulate the metabolism of isolated fat cells in vitro

    PubMed Central

    Caminhotto, R de O.; Sertié, R.A.L.; Andreotti, S.; Campaãa, A.B.; Lima, F.B.

    2016-01-01

    Due to the presence of the renin-angiotensin system (RAS) in tissues and its specific influence on white adipose tissue, fat cells are possible targets of pharmacological RAS blockers commonly used as anti-hypertensive drugs. In the present study, we investigated the effects of different RAS blockers on fat cell metabolism, more specifically on lipolysis, lipogenesis and oxidation of energy substrates. Isolated primary adipocytes were incubated with different RAS blockers (aliskiren, captopril and losartan) in vitro for 24 h and lipolysis, lipogenesis and glucose oxidation capacities were determined in dose-response assays to a β-adrenergic agonist and to insulin. Although no change was found in lipolytic capacity, the RAS blockers modulated lipogenesis and glucose oxidation in a different way. While captopril decreased insulin-stimulated lipogenesis (−19% of maximal response and −60% of insulin responsiveness) due to reduced glucose derived glycerol synthesis (−19% of maximal response and 64% of insulin responsiveness), aliskiren increased insulin-stimulated glucose oxidation (+49% of maximal response and +292% of insulin responsiveness) in fat cells. Our experiments demonstrate that RAS blockers can differentially induce metabolic alterations in adipocyte metabolism, characterized by a reduction in lipogenic responsiveness or an increase in glucose oxidation. The impact of RAS blockers on adipocyte metabolism may have beneficial implications on metabolic disorders during their therapeutic use in hypertensive patients. PMID:27487419

  3. Hypotension induced by the concomitant use of a calcium-channel blocker and clarithromycin

    PubMed Central

    Takeuchi, Sayako; Tsujimoto, Toshihide

    2017-01-01

    In the elderly, calcium-channel blockers are the first-line treatment for hypertension, and macrolides are commonly prescribed antibiotics. Here we report a 78-year-old man taking nifedipine, diltiazem and carvedilol who presented with persistent hypotension and bradycardia after clarithromycin was prescribed. He was diagnosed with drug-induced hypotension and treated with fluid resuscitation and vasoactive agents. His symptoms gradually improved. He was transferred out of the intensive care unit 3 days after hospitalisation. Combining calcium-channel blockers and clarithromycin can cause vasodilatory hypotension. The concomitant use of calcium-channel blockers and macrolide antibiotics increases the levels of calcium-channel blockers in the blood as they are metabolised by cytochrome P450 3A4 (CYP3A4), which is inhibited by macrolide antibiotics. Moreover, the addition of another calcium-channel blocker and a β blocker can lower cardiac output due to bradycardia and worsen hypotension. Therefore, it is important to consider drug interactions when the cause of hypotension is unknown. PMID:28069789

  4. Nebivolol versus other beta blockers in patients with hypertension and erectile dysfunction

    PubMed Central

    Sharp, Randall P.; Gales, Barry J.

    2017-01-01

    Erectile dysfunction (ED) impacts over 100 million men worldwide and occurs at a higher incidence in men with hypertension. Beta blockers are one of several antihypertensive drug classes associated with ED. Nebivolol is a beta blocker with vasodilating properties mediated through endothelial release of nitric oxide which facilitates penile erection. Thus, nebivolol may offer an advantage over other beta blockers in the patient with hypertension and ED. A literature search comparing nebivolol with other beta blockers identified four European studies of limited duration, with the longest study being 28 weeks. Survey scores for erectile function showed significant improvement in erectile function with nebivolol in two of the studies, while the other two studies showed erectile function did not significantly worsen with nebivolol as compared with other beta blocker agents. One study showed improved erectile function scores, possibly due to the presence of a Hawthorne effect. Based on this small sample of studies, nebivolol may be of use in the patient with or at risk of developing ED, when a practitioner specifically wants to use a beta blocker as add-on antihypertensive treatment. PMID:28203288

  5. Transiting exoplanets from the CoRoT space mission. III. The spectroscopic transit of CoRoT-Exo-2b with SOPHIE and HARPS

    NASA Astrophysics Data System (ADS)

    Bouchy, F.; Queloz, D.; Deleuil, M.; Loeillet, B.; Hatzes, A. P.; Aigrain, S.; Alonso, R.; Auvergne, M.; Baglin, A.; Barge, P.; Benz, W.; Bordé, P.; Deeg, H. J.; de La Reza, R.; Dvorak, R.; Erikson, A.; Fridlund, M.; Gondoin, P.; Guillot, T.; Hébrard, G.; Jorda, L.; Lammer, H.; Léger, A.; Llebaria, A.; Magain, P.; Mayor, M.; Moutou, C.; Ollivier, M.; Pätzold, M.; Pepe, F.; Pont, F.; Rauer, H.; Rouan, D.; Schneider, J.; Triaud, A. H. M. J.; Udry, S.; Wuchterl, G.

    2008-05-01

    We report on the spectroscopic transit of the massive hot-Jupiter CoRoT-Exo-2b observed with the high-precision spectrographs SOPHIE and HARPS. By modeling the radial velocity anomaly occurring during the transit due to the Rossiter-McLaughlin (RM) effect, we determine the sky-projected angle between the stellar spin and the planetary orbital axis to be close to zero λ = 7.2 ± 4.5 deg, and we secure the planetary nature of CoRoT-Exo-2b. We discuss the influence of the stellar activity on the RM modeling. Spectral analysis of the parent star from HARPS spectra are presented. Observations made with SOPHIE spectrograph at Observatoire de Haute Provence, France (PNP.07A.MOUT) and HARPS spectrograph at ESO La Silla Observatory (079.C-0127(F)). The CoRoT space mission, launched on December 27th 2006, has been developed and is operated by CNES, with the contribution of Austria, Belgium, Brasil, ESA, Germany, and Spain.

  6. Transiting exoplanets from the CoRoT space mission. II. CoRoT-Exo-2b: a transiting planet around an active G star

    NASA Astrophysics Data System (ADS)

    Alonso, R.; Auvergne, M.; Baglin, A.; Ollivier, M.; Moutou, C.; Rouan, D.; Deeg, H. J.; Aigrain, S.; Almenara, J. M.; Barbieri, M.; Barge, P.; Benz, W.; Bordé, P.; Bouchy, F.; de La Reza, R.; Deleuil, M.; Dvorak, R.; Erikson, A.; Fridlund, M.; Gillon, M.; Gondoin, P.; Guillot, T.; Hatzes, A.; Hébrard, G.; Kabath, P.; Jorda, L.; Lammer, H.; Léger, A.; Llebaria, A.; Loeillet, B.; Magain, P.; Mayor, M.; Mazeh, T.; Pätzold, M.; Pepe, F.; Pont, F.; Queloz, D.; Rauer, H.; Shporer, A.; Schneider, J.; Stecklum, B.; Udry, S.; Wuchterl, G.

    2008-05-01

    Context: The CoRoT mission, a pioneer in exoplanet searches from space, has completed its first 150 days of continuous observations of ~12 000 stars in the galactic plane. An analysis of the raw data identifies the most promising candidates and triggers the ground-based follow-up. Aims: We report on the discovery of the transiting planet CoRoT-Exo-2b, with a period of 1.743 days, and characterize its main parameters. Methods: We filter the CoRoT raw light curve of cosmic impacts, orbital residuals, and low frequency signals from the star. The folded light curve of 78 transits is fitted to a model to obtain the main parameters. Radial velocity data obtained with the SOPHIE, CORALIE and HARPS spectrographs are combined to characterize the system. The 2.5 min binned phase-folded light curve is affected by the effect of sucessive occultations of stellar active regions by the planet, and the dispersion in the out of transit part reaches a level of 1.09×10-4 in flux units. Results: We derive a radius for the planet of 1.465 ± 0.029 R_Jup and a mass of 3.31 ± 0.16 M_Jup, corresponding to a density of 1.31 ± 0.04 g/cm^3. The large radius of CoRoT-Exo-2b cannot be explained by current models of evolution of irradiated planets. Based on observations obtained with CoRoT, a space project operated by the French Space Agency, CNES, with participation of the Science Programme of ESA, ESTEC/RSSD, Austria, Belgium, Brazil, Germany and Spain; and on observations made with SOPHIE spectrograph at Observatoire de Haute Provence, France (PNP.07 A.MOUT), CORALIE, and HARPS spectrograph at ESO La Silla Observatroy (079.C-0127/F)). Table 2 is only available in electronic form at http://www.aanda.org

  7. Statin, Calcium Channel Blocker and Beta Blocker Therapy May Decrease the Incidence of Tuberculosis Infection in Elderly Taiwanese Patients with Type 2 Diabetes

    PubMed Central

    Lee, Mei-Yueh; Lin, Kun-Der; Hsu, Wei-Hao; Chang, Hsiu-Ling; Yang, Yi-Hsin; Hsiao, Pi-Jung; Shin, Shyi-Jang

    2015-01-01

    Background: It is well known that diabetes mellitus impairs immunity and therefore is an independent risk factor for tuberculosis. However, the influence of associated metabolic factors, such as hypertension, dyslipidemia and gout has yet to be confirmed. This study aimed to investigate whether the strong association between tuberculosis and diabetes mellitus is independent from the influence of hypertension and dyslipidemia, and its treatment in elderly Taiwanese patients. Methods: A total of 27,958 patients aged more than 65 years were identified from the National Health Insurance Research Database (NIHRD) in 1997 and were followed from 1998 to 2009. The demographic characteristics between the patients with and without diabetes were analyzed using the χ2 test. A total of 13,981 patients with type 2 diabetes were included in this study. Cox proportional hazard regression models were used to determine the independent effects of diabetes on the risk of tuberculosis. Results: After adjusting for age, sex, other co-morbidities and medications, calcium channel blocker, beta blocker and statin users had a lower independent association, with risk ratios of 0.76 (95% CI, 0.58–0.98), 0.72 (95% CI, 0.58–0.91) and 0.76 (95% CI, 0.60–0.97), respectively. Conclusion: Calcium channel blocker, beta blocker and statin therapy may decrease the incidence of tuberculosis infection in elderly Taiwanese patients with type 2 diabetes. PMID:25993300

  8. Ro-vibrational Stark effect on H2 and D2 molecules adsorbed in NaA zeolite

    NASA Astrophysics Data System (ADS)

    Bras, N.

    1999-03-01

    In order to explain the induced infrared bands of H2 and D2 adsorbed in NaA zeolites the Stark effect on the ro-vibrational levels of these molecules is considered for electric fields created by various charge distributions. The shift and intensity of the induced ro-vibration transitions are calculated.

  9. Establishment of rock bream Oplegnathus fasciatus embryo (RoBE-4) cells with cytolytic infection of red seabream iridovirus (RSIV).

    PubMed

    Oh, So-Young; Nishizawa, Toyohiko

    2016-12-01

    Red seabream iridovirus (RSIV) is a member of genus Megalocytivirus in the family Iridoviridae. RSIV infection causes significant economic losses of marine-fishes in East Asian countries. Grunt fin (GF) cell line has been commonly used for culturing RSIV. However, it is not suitable for definite evaluation of infectivity titer of RSIV because cells infected with RSIV are not completely cytolysed. Thus, we established a new cell line, RoBE-4, from rock bream (Oplegnathus fasciatus) eyed-egg embryos in this study. Morphologically, RoBE-4 cells were fibroblastic-like. They have been stably grown over two-years with 60 passages using Leibovitz's L-15 medium containing 10% (v/v) fetal bovine serum. RoBE-4 cells infected with RSIV exhibited cytopathic effects (CPE) with cell rounding. They were cytolysed completely after ≥2 weeks of culture. Numerous RSIV particles with icosahedral morphology of approximately 122nm in diameter were observed in cytoplasmic area of infected RoBE-4 cells. The RSIV-suceptibility and amount of extracellular RSIV released by RoBE-4 cells were 100-fold higher than those by GF cells. RSIV cultured with RoBE-4 cells was highly virulent to rock bream in infection experiments. Therefore, using RoBE-4 cells instead of GF cells will enable accurate and sensitive measurement of RSIV infectivity. In addition, RoBE-4 cells might be used to produce RSIV vaccine in the future with significant reduction in cost.

  10. Molecular cloning, expression, and chromosome 19 localization of a human Ro/SS-A autoantigen.

    PubMed Central

    McCauliffe, D P; Lux, F A; Lieu, T S; Sanz, I; Hanke, J; Newkirk, M M; Bachinski, L L; Itoh, Y; Siciliano, M J; Reichlin, M

    1990-01-01

    Ro/SS-A antibodies are found in a number of human autoimmune disorders including Sjogren's syndrome and several systemic lupus erythematosus-related disorders. These heterogeneous autoantibodies are known to recognize several distinct cellular antigens. With synthetic oligonucleotides corresponding to amino acid sequence information we have isolated a full-length cDNA clone which encodes a human Ro ribonucleoprotein autoantigen. The 1,890-base pair clone contains an open reading frame that encodes a 417-amino acid, 48-kD polypeptide that migrates aberrantly at 60 kD by SDS-PAGE. Rabbit antibodies raised against this protein's recently described amino-terminal epitope react with a previously identified 52-kD human Ro protein and immunoprecipitate the human cytoplasmic RNAs. Ultraviolet light cross-linking studies suggest that this Ro protein binds each of the four major human cytoplasmic RNAs. The deduced amino acid sequence is 63% homologous to an Onchocerca volvulus antigen. Southern filter hybridization analysis indicates that this gene is not highly polymorphic and exists as a single copy in the human genome. Chromosomal localization studies place this gene on the short arm of chromosome 19 near the gene encoding the low density lipoprotein receptor. Images PMID:2332496

  11. RO filtration of biologically treated textile and dyeing effluents using ozonation as a pre-treatment.

    PubMed

    Wang, H Y; Guan, Y T; Mizuno, T; Tsuno, H

    2010-01-01

    Bench-scale experiments were conducted to investigate the application of ozonation pre-treatment for biologically treated textile and dyeing wastewater to improve performance of the RO process. Based on ozonation experiments, four specific ozone consumptions (SOC), 0, 0.3, 0.6, 4.0 mg O₃/mg DOC₀ were chosen for study of the effects of ozonation on the reverse osmosis (RO) process. Membrane flux was recorded. Also, the permeate water quality parameters such as TOC, conductivity were analyzed. In addition, fouled membrane cleaning was studied. The study further examined the nature and mechanisms of membrane fouling using scanning electron microscopy (SEM) and the energy dispersive X-ray spectrometer (EDS). The effect of ozonation on RO filtration was found to depend on SOC. The study revealed that significant improvement can be achieved in the efficiency of RO filtration by employing ozonation with 0.6 mg O₃/mg DOC₀ SOC. Although the product water purity slightly decreased, the ozonation pre-treatment showed advantages at 0.6 mg O₃/mg DOC₀ SOC for the following: (i) mitigation of flux decline due to membrane fouling; (ii) improvement in foulants cleanability. In addition, hypotheses were put forward to explain the reasons from the aspect of organic matter characteristics changed by ozonation, such as changing on functional groups and molecular weight of organic matter.

  12. Uncovering the planets and stellar activity of CoRoT-7 using only radial velocities

    NASA Astrophysics Data System (ADS)

    Faria, J. P.; Haywood, R. D.; Brewer, B. J.; Figueira, P.; Oshagh, M.; Santerne, A.; Santos, N. C.

    2016-04-01

    Stellar activity can induce signals in the radial velocities of stars, complicating the detection of orbiting low-mass planets. We present a method to determine the number of planetary signals present in radial-velocity datasets of active stars, using only radial-velocity observations. Instead of considering separate fits with different number of planets, we use a birth-death Markov chain Monte Carlo algorithm to infer the posterior distribution for the number of planets in a single run. In a natural way, the marginal distributions for the orbital parameters of all planets are also inferred. This method is applied to HARPS data of CoRoT-7. We confidently recover the orbits of both CoRoT-7b and CoRoT-7c although the data show evidence for the presence of additional signals. All data and software presented in this article are available online at http://https://github.com/j-faria/exoBD-CoRoT7

  13. Draft Genome Sequence of the Xylella fastidiosa CoDiRO Strain

    PubMed Central

    Chiumenti, Michela; Saponari, Maria; Donvito, Giacinto; Italiano, Alessandro; Loconsole, Giuliana; Boscia, Donato; Cariddi, Corrado; Martelli, Giovanni Paolo; Saldarelli, Pasquale

    2015-01-01

    We determined the draft genome sequence of the Xylella fastidiosa CoDiRO strain, which has been isolated from olive plants in southern Italy (Apulia). It is associated with olive quick decline syndrome (OQDS) and characterized by extensive scorching and desiccation of leaves and twigs. PMID:25676759

  14. RoMPS concept review automatic control of space robot, volume 2

    NASA Technical Reports Server (NTRS)

    Dobbs, M. E.

    1991-01-01

    Topics related to robot operated materials processing in space (RoMPS) are presented in view graph form and include: (1) system concept; (2) Hitchhiker Interface Requirements; (3) robot axis control concepts; (4) Autonomous Experiment Management System; (5) Zymate Robot Controller; (6) Southwest SC-4 Computer; (7) oven control housekeeping data; and (8) power distribution.

  15. Possible role of anti-SSA/Ro antibodies in the pathogenesis of pulmonary hypertension

    PubMed Central

    Guerreso, Kelsey; Conner, Edward Alexander

    2016-01-01

    Introduction There are many different causes of pulmonary hypertension and the pathogenesis of the disease is still being elucidated. Although they are not the most common, autoimmunity and inflammation have been identified as possible causes. No one autoantibody has been identified as the definite cause of pulmonary hypertension. We present a rare association of anti-SSA/Ro antibodies and isolated pulmonary hypertension. Case presentation A 53 year old African American female presented with abdominal pain, nausea, weight loss, dyspnea and fatigue. Upon further exam she was found to have high titers of antinuclear antibodies and anti-SSA/Ro antibodies. This antibody profile would typically be suggestive of Sjögren's Syndrome, which is characterized by dry eyes and poor salivary gland function. However, since this patient did not have any symptoms consistent with the disease a diagnosis of Sjögren's Syndrome could not be made. A combination of laboratory, imaging and diagnostic studies were done that revealed a final diagnosis of pulmonary hypertension. Conclusion It is known that pulmonary hypertension has association with autoimmune diseases, however no clear markers yet exist. Anti-SSA/Ro antibodies have been rarely described in cases of pulmonary disease, and less so in pulmonary hypertension. This case describes a unique association between isolated pulmonary hypertension and anti-SSA/Ro antibody, thereby illustrating the need to investigate this autoantibody and others in the pathogenesis of autoimmune pulmonary hypertension. PMID:27222785

  16. CoRoT-2a Magnetic Activity: Hints for Possible Star-Planet Interaction

    NASA Astrophysics Data System (ADS)

    Pagano, Isabella; Lanza, Antonino F.; Leto, Giuseppe; Messina, Sergio; Barge, Pierre; Baglin, Annie

    2009-09-01

    CoRoT-2a is a young (≈0.5 Gyr) G7V star accompanied by a transiting hot-Jupiter, discovered by the CoRoT satellite (Alonso et al. Astron Astrophys 482:L21, 2008; Bouchy et al. Astron Astrophys 482:L25, 2008). An analysis of its photospheric activity, based on spot modelling techniques previously developed by our group for the analysis of the Sun as a star, shows that the active regions on CoRoT-2a arised within two active longitudes separated by about 180° and rotating with periods of 4.5221 and 4.5543 days, respectively, at epoch of CoRoT observations (112 continous days centered at ≈2007.6). We show that the total spotted area oscillates with a period of about 28.9 days, a value close to 10 times the synodic period of the planet with respect to the active longitude pattern rotating in 4.5221 days. Moreover, the variance of the stellar flux is modulated in phase with the planet orbital period. This suggests a possible star-planet magnetic interaction, a phenomenon already seen in other extrasolar planetary systems hosting hot-Jupiters.

  17. Jean Vigo's "Zéro De Conduite" and the Spaces of Revolt

    ERIC Educational Resources Information Center

    Vanobbergen, Bruno; Grosvenor, Ian; Simon, Frank

    2014-01-01

    In this article we will contribute to the contemporary theoretical debate about film by considering, from a history-of-education perspective, the film "Zéro de conduite" by Jean Vigo (1905--1934). This film is classified under the umbrella of "poetic realism": a product of "cinéma de gauche" and an avant-gardist,…

  18. Variation in Herrnstein's ro as a function of alternative reinforcement rate

    PubMed Central

    Dougan, James D.; McSweeney, Frances K.

    1985-01-01

    In a test of Herrnstein's (1970, 1974) equation for simple schedules, 15 pigeons pecked a key that produced food delivered according to variable-interval schedules. One group of birds was water deprived, and food-reinforced key pecking occurred in the presence of free water. Two other groups were not water deprived; water was present for one and absent for the other. As predicted by Herrnstein, the parameter ro was significantly higher in the water-deprived group than in the two nondeprived groups. Contrary to Herrnstein's interpretation of ro, the rate of drinking varied across schedules. Herrnstein's interpretation can be salvaged by considering ro to be an average. However, if ro is an average, the equation is not a good explanation of behavior because this average is not valid until all schedules have been sampled. In addition, low percentages of variance accounted for suggest that Herrnstein's equation may be of limited usefulness even as a descriptive model for these situations. PMID:16812413

  19. Spectral characterization and differential rotation study of active CoRoT stars

    NASA Astrophysics Data System (ADS)

    Nagel, E.; Czesla, S.; Schmitt, J. H. M. M.

    2016-05-01

    The CoRoT space telescope observed nearly 160 000 light curves. Among the most outstanding is that of the young, active planet host star CoRoT-2A. In addition to deep planetary transits, the light curve of CoRoT-2A shows strong rotational variability and a superimposed beating pattern. To study the stars that produce such an intriguing pattern of photometric variability, we identified a sample of eight stars with rotation periods between 0.8 and 11 days and photometric variability amplitudes of up to 7.5%, showing a similar CoRoT light curve. We also obtained high-resolution follow-up spectroscopy with TNG/SARG and carried out a spectral analysis with SME and MOOG. We find that the color dependence of the light curves is consistent with rotational modulation due to starspots and that latitudinal differential rotation provides a viable explanation for the light curves, although starspot evolution is also expected to play an important role. Our MOOG and SME spectral analyses provide consistent results, showing that the targets are dwarf stars with spectral types between F and mid-K. Detectable Li i absorption in four of the targets confirms a low age of 100-400 Myr also deduced from gyrochronology. Our study indicates that the photometric beating phenomenon is likely attributable to differential rotation in fast-rotating stars with outer convection zones.

  20. A New Method for Detecting and Monitoring Atmospheric Natural Hazards with GPS RO

    NASA Astrophysics Data System (ADS)

    Biondi, R.; Steiner, A. K.; Rieckh, T. M.; Kirchengast, G.

    2014-12-01

    Global Positioning System (GPS) Radio Occultation (RO) allows measurements in any meteorological condition, with global coverage, high vertical resolution, and high accuracy. With more than 13 years of data availability, RO also became a fundamental tool for studying climate change. We present here the application of RO for detecting and monitoring tropical cyclones (TCs), deep convective systems (CSs) and volcanic ash clouds (ACs).Deep CSs and TCs play a fundamental role in atmospheric circulation producing vertical transport, redistributing water vapor and trace gases, changing the thermal structure of the Upper Troposphere and Lower Stratosphere (UTLS) and affecting climate through overshooting into the stratosphere. Explosive volcanic eruptions produce large ACs dangerous for the aviation and they can impact climate when the ash is injected into the UTLS.The detection of cloud top height, the determination of cloud extent, the discrimination of ACs from CSs clouds and the detection of overshooting are main challenges for atmospheric natural hazards study. We created a reference atmosphere with a resolution of 5° in latitude and longitude, sampled on a 1° x 1° grid, and a vertical sampling of 100 m. We then compared RO profiles acquired during TCs, CSs and ACs to the reference atmosphere and computed anomaly profiles.CSs, TCs and the ACs leave a clear signature in the atmosphere which can be detected by RO. Using RO temperature and bending angle profiles we gain insight into the vertical thermal structure and developed a new method for detecting the cloud top altitude with high accuracy.We have characterized the TCs by ocean basins and intensities, showing that they have a different thermal structure and reach to different altitudes according to the basin. We provide statistics on overshooting frequency, achieving results consistent with patterns found in the literature and demonstrating that RO is well suited for this kind of study. We have analyzed the

  1. Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells

    PubMed Central

    Liang, Yayun; Mafuvadze, Benford; Aebi, Johannes D; Hyder, Salman M

    2016-01-01

    Standard treatment for primary prostate cancer includes systemic exposure to chemotherapeutic drugs that target androgen receptor or antihormone therapy (chemical castration); however, drug-resistant cancer cells generally emerge during treatment, limiting the continued use of systemic chemotherapy. Patients are then treated with more toxic standard therapies. Therefore, there is an urgent need for novel and more effective treatments for prostate cancer. The cholesterol biosynthetic pathway is an attractive therapeutic target for treating endocrine-dependent cancers because cholesterol is an essential structural and functional component of cell membranes as well as the metabolic precursor of endogenous steroid hormones. In this study, we have examined the effects of RO 48-8071 (4′-[6-(allylmethylamino)hexyloxy]-4-bromo-2′-fluorobenzophenone fumarate; Roche Pharmaceuticals internal reference: RO0488071) (RO), which is an inhibitor of 2, 3-oxidosqualene cyclase (a key enzyme in the cholesterol biosynthetic pathway), on prostate cancer cells. Exposure of both hormone-dependent and castration-resistant human prostate cancer cells to RO reduced prostate cancer cell viability and induced apoptosis in vitro. RO treatment reduced androgen receptor protein expression in hormone-dependent prostate cancer cells and increased estrogen receptor β (ERβ) protein expression in both hormone-dependent and castration-resistant prostate cancer cell lines. Combining RO with an ERβ agonist increased its ability to reduce castration-resistant prostate cancer cell viability. In addition, RO effectively suppressed the growth of aggressive castration-resistant human prostate cancer cell xenografts in vivo without any signs of toxicity to experimental animals. Importantly, RO did not reduce the viability of normal prostate cells in vitro. Our study is the first to demonstrate that the cholesterol biosynthesis inhibitor RO effectively suppresses growth of human prostate cancer cells

  2. Pre-clinical studies of Notch signaling inhibitor RO4929097 in inflammatory breast cancer cells.

    PubMed

    Debeb, Bisrat G; Cohen, Evan N; Boley, Kimberly; Freiter, Erik M; Li, Li; Robertson, Fredika M; Reuben, James M; Cristofanilli, Massimo; Buchholz, Thomas A; Woodward, Wendy A

    2012-07-01

    Basal breast cancer, common among patients presenting with inflammatory breast cancer (IBC), has been shown to be resistant to radiation and enriched in cancer stem cells. The Notch pathway plays an important role in self-renewal of breast cancer stem cells and contributes to inflammatory signaling which promotes the breast cancer stem cell phenotype. Herein, we inhibited Notch signaling using a gamma secretase inhibitor, RO4929097, in an in vitro model that enriches for cancer initiating cells (3D clonogenic assay) and conventional 2D clonogenic assay to compare the effect on radiosensitization of the SUM149 and SUM190 IBC cell lines. RO4929097 downregulated the Notch target genes Hes1, Hey1, and HeyL, and showed a significant reduction in anchorage independent growth in SUM190 and SUM149. However, the putative self-renewal assay mammosphere formation efficiency was increased with the drug. To assess radiosensitization of putative cancer stem cells, cells were exposed to increasing doses of radiation with or without 1 μM RO4929097 in their standard (2D) and self-renewal enriching (3D) culture conditions. In the conventional 2D clonogenic assay, RO4929097 significantly sensitized SUM190 cells to ionizing radiation and has a modest radiosensitization effect in SUM149 cells. In the 3D clonogenic assays, however, a radioprotective effect was seen in both SUM149 and SUM190 cells at higher doses. Both cell lines express IL-6 and IL-8 cytokines known to mediate the efficacy of Notch inhibition and to promote self-renewal of stem cells. We further showed that RO429097 inhibits normal T-cell synthesis of some inflammatory cytokines, including TNF-α, a potential mediator of IL-6 and IL-8 production in the microenvironment. These data suggest that additional targeting agents may be required to selectively target IBC stem cells through Notch inhibition, and that evaluation of microenvironmental influences may shed further light on the potential effects of this inhibitor.

  3. A Phase II Study of RO4929097 Gamma-Secretase Inhibitor in Metastatic Melanoma: SWOG 0933

    PubMed Central

    Lee, Sylvia M.; Moon, James; Redman, Bruce G.; Chidiac, Tarek; Flaherty, Lawrence E.; Zha, Yuanyuan; Othus, Megan; Ribas, Antoni; Sondak, Vernon K.

    2014-01-01

    Background Aberrant Notch activation confers a proliferative advantage onto many human tumors, including melanoma. This phase II trial assessed the antitumor activity of RO4929097, a gamma-secretase inhibitor of Notch signaling, on the progression-free and overall survival of patients with advanced melanoma. Methods Chemotherapy-naïve patients with metastatic melanoma of cutaneous or unknown origin were treated with RO4929097 at a dose of 20 mg orally daily, 3 consecutive days per week. A two-step accrual design was used, with an interim analysis on the first 32 patients, and continuation of enrollment if ≥4/32 patients responded. Results Thirty-six patients from 23 institutions were enrolled; 32 patients were evaluable. RO4929097 was well-tolerated, and most toxicities were grade 1 or 2. The most common toxicities were nausea (53%), fatigue (41%), and anemia (22%). There was 1 confirmed partial response lasting 7 months, and 8 patients with stable disease lasting at least through week 12, with one of these continuing for 31 months. The 6-month PFS was 9% (95% CI: 2–22%), and 1-year OS was 50% (95% CI: 32–66%). Peripheral blood T cell assays showed no significant inhibition of IL-2 production, a surrogate pharmacodynamic marker of Notch inhibition, suggesting that the drug levels were insufficient to achieve Notch target inhibition. Conclusions RO4929097 showed minimal clinical activity against metastatic melanoma in this phase II trial, possibly due to inadequate exposure to therapeutic drug levels. While Notch inhibition remains a compelling target in melanoma, our results do not support further investigation of RO4929097 at this dose and schedule. PMID:25250858

  4. Expression of the Memory Marker CD45RO on Helper T Cells in Macaques

    PubMed Central

    Valentine, Michael; Song, Kejing; Maresh, Grace A.; Mack, Heather; Huaman, Maria Cecilia; Polacino, Patricia; Ho, On; Cristillo, Anthony; Kyung Chung, Hye; Hu, Shiu-Lok; Pincus, Seth H.

    2013-01-01

    Background In humans it has been reported that a major site of the latent reservoir of HIV is within CD4+ T cells expressing the memory marker CD45RO, defined by the mAb UCHL1. There are conflicting reports regarding the expression of this antigen in macaques, the most relevant animal species for studying HIV pathogenesis and testing new therapies. There is now a major effort to eradicate HIV reservoirs and cure the infection. One approach is to eliminate subsets of cells housing the latent reservoir, using UCHL1 to target these cells. So that such studies may be performed in macaques, it is essential to determine expression of CD45RO. Methods We have used immunofluorescence and flow cytometry to study cell surface expression of CD45RO on lymphocytes from PBMC, lymphoid, and GI organs of rhesus, pigtailed, and cynomolgus macaques. Both direct and indirect immunofluorescence experiments were performed. Findings CD45RO is expressed on a subset of CD4+ lymphocytes of all pigtailed, a fraction of rhesus, and neither of the cynomolgus macaques studied. The binding of UCHL1 to macaque cells was of lower avidity than to human cells. This could be overcome by forming UCHL1 multimers. Directly conjugating fluors to UCHL1 can inhibit UCHL1 binding to macaque cells. Patterns of UCHL1 expression differ somewhat in macaques and humans, and from that of other memory markers often used in macaques. Conclusions CD45RO, defined with mAb UCHL1, is well expressed on CD4+ cells in pigtailed macaques. Using tissues recovered from latently infected pigtailed macaques we are determining whether UCHL1, or other memory markers, can define the cellular locus of the reservoir. The low avidity of this interaction could limit the utility of UCHL1, in its conventional form, to eliminate cells in vivo and test this approach in macaque models of HIV infection. PMID:24023920

  5. β blockers and mortality after myocardial infarction in patients without heart failure: multicentre prospective cohort study

    PubMed Central

    Riant, Elisabeth; Aissoui, Nadia; Soria, Angèle; Ducrocq, Gregory; Coste, Pierre; Cottin, Yves; Aupetit, Jean François; Bonnefoy, Eric; Blanchard, Didier; Cattan, Simon; Steg, Gabriel; Schiele, François; Ferrières, Jean; Juillière, Yves; Simon, Tabassome; Danchin, Nicolas

    2016-01-01

    Objective To assess the association between early and prolonged β blocker treatment and mortality after acute myocardial infarction. Design Multicentre prospective cohort study. Setting Nationwide French registry of Acute ST- and non-ST-elevation Myocardial Infarction (FAST-MI) (at 223 centres) at the end of 2005. Participants 2679 consecutive patients with acute myocardial infarction and without heart failure or left ventricular dysfunction. Main outcome measures Mortality was assessed at 30 days in relation to early use of β blockers (≤48 hours of admission), at one year in relation to discharge prescription, and at five years in relation to one year use. Results β blockers were used early in 77% (2050/2679) of patients, were prescribed at discharge in 80% (1783/2217), and were still being used in 89% (1230/1383) of those alive at one year. Thirty day mortality was lower in patients taking early β blockers (adjusted hazard ratio 0.46, 95% confidence interval 0.26 to 0.82), whereas the hazard ratio for one year mortality associated with β blockers at discharge was 0.77 (0.46 to 1.30). Persistence of β blockers at one year was not associated with lower five year mortality (hazard ratio 1.19, 0.65 to 2.18). In contrast, five year mortality was lower in patients continuing statins at one year (hazard ratio 0.42, 0.25 to 0.72) compared with those discontinuing statins. Propensity score and sensitivity analyses showed consistent results. Conclusions Early β blocker use was associated with reduced 30 day mortality in patients with acute myocardial infarction, and discontinuation of β blockers at one year was not associated with higher five year mortality. These findings question the utility of prolonged β blocker treatment after acute myocardial infarction in patients without heart failure or left ventricular dysfunction. Trial registration Clinical trials NCT00673036. PMID:27650822

  6. A beta-blocker, propranolol, decreases the efficacy from enzyme replacement therapy in Pompe disease

    PubMed Central

    Han, Sang-oh; Pope, Rand; Li, Songtao; Kishnani, Priya S.; Steet, Richard; Koeberl, Dwight D.

    2015-01-01

    Enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) fails to completely reverse muscle weakness in Pompe disease. β2-agonists enhanced ERT by increasing receptor-mediated uptake of rhGAA in skeletal muscles. Purpose To test the hypothesis that a β-blocker might reduce the efficacy of ERT, because the action of β-blockers opposes those of β2-agonists. Methods Mice with Pompe disease were treated with propranolol (a β-blocker) or clenbuterol in combination with ERT, or with ERT alone. Results Propranolol-treated mice had decreased weight gain (p<0.01), in comparison with clenbuterol-treated mice. Left ventricular mass was decreased (and comparable to wild-type) in ERT only and clenbuterol-treated groups of mice, and unchanged in propranolol-treated mice. GAA activity increased following either clenbuterol or propranolol in skeletal muscles. However, muscle glycogen was reduced only in clenbuterol-treated mice, not in propranolol-treated mice. Cell-based experiments confirmed that propranolol reduces uptake of rhGAA into Pompe fibroblasts and also demonstrated that the drug induces intracellular accumulation of glycoproteins at higher doses. Conclusion Propranolol, a commonly prescribed β-blocker, increased left ventricular mass and decreased glycogen clearance in skeletal muscle following ERT. β-blockers might therefore decrease the efficacy from ERT in patients with Pompe disease. PMID:26454691

  7. Effects of chloride channel blockers on hypoxic injury in rat proximal tubules.

    PubMed

    Reeves, W B

    1997-05-01

    These studies examined the pathways and consequences of chloride uptake into proximal tubule cells during in vitro hypoxia. The chloride channel blocker diphenylamine-2-carboxylate (DPC) markedly reduced the degree of hypoxia-induced membrane damage as measured by the release of lactate dehydrogenase (LDH). DPC reduced the release of LDH from hypoxic tubules from 38 +/- 2.7% to 16 +/- 1.7% after 30 minutes of hypoxia (P < 0.001, N = 16) and also reduced 36Cl- uptake by hypoxic tubules. The reduction in LDH release was not associated with better preservation of cell ATP content or with protection against hypoxia-induced DNA damage. Other Cl- channel blockers, such as niflumic acid, 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) and 2-[(2-cyclopentyl-6,7-dichloro-2,3-dihyrdo-2-methyl-1-oxo-1H-in den-5-yl)oxy] acetic acid (IAA-94) provided even greater protection than DPC and were as effective as 2 mM glycine. The Cl- channel blockers appear to act late in the course of hypoxic injury since DNA damage, an early manifestation of injury, is not prevented by the blockers and since addition of the Cl- channel blocker after the hypoxic injury has begun reduces further membrane damage. These results support the conclusion that transport through Cl- channels contributes to hypoxic cell injury in proximal tubular cells.

  8. The safety of histamine 2 (H2) blockers in pregnancy: a meta-analysis.

    PubMed

    Gill, Simerpal Kaur; O'Brien, Lisa; Koren, Gideon

    2009-09-01

    Heartburn and acid reflux increase the severity of nausea and vomiting of pregnancy, and may lead to more serious medical conditions. The fetal safety of histamine 2 (H2) blockers, the most common antireflux medication, during pregnancy needs to be determined. The aim herein is to determine the fetal safety of H2 blockers during pregnancy through systematic review. All original research assessing the safety of H2 blockers in pregnancy was sought. Data included congenital malformations, spontaneous abortions, preterm delivery, and small for gestational age. A random-effects model combined results. With data from 2,398 exposed and 119,892 nonexposed to H2 blockers, overall odds ratio was 1.14 [0.89, 1.45]. Further analysis revealed no increased risks for spontaneous abortions, preterm delivery, and small for gestational age with odds ratios and 95% confidence intervals (CIs) of 0.62 [0.36-1.05], 1.17 [0.94, 1.147], and 0.28 [0.06, 1.22], respectively. H2 blockers can be used safely in pregnancy.

  9. Fluvial biofilms: A pertinent tool to assess beta-blockers toxicity.

    PubMed

    Bonnineau, Chloé; Guasch, Helena; Proia, Lorenzo; Ricart, Marta; Geiszinger, Anita; Romaní, Anna M; Sabater, Sergi

    2010-02-18

    Among increasingly used pharmaceutical products, beta-blockers have been commonly reported at low concentrations in rivers and littoral waters of Europe and North America. Little is known about the toxicity of these chemicals in freshwater ecosystems while their presence may lead to chronic pollution. Hence, in this study the acute toxicity of 3 beta-blockers: metoprolol, propranolol and atenolol on fluvial biofilms was assessed by using several biomarkers. Some were indicative of potential alterations in biofilm algae (photosynthetic efficiency), and others in biofilm bacteria (peptidase activity, bacterial mortality). Propranolol was the most toxic beta-blocker, mostly affecting the algal photosynthetic process. The exposure to 531microg/L of propranolol caused 85% of inhibition of photosynthesis after 24h. Metoprolol was particularly toxic for bacteria. Though estimated No-Effect Concentrations (NEC) were similar to environmental concentrations, higher concentrations of the toxic (503microg/L metoprolol) caused an increase of 50% in bacterial mortality. Atenolol was the least toxic of the three tested beta-blockers. Effects superior to 50% were only observed at very high concentration (707mg/L). Higher toxicity of metoprolol and propranolol might be due to better absorption within biofilms of these two chemicals. Since beta-blockers are mainly found in mixtures in rivers, their differential toxicity could have potential relevant consequences on the interactions between algae and bacteria within river biofilms.

  10. Transiting exoplanets from the CoRoT space mission . XIX. CoRoT-23b: a dense hot Jupiter on an eccentric orbit

    NASA Astrophysics Data System (ADS)

    Rouan, D.; Parviainen, H.; Moutou, C.; Deleuil, M.; Fridlund, M.; Ofir, A.; Havel, M.; Aigrain, S.; Alonso, R.; Auvergne, M.; Baglin, A.; Barge, P.; Bonomo, A. S.; Bordé, P.; Bouchy, F.; Cabrera, J.; Cavarroc, C.; Csizmadia, Sz.; Deeg, H. J.; Diaz, R. F.; Dvorak, R.; Erikson, A.; Ferraz-Mello, S.; Gandolfi, D.; Gillon, M.; Guillot, T.; Hatzes, A.; Hébrard, G.; Jorda, L.; Léger, A.; Llebaria, A.; Lammer, H.; Lovis, C.; Mazeh, T.; Ollivier, M.; Pätzold, M.; Queloz, D.; Rauer, H.; Samuel, B.; Santerne, A.; Schneider, J.; Tingley, B.; Wuchterl, G.

    2012-01-01

    We report the detection of CoRoT-23b, a hot Jupiter transiting in front of its host star with a period of 3.6314 ± 0.0001 days. This planet was discovered thanks to photometric data secured with the CoRoT satellite, combined with spectroscopic radial velocity (RV) measurements. A photometric search for possible background eclipsing binaries conducted at CFHT and OGS concluded with a very low risk of false positives. The usual techniques of combining RV and transit data simultaneously were used to derive stellar and planetary parameters. The planet has a mass of Mp = 2.8 ± 0.3 MJup, a radius of Rpl= 1.05 ± 0.13RJup, a density of ≈ 3 g cm-3. RV data also clearly reveal a nonzero eccentricity of e = 0.16 ± 0.02. The planet orbits a mature G0 main sequence star of V = 15.5 mag, with a mass M⋆ = 1.14 ± 0.08 M⊙, a radius R ⋆ = 1. 61 ± 0.18 R⊙ and quasi-solarabundances. The age of the system is evaluated to be 7 Gyr, not far from the transition to subgiant, in agreement with the rather large stellar radius. The two features of a significant eccentricity of the orbit and of a fairly high density are fairly uncommon for a hot Jupiter. The high density is, however, consistent with a model of contraction of a planet at this mass, given the age of the system. On the other hand, at such an age, circularization is expected to be completed. In fact, we show that for this planetary mass and orbital distance, any initial eccentricity should not totally vanish after 7 Gyr, as long as the tidal quality factor Qp is more than a few 105, a value that is the lower bound of the usually expected range. Even if CoRoT-23b features a density and an eccentricity that are atypical of a hot Jupiter, it is thus not an enigmatic object. The CoRoT space mission, launched on 27 December 2006, has been developed and is operated by CNES, with the contribution of Austria, Belgium, Brazil, ESA, Germany, and Spain. First CoRoT data are available to the public from the CoRoT archive: http

  11. The autoantigen Ro52 is an E3 ligase resident in the cytoplasm but enters the nucleus upon cellular exposure to nitric oxide

    SciTech Connect

    Espinosa, Alexander; Oke, Vilija; Elfving, Ase; Nyberg, Filippa; Covacu, Ruxandra; Wahren-Herlenius, Marie

    2008-12-10

    Patients with the systemic autoimmune diseases Sjoegrens's syndrome and systemic lupus erythematosus often have autoantibodies against the intracellular protein Ro52. Ro52 is an E3 ligase dependent on the ubiquitin conjugation enzymes UBE2D1 and UBE2E1. While Ro52 and UBE2D1 are cytoplasmic proteins, UBE2E1 is localized to the nucleus. Here, we investigate how domains of human Ro52 regulate its intracellular localization. By expressing fluorescently labeled Ro52 and Ro52 mutants in HeLa cells, an intact coiled-coil domain was found to be necessary for the cytoplasmic localization of Ro52. The amino acids 381-470 of the B30.2 region were essential for translocation into the nucleus. Furthermore, after exposure of HeLa cells to the inflammatory mediator nitric oxide (NO), Ro52 translocated to the nucleus. A nuclear localization of Ro52 in inflamed tissue expressing inducible NO synthetase (iNOS) from cutaneous lupus patients was observed by immunohistochemistry and verified in NO-treated cultures of patient-derived primary keratinocytes. Our results show that the localization of Ro52 is regulated by endogenous sequences, and that nuclear translocation is induced by an inflammatory mediator. This suggests that Ro52 has both cytoplasmic and nuclear substrates, and that Ro52 mediates ubiquitination through UBE2D1 in the cytoplasm and through UBE2E1 in the nucleus.

  12. Transiting exoplanets from the CoRoT space mission. XVII. The hot Jupiter CoRoT-17b: a very old planet

    NASA Astrophysics Data System (ADS)

    Csizmadia, Sz.; Moutou, C.; Deleuil, M.; Cabrera, J.; Fridlund, M.; Gandolfi, D.; Aigrain, S.; Alonso, R.; Almenara, J.-M.; Auvergne, M.; Baglin, A.; Barge, P.; Bonomo, A. S.; Bordé, P.; Bouchy, F.; Bruntt, H.; Carone, L.; Carpano, S.; Cavarroc, C.; Cochran, W.; Deeg, H. J.; Díaz, R. F.; Dvorak, R.; Endl, M.; Erikson, A.; Ferraz-Mello, S.; Fruth, Th.; Gazzano, J.-C.; Gillon, M.; Guenther, E. W.; Guillot, T.; Hatzes, A.; Havel, M.; Hébrard, G.; Jehin, E.; Jorda, L.; Léger, A.; Llebaria, A.; Lammer, H.; Lovis, C.; MacQueen, P. J.; Mazeh, T.; Ollivier, M.; Pätzold, M.; Queloz, D.; Rauer, H.; Rouan, D.; Santerne, A.; Schneider, J.; Tingley, B.; Titz-Weider, R.; Wuchterl, G.

    2011-07-01

    We report on the discovery of a hot Jupiter-type exoplanet, CoRoT-17b, detected by the CoRoT satellite. It has a mass of 2.43 ± 0.30 MJup and a radius of 1.02 ± 0.07 RJup, while its mean density is 2.82 ± 0.38 g/cm3. CoRoT-17b is in a circular orbit with a period of 3.7681 ± 0.0003 days. The host star is an old (10.7 ± 1.0 Gyr) main-sequence star, which makes it an intriguing object for planetary evolution studies. The planet's internal composition is not well constrained and can range from pure H/He to one that can contain ~380 earth masses of heavier elements. The CoRoT space mission, launched on December 27th 2006, has been developed and is operated by CNES, with the contribution of Austria, Belgium, Brazil, ESA (RSSD and Science Programme), Germany and Spain. Part of the observations were obtained at the Canada-France-Hawaii Telescope (CFHT) which is operated by the National Research Council of Canada, the Institut National des Sciences de l'Univers of the Centre National de la Recherche Scientifique of France, and the University of Hawaii. Based on observations made with HARPS spectrograph on the 3.6-m European Organisation for Astronomical Research in the Southern Hemisphere telescope at La Silla Observatory, Chile (ESO program 184.C-0639). Based on observations made with the IAC80 telescope operated on the island of Tenerife by the Instituto de Astrofísica de Canarias in the Spanish Observatorio del Teide. Part of the data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundation.

  13. Chronic ethanol administration increases the binding of sup 3 H Ro-15-4513 in primary cultured spinal cord neurons

    SciTech Connect

    Mlatre, M.; Ticku, M.K. )

    1989-02-09

    Ro 15-4513 (ethyl-8-azido-5, 6-dihydro-5-methyl-6-oxo-4H-imidazo (1,5{alpha}), (1,4) benzodiazepine-3-carboxylate) is reported to be a selective ethanol antagonist in biochemical and behavioral studies. The effect of chronic ethanol treatment on the binding of ({sup 3}H)Ro 15-4513 was investigated in cultured spinal cord neurons, which are shown to possess all the elements of GABA benzodiazepine receptor complex. Chronic ethanol treatment (50 mM for 6 hr, 12 hr, 18 hr, 3 days, and 5{sub 3} days) produced an increase in the specific binding of ({sub 3}H)Ro 15-4513. The increase in binding in these neurons was due to an increase in the number (B{sub max}) of receptor sites. This effect was specific for Ro 15-4513, since identical ethanol treatment did not alter the binding of benzodiazepine antagonist ({sup 3}H)Ro 15-1788 or agonist ({sup 3}H)flunitrazepam or inverse agonist ({sup 3}H)methyl-{beta}-carboline-3-carboxylate. Similar results have been reported following chronic ethanol treatment to rats. These results suggest that the Ro 15-4513 binding sites on the oligomeric GABA receptor complex are altered following chronic ethanol administration, and support the notion of a unique role of Ro 15-4513 as an ethanol antagonist.

  14. Effect of beta-blockers on psychomotor performance in normal volunteers.

    PubMed

    Betts, T A; Knight, R; Crowe, A; Blake, A; Harvey, P; Mortiboy, D

    1985-01-01

    The effects of beta-adrenergic receptor antagonists on psychometric tests including vehicle handling, choice reaction time, and kinetic visual acuity (KVA), are reviewed. The beta-blockers had little effect on the performance tests, with the unexplained but reproducible effect of enhanced KVA performance with atenolol. Although the beta-blockers had little effect on performance tests they were shown to have psychotropic effects in normal volunteers. The reasons for the conflicting evidence concerning the effect of these drugs on performance tests is discussed in relation to the present experiments and to variables that may influence response. It is concluded that one should use tests that are as independent as possible from potentially confounding variables. The use of evoked potentials in the electroencephalogram is one such test. A preliminary study is described in which the effects of beta-blockers were detected using visual evoked responses on the electroencephalogram.

  15. Combination monoamine oxidase inhibitor and beta-blocker treatment of migraine, with anxiety and depression.

    PubMed

    Merikangas, K R; Merikangas, J R

    1995-11-01

    This paper presents the results of a study comparing the effectiveness of a beta-adrenergic blocking agent, atenolol, a monoamine oxidase inhibitor (MAO-I), phenelzine, and the combination in treatment of 61 adults with migraine headache. The goals of the study are (1) to investigate the safety of concomitant treatment of migraine with beta-blockers and phenelzine, (2) to assess whether orthostatic hypertension and other side effects would be relieved, and (3) to compare the results of this open trial of phenelzine to those of a previous study using similar methods. Phenelzine was associated with a large decrease in the frequency and severity of migraine attacks. Anxiety and depression were also reduced by phenelzine both alone, and in combination with a beta-blocker. The results show that the combination of MAO-I's and beta-blockers can be administered safely, and can lead to the reduction in the side effects with either drug alone.

  16. Determination of Na channel blockers in paralytic shellfish toxins and pufferfish toxins with a tissue biosensor.

    PubMed

    Cheun, B S; Takagi, S; Hayashi, T; Nagashima, Y; Watanabe, E

    1998-06-01

    The biosensor consisted of a sodium electrode and covered with the frog bladder membrane within a flow cell was tested for the estimation of tetrodotoxin (TTX) and saxitoxin (STX). This sensor was applied to detect very low amounts of the Na+ channel blockers, STX and TTX, in different shellfishes and swellfishes. A good agreement was obtained between TTX activities determined by mouse assay and amounts of Na+ channel blockers estimated by frog membrane sensor. The lowest level of TTX (fg) that can be determined by frog membrane sensor does not cause human poisoning. The channel blockers in short-necked clam, which was assumed to be STX, were monitored by this sensor continuously every week for one year. It was discovered that the STX content increased from July until September and then decreased from October until March. The biosensor proposed here may be used for the estimation of STX and TTX conventionally in the future.

  17. Is there any difference between angiotensin converting enzyme inhibitors and angiotensin receptor blockers for heart failure?

    PubMed

    Rain, Carmen; Rada, Gabriel

    2015-07-06

    Angiotensin receptor blockers are usually considered as equivalent to angiotensin converting enzyme inhibitors for patients with heart failure and low-ejection fraction. Some guidelines even recommend the former as first line treatment given their better adverse effects profile. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified four systematic reviews including eight pertinent randomized controlled trials. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded angiotensin receptor blockers and angiotensin converting enzyme inhibitors probably have a similar effect on mortality, and they might be equivalent in reducing hospitalization risk too. Treatment withdrawal due to adverse effects is probably lower with angiotensin receptor blockers than with angiotensin converting enzyme inhibitors.

  18. Is carvedilol better than other beta-blockers for heart failure?

    PubMed

    Rain, Carmen; Rada, Gabriel

    2015-06-26

    There is wide consensus about the benefits of beta-blockers in systolic heart failure. However, it is not clear if one specific beta-blocker is superior to the others. Some guidelines favor three “evidence-based” beta-blockers (carvedilol, bisoprolol and metoprolol) that have proved to decrease mortality. Carvedilol might have different physiological properties, commonly referred as pleiotropic effects, but the clinical meaning of them is not clear. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified four systematic reviews including eight pertinent randomized controlled trials. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded there is little or no difference in hospitalization risk between carvedilol and bisoprolol or metoprolol, but carvedilol might decrease mortality compared to metoprolol or bisoprolol. It is uncertain whether nebivolol can be an alternative because the certainty of the evidence is very low.

  19. Unambiguous observation of blocked states reveals altered, blocker-induced, cardiac ryanodine receptor gating

    PubMed Central

    Mukherjee, Saptarshi; Thomas, N. Lowri; Williams, Alan J.

    2016-01-01

    The flow of ions through membrane channels is precisely regulated by gates. The architecture and function of these elements have been studied extensively, shedding light on the mechanisms underlying gating. Recent investigations have focused on ion occupancy of the channel’s selectivity filter and its ability to alter gating, with most studies involving prokaryotic K+ channels. Some studies used large quaternary ammonium blocker molecules to examine the effects of altered ionic flux on gating. However, the absence of blocking events that are visibly distinct from closing events in K+ channels makes unambiguous interpretation of data from single channel recordings difficult. In this study, the large K+ conductance of the RyR2 channel permits direct observation of blocking events as distinct subconductance states and for the first time demonstrates the differential effects of blocker molecules on channel gating. This experimental platform provides valuable insights into mechanisms of blocker-induced modulation of ion channel gating. PMID:27703263

  20. Characterization of the Discriminative Stimulus Effects of a NOP Receptor Agonist Ro 64-6198 in Rhesus Monkeys

    PubMed Central

    Zelenock, Kathy A.; Lindsey, Angela M.; Sulima, Agnieszka; Rice, Kenner C.; Prinssen, Eric P.; Wichmann, Jürgen; Woods, James H.

    2016-01-01

    Nociceptin/orphanin FQ receptor (NOP) agonists have been reported to produce antinociceptive effects in rhesus monkeys with comparable efficacy to μ-opioid receptor (MOP) agonists, but without their limiting side effects. There are also known to be species differences between rodents and nonhuman primates (NHPs) in the behavioral effects of NOP agonists. The aims of this study were the following: 1) to determine if the NOP agonist Ro 64-6198 could be trained as a discriminative stimulus; 2) to evaluate its pharmacological selectivity as a discriminative stimulus; and 3) to establish the order of potency with which Ro 64-6198 produces discriminative stimulus effects compared with analgesic effects in NHPs. Two groups of rhesus monkeys were trained to discriminate either fentanyl or Ro 64-6198 from vehicle. Four monkeys were trained in the warm-water tail-withdrawal procedure to measure antinociception. Ro 64-6198 produced discriminative stimulus effects that were blocked by the NOP antagonist J-113397 and not by naltrexone. The discriminative stimulus effects of Ro 64-6198 partially generalized to diazepam, but not to fentanyl, SNC 80, ketocyclazocine, buprenorphine, phencyclidine, or chlorpromazine. Fentanyl produced stimulus effects that were blocked by naltrexone and not by J-113397, and Ro 64-6198 did not produce fentanyl-appropriate responding in fentanyl-trained animals. In measures of antinociception, fentanyl, but not Ro 64-6198, produced dose-dependent increases in tail-withdrawal latency. Together, these results demonstrate that Ro 64-6198 produced stimulus effects in monkeys that are distinct from other opioid receptor agonists, but may be somewhat similar to diazepam. In contrast to previous findings, Ro 64-6198 did not produce antinociception in the majority of animals tested even at doses considerably greater than those that produced discriminative stimulus effects. PMID:26801398

  1. Improved variability classification of CoRoT targets with Giraffe spectra

    NASA Astrophysics Data System (ADS)

    Sarro, L. M.; Debosscher, J.; Neiner, C.; Bello-García, A.; González-Marcos, A.; Prendes-Gero, B.; Ordieres, J.; León, G.; Aerts, C.; de Batz, B.

    2013-02-01

    Aims: We present an improved method for automated stellar variability classification, using fundamental parameters derived from high resolution spectra, with the goal to improve the variability classification obtained using information derived from CoRoT light curves only. Although we focus on Giraffe spectra and CoRoT light curves in this work, the methods are much more widely applicable. Methods: In order to improve the variability classification obtained from the photometric time series, only rough estimates of the stellar physical parameters (Teff and log (g)) are needed because most variability types that overlap in the space of time series parameters, are well separated in the space of physical parameters (e.g. γ Dor/SPB or δ Sct/β Cep). In this work, several state-of-the-art machine learning techniques are combined to estimate these fundamental parameters from high resolution Giraffe spectra. Next, these parameters are used in a multi-stage Gaussian-Mixture classifier to perform an improved supervised variability classification of CoRoT light curves. The variability classifier can be used independently of the regression module that estimates the physical parameters, so that non-spectroscopic estimates derived e.g. from photometric colour indices can be used instead. Results: Teff and log (g) are derived from Giraffe spectra, for 6832 CoRoT targets. The use of those parameters in addition to information extracted from the CoRoT light curves, significantly improves the results of our previous automated stellar variability classification. Several new pulsating stars are identified with high confidence levels, including hot pulsators such as SPB and β Cep, and several γ Dor-δ Sct hybrids. From our samples of new γ Dor and δ Sct stars, we find strong indications that the instability domains for both types of pulsators are larger than previously thought. The CoRoT space mission, launched on 27 December 2006, has been developed and is operated by CNES, with

  2. Photometric variability of the Be star CoRoT-ID 102761769

    NASA Astrophysics Data System (ADS)

    Emilio, M.; Andrade, L.; Janot-Pacheco, E.; Baglin, A.; Gutiérrez-Soto, J.; Suárez, J. C.; de Batz, B.; Diago, P.; Fabregat, J.; Floquet, M.; Frémat, Y.; Huat, A. L.; Hubert, A. M.; Espinosa Lara, F.; Leroy, B.; Martayan, C.; Neiner, C.; Semaan, T.; Suso, J.

    2010-11-01

    Context. Classical Be stars are rapid rotators of spectral type late O to early A and luminosity class V-III, which exhibit Balmer emission lines and often a near infrared excess originating in an equatorially concentrated circumstellar envelope, both produced by sporadic mass ejection episodes. The causes of the abnormal mass loss (the so-called Be phenomenon) are as yet unknown. Aims: For the first time, we can now study in detail Be stars outside the Earth's atmosphere with sufficient temporal resolution. We investigate the variability of the Be Star CoRoT-ID 102761769 observed with the CoRoT satellite in the exoplanet field during the initial run. Methods: One low-resolution spectrum of the star was obtained with the INT telescope at the Observatorio del Roque de los Muchachos. A time series analysis was performed using both cleanest and singular spectrum analysis algorithms to the CoRoT light curve. To identify the pulsation modes of the observed frequencies, we computed a set of models representative of CoRoT-ID 102761769 by varying its main physical parameters inside the uncertainties discussed. Results: We found two close frequencies related to the star. They are 2.465 c d-1 (28.5 μHz) and 2.441 c d-1 (28.2 μHz). The precision to which those frequencies were found is 0.018 c d-1 (0.2 μHz). The projected stellar rotation was estimated to be 120 km s-1 from the Fourier transform of spectral lines. If CoRoT-ID 102761769 is a typical Galactic Be star it rotates near the critical velocity. The critical rotation frequency of a typical B5-6 star is about 3.5 c d-1 (40.5 μHz), which implies that the above frequencies are really caused by stellar pulsations rather than star's rotation. The CoRoT space mission was developed and is operated by the French space agency CNES, with participation of ESA's RSSD and Science Programmes, Austria, Belgium, Brazil, Germany, and Spain.

  3. β-Blockers, heart disease and COPD: current controversies and uncertainties.

    PubMed

    Baker, Jillian G; Wilcox, Robert G

    2017-03-01

    Treating people with cardiovascular disease and COPD causes significant clinician anxiety. β-Blockers save lives in people with heart disease, specifically postinfarction and heart failure. COPD and heart disease frequently coexist and people with both disorders have particularly high cardiovascular mortality. There are concerns about giving β-blockers to people with concomitant COPD that include reduced basal lung function, diminished effectiveness of emergency β-agonist treatments, reduced benefit of long-acting β-agonist treatment and difficulty in discriminating between asthma and COPD. β-Blockers appear to reduce lung function in both the general population and those with COPD because they are poorly selective for cardiac β1-adrenoceptors over respiratory β2-adrenoceptors, and studies have shown that higher β-agonist doses are required to overcome the β-blockade. COPD and cardiovascular disease share similar environmental risks and both disease states have high adrenergic and inflammatory activation. β-Blockers may therefore be particularly helpful in reducing cardiovascular events in this high-risk group. They may reduce the background inflammatory state, and inhibit the tachycardia and hypertension associated with both the endogenous adrenaline and high-dose β-agonist treatment associated with acute exacerbations of COPD. Some studies have suggested no increased and, at times, reduced mortality in patients with COPD taking β-blockers for heart disease. However, these are all observational studies and there are no randomised controlled trials. Potential ways to improve this dilemma include the development of highly β1-selective β-blockers or the use of non-β-blocking heart rate reducing agents, such as ivabridine, if these are proven to be beneficial in randomised controlled trials.

  4. PCR amplification of RoTat 1.2 VSG gene in Trypanosoma evansi isolates in Kenya.

    PubMed

    Ngaira, J M; Njagi, E N M; Ngeranwa, J J N; Olembo, N K

    2004-02-26

    A direct card agglutination test for Trypanosoma evansi, CATT/T. evansi based on the predominant variable antigen-type (pVAT) RoTat 1.2 was evaluated previously in the field in Isiolo District, Kenya. Sixteen out of 51 (31.4%) parasitologically positive camels were negative by the antibody detection test. In the present study, trypanosomes isolated from the camels were analysed in an attempt to determine the cause of the false negative results of CATT/T. evansi. A total of 20 field isolates comprised 16 stocks from camels that were negative by CATT/T. evansi, and 4 from CATT/T. evansi-positive camels. In addition, 15 known T. evansi and four T. brucei were used as reference. Purified DNA samples were tested using an established RoTat 1.2-based polymerase chain reaction (PCR) that yields a 488 bp product for the specific detection of T. evansi. Antibodies to RoTat 1.2 variant surface glycoprotein (VSG) were used in Western blotting to detect RoTat 1.2 VSG linear epitopes. Results of PCR and Western blot showed that the 16 stocks isolated from CATT/T. evansi-negative camels fell into three groups. In Group 1, both the RoTat 1.2 VSG gene and the VSG were absent in three stocks. In five trypanosome stocks in Group 2, the RoTat 1.2 VSG gene was detected, but Western blot was negative indicating absence of the expressed VSG. Five other stocks containing the RoTat 1.2 VSG gene were also in this group. The RoTat 1.2 VSG gene was detected and Western blot was positive in all four trypanosome stocks in Group 3. All four stocks from CATT/T. evansi-positive camels contained the RoTat 1.2 VSG gene and the expressed VSG. The reference T. evansi KETRI 2479 lacked the RoTat 1.2 VSG gene and there was no immune reactivity detected by Western blot. The rest of the reference T. evansi stocks examined contained the RoTat 1.2 VSG gene. All the four T. brucei samples examined were negative by PCR and Western blot. In conclusion, this study showed that the RoTat 1.2 VSG gene was absent

  5. Effect of an imidazobenzodiazepine, Ro15-4513, on the incoordination and hypothermia produced by ethanol and pentobarbital

    SciTech Connect

    Hoffman, P.L.; Tabakoff, B.; Szabo, G.; Suzdak, P.D.; Paul, S.M.

    1987-08-03

    The imidazobenzodiazepine, Ro15-4513, which is a partial inverse agonist at brain benzodiazepine receptors, reversed the incoordinating effect of ethanol in mice, as measured on an accelerating Rotarod. This effect was blocked by benzodiazepine receptor antagonists. In contrast, Ro15-4513 had no effect on ethanol-induced hypothermia in mice. However, Ro15-4513 reversed the hypothermic effect of pentobarbital, and, at higher dose, also reversed the incoordinating effect of pentobarbital in mice. The data support the hypothesis that certain of the pharmacological effects of ethanol are mediated by actions at the GABA-benzodiazepine receptor-coupled chloride channel. 35 references, 2 figures.

  6. Understanding nuclear motions in molecules: Derivation of Eckart frame ro-vibrational Hamiltonian operators via a gateway Hamiltonian operator

    SciTech Connect

    Szalay, Viktor

    2015-05-07

    A new ro-vibrational Hamiltonian operator, named gateway Hamiltonian operator, with exact kinetic energy term, T-hat, is presented. It is in the Eckart frame and it is of the same form as Watson’s normal coordinate Hamiltonian. However, the vibrational coordinates employed are not normal coordinates. The new Hamiltonian is shown to provide easy access to Eckart frame ro-vibrational Hamiltonians with exact T-hat given in terms of any desired set of vibrational coordinates. A general expression of the Eckart frame ro-vibrational Hamiltonian operator is given and some of its properties are discussed.

  7. Are beta-blockers effective in heart failure with preserved ejection fraction?

    PubMed

    Alegría, Javier; Rada, Gabriel

    2016-11-02

    Beta-blockers constitute standard therapy for heart failure with reduced ejection. However, their role in patients with preserved ejection fraction is not clear. Searching in Epistemonikos database, which is maintained by screening multiple databases, we identified four systematic reviews covering 19 primary studies, including seven randomized trials answering the question of this summary. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded the use of beta-blockers probably leads to little or no difference in the risk of death or hospitalization in patients with heart failure with preserved ejection fraction.

  8. Association of β-blocker therapy with long-term clinical outcomes in patients with coronary chronic total occlusion.

    PubMed

    Hwang, Jin Kyung; Yang, Jeong Hoon; Hwang, Ji-Won; Jang, Woo Jin; Song, Young Bin; Hahn, Joo-Yong; Choi, Jin-Ho; Lee, Sang Hoon; Gwon, Hyeon-Cheol; Choi, Seung-Hyuk

    2016-07-01

    There are limited data regarding the efficacy of β-blockers for secondary prevention in patients with coronary chronic total occlusion (CTO). Therefore, we investigated the association of β-blocker therapy with long-term clinical outcomes in CTO patients. From March 2003 to February 2012, a total of 2024 CTO patients treated with either medical therapy alone or revascularization were enrolled in the study. We assessed 1596 patients with stable ischemic heart disease and divided them into the β-blocker group (n = 932) and the no-β-blocker group (n = 664). The primary outcome was all-cause death. The median follow-up duration was 3.9 (interquartile range: 2.0-6.2) years. All-cause death occurred in 11.6% patients in the β-blocker group and 13.6% patients in the no-β-blocker group (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.61-1.08; P = 0.15). In the propensity score-matched population (570 pairs), all-cause death occurred in 12.3% patients in the β-blocker group and 12.8% patients in the no-β-blocker group (HR: 0.93, 95% CI: 0.67-1.29; P = 0.66). In subgroup analysis, β-blocker therapy was associated with better outcome, in terms of all-cause death, in patients with CTO of the left anterior descending coronary artery and Synergy Between PCI with Taxus and Cardiac Surgery (SYNTAX) score ≥23 (P for interaction = 0.01 and 0.02, respectively). In conclusion, β-blocker therapy was not associated with favorable long-term clinical outcomes in stable CTO patients, regardless of treatment strategy. However, β-blocker therapy might be beneficial in a highly selective group of CTO patients with a high ischemic burden.

  9. BEER analysis of Kepler and CoRoT light curves. III. Spectroscopic confirmation of seventy new beaming binaries discovered in CoRoT light curves

    NASA Astrophysics Data System (ADS)

    Tal-Or, L.; Faigler, S.; Mazeh, T.

    2015-08-01

    Context. The BEER algorithm searches stellar light curves for the BEaming, Ellipsoidal, and Reflection photometric modulations that are caused by a short-period companion. These three effects are typically of very low amplitude and can mainly be detected in light curves from space-based photometers. Unlike eclipsing binaries, these effects are not limited to edge-on inclinations. Aims: Applying the algorithm to wide-field photometric surveys such as CoRoT and Kepler offers an opportunity to better understand the statistical properties of short-period binaries. It also widens the window for detecting intrinsically rare systems, such as short-period brown-dwarf and massive-planetary companions to main-sequence stars. Methods: Applying the search to the first five long-run center CoRoT fields, we identified 481 non-eclipsing candidates with periodic flux amplitudes of 0.5-87 mmag. Optimizing the Anglo-Australian-Telescope pointing coordinates and the AAOmega fiber-allocations with dedicated softwares, we acquired six spectra for 231 candidates and seven spectra for another 50 candidates in a seven-night campaign. Analysis of the red-arm AAOmega spectra, which covered the range of 8342-8842 Å, yielded a radial-velocity precision of ~1 km s-1. Spectra containing lines of more than one star were analyzed with the two-dimensional correlation algorithm TODCOR. Results: The measured radial velocities confirmed the binarity of seventy of the BEER candidates - 45 single-line binaries, 18 double-line binaries, and 7 diluted binaries. We show that red giants introduce a major source of false candidates and demonstrate a way to improve BEER's performance in extracting higher fidelity samples from future searches of CoRoT light curves. The periods of the confirmed binaries span a range of 0.3-10 days and show a rise in the number of binaries per ΔlogP toward longer periods. The estimated mass ratios of the double-line binaries and the mass ratios assigned to the single

  10. Arrachements des épines iliaques antéro-supérieures et antéro-inférieures chez l'adolescent sportifs: à propos de deux cas

    PubMed Central

    Louaste, Jamal; Cherrad, Taoufik; Rachid, Khalid

    2015-01-01

    Les arrachements des épines iliaques antéro-supérieures et antéro-inférieures sont des entités rares qui touchent surtout l'enfant et l'adolescent. Elles se voient généralement lors d'une activité sportive. Le tableau clinique est dominé par une douleur brutale et importante de la hanche de type mécanique. Alors que le diagnostic est confirmé par les examens radiologiques. Nous rapportons deux cas de fractures arrachement des épines iliaques l'une antéro-supérieure et l'autre antéro-inférieure. PMID:26985274

  11. Side band suppression for wide band optical RoF systems

    NASA Astrophysics Data System (ADS)

    Abir, Hraghi; Ben Abid, Samir; Menif, Mourad

    2015-05-01

    In this paper, we propose a flexible monocycle generator that is based on multi-tonal excitation of a dual-arm MZM. The proposed generator permits the generation of different waveforms, such as Gaussian, first order Gaussian derivative, sinusoidal, cosine and sinc pulses. We exploit the proposed generator in order to generate the International Telecommunication Union-Radiocommunication( ITU-R) recommended channelization which contains four carrier frequencies, spaced by 2.16 GHz (58.32 GHz, 60.48 GHz, 62.64 GHz and 64.80 GHz). This millimeter waves (mmwaves) have attracted a great deal of attention in the Radio over Fiber (RoF) systems. The main challenge of the RoF system is to provide higher bands and increase significantly data rate with using millimeter-wave (mm-wave) band.

  12. Magnetic order on a frustrated lattice due to orbital degrees of freedom in RO2 hyperoxides

    NASA Astrophysics Data System (ADS)

    Oleś, Andrzej M.; Wohlfeld, Krzysztof; Daghofer, Maria

    2012-02-01

    The alkali RO2 hyperoxides (R=Rb,Cs,K) crystallize in a frustrated bct lattice. Nevertheless, all of the members of the family of alkali RO2 hyperoxides have long range layered C-type antiferromagnetic (C-AF) order at low temperature. We show that including the almost degenerate p-orbital degrees of freedom in a realistic spin-orbital model can resolve this contradiction [1]. Although a priori the orbital degrees of freedom do not remove frustration in spin system, we show that the anomalously large interorbital hopping together with the orbital order induced by the lattice stabilize the C-AF order in this class of compounds, in agreement with generalized Goodenough-Kanamori rules formulated here. [4pt] [1] K. Wohlfeld, M. Daghofer, and A.M. Ole's, EPL 96, 27001 (2011).

  13. Aspects of the Eckart frame ro-vibrational kinetic energy operator

    NASA Astrophysics Data System (ADS)

    Szalay, Viktor

    2015-08-01

    A most decisive part of developing the Eckart frame ro-vibrational kinetic energy operator (KEO) in terms of curvilinear internal coordinates is the introduction of vibrational displacements obeying the Eckart conditions. It is examined here, how such displacements may be constructed by orthogonal and nonorthogonal transformations, and how they can be employed in developing the KEO. In particular, it is shown analytically, by term by term comparison, that the Eckart KEOs obtained by employing Pickett's method and the gateway Hamiltonian method are equivalent. That is, although it may appear in the form of very different expressions, the general, exact ro-vibrational Eckart frame KEO is unique. As side result, it has been shown that the simple formula of the pseudo-potential derived by Watson for the exact KEO given in normal coordinates applies to any Eckart frame KEO, irrespective of the choice of the vibrational coordinates.

  14. Simple and reconfigured single-sideband OFDM RoF system.

    PubMed

    Xu, Yuming; Li, Xinying; Yu, Jianjun; Chang, Gee-Kung

    2016-10-03

    We propose a simple and reconfigured dispersion-tolerant single sideband (SSB) orthogonal frequency division multiplexing (OFDM) radio over fiber (RoF) system enabled by digital signal processing (DSP), one in-phase/quadrature (I/Q) modulator and direct-detection. The generated radio frequency (RF) is based on DSP and the frequency can be flexibly adjusted, which can be employed in the future software-defined radio access network (RAN). Based on our proposed system, we have experimentally demonstrated 16-ary quadrature amplitude modulation (16QAM) 21.87-Gb/s 21-GHz and 38-GHz SSB-OFDM RoF signal generation and transmission over 80-km single-mode fiber (SMF), respectively.

  15. Stellar parameters for stars of the CoRoT exoplanet field

    NASA Astrophysics Data System (ADS)

    Cortés, C.; Maciel, S. C.; Vieira, S.; Ferreira Lopes, C. E.; Leão, I. C.; de Oliveira, G. P.; Correia, C.; Canto Martins, B. L.; Catelan, M.; De Medeiros, J. R.

    2015-09-01

    Context. Spectroscopic observations represent a fundamental step in the physical characterization of stars and, in particular, in the precise location of stars in the HR diagram. Rotation is also a key parameter, impacting stellar properties and evolution, which modulates the interior and manifests itself on the surface of stars. To date, the lack of analysis based on large samples has prevented our understanding of the real impact of stellar parameters and rotation on the stellar evolution as well as on the behavior of surface abundances. The space missions, CoRoT and Kepler, are providing us with rotation periods for thousands of stars, thus enabling a robust assessment of the behavior of rotation for different populations and evolutionary stages. For these reasons, the follow-up programs are fundamental to increasing the returns of these space missions. An analysis that combines spectroscopic data and rotation/modulation periods obtained from these space missions provides the basis for establishing the evolutionary behavior of the angular momentum of solar-like stars at different evolutionary stages, and the relation of rotation with other relevant physical and chemical parameters. Aims: To support the computation and evolutionary interpretation of periods associated with the rotational modulation, oscillations, and variability of stars located in the CoRoT fields, we are conducting a spectroscopic survey for stars located in the fields already observed by the satellite. These observations allow us to compute physical and chemical parameters for our stellar sample. Methods: Using spectroscopic observations obtained with UVES/VLT and Hydra/Blanco, and based on standard analysis techniques, we computed physical and chemical parameters (Teff, log (g), [Fe/H], vmic, vrad, vsin (i), and A(Li)) for a large sample of CoRoT targets. Results: We provide physical and chemical parameters for a sample comprised of 138 CoRoT targets. Our analysis shows the stars in our

  16. Membrane autopsy based bio-fouling investigation of distillery spent wash RO treatment plant.

    PubMed

    Sharma, Pinki; Joshi, Himanshu

    2014-01-01

    In this paper, a thorough investigation has been done to evaluate the effects of different pollutants on membrane performance by autopsy. Autopsy was performed on fresh and fouled reverse osmosis (RO) membrane elements from a distillery spent wash treatment plant by different analyses, such as field emission scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy and X-ray diffraction, to identify the cause of poor performance of an RO plant. Results obtained from the analysis of membranes indicate that a mixture of colloids and organic matters (polysaccharides and amines) along with the presence of multivalent ions (Ca, Mg, Fe and SO4) causes membrane fouling, which in turn affects membrane performance. Possible measures to improve treated effluent quality and mitigate fouling have been suggested for this particular case study.

  17. Thematic trip: "Save Roşia MontanÄă"

    NASA Astrophysics Data System (ADS)

    Eugenia, Marcu

    2015-04-01

    The name Roşia Montană, situated in Transylvania, became well known after a Romanian-Canadian company, Roşia Montană Gold Company (RMGC), obtained the concession license on exploitation for gold and silver minerals in the Roşia Montană area. The project consists of opening the largest surface gold mines in Europe using cyanide, which will include four open pits and a processing plant for gold and silver in The Roşia Valley and a tailings facility with an area of 367 hectares in the Corna Valley. One of the main fears is related to a possible ecological accident like the one in Baia Mare in 2000, when a tailing facility dam break led to cyanide pollution of Tisa and Danube rivers that resulted in the death of 1,200 tons of fish and contamination of water resources for 2 million people. This thematic trip is important for the scientific preparation of students and an opportunity to educate them in the spirit of environmental protection. The training and education of students will require assimilation and understanding, actively and consciously, using the knowledge acquired during the compulsory curriculum and training skills. REASON: The continuous degradation of the environment is a major crisis due to human intervention in nature, and the proposed Roşia Montană mining project will continue this trend. The company proposes to extract gold from mines by using the gold separation technique using cyanide, a process that involves destroying a total area of 16 km² which includes 5 mountains, 7 churches, 11 cemeteries and the ruins of Alburnus Maior Citadel, as well as creating pollution that would last for hundreds of years. The extraction of gold from low-grade ores using cyanide processes was estimated to result in a worldwide emission of 45,300 tons of hydrogen cyanide. Environmental education for a healthy life has children as target group, because they are the trustees and beneficiaries of tomorrow's natural resources and can influence the attitudes of

  18. Detection of new pulsations in the roAp star HD 177765

    NASA Astrophysics Data System (ADS)

    Holdsworth, Daniel L.

    2016-10-01

    We report the discovery of 2 previously undetected pulsation frequencies in the known roAp star HD 177765. Photometric observations by the Kepler space telescope during K2 Campaign 7 show low-amplitude pulsations (4-11 micro mag) previously unseen in photometry. We show the pulsations to be stable over the observation period, and demonstrate that the separation of the frequencies is not representative of the large frequency separation quantity needed to perform asteroseismic analysis.

  19. Multiple dose study of the combined radiosensitizers Ro 03-8799 (pimonidazole) and SR 2508 (etanidazole)

    SciTech Connect

    Bleehen, N.M.; Newman, H.F.; Maughan, T.S.; Workman, P.

    1989-04-01

    The hypoxic cell radiosensitizers Ro 03-8799 and SR 2508 have different clinical toxicities. The former produces an acute but transient central nervous system syndrome, whereas the latter produces cumulative peripheral neuropathy. Following single dose studies, an escalating multiple dose schedule using both drugs in combination showed no unexpected adverse reactions at lower doses. This study identifies the clinical tolerance and pharmacokinetics when doses in the region of the maximal tolerated dose are given to 26 patients receiving infusions of 0.75 g/m2 Ro 03-8799 and 2 g/m2 SR 2508 three times per week. At 15 doses, 3/4 patients experienced WHO grade 2 peripheral neuropathy, whereas at 12 doses 1/9 developed grade 2 and 6/9 developed grade 1 neuropathies. This represents a lower dose of SR 2508 than can be given alone suggesting that some interaction between the two drugs does exist in terms of chronic peripheral neurotoxicity. Pharmacokinetic studies show no adverse interactions between the two drugs and minimal inter-patient variation. From bivariate analysis, cumulative AUC for Ro 03-8799 has the most significant correlation with the development of peripheral neuropathy. Tumor drug concentrations normalized to the administered dose show mean values of 34 micrograms/g Ro 03-8799 and 76 micrograms/g SR 2508 30 minutes after infusion. These could be expected to produce a single dose sensitizer enhancement ratio of 1.5. The combination of the two sensitizers at the maximum tolerable dose may be expected to give an increased therapeutic efficacy over either drug alone.

  20. VizieR Online Data Catalog: CoRoT 105906206 frequencies analysis (da Silva+, 2014)

    NASA Astrophysics Data System (ADS)

    da Silva, R.; Maceroni, C.; Gandolfi, D.; Lehmann, H.; Hatzes, A. P.

    2014-03-01

    The file frequenc.dat contains the table with 220 frequencies, amplitudes, and phases, together with their uncertainties, derived for the light curve of CoRoT 105906206 with pulsations only (after subtracting the best binary model). The uncertainties are the formal values computed using equations (4), (10), and (11) of Montgomery & O'Donoghue (1999DSSN...13...28M). (1 data file).

  1. Exploring the Helium Core of the δ Scuti Star CoRoT 102749568 with Asteroseismology

    NASA Astrophysics Data System (ADS)

    Chen, Xinghao; Li, Yan; Lin, Guifang; Chen, Yanhui; Guo, Junjun

    2017-01-01

    Based on regularities in rotational splitting, we seek possible multiplets for the observed frequencies of CoRoT 102749568. There are 21 sets of multiplets identified, including four sets of multiplets with l = 1, nine sets of multiplets with l = 2, and eight sets of multiplets with l = 3. In particular, there are three complete triplets (f10, f12, f14), (f31, f34, f35), and (f41, f43, f44). The rotational period of CoRoT 102749568 is estimated to be {1.34}-0.05+0.04 days. When doing model fittings, three l = 1 modes (f12, f34, and f43) and the radial first overtone f13 are used. Our results shows that the three nonradial modes (f12, f34, and f43) are mixed modes, which mainly provide constraints on the helium core. The radial first overtone f13 mainly provides constraint on the stellar envelope. Hence the size of the helium core of CoRoT 102749568 is determined to be {M}{He} = 0.148 ± 0.003 M⊙ and {R}{He} = 0.0581 ± 0.0007 R⊙. The fundamental parameters of CoRoT 102749568 are determined to be M = 1.54 ± 0.03 M⊙, Z=0.006, {f}{ov}=0.004+/- 0.002, {log} g=3.696+/- 0.003, {T}{eff}=6886+/- 70 K, R = 2.916 ± 0.039 R⊙, and L = 17.12 ± 1.13 L⊙.

  2. Raman investigation of ro-vibrational modes of interstitial H2 in Si

    NASA Astrophysics Data System (ADS)

    Koch, S. G.; Lavrov, E. V.; Weber, J.

    2012-08-01

    A Raman scattering study of ro-vibrational transitions Q(J) of the interstitial H2 in Si is presented. It is shown that the Q(2) mode of para hydrogen is coupled to the TAX phonon of Si. The mode appears in the spectra at temperatures above 200 K. The results presented also suggest that the Q(3) transition of ortho hydrogen is resonantly coupled to the OΓ phonon.

  3. Benzodiazepine receptor binding in vivo with (/sup 3/)-Ro 15-1788

    SciTech Connect

    Goeders, N.E.; Kuhar, M.J.

    1985-07-29

    In vivo benzodiazepine receptor binding has generally been studied by ex vivo techniques. In this investigation, the authors identify the conditions where (/sup 3/H)-Ro 15-1788 labels benzodiazepine receptors by true in vivo binding, i.e. where workable specific to nonspecific ratios are obtained in intact tissues without homogenization or washing. (/sup 3/H)-Flunitrazepam and (/sup 3/H)-clonazepam did not exhibit useful in vivo receptor binding. 39 references, 5 figures, 1 table.

  4. CoRoT observations of the young open cluster Dolidze 25

    NASA Astrophysics Data System (ADS)

    Ripepi, V.; Leccia, S.; Baglin, A.; Ruoppo, A.; Bernabei, S.; Zwintz, K.; Cusano, F.; Gandolfi, D.; Guenter, E. W.; Alencar, S.; Marconi, M.; Monteiro, M. J. P. F. G.; Palla, F.; Alcalá, J. M.; Boehm, T.; Catala, C.; Chavero, C.; Corradi, W. S.; Degl'Innocenti, S.; de La Reza, R.; Deluil, M.; Favata, F.; Fernandez, M.; Gregorio-Hetem, J.; Lepine, J. D. R.; Pinheiro, F. J. G.; Prada Moroni, P. G.; Quast, G.; Torres, C. A. O.; Weiss, W.

    2010-07-01

    We present some preliminary results based on the CoRoT observations of the young distant cluster Dolidze 25. The light curve for the 28 stars observed by the satellite have been analyzed and the relevant periodogram presented. As a result we have found two binary, three Pulsating Be, three SPB, two Spotted and one ellipsoidal variables. Noteworthy, we have also identified one PMS δ Scuti candidate.

  5. Antiscalant removal in accelerated desupersaturation of RO concentrate via chemically-enhanced seeded precipitation (CESP).

    PubMed

    McCool, Brian C; Rahardianto, Anditya; Cohen, Yoram

    2012-09-01

    An experimental study was carried out to demonstrate and quantify the feasibility of antiscalant (AS) removal from brackish water RO concentrate of high gypsum scaling propensity via lime treatment prior to seeded gypsum precipitation. Based on studies with model solutions, it was shown that sufficient AS removal (up to ∼90%) from RO concentrate is feasible via a lime treatment step (at a dose significantly lower than that required for conventional lime softening) to enable effective subsequent seeded gypsum precipitation. This two-step chemically-enhanced seeded precipitation (CESP) treatment of primary RO concentrate is suitable as an intermediate concentrate demineralization (ICD) stage for high recovery desalting employing secondary RO desalination. Analysis of gypsum precipitation and lime treatment kinetic data suggests that, after adequate CaCO(3) precipitation has been induced for effective AS scavenging, CaSO(4) desupersaturation can be achieved via seeded gypsum precipitation without retardation due to seed poisoning by AS. Also, the lime dose required to prevent seed poisoning during subsequent gypsum desupersaturation via seeded gypsum precipitation can be adequately assessed with a precipitation kinetics model that considers AS seed poisoning based on a Langmuir adsorption isotherm. The degree of AS removal after lime treatment increased linearly with the logarithm of the single lime dose additions. Staged lime dosing (i.e., multiple lime additions), however, removed a higher degree of AS relative to an equivalent single lime dose addition since a higher driving force for CaCO(3) precipitation could be maintained over the course of the lime treatment period.

  6. Growth conditions, compact perturbations and operator subdecomposability, with applications to generalized Cesàro operators

    NASA Astrophysics Data System (ADS)

    Miller, T. L.; Miller, V. G.; Neumann, M. M.

    2005-01-01

    We adapt recent results of Albrecht and Ricker to obtain conditions under which growth constraints on the left resolvent of a Banach space operator are preserved under suitable perturbations. As an application, we establish Bishop's property ([beta]) for certain generalized Cesàro operators on the classical Hardy spaces Hp, 1

  7. Learning to Improve E-mail Classification with numéro interactive

    NASA Astrophysics Data System (ADS)

    Jones, Dean M.

    This paper describes some of the ways in which we use artificial intelligence technologies in numéro interactive, a Customer Interaction Management system. In particular, we focus on the classification of e-mail messages into one of multiple business categories. We describe different features that are extracted from e-mail messages to help in this classification, and the improvement in the overall classification accuracy that results from the use of each kind of feature.

  8. THE CoRoT DISCOVERY OF A UNIQUE TRIPLE-MODE CEPHEID IN THE GALAXY

    SciTech Connect

    Poretti, E.; Baglin, A.; Weiss, W. W.

    2014-11-10

    The exploitation of the CoRoT treasure of stars observed in the exoplanetary field allowed the detection of a unusual triple-mode Cepheid in the Milky Way, CoRoT 0223989566. The two modes with the largest amplitudes and a period ratio of 0.80 are identified with the first (P {sub 1} = 1.29 days) and second (P {sub 2} = 1.03 days) radial overtones. The third period, which has the smallest amplitude but is able to produce combination terms with the other two, is the longest one (P {sub 3} = 1.89 days). The ratio of 0.68 between the first-overtone period and the third period is the unusual feature. Its identification with the fundamental radial or a nonradial mode is discussed with respect to similar cases in the Magellanic Clouds. In both cases, the period triplet and the respective ratios make the star unique in our Galaxy. The distance derived from the period-luminosity relation and the galactic coordinates put CoRoT 0223989566 in the metal-rich environment of the ''outer arm'' of the Milky Way.

  9. Ro-vibrational excitation, alignment and orientation distributions of fast non-dissociatively scattered molecules

    NASA Astrophysics Data System (ADS)

    Harder, R.; Snowdon, K. J.

    1997-12-01

    The ro-vibrational distribution of fast diatomic molecules scattered from an uncorrugated surface under strongly dissipative glancing incidence conditions is calculated. The classical trajectory simulation includes potential surface switching associated with hot-electron scattering processes. Both ro-vibrational excitation and strong alignment of the classical angular momentum vector in the surface plane ("cartwheel motion") are observed, independent of the occurrence of potential surface switching. Ro-vibrational excitation is enhanced strongly by transitions between potential surfaces. The resultant larger proportion of molecules in highly rotationally excited states leads to a higher fraction of cartwheel-aligned molecules in the scattered molecule ensemble. The molecules which dissociate in the simulation are characterised by surface normal peaked internuclear axis orientation distributions. This is in agreement with the results of recent experiments [A. Nesbitt et al., Surf. Sci. 331-333 (1995) 321]. We observe, in addition, an enhanced rotational population of "topspin" oriented molecules, which arises from differences in the surface parallel oriented friction forces acting on each atom of the molecule. Glancing incidence scattering from well-prepared close-packed metal surfaces would appear to provide an efficient, general method to obtain a beam of preferentially aligned fast neutral diatomic molecules.

  10. Water Quality of Hills Water, Supply Water and RO Water Machine at Ulu Yam Selangor

    NASA Astrophysics Data System (ADS)

    Ngadiman, N.; ‘I Bahari, N.; Kaamin, M.; Hamid, N. B.; Mokhtar, M.; Sahat, S.

    2016-07-01

    The rapid development resulted in the deterioration of the quality of drinking water in Malaysia. Recognizing the importance of water quality, new alternatives for drinking water such as mineral water processing from reverse osmosis (RO) machine become more popular. Hence, the demand for mineral water, natural spring water or water from the hills or mountains rose lately. More consumers believed the quality of these spring water better than other source of drinking water. However, the quality of all the drinking water sources is to meet the required quality standard. Therefore, this paper aims to measure the quality of the waters from hills, from RO machine and the water supply in Ulu Yam, Selangor Batang Kali, Malaysia. The water quality was determined based on following parameters: ammoniacal nitrogen (NH3), iron (Fe), turbidity (NTU) and pH. The results show that the water from hills has better quality compared to water supply and water from RO machine. The value of NH3 ranged from 0.03 mg/L- 0.67 mg/L; Fe was from 0.03mg/L - 0.12 mg/L, turbidity at 0.42 NTU - 0.88 NTU and pH is at 6.60 - 0.71. Based on the studied parameters, all three types of water are fit for drinking and have met the required national drinking water quality standard.

  11. Threshold scaling limits of RO concentrates flowing in a long waste disposal pipeline.

    PubMed

    Semiat, R; Hasson, D; Zelmanov, G; Hemo, I

    2004-01-01

    Disposal of RO concentrates emanating from inland brackish water desalination plants presents a difficult environmental problem. The solution adopted by Mekorot--the National Water Company of Israel--is to construct a 30 km waste disposal pipeline for collecting concentrates emanating from several RO desalination plants and discharging them into the sea. The discharged concentrates are highly supersaturated with respect to CaCO3. Scale precipitation during concentrate flow through the RO module is inhibited by the presence of anti-scalants. The retention time of the concentrate solution in the discharge pipe will exceed 100 hours. This raises the issue of the risk of scale precipitation in the discharge pipe that could impair its proper functioning. The aim of the present study was to provide data for guiding the design and operation of the disposal pipeline. The extent of the induction period prior to the onset of precipitation was measured in a pilot plant simulating flow of concentrate solutions dosed with anti-scalants. The parameters investigated were the scaling potential, the anti-scalant concentration and the presence of a mixture of several anti-scalants. The results of this study provide threshold scaling limits under various conditions.

  12. [Demographic profile of Boróro Indians from Mato Grosso State, Brazil, 1993-1996].

    PubMed

    Souza, Luciene Guimarães de; Pagliaro, Heloisa; Santos, Ricardo Ventura

    2009-02-01

    This paper analyzes the demographic profile of the Boróro Indians from Mato Grosso State, Brazil, from 1993 to 1996. Data came from annual collection and registration of vital statistics conducted by the health service in three villages (Garças, Meruri, and Morada dos Boróro). The average annual population growth rate was 2.4%. Nearly half (44%) of the population was younger than 15 years (median 16 years). The crude birth rate was 30.9 per 1,000 and the crude death rate 7.3 per 1,000 inhabitants. The infant mortality rate was high (58.8 per thousand live births), probably resulting from precarious health conditions in the villages. The results showed that women married younger than men and that there were numerous unmarried adult men (26.7%) and women (13.3%), as compared to data from other indigenous groups. The total fertility rate of Boróro women was 4.3, quite low compared to other indigenous communities in Brazil. The study emphasizes the importance of systematically collecting and analyzing demographic data on indigenous populations.

  13. On Cesàro Limit Distribution of a Class of Permutative Cellular Automata

    NASA Astrophysics Data System (ADS)

    Maass, Alejandro; Martinez, Servet

    1998-01-01

    We study Cesàro means (time averages) of the evolution measures of the class of permutative cellular automata over {0, 1}ℕ defined by (\\varphi _B x)_n = x_{n{kern 1pt} {kern 1pt} + {kern 1pt} {kern 1pt} R} + Pi _{j{kern 1pt} {kern 1pt} = {kern 1pt} {kern 1pt} 0}^{R{kern 1pt} {kern 1pt} - {kern 1pt} {kern 1pt} 1} {kern 1pt} {kern 1pt} {kern 1pt} {kern 1pt} {kern 1pt} {kern 1pt} (1 + b_j + x_{n{kern 1pt} {kern 1pt} + {kern 1pt} {kern 1pt} j} ) where B= b 0 ⋯ b R-1is an aperiodic block in {0, 1} R and operations are taken mod 2. If the initial measure is Bernoulli, we prove that the limit of the Cesàro mean of the first column distribution exists. When R = 1 and B = 1, φ B is the mod 2 sum automaton. For this automaton we show that the limit is the (1/2, 1/2(-Bernoulli measure, and if the initial measure is Markov, we show that the limit of Cesàro mean of the one-site distribution is equidistributed.

  14. Tropical temperature variability and Kelvin-wave activity in the UTLS from GPS RO measurements

    NASA Astrophysics Data System (ADS)

    Scherllin-Pirscher, Barbara; Randel, William J.; Kim, Joowan

    2017-01-01

    Tropical temperature variability over 10-30 km and associated Kelvin-wave activity are investigated using GPS radio occultation (RO) data from January 2002 to December 2014. RO data are a powerful tool for quantifying tropical temperature oscillations with short vertical wavelengths due to their high vertical resolution and high accuracy and precision. Gridded temperatures from GPS RO show the strongest variability in the tropical tropopause region (on average 3 K2). Large-scale zonal variability is dominated by transient sub-seasonal waves (2 K2), and about half of sub-seasonal variance is explained by eastward-traveling Kelvin waves with periods of 4 to 30 days (1 K2). Quasi-stationary waves associated with the annual cycle and interannual variability contribute about a third (1 K2) to total resolved zonal variance. Sub-seasonal waves, including Kelvin waves, are highly transient in time. Above 20 km, Kelvin waves are strongly modulated by the quasi-biennial oscillation (QBO) in stratospheric zonal winds, with enhanced wave activity during the westerly shear phase of the QBO. In the tropical tropopause region, however, peaks of Kelvin-wave activity are irregularly distributed in time. Several peaks coincide with maxima of zonal variance in tropospheric deep convection, but other episodes are not evidently related. Further investigations of convective forcing and atmospheric background conditions are needed to better understand variability near the tropopause.

  15. RoCoMAR: robots' controllable mobility aided routing and relay architecture for mobile sensor networks.

    PubMed

    Le, Duc Van; Oh, Hoon; Yoon, Seokhoon

    2013-07-05

    In a practical deployment, mobile sensor network (MSN) suffers from a low performance due to high node mobility, time-varying wireless channel properties, and obstacles between communicating nodes. In order to tackle the problem of low network performance and provide a desired end-to-end data transfer quality, in this paper we propose a novel ad hoc routing and relaying architecture, namely RoCoMAR (Robots' Controllable Mobility Aided Routing) that uses robotic nodes' controllable mobility. RoCoMAR repeatedly performs link reinforcement process with the objective of maximizing the network throughput, in which the link with the lowest quality on the path is identified and replaced with high quality links by placing a robotic node as a relay at an optimal position. The robotic node resigns as a relay if the objective is achieved or no more gain can be obtained with a new relay. Once placed as a relay, the robotic node performs adaptive link maintenance by adjusting its position according to the movements of regular nodes. The simulation results show that RoCoMAR outperforms existing ad hoc routing protocols for MSN in terms of network throughput and end-to-end delay.

  16. Beta-1-Selective Beta-Blockers and Cognitive Functions in Patients With Coronary Artery Disease: A Cross-Sectional Study.

    PubMed

    Burkauskas, Julius; Noreikaite, Aurelija; Bunevicius, Adomas; Brozaitiene, Julija; Neverauskas, Julius; Mickuviene, Narseta; Bunevicius, Robertas

    2016-01-01

    The association between current beta-1-selective beta-blocker use and cognitive function was evaluated in 722 patients with coronary artery disease without dementia. Beta-1-selective beta-blocker use was associated with worse incidental learning independently of sociodemographic characteristics, clinical coronary artery disease severity, and depression/anxiety.

  17. Brain death provokes very acute alteration in myocardial morphology detected by echocardiography: preventive effect of beta-blockers.

    PubMed

    Ferrera, René; Hadour, Guylaine; Tamion, Fabienne; Henry, Jean-Paul; Mulder, Paul; Richard, Vincent; Thuillez, Christian; Ovize, Michel; Derumeaux, Geneviève

    2011-03-01

    Our objective was to evaluate immediate acute changes in myocardial function during the autonomic storm of brain death (BD). Wistar rats were divided into four groups (n = 8/group): controls without any treatment, β-blocker (Esmolol®, 10 mg/kg), calcium channel blocker (Diltiazem®, 10 mg/kg), or alpha-blocker (Prazosin®, 0.3 mg/kg). Treatments were administered intravenously 5 min before BD induction. Echocardiography (ATL-5000, 8 MHz) was performed to measure left ventricular (LV) dimensions and fractional shortening at baseline, during BD induction and 5 min and 15 min after BD. In controls, BD was immediately associated with an increase in wall thickness and a decrease in LV cavity dimension. This myocardial wall hypertrophy was completely prevented by β-blockers, but not with calcium- and alpha-blockers. Extensive myocardial interstitial edema was found in all groups, except in the β-blocker group. Myocardial wall hypertrophy was also prevented during a longer follow-up of 180 min after BD in β-blocker group as opposed to controls. In conclusion, BD is associated with an immediate and severe myocardial damage related to an important interstitial edema which is prevented by β-blockers.

  18. Systemic delivery of β-blockers via transdermal route for hypertension

    PubMed Central

    Ahad, Abdul; Al-Jenoobi, Fahad I.; Al-Mohizea, Abdullah M.; Akhtar, Naseem; Raish, Mohammad; Aqil, Mohd.

    2014-01-01

    Hypertension is the most common cardiovascular disease worldwide. Moreover, management of hypertension requires long-term treatment that may result in poor patient compliance with conventional dosage forms due to greater frequency of drug administration. Although there is availability of a plethora of therapeutically effective antihypertensive molecules, inadequate patient welfare is observed; this arguably presents an opportunity to deliver antihypertensive agents through a different route. Ever since the transdermal drug delivery came into existence, it has offered great advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. Attempts were made to develop the transdermal therapeutic system for various antihypertensive agents, including β-blockers, an important antihypertensive class. β-blockers are potent, highly effective in the management of hypertension and other heart ailments by blocking the effects of normal amounts of adrenaline in the heart and blood vessels. The shortcomings associated with β-blockers such as more frequent dose administration, extensive first pass metabolism and variable bioavailability, make them an ideal candidate for transdermal therapeutic systems. The present article gives a brief view of different β-blockers formulated as transdermal therapeutic system in detail to enhance the bioavailability as well as to improve patient compliance. Constant improvement in this field holds promise for the long-term success in technologically advanced transdermal dosage forms being commercialized sooner rather than later. PMID:26702253

  19. Remission of post-transplant focal segmental glomerulosclerosis with angiotensin receptor blockers

    PubMed Central

    Bansal, S. B.; Sethi, S. K.; Jha, P.; Duggal, R.; Kher, V.

    2017-01-01

    Recurrence of focal segmental glomerulosclerosis (FSGS) is common after kidney transplantation. Plasmapheresis (PP) is considered to be the most effective treatment; however, results are variable and relapse is common after stopping plasmapheresis. Here, we report an unusual case of recurrent FSGS, who achieved complete remission with angiotensin receptor blocker therapy.

  20. Systemic delivery of β-blockers via transdermal route for hypertension.

    PubMed

    Ahad, Abdul; Al-Jenoobi, Fahad I; Al-Mohizea, Abdullah M; Akhtar, Naseem; Raish, Mohammad; Aqil, Mohd

    2015-11-01

    Hypertension is the most common cardiovascular disease worldwide. Moreover, management of hypertension requires long-term treatment that may result in poor patient compliance with conventional dosage forms due to greater frequency of drug administration. Although there is availability of a plethora of therapeutically effective antihypertensive molecules, inadequate patient welfare is observed; this arguably presents an opportunity to deliver antihypertensive agents through a different route. Ever since the transdermal drug delivery came into existence, it has offered great advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. Attempts were made to develop the transdermal therapeutic system for various antihypertensive agents, including β-blockers, an important antihypertensive class. β-blockers are potent, highly effective in the management of hypertension and other heart ailments by blocking the effects of normal amounts of adrenaline in the heart and blood vessels. The shortcomings associated with β-blockers such as more frequent dose administration, extensive first pass metabolism and variable bioavailability, make them an ideal candidate for transdermal therapeutic systems. The present article gives a brief view of different β-blockers formulated as transdermal therapeutic system in detail to enhance the bioavailability as well as to improve patient compliance. Constant improvement in this field holds promise for the long-term success in technologically advanced transdermal dosage forms being commercialized sooner rather than later.

  1. Determination of nine beta-blockers in serum by micellar electrokinetic capillary chromatography.

    PubMed

    Lukkari, P; Nyman, T; Riekkola, M L

    1994-07-15

    beta-Adrenergic blocking agents are used for the treatment of angina pectoris, cardiac arrhythmia, hypertension, anxiety attacks, thyrotoxicosis, migraine and glaucoma. Owing to their sedative effect, they are also used as doping agents in sport. All beta-blockers have an alkanol amine side chain terminating in a secondary amino group in their structure. The pKa values vary from 9.2 to 9.8. Because some beta-blockers are hydrophilic and some lipophilic, simultaneous determination is difficult. In this work, a method based on micellar electrokinetic capillary chromatography (MECC) was developed for the separation and determination of beta-blockers in serum. The phosphate buffer 0.08 M (pH 6.7) solution contained 15 mM N-cetyl-N,N,N-trimethylammonium bromide. Nine parent beta-blockers could be separated in a single run and the concentrations determined by internal standard (ephedrine) method. The simple clean-up procedure consisted of enzyme hydrolysis (Helix pomatia), protein precipitation, and filtration through 0.5-microns PTFE membranes. The MECC method exhibited good repeatability and a linear range of 75-300 micrograms/ml. The method was successfully applied after concentration to the determination of propranolol in real samples.

  2. QSAR study on the antibacterial activity of some sulfa drugs: building blockers of Mannich bases.

    PubMed

    Mandloi, Dheeraj; Joshi, Sheela; Khadikar, Padmakar V; Khosla, Navita

    2005-01-17

    Sulfa drugs are building blockers of several types of Mannich bases. Consequently, the antibacterial activities of sulfa drugs are reported in this paper, which will help in explaining and understanding antibacterial activities of Mannich bases. Reported QSAR is carried out using distance-based topological indices and discussed critically on the basis of statistical parameters.

  3. Pharmacological, pharmacokinetic, and clinical properties of benidipine hydrochloride, a novel, long-acting calcium channel blocker.

    PubMed

    Yao, Kozo; Nagashima, Ken; Miki, Hiroyuki

    2006-04-01

    Benidipine is a dihydropyridine-derived calcium channel blocker developed in Japan, with several unique mechanisms of action, that is, triple calcium channels (L, N, and T) blocking action with a membrane approach. Benidipine has relatively high vascular selectivity and is expected to show protective effects on vascular endothelial cells. Renal protective effects of benidipine also have been shown in several basic and clinical studies. Moreover, anti-oxidative action and enhancing nitric oxide production have been noted with this drug, following its cardio-protective effects in patients with ischemic heart diseases. In fact, benidipine exerted a better prognostic effect than other calcium channel blockers in the therapy for patients with vasospastic angina. In addition, benidipine showed reliable antihypertensive, renoprotective effects if used in combination with angiotensin II type 1 receptor blockers (ARBs) when adequate anti-hypertensive effects are not achieved by ARBs alone, indicating that benidipine is an useful calcium channel blocker in combination therapy for hypertension. Benidipine was launched on the Japanese market 14 years ago, but few severe side effects have been reported, suggesting that this is a drug with established safety and long-acting pharmacological effects.

  4. Attenuation of malonate toxicity in primary mesencephalic cultures using the GABA transport blocker, NO-711.

    PubMed

    Stokes, A H; Bernard, L P; Nicklas, W J; Zeevalk, G D

    2001-04-01

    Cultured rat mesencephalic neurons were used to assess the effects of gamma-aminobutyric acid (GABA) transport blockers on toxicity caused by malonate, a reversible, competitive inhibitor of succinate dehydrogenase. Previous studies utilizing an ex vivo chick retinal preparation have shown that GABA release and cell swelling are early consequences of acute energy impairment and that GABA transport blockers attenuate this toxicity. The present results demonstrate that the nonsubstrate GABA transport blocker, NO-711 (1 nM-1 microM), dose-dependently protected cultured mesencephalic dopamine (DA) and GABA neurons from malonate-induced toxicity. Similar protection was demonstrated with nipecotic acid (1 mM) and SKF89976A (100 nM), substrate and nonsubstrate GABA transport blockers, respectively. These compounds by themselves produced no signs of toxicity, although nipecotic acid caused a long-term decrease in GABA uptake not associated with toxicity. Compounds which decrease intracellular reactive oxygen species (ROS) are protective in this model, but NO-711 did not prevent the rise in intracellular ROS induced by malonate, indicating its protective effects were downstream of ROS production. Supplementation of malonate treated cultures with the GABA(A) agonist, muscimol (10 microM), increased the toxicity toward the DA and GABA neuron populations. Antagonists at the GABA(A) and glycine receptors provided partial protection to both the GABA and DA neurons. These findings suggest that the GABA transporter, GABA(A), and/or glycine channels contribute to cell damage associated with energy impairment in this model.

  5. Nonadherence to beta blockers is a big issue with patients post-MI.

    PubMed

    2006-11-01

    Although healthcare organizations have made great strides in boosting prescribing rates for beta blockers in patients who have suffered a myocardial infarction, (MI) data show that patients are not reaping the full value from these life-saving drugs. The problem is poor medication compliance. Experts maintain that providers and healthcare organizations should now turn their attention to this pressing problem.

  6. Rigid body Brownian dynamics as a tool for studying ion channel blockers.

    PubMed

    Gordon, Dan; Chen, Rong; Ho, Junming; Coote, Michelle L; Chung, Shin-Ho

    2012-02-16

    Using a novel rigid body Brownian dynamics algorithm, we investigate how a spherically asymmetrical polyamine molecule, a branched analogue of spermine, interacts with the external vestibule of the voltage-gated potassium channel, Kv1.2. Simulations reveal that the blocker, with a charge of +4e, inserts one of its charged amine groups into the selectivity filter, while another forms a salt bridge with an aspartate residue located just outside the entrance of the pore. This binding mode mimics features of the binding of polypeptides such as the scorpion venom charybdotoxin to the channel. The potential of mean force constructed with Brownian dynamics is a reasonable match to that obtained from molecular dynamics simulations, with dissociation constants of 4.7 and 22 μM, respectively. The current-voltage relationships obtained with and without a blocker in the external reservoir show that the inward current is severely attenuated by the presence of the blocker, whereas the outward current is only moderately reduced. The computational molecular modeling technique we introduce here can provide detailed insights into ligand-channel interactions and can be used for rapidly screening potential blocker molecules.

  7. Pharmacodynamic models of various beta blockers: an explanation for the long duration of action of bopindolol.

    PubMed

    Grevel, J

    1986-01-01

    Models describing the time course of effects (pharmacodynamic models) of various beta blockers in man are used to explain the long duration of action of bopindolol. No matter what effect is used [reduction in exercise heart rate (RER) or isoproterenol dose ratio (DR)] human data show clearly that bopindolol is very potent compared to other beta blockers such as atenolol, metoprolol, pindolol, practolol, and propranolol. In pharmacokinetic terms, however, these drugs show no pronounced difference in their elimination half-life (ranging between 4 and 8 h). Also the site of action of the therapeutic effects (beta 1 receptors) is obviously identical for all beta blockers. Furthermore, there is no evidence to suggest that bopindolol (the prodrug) or hydrolyzed bopindolol (the active substance) is further metabolized to a slowly eliminated active metabolite. Thus, drug disposition provides no argument to explain the long-lasting effects of bopindolol as compared other beta blockers. The long duration of action of bopindolol seems to reflect an usually flat plasma concentration-response curve.

  8. [Influence of rifampicin on antihypertensive effects of dihydropiridine calcium-channel blockers in four elderly patients].

    PubMed

    Yoshimoto, H; Takahashi, M; Saima, S

    1996-09-01

    Rifamicin, an antituberculosis agent, is one of the most potent inducers of hepatic drug-oxidation enzymes. Rifampicin can reduce the efficacy of several therapeutically important drugs (including verapamil and diltiazem) by accelerating systemic elimination or by increasing hepatic first-pass metabolism. Because dihydropyridine calcium-channel blockers are mainly metabolized by the liver, rifampicin may also increase the extraction of these drugs and thereby reduce their antihypertensive effects. Here we report four possible cases of interaction between rifampicin and dihydropiridine calcium-channel blockers. Rifampicin was given to treat tuberculosis in four elderly hypertensive patients whose blood pressure was well-controlled by one or more dihydropiridine calcium-channel blockers (nisoldipine, nifedipine, or barnidipine and manidipine), shortly after the start of antituberculosis therapy, their blood pressures rose. Either much greater doses of dihydropyridines or additional antihypertensive agents had to be given to keep blood pressure under control. After withdrawal of rifampicin, blood pressure fell in all patients and the doses of the antihypertensive agents had to be reduced. These findings indicate that rifampicin may lessen the antihypertensive effects of dihydropiridine calcium-channel blockers.

  9. Beta-Blockers and the Kidney: Implications for Renal Function and Renin Release.

    ERIC Educational Resources Information Center

    Epstein, Murray; And Others

    1985-01-01

    Reviews and discusses current information on the human renal response as related to beta-blockers (antihypertension agents). Topic areas considered include cardioselectivity, renal hemodynamics, systemic hemodynamics, changes with acute and chronic administration, influence of dose, and others. Implications and an 11-item multiple-choice self-quiz…

  10. Playing with Performance: The Use and Abuse of Beta-Blockers in the Performing Arts

    ERIC Educational Resources Information Center

    Patston, Tim; Loughlan, Terence

    2014-01-01

    This article discusses the use of beta-blockers by performing artists, the reasons why they are taken, and the potential associated risks. We argue that there are high levels of usage within sectors of the professional performing arts community and that there may be high levels of risk in using these medications, particularly without medical…

  11. Dissociation of POMC Peptides after Self-Injury Predicts Responses To Centrally Acting Opiate Blockers.

    ERIC Educational Resources Information Center

    Sandman, Curt A.; Hetrick, William; Taylor, Derek V.; Chicz-DeMet, Aleksandra

    1997-01-01

    This study investigated whether blood plasma levels of pro-opiomelanocortin-derived (POMC) peptides, beta-endorphin-like activity, adrenocorticotrophic hormone, and adrenal cortisol immediately after self injurious behavior (SIB) episodes predicted subsequent response to an opiate blocker in 10 patients with mental retardation. Results suggest…

  12. Pre-Clinical studies of Notch Signaling Inhibitor RO4929097 in Inflammatory Breast Cancer Cells

    PubMed Central

    Debeb, Bisrat G.; Cohen, Evan N.; Boley, Kimberly; Freiter, Erik M.; Li, Li; Robertson, Fredika M.; Reuben, James M.; Cristofanilli, Massimo; Buchholz, Thomas A.; Woodward, Wendy A.

    2015-01-01

    Basal breast cancer, common among patients presenting with inflammatory breast cancer, has been shown to be resistant to radiation and enriched in cancer stem cells. The Notch pathway plays an important role in self-renewal of breast cancer stem cells and contributes to inflammatory signaling that promotes the breast cancer stem cell phenotype. Herein we inhibited Notch signaling using a gamma secretase inhibitor, RO4929097, in an in vitro model that enriches for cancer initiating cells (3D clonogenic assay) and conventional 2D clonogenic assay to compare the effect on radiosensitization of the SUM149 and SUM190 inflammatory breast cancer (IBC) cell lines. RO4929097 downregulated the Notch target genes Hes1, Hey1 and HeyL and showed a significant reduction in anchorage independent growth in SUM190 and SUM149. However, the putative self-renewal assay mammosphere formation efficiency was increased with the drug. To assess radiosensitization of putative cancer stem cells, cells were exposed to increasing doses of radiation with or without 1uM RO4929097 in their standard (2D) and self-renewal enriching (3D) culture conditions. In the conventional 2D clonogenic assay, RO4929097 significantly sensitized SUM190 cells to ionizing radiation and has a modest radiosensitization effect in SUM149 cells. In the 3D clonogenic assays, however, a radioprotective effect was seen in both SUM149 and SUM190 cells at higher doses. Both cell lines express IL-6 and IL-8, cytokines known to mediate the efficacy of notch inhibition and to promote self-renewal of stem cells. We further showed that RO429097 inhibits normal T-cell synthesis of some inflammatory cytokines, including TNF-α, a potential mediator of IL-6 and IL-8 production in the microenvironment. These data suggest additional targeting agents may be required to selectively target IBC stem cells through notch inhibition, and that evaluation of microenvironmental influences may shed further light on the potential effects of this

  13. Galactic archaeology with asteroseismology and spectroscopy: Red giants observed by CoRoT and APOGEE

    NASA Astrophysics Data System (ADS)

    Anders, F.; Chiappini, C.; Rodrigues, T. S.; Miglio, A.; Montalbán, J.; Mosser, B.; Girardi, L.; Valentini, M.; Noels, A.; Morel, T.; Johnson, J. A.; Schultheis, M.; Baudin, F.; de Assis Peralta, R.; Hekker, S.; Themeßl, N.; Kallinger, T.; García, R. A.; Mathur, S.; Baglin, A.; Santiago, B. X.; Martig, M.; Minchev, I.; Steinmetz, M.; da Costa, L. N.; Maia, M. A. G.; Allende Prieto, C.; Cunha, K.; Beers, T. C.; Epstein, C.; García Pérez, A. E.; García-Hernández, D. A.; Harding, P.; Holtzman, J.; Majewski, S. R.; Mészáros, Sz.; Nidever, D.; Pan, K.; Pinsonneault, M.; Schiavon, R. P.; Schneider, D. P.; Shetrone, M. D.; Stassun, K.; Zamora, O.; Zasowski, G.

    2017-01-01

    With the advent of the space missions CoRoT and Kepler, it has recently become feasible to determine precise asteroseismic masses and relative ages for large samples of red giant stars. We present the CoRoGEE dataset, obtained from CoRoT light curves for 606 red giants in two fields of the Galactic disc that have been co-observed by the Apache Point Observatory Galactic Evolution Experiment (APOGEE). We used the Bayesian parameter estimation code PARAM to calculate distances, extinctions, masses, and ages for these stars in a homogeneous analysis, resulting in relative statistical uncertainties of ≲2% in distance, 4% in radius, 9% in mass and 25% in age. We also assessed systematic age uncertainties stemming from different input physics and mass loss. We discuss the correlation between ages and chemical abundance patterns of field stars over a broad radial range of the Milky Way disc (5 kpc RoGEE observations of a chemodynamical Milky Way disc model indicate that the number of high-metallicity stars in the outer disc is too high to be accounted for even by the strong radial mixing present in the model. The mock observations also show that the age distribution of the [α/Fe]-enhanced sequence in the CoRoGEE inner-disc field is much broader than expected from a combination of radial mixing and observational errors. We suggest that a thick-disc/bulge component that formed stars for more than 3 Gyr may account for these discrepancies. Our results are subject to future improvements due to (a) the still low statistics, because our sample had to be

  14. Ro 32-3555, an orally active collagenase inhibitor, prevents cartilage breakdown in vitro and in vivo.

    PubMed

    Lewis, E J; Bishop, J; Bottomley, K M; Bradshaw, D; Brewster, M; Broadhurst, M J; Brown, P A; Budd, J M; Elliott, L; Greenham, A K; Johnson, W H; Nixon, J S; Rose, F; Sutton, B; Wilson, K

    1997-06-01

    1. Ro 32-3555 (3(R)-(cyclopentylmethyl)-2(R)-[(3,4,4-trimethyl-2,5-dioxo-1- imidazolidinyl)methyl]-4-oxo-4-piperidinobutyrohydroxamic acid) is a potent, competitive inhibitor of human collagenases 1, 2 and 3 (Ki values of 3.0, 4.4 and 3.4 nM, respectively). The compound is a selective inhibitor of collagenases over the related human matrix metalloproteinases stromelysin 1, and gelatinases A and B (Ki values of 527, 154 and 59 nM, respectively). 2. Ro 32-3555 inhibited interleukin-1 alpha (IL-1 alpha)-induced cartilage collagen degradation in vitro in bovine nasal cartilage explants (IC50 = 60 nM). 3. Ro 32-3555 was well absorbed in rats when administered orally. Systemic exposure was dose related, with an oral bioavailability of 26% at a dose of 25 mg kg-1. 4. Ro 32-3555 prevented granuloma-induced degradation of bovine nasal cartilage cylinders implanted subcutaneously into rats (ED50 = 10 mg kg-1, twice daily, p.o.). 5. Ro 32-3555 dosed once daily for 14 days at 50 mg kg-1, p.o., inhibited degradation of articular cartilage in a rat monoarthritis model induced by an intra-articular injection of Propionibacterium acnes. 6. Ro 32-3555 is a potential therapy for the treatment of the chronic destruction of articulating cartilage in both rheumatoid and osteoarthritis.

  15. Evaluation of the ethanol antagonist' Ro15-4513 on cardiovascular and metabolic responses induced by ethanol

    SciTech Connect

    Lerner, M.R.; Gauvin, D.V.; Holloway, F.A.; Wilson, M.F.; Brackett, D.J. Veterans Affairs Medical Center, Oklahoma City, OK )

    1992-02-26

    The putative ethanol antagonist Ro15-4513 has been reported to attenuate many behavioral responses induced by ethanol, including motor coordination, narcosis, ethanol self administration and intake, and anticonvulsant actions. This study was designed to study the effect of Ro15-4513 on cardiovascular and metabolic responses elicited by intragastric ethanol in conscious rats. Four groups of rats were catheterized under enflurane anesthesia and allowed to regain consciousness. Each group was given either 3.2, 10.0, or 32.0 mg/kg Ro15-4513 or equivalent Tween (i.p.) following ethanol. Ro15-4513 had no effect at any concentration on the decreases in mean arterial pressure, cardiac output, central venous pressure, respiration rate, and cardiac stroke volume and the increases in systemic vascular resistance, heart rate, and glucose evoked by the ethanol challenge. Blood alcohol concentrations measured throughout the study were not affected by any concentration of Ro15-4513. These data suggest that even though Ro15-4513 has significant effects on behavioral responses induced by ethanol it has no effect on the cardiovascular and metabolic responses elicited during ethanol intoxication.

  16. Standard and Short RoM Isokinetic Testing: Comparative Analysis in Identifying Submaximal Shoulder External Rotator Effort.

    PubMed

    Pujol, Eduard; Chaler, Joaquim; Sucarrats, Laura; López, Inés; Zeballos, Blanca; Garreta, Roser; Dvir, Zeevi

    2017-01-31

    An isokinetic-related parameter termed the difference between eccentric-concentric strength ratios at two distinct test velocities (DEC) based on 60° (standard) range of motion (RoM) has been proven to be highly efficient detecting feigned muscular efforts. This study aimed to verify whether a DEC derived from a much shorter test RoM (20°) was equally useful than a long RoM-derived one. Eighteen healthy men (32.4 ± 6.4 years old) took part in a study focusing on shoulder external rotation isokinetic strength. Participants performed a genuine shoulder external rotator maximal effort (eight pairs of concentric and eccentric contractions at high and low velocities at short and long RoM) and then instructed to feign maximal effort. Contraction velocities were adjusted accordingly by applying a 1:4 gradient and peak moments registered. Both condition DEC was then calculated by subtracting the eccentric and concentric strength ratios at low velocities from those at high velocities. DEC scores in the feigned effort were significantly higher than maximal effort ones in both conditions in men. It enabled the setting of specific cutoff levels for separating the efforts. Both approaches revealed a coincident sensitivity (78%) whereas short RoM showed an even higher specificity: 88% versus 78%. Thus, the short RoM protocol provides clinically acceptable detection power.

  17. The interactions with Ro60 and La differentially affect nuclear export of hY1 RNA.

    PubMed Central

    Simons, F H; Rutjes, S A; van Venrooij, W J; Pruijn, G J

    1996-01-01

    Ro RNPs are evolutionarily conserved ribonucleoprotein particles that consist of a small RNA, known as Y RNA, associated with several proteins, such as La, Ro60, and Ro52. The Y RNAs (Y1-Y5), which are transcribed by RNA polymerase III, have been shown to reside almost exclusively in the cytoplasm as Ro RNPs. To obtain more insight into the nuclear export pathway of Y RNAs, hY1 RNA export was studied in Xenopus laevis oocytes. Injection of various hY1 RNA mutants showed that an intact Ro60 binding site is a prerequisite for nuclear export, whereas the presence of an intact La binding site resulted in strong nuclear retention of hY1 RNA. Competition studies with various classes of RNAs indicated that, in addition to Ro60, another titratable factor was necessary for nuclear export of hY1 RNA. This factor appears also to be involved in nuclear export of tRNA. Because export of hY1 RNA could not be blocked by a synthetic peptide containing the recently identified nuclear export signal of the HIV-1 Rev protein, nuclear export of hY1 RNA does not seem to be dependent on a Rev-like nuclear export signal. PMID:8608450

  18. Determination of the in vivo redox potential using roGFP and fluorescence spectra obtained from one-wavelength excitation

    NASA Astrophysics Data System (ADS)

    Wierer, S.; Elgass, K.; Bieker, S.; Zentgraf, U.; Meixner, A. J.; Schleifenbaum, F.

    2011-02-01

    The analysis of molecular processes in living (plant) cells such as signal transduction, DNA replication, carbon metabolism and senescence has been revolutionized by the use of green fluorescent protein (GFP) and its variants as specific cellular markers. Many cell biological processes are accompanied by changes in the intracellular redox potential. To monitor the redox potential, a redox-sensitive mutant of GFP (roGFP) was created, which shows changes in its optical properties in response to changes in the redox state of its surrounding medium. For a quantitative analysis in living systems, it is essential to know the optical properties of roGFP in vitro. Therefore, we applied spectrally resolved fluorescence spectroscopy on purified roGFP exposed to different redox potentials to determine shifts in both the absorption and the emission spectra of roGFP. Based on these in vitro findings, we introduce a new approach using one-wavelength excitation to use roGFP for the in vivo analysis of cell biological processes. We demonstrate the ability this technique by investigating chloroplast-located Grx1-roGFP2 expressing Arabidopsis thaliana cells as example for dynamically moving intracellular compartments. This is not possible with the two-wavelength excitation technique established so far, which hampers a quantitative analysis of highly mobile samples due to the time delay between the two measurements and the consequential displacement of the investigated area.

  19. Effect of β-Blockers on the Risk of Atrial Fibrillation in Patients with Acute Myocardial Infarction

    PubMed Central

    Pesaro, Antonio Eduardo; de Matos Soeiro, Alexandre; Serrano, Carlos Vicente; Giraldez, Roberto Rocha; Ladeira, Renata Teixeira; Nicolau, José Carlos

    2010-01-01

    INTRODUCTION: Oral β-blockers improve the prognosis of patients with acute myocardial infarction, while atrial fibrillation worsens the prognosis of this population. The reduction of atrial fibrillation incidence in patients treated with β-blockers could at least in part explain the benefits of this drug. OBJECTIVE: To investigate the effect of β-blockers on the incidence of atrial fibrillation in patients with acute myocardial infarction. METHODS: We analyzed 1401 patients with acute myocardial infarction and evaluated the occurrence or absence of atrial fibrillation, the use of oral β-blockers and mortality during the first 24 hours. RESULTS: a) The use of β-blockers was inversely correlated with the presence of atrial fibrillation (ρ = 0.004; OR = 0.54). b) Correlations with mortality were as follows: 31.5% in patients with atrial fibrillation, 9.2% in those without atrial fibrillation (ρ < 0.001; Odds Ratio = 4.52), and 17.5% in patients not treated with β-blockers and 6.7% in those who received the drug (ρ < 0.001; OR = 0.34). c) Adjusted Models: The presence of atrial fibrillation was independently correlated with mortality (OR = 2.48, ρ = 0.002). The use of β-blockers was inversely and independently correlated with mortality (OR = 0.53; ρ = 0.002). The patients who used β-blockers showed a lower risk of atrial fibrillation (OR = 0.59; ρ = 0.029) in the adjusted model. CONCLUSION: The presence of atrial fibrillation and the absence of oral β-blockers increased in-hospital mortality in patients with acute myocardial infarction. Oral β-blockers reduced the incidence of atrial fibrillation, which might be at least partially responsible for the drug’s benefit. PMID:20360916

  20. HD 50844: a new look at δ Scuti stars from CoRoT space photometry

    NASA Astrophysics Data System (ADS)

    Poretti, E.; Michel, E.; Garrido, R.; Lefèvre, L.; Mantegazza, L.; Rainer, M.; Rodríguez, E.; Uytterhoeven, K.; Amado, P. J.; Martín-Ruiz, S.; Moya, A.; Niemczura, E.; Suárez, J. C.; Zima, W.; Baglin, A.; Auvergne, M.; Baudin, F.; Catala, C.; Samadi, R.; Alvarez, M.; Mathias, P.; Paparò, M.; Pápics, P.; Plachy, E.

    2009-10-01

    Context: Aims: This work presents the results obtained by CoRoT on HD 50844, the only δ Sct star observed in the CoRoT initial run (57.6 d). The aim of these CoRoT observations was to investigate and characterize for the first time the pulsational behaviour of a δ Sct star, when observed at a level of precision and with a much better duty cycle than from the ground. Methods: The 140 016 datapoints were analysed using independent approaches (SigSpec software and different iterative sine-wave fittings) and several checks performed (splitting of the timeseries in different subsets, investigation of the residual light curves and spectra). A level of 10-5 mag was reached in the amplitude spectra of the CoRoT timeseries. The space monitoring was complemented by ground-based high-resolution spectroscopy, which allowed the mode identification of 30 terms. Results: The frequency analysis of the CoRoT timeseries revealed hundreds of terms in the frequency range 0-30 d-1. All the cross-checks confirmed this new result. The initial guess that δ Sct stars have a very rich frequency content is confirmed. The spectroscopic mode identification gives theoretical support since very high-degree modes (up to ℓ=14) are identified. We also prove that cancellation effects are not sufficient in removing the flux variations associated to these modes at the noise level of the CoRoT measurements. The ground-based observations indicate that HD 50844 is an evolved star that is slightly underabundant in heavy elements, located on the Terminal Age Main Sequence. Probably due to this unfavourable evolutionary status, no clear regular distribution is observed in the frequency set. The predominant term (f_1=6.92 d-1) has been identified as the fundamental radial mode combining ground-based photometric and spectroscopic data. Conclusions: The CoRoT space mission was developed and is operated by the French space agency CNES, with participation of ESA's RSSD and Science Programmes, Austria

  1. Mortality reduction with use of oral beta-blockers in patients with acute coronary syndrome

    PubMed Central

    de Matos Soeiro, Alexandre; de Barros e Silva, Pedro Gabriel Melo; de Castro Roque, Eduardo Alberto; Bossa, Aline Siqueira; Zullino, Cindel Nogueira; Simões, Sheila Aparecida; Okada, Mariana Yumi; de Carvalho Andreucci Torres Leal, Tatiana; de Almeida Soeiro, Maria Carolina Feres; Serrano, Carlos V.; Oliveira, Múcio Tavares

    2016-01-01

    OBJECTIVES: Recent studies have revealed a relationship between beta-blocker use and worse prognosis in acute coronary syndrome, mainly due to a higher incidence of cardiogenic shock. However, the relevance of this relationship in the reperfusion era is unknown. The aim of this study was to analyze the outcomes of patients with acute coronary syndrome that started oral beta-blockers within the first 24 hours of hospital admission (group I) compared to patients who did not use oral beta-blockers in this timeframe (group II). METHODS: This was an observational, retrospective and multicentric study with 2,553 patients (2,212 in group I and 341 in group II). Data regarding demographic characteristics, coronary treatment and medication use in the hospital were obtained. The primary endpoint was in-hospital all-cause mortality. The groups were compared by ANOVA and the chi-square test. Multivariate analysis was conducted by logistic regression and results were considered significant when p<0.05. RESULTS: Significant differences were observed between the groups in the use of angiotensin-converting enzyme inhibitors, enoxaparin, and statins; creatinine levels; ejection fraction; tabagism; age; and previous coronary artery bypass graft. Significant differences were also observed between the groups in mortality (2.67% vs 9.09%, OR=0.35, p=0.02) and major adverse cardiovascular events (11% vs 29.5%, OR=4.55, p=0.02). CONCLUSIONS: Patients with acute coronary syndrome who underwent early intervention with oral beta-blockers during the first 24 hours of hospital admission had a lower in-hospital death rate and experienced fewer major adverse cardiovascular events with no increase in cardiogenic shock or sustained ventricular arrhythmias compared to patients who did not receive oral beta-blockers within this timeframe. PMID:27982163

  2. β-Blockers Reduce Breast Cancer Recurrence and Breast Cancer Death: A Meta-Analysis.

    PubMed

    Childers, W Kurtis; Hollenbeak, Christopher S; Cheriyath, Pramil

    2015-12-01

    The normal physiologic stress mechanism, mediated by the sympathetic nervous system, causes a release of the neurotransmitters epinephrine and norepinephrine. Preclinical data have demonstrated an effect on tumor progression and metastasis via the sympathetic nervous system mediated primarily through the β-adrenergic receptor (β-AR) pathway. In vitro data have shown an increase in tumor growth, migration, tumor angiogenesis, and metastatic spread in breast cancer through activation of the β-AR. Retrospective cohort studies on the clinical outcomes of β-blockers in breast cancer outcomes showed no clear consensus. The purpose of this study was to perform a systematic review and meta-analysis of the effect of β-blockers on breast cancer outcomes. A systematic review was performed using the Cochrane library and PubMed. Publications between the dates of January 2010 and December 2013 were identified. Available hazard ratios (HRs) were extracted for breast cancer recurrence, breast cancer death, and all-cause mortality and pooled using a random effects meta-analysis. A total of 7 studies contained results for at least 1 of the outcomes of breast cancer recurrence, breast cancer death, or all-cause mortality in breast cancer patients receiving β-blockers. In the 5 studies that contained results for breast cancer recurrence, there was no statistically significant risk reduction (HR, 0.67; 95% confidence interval [CI], 0.39-1.13). Breast cancer death results were contained in 4 studies, which also suggested a significant reduction in risk (HR, 0.50; 95% CI, 0.32-0.80). Among the 4 studies that reported all-cause mortality, there was no significant effect of β-blockers on risk (HR, 1.02; 95% CI, 0.75-1.37). Results of this systematic review and meta-analysis suggest that the use of β-blockers significantly reduced risk of breast cancer death among women with breast cancer.

  3. Effect of subcutaneous administration of calcium channel blockers on nerve injury-induced hyperalgesia.

    PubMed

    White, D M; Cousins, M J

    1998-08-10

    Recent studies suggest that calcium contributes to peripheral neural mechanisms of hyperalgesia associated with nerve damage. In this animal behavioural study, we examined further the contribution of calcium in neuropathic pain by testing whether subcutaneous administration of either a calcium chelating agent or voltage-dependent calcium channel blockers attenuate nerve injury-induced hyperalgesia to mechanical stimulation. Studies were carried out in animals with partially ligated sciatic nerves, an established animal model of neuropathic pain. The nociceptive flexion reflex was quantified using an Ugo Basile Analgesymeter. Partial nerve injury induced a significant decrease in mechanical threshold compared to the sham operated controls. Daily subcutaneous injections of the calcium chelating agent, Quin 2 (20 microgram/2.5 microliter), significantly attenuated the nerve injury-induced hyperalgesia. Similarly, SNX-111, a N-type channel blocker, also significantly attenuated the nerve injury-induced hyperalgesia. SNX-230, a P and/or Q-type channel blocker, and nifedipine, a L-type channel blocker, had no effect on the hyperalgesia to mechanical stimulation. In control experiments, SNX-111 had no effect on mechanical thresholds when administered subcutaneously in either the hindpaw of normal animals or the back of the neck in nerve injury animals. This study shows that neuropathic pain involves a local calcium-dependent mechanism in the receptive field of intact neurons of an injured nerve, since it can be alleviated by subcutaneous injections of either a calcium chelating agent or SNX-111, a N-type calcium channel blocker. These agents may be effective, peripherally acting therapeutic agents for neuropathic pain.

  4. ß-adrenoceptor blockers increase cardiac sympathetic innervation by inhibiting autoreceptor suppression of axon growth.

    PubMed

    Clarke, Gwenaëlle L; Bhattacherjee, Aritra; Tague, Sarah E; Hasan, Wohaib; Smith, Peter G

    2010-09-15

    β-Adrenoceptor antagonists are used widely to reduce cardiovascular sympathetic tone, but withdrawal is accompanied by sympathetic hyperactivity. Receptor supersensitivity accounts for some but not all aspects of this withdrawal syndrome. Therefore, we investigated effects of β-blockers on sympathetic innervation. Rats received infusions of adrenergic receptor blockers or saline for 1 week. The nonselective β-blocker propranolol and the β(1)-antagonist metoprolol both increased myocardial sympathetic axon density. At 2 d after propranolol discontinuation, β-receptor sensitivity and responsiveness to isoproterenol were similar to controls. However, tyramine-induced mobilization of norepinephrine stores produced elevated ventricular contractility consistent with enhanced sympathetic neuroeffector properties. In addition, rats undergoing discontinuation showed exaggerated increases in mean arterial pressure in response to air puff or noise startle. In sympathetic neuronal cell cultures, both propranolol and metoprolol increased axon outgrowth but the β(2)-blocker ICI 118551 did not. Norepinephrine synthesis suppression by α-methyl-p-tyrosine also increased sprouting and concurrent dobutamine administration reduced it, confirming that locally synthesized norepinephrine inhibits outgrowth via β(1)-adrenoceptors. Immunohistochemistry revealed β(1)-adrenoceptor protein on sympathetic axon terminations. In rats with coronary artery ligation, propranolol reversed heart failure-induced ventricular myocardial sympathetic axon depletion, but did not affect infarct-associated sympathetic hyperinnervation. We conclude that sympathetic neurons possess β(1)-autoreceptors that negatively regulate axon outgrowth. Chronic β-adrenoceptor blockade disrupts this feedback system, leading to ventricular sympathetic axon proliferation and increased neuroeffector gain, which are likely to contribute to β-blocker withdrawal syndrome.

  5. Effects of β-blocker therapy on electrocardiographic and echocardiographic characteristics of left ventricular noncompaction.

    PubMed

    Li, Jin; Franke, Jennifer; Pribe-Wolferts, Regina; Meder, Benjamin; Ehlermann, Philipp; Mereles, Derliz; Andre, Florian; Abdelrazek, Mohamed Assem; Merten, Constanze; Schweizer, Patrick A; Becker, Rüdiger; Katus, Hugo A; Thomas, Dierk

    2015-03-01

    Left ventricular noncompaction (LVNC) is a cardiomyopathy with hypertrabeculation of the LV, often complicated by heart failure, arrhythmia and thromboembolic events. The features of LVNC are still incompletely characterized due to its late recognition as clinically relevant condition. The aims of this study were to describe echocardiographic and electrophysiologic characteristics of LVNC patients and to assess the effects of chronic β-blocker treatment. Study patients (n = 20; 42.5 [36.3; 52.5] years; 12 men) exhibited reduced LV ejection fraction (median LVEF = 32 %) and an increased LV mass of 210 g. Sinus rhythm was present in 19 patients, whereas one patient was in atrial fibrillation. Baseline heart rate was 77.5 beats per minute. Left bundle branch block was detected in five cases. In a subgroup of patients receiving β-blocker therapy (n = 17), LV mass was reduced from 226 [178; 306] g to 220 [169; 254] g (p = 0.007) at 13 ± 6 months follow-up. By contrast, a subgroup of three patients that were not treated with an anti-β-adrenergic agent showed LV mass increase from 180 [169; 197] g to 199 [185; 213] g (p = 0.023). LVEF and electrocardiographic parameters were not significantly modulated during chronic β-blocker treatment. There was no sustained symptomatic ventricular tachyarrhythmia, thromboembolic event or death in either group. In conclusion, this study reveals reduction of LV mass among LVNC patients during β-blocker therapy. Effects of β-blocker treatment in LVNC require validation in prospective controlled studies.

  6. Molecular Mechanism of Dihydropyridine Ca(2+) Channel Blockers in Pulmonary Hypertension.

    PubMed

    Yamamura, Aya

    2016-01-01

     Idiopathic pulmonary arterial hypertension (IPAH) is a progressive and fatal disease of unidentified pathogenesis. IPAH is pathologically characterized as sustained vasoconstriction and vascular remodeling of the pulmonary artery. In pulmonary arterial smooth muscle cells (PASMCs), an increase in cytosolic Ca(2+) concentration ([Ca(2+)]cyt) triggers vasoconstriction and stimulates cell proliferation leading to vascular remodeling. However, dihydropyridine-type voltage-dependent Ca(2+) channel blockers are only effective in very few patients with IPAH (<10%). It is unclear why dihydropyridine Ca(2+) channel blockers are not therapeutically effective in a majority of IPAH patients. We have previously shown that extracellular Ca(2+)-sensing receptor (CaSR) is upregulated in PASMCs from IPAH patients, and it contributes to enhanced [Ca(2+)]cyt responses and augmented cell proliferation. In this study, the effects of dihydropyridine Ca(2+) channel blockers on [Ca(2+)]cyt responses mediated by CaSR were examined in IPAH-PASMCs. Nifedipine (dihydropyridines) enhanced the CaSR-mediated increase in [Ca(2+)]cyt in IPAH-PASMCs, but not in PASMCs from normal subjects. Nicardipine (dihydropyridines) and Bay K 8644 (a dihydropyridine Ca(2+) channel activator) also augmented the CaSR-mediated [Ca(2+)]cyt increase in IPAH-PASMCs. In contrast, non-dihydropyridine Ca(2+) channel blockers such as diltiazem (benzothiazepines) and verapamil (phenylalkylamines) had no effect on the [Ca(2+)]cyt response in IPAH-PASMCs. Finally, in monocrotaline-induced pulmonary hypertensive rats, nifedipine caused further increase in right ventricular systolic pressure and thus right ventricular hypertrophy. In conclusion, dihydropyridine Ca(2+) channel blockers could exacerbate symptoms of pulmonary hypertension in IPAH patients with upregulated CaSR in PASMCs.

  7. High-affinity antibodies to the 1,4-dihydropyridine Ca2+-channel blockers

    SciTech Connect

    Campbell, K.P.; Sharp, A.; Strom, M.; Kahl, S.D.

    1986-05-01

    Antibodies with high affinity and specificity for the 1,4-dihydropyridine Ca2+-channel blockers have been produced in rabbits by immunization with dihydropyridine-protein conjugates. Anti-dihydropyridine antibodies were found to specifically bind (/sup 3/H)nitrendipine, (/sup 3/H)-nimodipine, (/sup 3/H)nisoldipine, and (/sup 3/H)PN 200-110 (all 1,4-dihydropyridine Ca2+-channel blockers) with high affinity, while (/sup 3/H)verapamil, (/sup 3/H)diltiazem, and (/sup 3/H)trifluoperazine were not recognized. The average dissociation constant of the (/sup 3/H)nitrendipine-antibody complex was 0.06 (+/- 0.02) X 10(-9) M for an antiserum studied in detail and ranged from 0.01 to 0.24 X 10(-9) M for all antisera. Inhibition of (/sup 3/H)nitrendipine binding was specific for the 1,4-dihydropyridine Ca2+-channel modifiers and the concentrations required for half-maximal inhibition ranged between 0.25 and 0.90 nM. Structurally unrelated Ca2+-channel blockers, calmodulin antagonists, inactive metabolites of nitrendipine, and UV-inactivated nisoldipine did not modify (/sup 3/H)nitrendipine binding to the anti-dihydropyridine antibodies. Dihydropyridines without a bulky substituent in the 4-position of the heterocycle were able to displace (/sup 3/H)nitrendipine binding, but the concentrations required for half-maximal inhibition were greater than 800 nM. In summary, anti-dihydropyridine antibodies have been shown to have high affinity and specificity for the 1,4-dihydropyridine Ca2+-channel blockers and to exhibit dihydropyridine binding properties similar to the membrane receptor for the 1,4-dihydropyridine Ca2+-channel blockers.

  8. CoRoT light curves of Blazhko RR Lyrae stars. Evidence of a strong correlation between phase and amplitude modulations of CoRoT ID 0105288363

    NASA Astrophysics Data System (ADS)

    Chadid, M.; Perini, C.; Bono, G.; Auvergne, M.; Baglin, A.; Weiss, W. W.; Deboscher, J.

    2011-03-01

    Context. The CoRoT - Convection Rotation and planetary Transits - space mission provides a unique opportunity to monitor RR Lyrae stars with excellent time-sampling, unprecedented photometric precision, and a long time base of 150 days. Aims: The pulsation characteristics of RR Lyrae stars rely on robust physics, but we still lack a firm quantitative understanding of the physical mechanisms driving the Blazhko modulation and the long-term changes in their pulsation behavior. We use the high-precision space data of an unknown RR Lyrae star CoRoT ID 0105288363 observed during a second long run centered on the Galaxy - LRc02 -, to improve our understanding of the pulsation properties of RR Lyrae stars. Methods: The CoRoT data were corrected using a jump and trend filtering code. We applied different period-finding techniques including Period04, MuFrAn, PDM, and SigSpec. Amplitude and phase modulation were investigated using an analytical function method as well as traditional O-C diagrams. Results: For the first time, we detect significant cycle-to-cycle changes in the Blazhko modulation, which appear to be analogous to those predicted by Stothers - owing to the suppression of turbulent convection - to explain this phenomenon. We discuss the clear correlations between the phase and the amplitude of the bump, and the skewness and acuteness of the light curve during different Blazhko cycles. We find that these quantities are strongly anticorrelated with the fundamental pulsation period. This provides a strong support to the slow convective cycle model suggested by Stothers. We also detect a long-term modulation period in the maximum brightness spectrum. A more extended coverage of the long-term modulation is required to constrain its period. Seventh-order side peaks of the pulsation multiplet structure are also visible with the left-side peak amplitudes being higher than those of the right. This has never previously been detected. Future theoretical investigations are

  9. Combination therapy of angiotensin II receptor blocker and calcium channel blocker exerts pleiotropic therapeutic effects in addition to blood pressure lowering: amlodipine and candesartan trial in Yokohama (ACTY).

    PubMed

    Maeda, Akinobu; Tamura, Kouichi; Kanaoka, Tomohiko; Ohsawa, Masato; Haku, Sona; Azushima, Kengo; Dejima, Toru; Wakui, Hiromichi; Yanagi, Mai; Okano, Yasuko; Fujikawa, Tetsuya; Toya, Yoshiyuki; Mizushima, Shunsaku; Tochikubo, Osamu; Umemura, Satoshi

    2012-01-01

    Recent guidelines recommend combination antihypertensive therapy to achieve the target blood pressure (BP) and to suppress target organ damage. This study aimed to examine the beneficial effects of combination therapy with candesartan and amlodipine on BP control and markers of target organ function in Japanese essential hypertensive patients (N = 20) who did not achieve the target BP level during the monotherapy period with either candesartan or amlodipine. After the monotherapy period, for patients already being treated with amlodipine, a once-daily 8 mg dose of candesartan was added on during the combination therapy period (angiotensin II receptor blocker [ARB] add-on group, N = 10), and a once-daily 5 mg dose of amlodipine was added on for those already being treated with candesartan (calcium channel blocker [CCB] add-on group, N = 10). Combination therapy with candesartan and amlodipine for 12 weeks significantly decreased clinic and home systolic blood pressure (SBP) and diastolic blood pressure (DBP). In addition, the combination therapy was able to significantly reduce urine albumin excretion without decrease in estimated glomerular filtration ratio and resulted in significant improvements in brachial-ankle pulse wave velocity, central SBP, and insulin sensitivity. Furthermore, the CCB add-on group showed a significantly greater decrease in clinic and home DBP than the ARB add-on group. The calcium channel blocker add-on group also exhibited better improvements in vascular functional parameters than the ARB add-on group. These results suggest that combination therapy with candesartan and amlodipine is an efficient therapeutic strategy for hypertension with pleiotropic benefits.

  10. Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis

    PubMed Central

    Canales, Benjamin K; Rogers, Mary A M; Sukumar, Shyam; Yan, Phyllis; Kuntz, Gretchen M; Dahm, Philipp

    2016-01-01

    Objective To investigate the efficacy and safety of alpha blockers in the treatment of patients with ureteric stones. Design Systematic review and meta-analysis. Data sources Cochrane Central Register of Controlled Trials, Web of Science, Embase, LILACS, and Medline databases and scientific meeting abstracts to July 2016. Review methods Randomized controlled trials of alpha blockers compared with placebo or control for treatment of ureteric stones were eligible.Two team members independently extracted data from each included study. The primary outcome was the proportion of patients who passed their stone. Secondary outcomes were the time to passage; the number of pain episodes; and the proportions of patients who underwent surgery, required admission to hospital, and experienced an adverse event. Pooled risk ratios and 95% confidence intervals were calculated for the primary outcome with profile likelihood random effects models. Cochrane Collaboration’s tool for assessing risk of bias and the GRADE approach were used to evaluate the quality of evidence and summarize conclusions. Results 55 randomized controlled trials were included. There was moderate quality evidence that alpha blockers facilitate passage of ureteric stones (risk ratio 1.49, 95% confidence interval 1.39 to 1.61). Based on a priori subgroup analysis, there seemed to be no benefit to treatment with alpha blocker among patients with smaller ureteric stones (1.19, 1.00 to 1.48). Patients with larger stones treated with an alpha blocker, however, had a 57% higher risk of stone passage compared with controls (1.57, 1.17 to 2.27). The effect of alpha blockers was independent of stone location (1.48 (1.05 to 2.10) for upper or middle stones; 1.49 (1.38 to 1.63) for lower stones). Compared with controls, patients who received alpha blockers had significantly shorter times to stone passage (mean difference −3.79 days, −4.45 to −3.14; moderate quality evidence), fewer episodes of pain (−0

  11. The effect of quorum-sensing blockers on the formation of marine microbial communities and larval attachment.

    PubMed

    Dobretsov, Sergey; Dahms, Hans-Uwe; Yili, Huang; Wahl, Martin; Qian, Pei-Yuan

    2007-05-01

    We studied the effect of the quorum-sensing (QS) blockers 5-hydroxy-3[(1R)-1-hydroxypropyl]-4-methylfuran-2(5H)-one (FUR1), (5R)-3,4-dihydroxy-5-[(1S)-1,2-dihydroxyethyl]furan-2(5H)-one (FUR2) and triclosan (TRI) on the formation of bacterial biofilms, and the effect of these biofilms on the larval attachment of the polychaete Hydroides elegans and the bryozoan Bugula neritina. 14-day-old subtidal biofilms were harvested from artificial substrata and were allowed to develop in the laboratory with and without QS blockers. QS blockers inhibited the production of violacein by the QS reporter strain Chromobacterium violaceum CV026 and did not affect the metabolic activity of bacteria in multispecies biofilms. At a concentration of 10(-3) M all three tested compounds inhibited the establishment of microbial communities, but at one of 10(-4) M only FUR2 inhibited establishment. The tested QS blockers caused changes in bacterial density and bacterial community structure, as revealed by terminal restriction fragment length polymorphism and FISH. The groups most affected by QS blockers were Alphaproteobacteria, Gammaproteobacteria and the Cytophagales. Larvae of H. elegans and B. neritina avoided settling on biofilms that had developed in the presence of QS blockers. Our results suggest that QS blockers directly control the formation of multi-species biofilms, and indirectly - by means of biofilm properties - affect larval attachment on these modified biofilms.

  12. Protective effects of beta-blockers against 2,2'-azobis(2-amidinopropane)-dihydrochloride-induced damage.

    PubMed

    Miura, T; Muraoka, S; Ogiso, T

    1995-06-30

    The protective effects of beta-blockers against 2,2'-azobis(2- amidinopropane)-dihydrochloride (AAPH)-induced damage were investigated. With the exception of pindolol, none of the beta-blockers tested inhibited arachidonate peroxidation induced by AAPH in the absence of iron. In contrast, ADP-Fe(3+)- and NADPH-dependent microsomal lipid peroxidation was inhibited by all the beta-blockers tested, although the inhibitory effects of atenolol and metoprolol were very slight. Oxidation of tryptophan residues in bovine serum albumin (BSA) induced by AAPH was strongly inhibited by pindolol and propranolol but not by atenolol or metoprolol. All the beta-blockers tested, however, inhibited AAPH-induced carbonyl formation of BSA. Furthermore, all the beta-blockers tested also strongly inhibited the deoxyribose degradation induced by AAPH, suggesting that these agents act as hydroxyl radical scavengers to inhibit carbonyl formation. DNA strand scission was induced by AAPH in the absence or presence of O2. Only pindolol strongly inhibited the DNA damage in the absence of O2. In the presence of O2, however, all the beta-blockers tested effectively prevented the DNA damage. These results suggested that the hydroxyl radicals produced from AAPH damaged DNA and, that beta-blockers might act as hydroxyl radical scavengers to protect DNA against the AAPH-induced oxidative damage.

  13. Effects of the novel 5-HT(6) receptor antagonist RO4368554 in rat models for cognition and sensorimotor gating.

    PubMed

    Schreiber, Rudy; Vivian, Jef; Hedley, Linda; Szczepanski, Krystine; Secchi, Rob L; Zuzow, Marcus; van Laarhoven, Susanne; Moreau, Jean-Luc; Martin, James R; Sik, Ayhan; Blokland, Arjan

    2007-03-01

    Serotonin(6) (5-HT(6)) receptors are almost exclusively located in the central nervous system. High expression in the hippocampus, nucleus accumbens and striatum is consistent with a potential role in cognition and psychosis. The availability of potent, selective and brain-penetrating 5-HT(6) antagonists such as RO4368554 allows further characterization of the role of the 5-HT(6) receptor in these processes. Herein, we tested RO4368554 in several cognition tasks, as well as sensorimotor gating tests. Using scopolamine-impaired and unimpaired adult male rats, RO4368554 was given in novel object discrimination, social recognition, social discrimination, Morris water maze, passive avoidance and autoshaping procedures. RO4368554 reversed the effects of scopolamine in novel object discrimination (active doses in mg/kg, i.p., 3, 10), social recognition (3, 10), social discrimination (1, 3, 10) and passive avoidance (10, 30 i.p. and 100 p.o.) tasks. In unimpaired rats, RO4368554 enhanced object discrimination (3, 10; 4-h forgetting interval) and autoshaping learning (3), but was inactive in a water maze task (doses tested: 1-10 mg/kg, i.p.). In tests sensitive to antipsychotics, RO4368554 did not reverse sensorimotor gating deficits induced by the psychostimulants dizocilpine and amphetamine (doses tested: 1-30 mg/kg, i.p.) or neonatal lesion of the ventral hippocampus (1-10 mg/kg, i.p.). In conclusion, RO4368554 enhanced learning and memory processes in unimpaired and scopolamine-impaired rats, supporting the notion that the cognitive enhancing effects of 5-HT(6) receptor antagonists involve modulation of cholinergic neurotransmission.

  14. Characterization and biotoxicity assessment of dissolved organic matter in RO concentrate from a municipal wastewater reclamation reverse osmosis system.

    PubMed

    Sun, Ying-Xue; Gao, Yue; Hu, Hong-Ying; Tang, Fang; Yang, Zhe

    2014-12-01

    Reverse osmosis (RO) concentrate from municipal wastewater reclamation reverse osmosis (mWRRO) system containing organic compounds may associate with toxic risk, and its discharge might pose an environmental risk. To identify a basis for the selection of feasible technology in treating RO concentrates, the characteristics and biotoxicity of different fractions of dissolved organic matter (DOM) in RO concentrates from an mWRRO system were investigated. The results indicated that the hydrophilic neutrals (HIN), hydrophobic acids (HOA) and hydrophobic bases (HOB) accounted for 96% of the dissolved organic carbon (DOC) of the total DOM in the RO concentrate. According to the SEC chromatograph detected at 254 nm wavelength of UV, the DOM with molecular weight (MW) 1-3 kDa accounted for the majority of the basic and neutral fractions. The fluorescence spectra of the excitation emission matrix (EEM) indicated that most aromatic proteins, humic/fulvic acid-like and soluble microbial by-product-like substances existed in the fractions HOA and hydrophobic neutrals (HON). The genotoxicity and anti-estrogenic activity of the RO concentrate were 1795.6 ± 57.2 μg 4-NQOL(-1) and 2.19 ± 0.05 mg TAM L(-1), respectively. The HIN, HOA, and HOB contributed to the genotoxicity of the RO concentrate, and the HIN was with the highest genotoxic level of 1007.9 ± 94.8 μg 4-NQOL(-1). The HOA, HON, and HIN lead to the total anti-estrogenic activity of the RO concentrate, and HOA occupied approximately 60% of the total, which was 1.3 ± 0.17 mg TAM L(-1).

  15. Surface display of roGFP for monitoring redox status of extracellular microenvironments in Shewanella oneidensis biofilms.

    PubMed

    Sivakumar, Krishnakumar; Mukherjee, Manisha; Cheng, Hsin-I; Zhang, Yingdan; Ji, Lianghui; Cao, Bin

    2015-03-01

    Biofilms are the most ubiquitous and resilient form of microbial life on earth. One most important feature of a biofilm is the presence of a self-produced matrix, which creates highly heterogeneous and dynamic microenvironments within biofilms. Redox status in biofilm microenvironments plays a critical role in biofilm development and function. However, there is a lack of non-intrusive tools to quantify extracellular redox status of microenvironments within a biofilm matrix. In this study, using Shewanella oneidensis as a model organism, we demonstrated a novel approach to monitor extracellular redox status in biofilm microenvironments. Specifically, we displayed a redox sensitive fluorescence protein roGFP onto the cell surface of S. oneidensis by fusing it to the C-terminus of BpfA, a large surface protein, and used the surface displayed roGFP as a sensor to quantify the extracellular redox status in the matrix of S. oneidensis biofilms. The fusion of roGFP into BpfA has no negative impacts on cell growth and biofilm formation. Upon exposure to oxidizing agents such as H2 O2 , Ag(+) , and SeO3 (2-) , S. oneidensis BpfA-roGFP cells exhibited a characteristic fluorescence of roGFP. Proteinase treatment assay and super-resolution structured illumination microscopy confirmed the surface localization of BpfA-roGFP. We further used the surface displayed roGFP monitored the extracellular redox status in the matrix at different depths of a biofilm exposed to H2 O2 . This study provides a novel approach to non-invasively monitor extracellular redox status in microenvironments within biofilms, which can be used to understand redox responses of biofilms to environmental perturbations.

  16. Five Years of the RoBOT "Rocks Beneath Our Toes" High School Outreach Program

    NASA Astrophysics Data System (ADS)

    Baxter, E. F.

    2011-12-01

    The "Rocks Beneath Our Toes" or RoBOT Program began in 2006 as part of an NSF CAREER award through the Geochemistry and Petrology Program. The educational outreach program engages Boston area high school students in a hands on study of rocks and minerals collected in their communities. The goal is to provide high school students a unique window into modern scientific methods of geochemistry and mineralogy and create a higher level of interest and awareness of geoscience amongst Massachusetts secondary school students who are less often exposed to earth science coursework. Beginning with a joint field trip to sampling sites identified by participants, high school students work with Boston University undergraduates enrolled in Mineralogy to analyze their samples in thin section. During the field trip, each BU undergraduate is paired with a high school student. The assignment of student pairings (started in year 2) dramatically increased student interactions and enjoyment. The program culminates with a visit by the high school group to tour BU's lab facilities and work with the undergraduates using the petrographic microscopes to explore their rock. At this visit, BU undergraduates present their semester's work in one-on-one powerpoint presentations from which discussion and microscope work follow. Thus far, >50 high school students, >40 undergraduates, and 7 high school educators were involved in the program. This included participants from three different suburban Boston area high schools and with students enrolled in the BU "Upward Bound" program: an existing program designed to enhance educational opportunities for Boston inner city high school students. Participant reviews indicate great success in achieving the program's goals. Notably, both BU undergraduates and high school students rated the opportunities for interaction with eachother among the best aspects of RoBOT. On a scale of 1 to 10, BU undergraduates rated the following four categories highest

  17. Efficacy of beta-blocker therapy in symptomatic athletes with exercise-induced intra-ventricular gradients

    PubMed Central

    2010-01-01

    Background Upright exercise stress echocardiography (SE) induces significant intraventricular gradient (IVG) and systolic anterior motion (SAM) in a large proportion of symptomatic athletes, who may therefore benefit from a negative inotropic therapy. The purpose of the present study was to assess the effect of chronic oral β blocker therapy on the occurrence of exercise-induced IVG and mitral valve SAM, in symptomatic athletes. Methods We enrolled 35 symptomatic athletes (age = 23 ± 11 years) with IVG (>30 mmHg) during SE off therapy. All repeated SE on chronic oral beta-blocker therapy (atenolol up to 50 mg, bisoprolol up to 10 mg, or metoprolol up to 100 mg daily according to physician-driven choice). Results On therapy, there was during SE a reduction in IVG (35 off vs 17 on beta blocker, p < 0.01), decrease of IVG (102 ± 34 mmHg off vs 69 ± 24 mmHg on beta blocker, p < 0.01), peak heart rate (178 ± 15 bpm off vs 157 ± 9 bpm on beta blocker), SAM (24 off vs 9 on beta blocker, p < 0.001), symptoms during SE (17 off vs 2 on beta blocker p < 0.001), ST segment depression (13 off vs 2 on beta blocker, p < 0.001). Conclusions In athletes with positive screening on medical evaluation for sports practice and IVG on exertion, treatment with oral beta blockers improved symptoms in the large majority of patients. Symptomatic benefit was mirrored by objective evidence of improvement of echocardiographic signs of obstruction (IVG and SAM) and reduction of ischemia-like electrocardiographic changes. PMID:20813061

  18. In silico screening for agonists and blockers of the β2 adrenergic receptor: implications of inactive and activated state structures

    PubMed Central

    Costanzi, Stefano; Vilar, Santiago

    2011-01-01

    Ten crystal structures of the β2 adrenergic receptor (β2AR) have been published, reflecting different signaling states. Here, through controlled docking experiments, we examined the implications of using inactive or activated structures on the in silico screening for agonists and blockers of the receptor. Specifically, we targeted the crystal structures solved in complex with carazolol (2RH1), the neutral antagonist alprenalol (3NYA), the irreversible agonist FAUC50 (3PDS) and the full agonist BI-167017 (3P0G). Our results indicate that activated structures favor agonists over blockers while inactive structures favor blockers over agonists. This tendency is more marked for activated than for inactive structures. Additionally, agonists tend to receive more favorable docking scores when docked at activated rather than inactive structures, while blockers do the opposite. Hence, the difference between the docking scores attained with an activated and an inactive structure is an excellent means for the classification of ligands into agonists and blockers, as we determined through receiver operating characteristic (ROC) curves and linear discriminant analysis (LDA). With respect to virtual screening, all structures prioritized well agonists and blockers over non-binders. However, inactive structures worked better for blockers and activated structures worked better for agonists. Notably, the combination of individual docking experiments through receptor ensemble docking (RED) resulted in an excellent performance in the retrieval of both agonists and blockers. Finally, we demonstrated that the induced fit docking of agonists is a viable way of modifying an inactive crystal structure and bias it towards the in silico recognition of agonists rather than blockers. PMID:22170280

  19. New RoF-PON architecture using polarization multiplexed wireless MIMO signals for NG-PON

    NASA Astrophysics Data System (ADS)

    Elmagzoub, M. A.; Mohammad, Abu Bakar; Shaddad, Redhwan Q.; Al-Gailani, Samir A.

    2015-06-01

    Next-generation access networks require provision of wireless services and high data rate to meet the huge demands for mobility and multiple services. Moreover, reusing the currently deployed optical distribution networks (ODNs) is highly beneficial and cost effective for providing the new high data rate wireless demands. In this paper, bidirectional radio over fiber passive optical network (RoF-PON) capable of handling multiple-input-multiple-output (MIMO) streams at low cost, high spectral efficiency and backward compatibility with currently deployed PON, is proposed. To the best of our knowledge, all the existing RoF MIMO solutions have not considered compatibility with currently deployed ODNs. Eight laser diodes (LDs) at the central office (CO) are enough for the whole system, instead of having LD or optical transmitter at each remote antenna unit (RAU), which makes a colorless and cost-effective RAU. Twenty four wavelengths are generated using optical comb technique. Each two 16-QAM MIMO signals that have the same carrier frequency in the downstream (DS) transmission are optically combined using polarization-division-multiplexing (PDM), where each two upstream (US) MIMO signals are time division multiplexed. The PDM configuration doubles spectral efficiency with a power penalty of only 1.5 dB. The proposed architecture is a bidirectional asymmetric RoF-PON with total 40/10 Gb/s for DS/US transmission. Even after transmission over 20 km SMF and splitting ratio of 32, acceptable transmission performance and widely separated constellation diagrams for the 16-QAM signals are achieved, with bit error rate (BER) of 10-6 for DS signals and 10-3 for the US signals which can be reduced down to 10-6 by using forward error correction (FEC).

  20. Potential Return on Investment (RoI) on web-based diabetes education in UK.

    PubMed

    Shabestari, Omid; Roudsari, Abdul

    2009-01-01

    The incidence of diabetes mellitus is growing in the UK. As most diabetes care is performed by the patients themselves, structured education is one way to encourage their responsible participation in delivering effective care. Continuous e-learning by Internet has proven to be a useful method of diabetes education. "Return on Investment" (RoI) can be used as an indicator of the cost-benefit of web-based education. RoI is the ratio of money gained or lost on an investment relative to the amount of money invested. This report uses system dynamics modeling to predict the flow of patients in the educational system and the cost of their care. The analysis compared traditional and web-based education. Separate models were developed for each educational method and simulated until 2020 in one year intervals. The population of diabetic patients was adjusted at each cycle according to anticipated incidence and mortality rates. The population of educated diabetic patients was based on the educational capacity and literacy limits of each method. A report by the National Health Service (NHS) was used to calculate the cost of care by considering the cost difference between uneducated and educated patients. By 2020 with an annual rate of inflation of 3%, the annual cost of care is projected to increase to pound 3.67 billion for the traditional model as compared to pound 3.39 billion for the web-based model. RoI is estimated to be a ratio of 32.33. Investment in web-based diabetes education is not only a health benefit but also a reduction in care cost.

  1. Current use of beta blockers in patients with reactive airway disease who are hospitalized with acute coronary syndromes.

    PubMed

    Olenchock, Benjamin A; Fonarow, Gregg G; Pan, Wenqin; Hernandez, Adrian; Cannon, Christopher P

    2009-02-01

    Beta blockers have a proven benefit in the management of patients with acute coronary syndromes (ACS) and for secondary prevention of coronary events. Current guidelines list such reactive airway diseases (RADs) such as asthma and chronic obstructive pulmonary disease as relative contraindications to beta-blocker use. However, the co-morbid burden of RAD and coronary heart disease is substantial, and data suggest that the treatment benefit of beta blockers is shared by patients with RAD. The Get with the Guidelines (GWTG) database was used to evaluate use of beta blockers within 24 hours of admission and at discharge in patients with ACS with (n = 12,967) and without (n = 81,140) a history of RAD. Data were collected in 435 hospitals between January 2000 and September 2006. A multivariable logistic regression model was used to determine predictors of beta-blocker treatment. In patients with no RAD history, beta-blocker prescription rates were 78.3% at admission and 88.7% at discharge; in patients with a RAD history, rates were 65.6% at admission and 77.2% at discharge. Compared with patients with no history of RAD, patients with a history of RAD were 42% less likely (odds ratio 0.58, confidence interval 0.54 to 0.62, p <0.0001) to receive a beta blocker upon admission and 55% less likely (odds ratio 0.45, confidence interval 0.41 to 0.48, p <0.0001) to receive a beta blocker at discharge in multivariable analysis. Among all other clinical factors, RAD history was the most significant predictor of likelihood of not receiving a beta blocker at admission or discharge. Receipt of beta blockers within 24 hours after admission was associated with a lower in-hospital mortality rate for patients with RAD (odds ratio = 0.52, p <0.001) and for patients without RAD (odds ratio = 0.38, p <0.001). Careful assessment of beta-blocker safety and RAD severity by physicians is needed to improve beta-blocker prescription rates in this large group of patients with ACS.

  2. Rotation period distribution of CoRoT and Kepler Sun-like stars

    NASA Astrophysics Data System (ADS)

    Leão, I. C.; Pasquini, L.; Ferreira Lopes, C. E.; Neves, V.; Valcarce, A. A. R.; de Oliveira, L. L. A.; Freire da Silva, D.; de Freitas, D. B.; Canto Martins, B. L.; Janot-Pacheco, E.; Baglin, A.; De Medeiros, J. R.

    2015-10-01

    Aims: We study the distribution of the photometric rotation period (Prot), which is a direct measurement of the surface rotation at active latitudes, for three subsamples of Sun-like stars: one from CoRoT data and two from Kepler data. For this purpose, we identify the main populations of these samples and interpret their main biases specifically for a comparison with the solar Prot. Methods: Prot and variability amplitude (A) measurements were obtained from public CoRoT and Kepler catalogs, which were combined with public data of physical parameters. Because these samples are subject to selection effects, we computed synthetic samples with simulated biases to compare with observations, particularly around the location of the Sun in the Hertzsprung-Russel (HR) diagram. Publicly available theoretical grids and empirical relations were used to combine physical parameters with Prot and A. Biases were simulated by performing cutoffs on the physical and rotational parameters in the same way as in each observed sample. A crucial cutoff is related with the detectability of the rotational modulation, which strongly depends on A. Results: The synthetic samples explain the observed Prot distributions of Sun-like stars as having two main populations: one of young objects (group I, with ages younger than ~1 Gyr) and another of main-sequence and evolved stars (group II, with ages older than ~1 Gyr). The proportions of groups I and II in relation to the total number of stars range within 64-84% and 16-36%, respectively. Hence, young objects abound in the distributions, producing the effect of observing a high number of short periods around the location of the Sun in the HR diagram. Differences in the Prot distributions between the CoRoT and Kepler Sun-like samples may be associated with different Galactic populations. Overall, the synthetic distribution around the solar period agrees with observations, which suggests that the solar rotation is normal with respect to Sun

  3. Reassessing the radial-velocity evidence for planets around CoRoT-7

    NASA Astrophysics Data System (ADS)

    Pont, Frédéric; Aigrain, Suzanne; Zucker, Shay

    2011-03-01

    CoRoT-7 is an 11 th magnitude K-star whose light curve shows transits with a depth of 0.3 mmag and a period of 0.854 d, superimposed on variability at the 1 per cent level, due to the modulation of evolving active regions with the star's 23-d rotation period. In this paper, we revisit the published HARPS radial-velocity (RV) measurements of the object, which were previously used to estimate the companion mass, but have been the subject of ongoing debate. We build a realistic model of the star's activity during the HARPS observations, by fitting simultaneously the linewidth (as measured by the width of the cross-correlation function) and the line bisector, and use it to evaluate the contribution of activity to the RV variations. The data show clear evidence of errors above the level of the formal uncertainties, which are accounted for neither by activity nor by any plausible planet model and which increase rapidly with a decreasing signal-to-noise ratio (S/N) of the spectra. We cite evidence of similar systematics in mid-S/N spectra of other targets obtained with HARPS and other high-precision RV spectrographs, and discuss possible sources. Allowing for these, we re-evaluate the semi-amplitude of the CoRoT-7b signal, finding Kb= 1.6 ± 1.3 m s-1, a tentative detection with a much reduced significance (1.2σ) compared to previous estimates. We also argue that the combined presence of activity and additional errors precludes a meaningful search for additional low-mass companions, despite previous claims to the contrary. Taken at face value, our analysis points to a lower density for CoRoT-7b, the 1σ mass range spanning 1-4 M ⊕ and allowing for a wide range of bulk compositions. In particular, an ice-rich composition is compatible with the RV constraints. More generally, this study highlights the importance of a realistic treatment of both activity and uncertainties, particularly in the medium S/N regime, which applies to most small planet candidates from CoRoT and

  4. roAp stars: surface lithium abundance distribution and magnetic field configuration

    NASA Astrophysics Data System (ADS)

    Polosukhina, N.; Shulyak, D.; Shavrina, A.; Lyashko, D.; Drake, N. A.; Glagolevski, Yu.; Kudryavtsev, D.; Smirnova, M.

    2014-08-01

    High-resolution spectra obtained with the 6m BTA telescope, Russia, and with HARPS and VLT/UVES telescopes at ESO, Chile, were used for Doppler Imaging analysis of two roAp stars, HD 12098 and HD 60435, showing strong and variable Li resonance line in their spectra. We found that Li has highly inhomogeneous distribution on the surfaces of these stars. We compared our results with previously obtained Doppler Imaging mapping of two CP2 stars, HD 83368 and HD 3980, and discuss the correlation between the position of the high Li-abundance spots and magnetic field.

  5. The combination of OLmesartan and a CAlcium channel blocker (azelnidipine) or candesartan and a calcium channel blocker (amlodipine) in type 2 diabetic hypertensive patients: the OLCA study.

    PubMed

    Daikuhara, Hiroyuki; Kikuchi, Fumi; Ishida, Toshihiko

    2012-10-01

    Angiotensin II receptor blockers (ARB) are often co-administered with a calcium channel blocker (CCB) for treating hypertension. In this open-label randomised study, untreated diabetic hypertensive patients were randomised to receive either olmesartan 20 mg/day or candesartan 8 mg/day for 12 weeks. Patients with blood pressure exceeding 130/80 mm Hg received add-on 16 mg/day azelnidipine to ongoing olmesartan (OL group) or 5 mg/day amlodipine to ongoing candesartan (CA group) for 24 weeks. Home-measured and clinic-measured blood pressure decreased in both groups. Fasting blood glucose, haemoglobin A1c (HbA1c) and urinary albumin levels decreased significantly in the OL group but not in the CA group. In conclusion, this study revealed clinically relevant differences between two combinations of an ARB+CCB in diabetic hypertensive patients. Olmesartan and azelnidipine had a more persistent early morning antihypertensive effect and produced greater decreases in heart rate, fasting blood glucose and HbA1c (National Glycohemoglobin Standardization Program values) levels, and microalbuminuria than did candesartan and amlodipine.

  6. Characterization of in vivo and in vitro electrophysiological and antiarrhythmic effects of a novel IKACh blocker, NIP-151: a comparison with an IKr-blocker dofetilide.

    PubMed

    Hashimoto, Norio; Yamashita, Toru; Tsuruzoe, Nobutomo

    2008-02-01

    We investigated the electrophysiological and antiarrhythmic effects of a novel antiarrhythmic agent, NIP-151, and compared these effects with those of an IKr-blocker dofetilide. NIP-151 potently inhibited acetylcholine-activated K current (IKACh) with an IC50, with 1.6 nM in HEK293 cells expressing the GIRK1/4 channel, but it had little effect on IKr (IC50 = 57.6 microM). NIP-151 dose-dependently terminated AF both in vagal nerve stimulation-induced AF (at 5 and 15 microg/kg per minute) and aconitine-induced AF (at 30 and 100 microg/kg) models. This compound significantly prolonged the atrial effective refractory period (ERP), but it had no significant effects on ventricular ERP. There were no significant changes on electrocardiographic variables with NIP-151 (up to 1,000 microg/kg per minute) administration. In contrast, dofetilide had little effect in either AF model, even though this compound potently prolonged atrial ERP. Dofetilide also significantly prolonged ventricular ERP and the QT interval in anesthetized dogs, which are related to proarrhythmic risk. In conclusion, a novel antiarrhythmic agent NIP-151, which potently blocked IKACh, was highly effective in the two types of canine AF models with an atrial-specific ERP-prolonging profile. Therefore, NIP-151 might be useful for the treatment of AF with lower risk of proarrhythmia, compared with IKr blockers.

  7. Renoprotective effect of calcium channel blockers in combination with an angiotensin receptor blocker in elderly patients with hypertension. A randomized crossover trial between benidipine and amlodipine.

    PubMed

    Miyagawa, Koichi; Dohi, Yasuaki; Nakazawa, Ai; Sugiura, Tomonori; Yamashita, Sumiyo; Sato, Koichi; Kimura, Genjiro

    2010-01-01

    Anti-hypertensive medication with an angiotensin II receptor blocker (ARB) is effective in slowing the progression of chronic kidney disease. The present study was designed to investigate whether calcium channel blockers (CCBs) in combination with an ARB differentially affect kidney function. Elderly hypertensive patients with chronic kidney disease (n = 17, 72 +/- 6 years old) were instructed to self-measure blood pressure. They were randomly assigned to receive either benidipine (4-8 mg/day) or amlodipine (5-10 mg/day) combined with olmesartan (10 mg/day). After 3 months, CCBs were switched in each patient and the same protocol was applied for another 3 months. At baseline, significant correlation was obtained between urine albumin (22.8 +/- 16.7 (median +/- median absolute deviation) mg/g creatinine) and self-measured blood pressure (170 +/- 23/87 +/- 10 (mean +/- SD) mmHg, r = 0.65, p < 0.01). Both regimens reduced blood pressure to a similar extent (139 +/- 22/75 +/- 11 mmHg and 133 +/- 17/72 +/- 10 mmHg, respectively; both p < 0.001), while urine albumin decreased only after combination therapy including benidipine (11.7 +/- 6.1 mg/g creatinine, p < 0.05). Benidipine, but not amlodipine, in combination with olmesartan, reduced urinary albumin excretion in elderly hypertensive patients with chronic kidney disease. The results suggest the importance of selecting medications used in combination with ARB in hypertensive patients with chronic kidney disease.

  8. Efficacy and Safety of Combination Therapy Consisting of Angiotensin II Type 1 Receptor Blocker, Calcium Channel Blocker and Hydrochlorothiazide in Patients With Hypertension

    PubMed Central

    Shiga, Yuhei; Miura, Shin-ichiro; Motozato, Kota; Yoshimine, Yuka; Norimatsu, Kenji; Arimura, Tadaaki; Koyoshi, Rie; Morii, Joji; Kuwano, Takashi; Inoue, Ken; Shirotani, Tetsuro; Fujisawa, Kazuaki; Matsunaga, Eiyu; Saku, Keijiro

    2017-01-01

    Background Many patients continue to have high blood pressure (BP) even after treatment with high-dose (H)-angiotensin II type 1 receptor blocker (ARB)/calcium channel blocker (CCB) or middle-dose (M)-ARB/CCB/hydrochlorothiazide (HCTZ). Methods Thirty-two hypertensive patients who had the use of H-ARB/CCB or M-ARB/CCB/HCTZ were enrolled in this study. We applied a changeover with a switch to H-ARB (telmisartan 80 mg/day)/CCB (amlodipine 5 mg/day or nifedipine CR 40 mg/day)/HCTZ (12.5 mg/day). Results Systolic BP (SBP) and diastolic BP (DBP) were significantly decreased in all patients and in the H-ARB/CCB and M-ARB/CCB/HCTZ groups after 3 months. Percentage (%) of patients who reached the target BP after 3 months (72%) in all patients was significantly higher than that at 0 months (19%). There were no serious adverse effects in any of the patients. Conclusions Combination therapy with H-ARB/CCB/HCTZ was associated with a significant reduction of BP. PMID:28090225

  9. Perioperative beta-blockers for preventing surgery-related mortality and morbidity.

    PubMed

    Bolton, Nerys

    2016-03-01

    For many patients any type of surgical invention can increase their stress response which can make the body vulnerable to untoward outcomes. An extreme consequence of the stress response is death with other responses including heart attacks and stroke, to impacting on the patients' postoperative reviver such as their psychological status and pain recovery. Therefore there is a need to consider the attenuation of the perioperative stress response through the use of drugs such as beta-blockers. These drugs have been shown to reduce the heart rate and lower the patients' blood pressure. Although this is a desired result in trying to eliminate the effects of the stress response it can also have the opposite effect on reducing the patients' blood pressure and pulse to a point where the patients suffers ill effects such as stroke or death. Therefore it is vital to understand the influence of beta-blockers and their ability to influence perioperative cardiovascular morbidity and mortality.

  10. Differential Metabolic Effects of Beta-Blockers: an Updated Systematic Review of Nebivolol.

    PubMed

    Marketou, Maria; Gupta, Yashaswi; Jain, Shashank; Vardas, Panos

    2017-03-01

    Blood pressure management in hypertensive patients with metabolic abnormalities is challenging, since many of the antihypertensive drugs adversely affect metabolism. Besides effective control of blood pressure in patients with hypertension, third-generation beta-blockers such as nebivolol offer additional benefits for central hemodynamics and neutral or beneficial effects on metabolism. Emerging clinical data suggest that nebivolol also has similar effects on metabolism in obese hypertensive and hypertensive diabetic patients. The present article will provide a systematic analysis of the pathophysiological links among hypertension, insulin resistance, and metabolic syndrome. We will also summarize the available clinical evidence regarding the metabolic effects of beta-blockers in hypertensive patients, with an emphasis on nebivolol. Nebivolol exerts neutral or beneficial effects on insulin sensitivity and lipid metabolism in hypertensive patients, owing to its nitric oxide-mediated vasodilatory and antioxidative properties. Thus, nebivolol could be a favorable therapeutic option for the treatment of hypertension in patients with impaired glucose and lipid metabolism.

  11. Evolution of β-blockers: from anti-anginal drugs to ligand-directed signalling.

    PubMed

    Baker, Jillian G; Hill, Stephen J; Summers, Roger J

    2011-04-01

    Sir James Black developed β-blockers, one of the most useful groups of drugs in use today. Not only are they being used for their original purpose to treat angina and cardiac arrhythmias, but they are also effective therapeutics for hypertension, cardiac failure, glaucoma, migraine and anxiety. Recent studies suggest that they might also prove useful in diseases as diverse as osteoporosis, cancer and malaria. They have also provided some of the most useful tools for pharmacological research that have underpinned the development of concepts such as receptor subtype selectivity, agonism and inverse agonism, and ligand-directed signalling bias. This article examines how β-blockers have evolved and indicates how they might be used in the future.

  12. 2-Ethynylbenzenealkanamines: a new class of calcium entry blockers with potential antihypertensive and antianginal properties

    SciTech Connect

    Brannan, M.D.; Carson, J.R.; Gill, A.; Keely, S.L.; Flaim, S.F.; Sit, S.P.; Damiano, B.P.; Carmosin, R.R.J.; Gleason, M.M.; Ludovici, D.W.; Pitis, P.M.

    1986-03-05

    2-Ethynylbenzenealkanamines represent a newly discovered class of calcium channel blockers in that they inhibited KCl-stimulated /sup 45/Ca influx and isometric tension development in isolated vascular smooth muscle and prolonged AV-nodal conduction time in canine hearts. Testing revealed optimal activity in the following structure where R1 is aryl, R2 and R4 are methyl, R3 is aralkyl and X is methoxy: compounds in this group lowered arterial pressures in conscious spontaneously hypertensive rats and renal hypertensive dogs following either oral or parenteral administration, and thus are potential antihypertensive agents. These compounds also caused coronary vasodilation at concentrations which did not affect rate or force of contraction in the isolated, perfused guinea pig heart preparation, they increased coronary blood flow and decreased coronary vascular resistance in the anesthetized canine, and thus are potential antianginal agents. In summary, 2-ethynylbenzenealkanamines represent a new class of calcium entry blockers which have potential antihypertensive and antianginal properties.

  13. Therapeutic considerations in the African-American patient with hypertension: considerations with calcium channel blocker therapy.

    PubMed

    Flack, John M; Sica, Domenic A

    2005-04-01

    African Americans have a higher prevalence, earlier onset, and more rapid progression of hypertensive end-organ disease, as well as excessive hypertensive mortality compared with other racial/ethnic groups. Most differences in hypertension and pressure-related complications between African Americans and whites appear to be quantitative and not qualitative. Improving the diagnosis, treatment, and control of hypertension in this highly vulnerable population is a major health care goal for the new millennium. In this regard the dietary pattern to be promoted for reduction of hypertension risk in African Americans is one of increased consumption of dairy products, fruit, and vegetables as well as a continued emphasis on decreased Na+ intake. When pharmacologic therapy is considered, multi-drug approaches are generally required, with diuretics, angiotensin-converting enzyme inhibitors (or angiotensin receptor blockers), and calcium channel blocker therapy as oft-selected components of most such treatment regimens.

  14. Pharmacological correction of obesity-induced autophagy arrest using calcium channel blockers

    PubMed Central

    Park, Hwan-Woo; Park, Haeli; Semple, Ian A.; Jang, Insook; Ro, Seung-Hyun; Kim, Myungjin; Cazares, Victor A.; Stuenkel, Edward L.; Kim, Jung-Jae; Kim, Jeong Sig; Lee, Jun Hee

    2014-01-01

    Autophagy deregulation during obesity contributes to the pathogenesis of diverse metabolic disorders. However, without understanding the molecular mechanism of obesity interference in autophagy, development of therapeutic strategies for correcting such defects in obese individuals is challenging. Here we show that chronic increase of cytosolic calcium concentration in hepatocytes upon obesity and lipotoxicity attenuates autophagic flux by preventing the fusion between autophagosomes and lysosomes. As a pharmacological approach to restore cytosolic calcium homeostasis in vivo, we administered the clinically approved calcium channel blocker verapamil to obese mice. Such treatment successfully increases autophagosome-lysosome fusion in liver, preventing accumulation of protein inclusions and lipid droplets and suppressing inflammation and insulin resistance. As calcium channel blockers have been safely used in clinics for the treatment of hypertension for more than thirty years, our results suggest they may be a safe therapeutic option for restoring autophagic flux and treating metabolic pathologies in obese patients. PMID:25189398

  15. Should we add beta-blockers to band ligation for secondary prophylaxis of variceal bleeding?

    PubMed

    Cotoras, Petre; Faúndez, Jorge; Candia, Roberto

    2017-02-23

    Cirrhotic patients who have had an episode of bleeding from gastroesophageal varices are at high risk of rebleeding, despite treatment with endoscopic variceal ligation. Adding beta-blockers could reduce this risk, but it is associated with adverse effects. Searching in Epistemonikos database, which is maintained by screening multiple databases, we identified seven systematic reviews including 21 randomized controlled trials addressing the question of this article. We extracted data, combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded the addition of beta-blockers to endoscopic variceal ligation as secondary prophylaxis of variceal bleeding reduces the risk of rebleeding, but probably does not lead to any difference in terms of mortality. Even though it is associated to frequent adverse effects, these would be mild and generally do not lead to discontinuation of treatment.

  16. Comparison of Alpha Blockers in Treatment of Premature Ejaculation: A Pilot Clinical Trial

    PubMed Central

    Akin, Yigit; Gulmez, Hakan; Ates, Mutlu; Bozkurt, Aliseydi; Nuhoglu, Baris

    2013-01-01

    Background: Premature ejaculation (PE) is the most common sexual disorder in men and studies reported prevalence up to 30% (1, 2). PE is not a life-threatening medical condition but it influences the quality of life (QoL). Objectives: The aim of this study was to compare the efficiency, and safety of alpha blocker drugs in the treatment of patients with premature ejaculation (PE). Additionally we investigated the quality of life (QoL) in patients with PE who were treated with alpha blocker drugs. Materials and Methods: This study was a pilot clinical trial. Prospectively documented 108 patients with PE were treated and were followed-up in urology outpatient clinic. All patients were divided into 5 groups according to used alpha blocker agents which were determined by simple randomization. Silodosin 4mg (Group 1, n = 21), tamsulosin hydrochloride 0.4mg (Group 2, n = 23), alfuzosin 10mg (Group 3, n = 22), terazosin 5mg (Group 4, n = 21), doksazosin mesylate 4mg (Group5, n = 21), were used for treatment. The demographic parameters of patients, pre and post treatment intravaginal ejaculation latency time (IELT), PE Profile (PEP), and QoL index were recorded and evaluated. Effectiveness of treatment was evaluated by measuring IELT. Additionally, side effects of drugs were recorded. P < 0.05 was considered statistically significant. Results: All alpha blocker drugs were statistically effective for preventing PE. Notably, silodosin seemed to be more effective for preventing PE than other alpha blockers (P < 0.05). However all alpha blockers provided development in QoL scores, silodosin was a little better than other drugs in statistical analyses. Furthermore statistical increase in IELT and decrease in PEP were provided more in Group 1 than other groups (P < 0.05). Conclusions: Silodosin seems to be able to even more prevent PE. Silodosin may provide development in QoL than other alpha blocker agents. Additionally, lower systemic adverse events and more effectivity are

  17. New Evidence Supporting the Use of Mineralocorticoid Receptor Blockers in Drug-Resistant Hypertension.

    PubMed

    Narayan, Hafid; Webb, David J

    2016-04-01

    Treatment resistant hypertension (TRH), defined as a blood pressure above goal despite treatment with optimally tolerated doses of 3 antihypertensive agents of different classes, ideally including a diuretic, remains a significant problem and its management an area of uncertainty for physicians. One hypothesis is that resistant hypertension is due to abnormal sodium retention, mediated by aldosterone breakthrough occurring despite blockade of the renin-angiotensin-aldosterone system with angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). Thus, there has been renewed interest in the use of mineralocorticoid receptor blockers (MRB) to treat this condition. This article critically evaluates new evidence supporting the use of MRB in TRH published in the last 3 years. We conclude that there is now sufficient evidence to recommend MRB, in particular spironolactone, as the first choice medication to treat this condition, and for its inclusion in future guidelines.

  18. Li and Ag Co-Doped ZnO Photocatalyst for Degradation of RO 4 Dye Under Solar Light Irradiation.

    PubMed

    Dhatshanamurthi, P; Shanthi, M

    2016-06-01

    The synthesis of Li doped Ag-ZnO (Li-Ag-ZnO) has been successfully achieved by a sonochemically assisted precipitation-decomposition method. The synthesized catalyst was characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), energy dispersive spectroscopy (EDS), diffuse reflectance spectra (DRS), photoluminescence spectra (PL), X-ray photoelectron spectra (XPS) and BET surface area measurements. The photocatalytic activity of Li-Ag-ZnO was investigated for the degradation of Reactive orange 4 (RO 4) dye in aqueous solution under solar light irradiation. Co-dopants shift the absorbance of ZnO to the visible region. Li-Ag-ZnO is found to be more efficient than Ag-ZnO, Li-ZnO, commercial ZnO and prepared ZnO at pH 7 for the mineralization of RO 4 dye under solar light irradiation. The influences of operational parameters such as the amount of photocatalyst, dye concentration, initial pH on photo-mineralization of RO 4 have been analyzed. The mineralization of RO 4 dye has been confirmed by COD measurements. A degradation mechanism is proposed for the degradation of RO 4 under solar light. The catalyst was found to be more stable and reusable.

  19. Refractory depression: mechanisms and evaluation of radically open dialectical behaviour therapy (RO-DBT) [REFRAMED]: protocol for randomised trial

    PubMed Central

    Lynch, T R; Whalley, B; Hempel, R J; Byford, S; Clarke, P; Clarke, S; Kingdon, D; O'Mahen, H; Russell, I T; Shearer, J; Stanton, M; Swales, M; Watkins, A; Remington, B

    2015-01-01

    Introduction Only 30–40% of depressed patients treated with medication achieve full remission. Studies that change medication or augment it by psychotherapy achieve only limited benefits, in part because current treatments are not designed for chronic and complex patients. Previous trials have excluded high-risk patients and those with comorbid personality disorder. Radically Open Dialectical Behaviour Therapy (RO-DBT) is a novel, transdiagnostic treatment for disorders of emotional over-control. The REFRAMED trial aims to evaluate the effectiveness and cost-effectiveness of RO-DBT for patients with treatment-resistant depression. Methods and analysis REFRAMED is a multicentre randomised controlled trial, comparing 7 months of individual and group RO-DBT treatment with treatment as usual (TAU). Our primary outcome measure is depressive symptoms 12 months after randomisation. We shall estimate the cost-effectiveness of RO-DBT by cost per quality-adjusted life year. Causal analyses will explore the mechanisms by which RO-DBT is effective. Ethics and dissemination The National Research Ethics Service (NRES) Committee South Central – Southampton A first granted ethical approval on 20 June 2011, reference number 11/SC/0146. Trial registration number ISRCTN85784627. PMID:26187121

  20. The study of CD20 and CD45.Ro antibodies in the inflammatory infiltrate involved in acne and seborrheic dermatitis.

    PubMed

    Ianoşi, Simona; Stoicescu, Irina; Ianoşi, G; Neagoe, Daniela; Georgescu, Claudia Valentina

    2007-01-01

    The aim of our study was to evaluate the role of CD20 and CD45.Ro antibodies in acne and seborrheic dermatitis. A number of 20 patients with papular, pustular or nodular acne and another 20 patients with seborrheic dermatitis were available for our study. We removed bioptic material from all of them and we perform histochemical and immunohistochemical processing within the Laboratory of Histology, Histopathology and Immunohistochemistry of the University of Medicine and Pharmacy of Craiova. In acne, we could reveal a positive CD45.Ro immunomarking in rare lymphoid cells situated in the middle derma at a distance from the affected pilosebaceous follicle and in the inflammatory infiltrate subepidermically, and also a negative immunomarking in the inflammatory cells from the proximity of the affected pilosebaceous follicle. In patients with seborrheic dermatitis we noticed a positive immunomarking infiltrate of the papillary derma and a positive immunomarking of membrane for CD45.Ro in many lymphoid cells of the inflammatory infiltrate situated in the papillary derma predominantly disposed perivasculary. Conclusions. The absence of the cells marked with CD45.Ro in the proximity of the pilosebaceous follicle interested in acne excludes the direct participation of B- and T-lymphocytes in the perifollicular inflammatory process, though the T-lymphocytes can be revealed in a small number at a distance from the affected follicle. The inflammatory infiltrate from the seborrheic dermatitis proved to be rich in positive CD45.Ro cells and poorer in positive CD20 cells.

  1. A new approach for determination of fouling potential by colloidal nanoparticles during reverse osmosis (RO) membrane filtration of seawater

    NASA Astrophysics Data System (ADS)

    Park, Ji Yeon; Lim, Sungil; Park, Kihong

    2013-04-01

    A direct measurement of number concentration of colloidal nanoparticles (15-450 nm) in water was made with the membrane filtration-differential mobility analyzer technique, and its corresponding flux decline rate (FDR) was determined by laboratory-scale RO fouling test unit using varying number concentrations of silica nanoparticles in artificial seawaters. This relationship was used to predict fouling potential of colloidal nanoparticles in reverse osmosis (RO) membrane process of seawaters in RO plant. It was found that the FDR linearly increased with the increasing number of colloidal nanoparticles for the given concentration range and that the relationship between the number concentration and the FDR also depended on RO membrane surface properties. Data for estimated FDR values for natural seawaters after pretreatment showed a clear difference among samples, which is contrary to the pre-existing index such as silt density index and modified fouling index. Our data suggest that measurement of colloidal nanoparticles is useful for selection of proper pretreatment and successful operation of RO membrane process along with other particle fouling predictors accounting for large particles (>450 nm).

  2. BCFtools/RoH: a hidden Markov model approach for detecting autozygosity from next-generation sequencing data

    PubMed Central

    Narasimhan, Vagheesh; Danecek, Petr; Scally, Aylwyn; Xue, Yali; Tyler-Smith, Chris; Durbin, Richard

    2016-01-01

    Summary: Runs of homozygosity (RoHs) are genomic stretches of a diploid genome that show identical alleles on both chromosomes. Longer RoHs are unlikely to have arisen by chance but are likely to denote autozygosity, whereby both copies of the genome descend from the same recent ancestor. Early tools to detect RoH used genotype array data, but substantially more information is available from sequencing data. Here, we present and evaluate BCFtools/RoH, an extension to the BCFtools software package, that detects regions of autozygosity in sequencing data, in particular exome data, using a hidden Markov model. By applying it to simulated data and real data from the 1000 Genomes Project we estimate its accuracy and show that it has higher sensitivity and specificity than existing methods under a range of sequencing error rates and levels of autozygosity. Availability and implementation: BCFtools/RoH and its associated binary/source files are freely available from https://github.com/samtools/BCFtools. Contact: vn2@sanger.ac.uk or pd3@sanger.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26826718

  3. The use of vasopressin in the setting of recalcitrant hypotension due to calcium channel blocker overdose.

    PubMed

    Kanagarajan, Karthikeyan; Marraffa, Jeanna M; Bouchard, Nicole C; Krishnan, Padmanabhan; Hoffman, Robert S; Stork, Christine M

    2007-01-01

    Treatment of hypotension caused by calcium channel blocker overdose (CCB) remains a challenge. We describe the successful use of vasopressin in two patients with massive CCB overdoses in whom hypotension was unresponsive to calcium, glucagon, insulin, and conventional vasopressor therapies. While various modes of treatments have been used to treat the hypotension of CCB overdose, this is the first report to our knowledge of the successful use of vasopressin in this clinical setting.

  4. Pineal perfusion with calcium channel blockers inhibits differently daytime and nighttime melatonin production in rat.

    PubMed

    Zhao, Z Y; Touitou, Y

    1994-05-01

    In a previous study we have shown that the response of perifused pineal glands to calcium was different according to the circadian stage at which the glands were removed. This difference may be explained by circadian changes in calcium channel function. Therefore in the present study we documented the effects of calcium channel blockers in perifused rat pineal glands removed in the middle of the light and dark spans (7 and 19 HALO (hours after light onset), in a L/D 12:12 regimen). Moreover, we have studied the effect of calcium channel blockers on adrenergically stimulated pineal glands removed 7 HALO. Inorganic (Co2+ and Cd2+) and organic (nifedipine and diltiazem) calcium channel blockers at 10(-4) mol/l all significantly reduced melatonin production and this inhibition was more effective with the glands removed 7 HALO. In a concentration of 10(-)5 mol/l, only Cd2+ and diltiazem reduced melatonin production significantly in pineal glands removed 7 HALO. Verapamil at 10(-4) and 10(-5) mol/l showed no significant effect on melatonin production in glands removed both during the light and dark spans. Mn2+ at 10(-4) mol/l (but not at 10[-5] mol/l) appeared to stimulate melatonin production in glands removed both during the light and the dark (significant increase only with glands removed during the dark). Cobalt showed an immediate short inhibitory effect on both isoproterenol and norepinephrine-stimulated melatonin release, whereas nifedipine showed a significant inhibition only on isoproterenol-stimulated melatonin release. These results strongly suggest a circadian stage dependence of the pineal gland response to some calcium channel blockers and the involvement of calcium in the release of melatonin from pinealocytes.

  5. Indistinguishable Synaptic Pharmacodynamics of the N-Methyl-d-Aspartate Receptor Channel Blockers Memantine and Ketamine

    PubMed Central

    Emnett, Christine M.; Eisenman, Lawrence N.; Taylor, Amanda M.; Izumi, Yukitoshi; Zorumski, Charles F.

    2013-01-01

    Memantine and ketamine, voltage- and activation-dependent channel blockers of N-methyl-d-aspartate (NMDA) receptors (NMDARs), have enjoyed a recent resurgence in clinical interest. Steady-state pharmacodynamic differences between these blockers have been reported, but it is unclear whether the compounds differentially affect dynamic physiologic signaling. In this study, we explored nonequilibrium conditions relevant to synaptic transmission in hippocampal networks in dissociated culture and hippocampal slices. Equimolar memantine and ketamine had indistinguishable effects on the following measures: steady-state NMDA currents, NMDAR excitatory postsynaptic current (EPSC) decay kinetics, progressive EPSC inhibition during repetitive stimulation, and extrasynaptic NMDAR inhibition. Therapeutic drug efficacy and tolerability of memantine have been attributed to fast kinetics and strong voltage dependence. However, pulse depolarization in drug presence revealed a surprisingly slow and similar time course of equilibration for the two compounds, although memantine produced a more prominent fast component (62% versus 48%) of re-equilibration. Simulations predicted that low gating efficacy underlies the slow voltage–dependent relief from block. This prediction was empirically supported by faster voltage-dependent blocker re-equilibration with several experimental manipulations of gating efficacy. Excitatory postsynaptic potential–like voltage commands produced drug differences only with large, prolonged depolarizations unlikely to be attained physiologically. In fact, we found no difference between drugs on measures of spontaneous network activity or acute effects on plasticity in hippocampal slices. Despite indistinguishable synaptic pharmacodynamics, ketamine provided significantly greater neuroprotection from damage induced by oxygen glucose deprivation, consistent with the idea that under extreme depolarizing conditions, the biophysical difference between drugs

  6. Postnatal acute renal failure after fetal exposure to angiotensin receptor blockers.

    PubMed

    Marchetto, Luca; Sordino, Desiree; De Bernardo, Giuseppe; Trevisanuto, Daniele

    2015-07-02

    Maternal hypertensive treatment with angiotensin receptor blockers (ARBs) during the second and third trimester of pregnancy is associated with several fetal and neonatal complications, and potential adverse outcomes. We report a neonate presenting with transient renal acute failure during the first days of life after maternal treatment with ARBs. Women who became pregnant while taking one of these drugs must modify antihypertensive therapy with a different class drug as soon as pregnancy is recognised.

  7. Long-term effect of β-blocker in ST-segment elevation myocardial infarction in patients with preserved left ventricular systolic function: a propensity analysis.

    PubMed

    Konishi, Hirokazu; Miyauchi, Katsumi; Kasai, Takatoshi; Tsuboi, Shuta; Ogita, Manabu; Naito, Ryo; Nishizaki, Yuji; Okai, Iwao; Tamura, Hiroshi; Okazaki, Shinya; Isoda, Kikuo; Daida, Hiroyuki

    2016-04-01

    The current guidelines for acute myocardial infarction (AMI) recommended that β-blocker should be used in patients with decreased left ventricular (LV) systolic function for long-term period. However, the effect of β-blocker in AMI patients with preserved LV systolic function is uncertain. We sought to assess the long-term effect of β-blocker in AMI patients with preserved LV systolic function. During the follow-up period (1997-2011), total 3508 patients were performed percutaneous coronary intervention (PCI). Of these patients, 424 AMI patients with preserved LV systolic function [ejection fraction (EF) > 40 %] were analyzed. Median follow-up period was 4.7 years. Then, patients were divided into two groups (β-blocker group 197 patients and no-β-blocker group 227 patients). However, there are substantial differences in baseline characteristics between two groups. Therefore, we calculated propensity score to match the patients in β-blocker and no-β-blocker groups. After post-match patients (N = 206, 103 matched pair), β-blocker therapy significantly reduced cardiac death compared with no-β-blocker [hazard ratio (HR) 0.40, p = 0.04], whereas β-blocker therapy was not associated with major adverse cardiac events (MACE) and all-cause death. β-Blocker is an effective treatment for AMI patients who underwent PCI with preserved LV systolic function.

  8. Ca sup 2+ channel blockers interact with. alpha. sub 2 -adrenergic receptors in rabbit ileum

    SciTech Connect

    Homaidan, F.R.; Donowitz, M.; Wicks, J.; Cusolito, S.; El Sabban, M.E.; Weiland, G.A.; Sharp, G.W.G. Tufts Univ. School of Medicine and New England Medical Center Hospital, Boston, MA )

    1988-04-01

    An interaction between Ca{sup 2+} channel blockers and {alpha}{sub 2}-adrenergic receptors has been demonstrated in rabbit ileum by studying the effect of clonidine on active electrolyte transport, under short-circuited conditions, in the presence and absence of several Ca{sup 2+} channel blocking agents. Clonidine, verapamil, diltiazem, cadmium, and nitrendipine all decrease short-circuit current and stimulate NaCl absorption to different extents with clonidine having the largest effect. Exposure to verapamil, diltiazem, and cadmium inhibited the effects of clonidine on transport, whereas nitrendipine had no such effect. Verapamil, diltiazem, and cadmium, but not nitrendipine, also decreased the specific binding of ({sup 3}H){alpha}{sub 2}-adrenergic agents to a preparation of ileal basolateral membranes explaining the observed decrease in the transport effects of clonidine. The effective concentrations of the Ca{sup 2+} channel blockers that inhibited the effects of clonidine on transport were fairly similar to the concentrations needed to inhibit its specific binding. The displacement of clonidine by calcium channel blockers is ascribed to a nonspecific effect of these agents, although the possibility that their effects are exerted via their binding to the calcium channels is not excluded.

  9. Persistent current blockers of voltage-gated sodium channels: a clinical opportunity for controlling metastatic disease.

    PubMed

    Djamgoz, Mustafa B A; Onkal, Rustem

    2013-01-01

    A range of experimental and clinical data suggests strongly (i) that metastatic progression in carcinomas is accompanied (maybe even preceded) by upregulation of functional voltage-gated sodium channels (VGSCs) and (ii) that VGSC activity enhances cancer cell invasiveness. First, this review outlines the available in vitro and in vivo evidence for the VGSC expression and its proposed pathophysiological role. Second, we question the mechanism(s) whereby VGSC activity can induce such a cancer-promoting effect. We advance the hypothesis that it is the hypoxia-sensitive persistent component of the VGSC current (INaP) that is central to the phenomenon. Indeed, blockers of INaP are very effective in suppressing cancer cell invasiveness in vitro. Based upon these data, UK and international patent applications have been filed which describe the use of INaP blockers, like ranolazine ("Ranexa") and riluzole ("Rilutex"), as anti-metastatic agents. Importantly, since these drugs are already in clinical use, against conditions like cardiac angina and amyotrophic lateral scelerosis, there are no issues of dosage, unacceptable side effects or long-term use. Thus, INaP blockers have the potential to turn cancer into a chronic condition.

  10. Interrupting autocrine ligand-receptor binding: comparison between receptor blockers and ligand decoys.

    PubMed Central

    Forsten, K E; Lauffenburger, D A

    1992-01-01

    Stimulation of cell behavioral functions by ligand/receptor binding can be accomplished in autocrine fashion, where cells secrete ligand capable of binding to receptors on their own surfaces. This proximal secretion of autocrine ligands near the surface receptors on the secreting cell suggests that control of these systems by inhibitors of receptor/ligand binding may be more difficult than for systems involving exogenous ligands. Hence, it is of interest to predict the conditions under which successful inhibition of cell receptor binding by the autocrine ligand can be expected. Previous theoretical work using a compartmentalized model for autocrine cells has elucidated the conditions under which addition of solution decoys for the autocrine ligand can interrupt cell receptor/ligand binding via competitive binding of the secreted molecules (Forsten, K. E., and D. A. Lauffenburger. 1992. Biophys. J. 61:1-12.) We now apply a similar modeling approach to examine the addition of solution blockers targeted against the cell receptor. Comparison of the two alternative inhibition strategies reveals that a significantly lower concentration of receptor blockers, compared to ligand decoys, will obtain a high degree of inhibition. The more direct interruption scheme characteristic of the receptor blockers may make them a preferred strategy when feasible. PMID:1330038

  11. How Administration of the Beta-Blocker Propranolol Before Extinction can Prevent the Return of Fear.

    PubMed

    Kroes, Marijn C W; Tona, Klodiana-Daphne; den Ouden, Hanneke E M; Vogel, Susanne; van Wingen, Guido A; Fernández, Guillén

    2016-05-01

    Combining beta-blockers with exposure therapy has been advocated to reduce fear, yet experimental studies combining beta-blockers with memory reactivation have had contradictory results. We explored how beta-blockade might affect the course of safety learning and the subsequent return of fear in a double-blind placebo-controlled functional magnetic resonance imaging study in humans (N=46). A single dose of propranolol before extinction learning caused a loss of conditioned fear responses, and prevented the subsequent return of fear and decreased explicit memory for the fearful events in the absence of drug. Fear-related neural responses were persistently attenuated in the dorsal medial prefrontal cortex (dmPFC), increased in the hippocampus 24 h later, and correlated with individual behavioral indices of fear. Prediction error-related responses in the ventral striatum persisted during beta-blockade. We suggest that this pattern of results is most consistent with a model where beta-blockade can prevent the return of fear by (i) reducing retrieval of fear memory, via the dmPFC and (ii) increasing contextual safety learning, via the hippocampus. Our findings suggest that retrieval of fear memory and contextual safety learning form potential mnemonic target mechanisms to optimize exposure-based therapy with beta-blockers.

  12. Obesity and beta-blockers: influence of body fat on their kinetics and cardiovascular effects.

    PubMed

    Galletti, F; Fasano, M L; Ferrara, L A; Groppi, A; Montagna, M; Mancini, M

    1989-03-01

    Beta-blockers are among the most widely used antihypertensive drugs. They differ from each other in regard to several factors such as: beta-agonist activity, beta 1-selectivity and solubility. Aim of this work was to evaluate the influence of obesity on the kinetics and the antihypertensive effect of two Beta-blockers with different solubility such as: the water-soluble, atenolol and the liposoluble, metoprolol. The study was carried out according to an open randomized cross-over design. Eight obese hypertensive patients, after a two week washout period, were randomly allocated to a four week treatment. After a two week intermediate washout period, each patient switched to the other treatment for an additional four week period. On the first and the last day of each treatment the subjects were hospitalized to collect blood samples for the assay of the two drugs and to measure cardiovascular parameters. Obesity does not exert any effect on the kinetics of the water-soluble beta-blocker, atenolol, while markedly interferes with that of the liposoluble, without any apparent influence on its anti-hypertensive effect. These findings extend to obese hypertensives the concept that the plasma concentrations of beta-blocking agents are not reliable predictors of their therapeutic effect.

  13. A potent 1,4-dihydropyridine L-type calcium channel blocker, benidipine, promotes osteoblast differentiation.

    PubMed

    Nishiya, Y; Kosaka, N; Uchii, M; Sugimoto, S

    2002-01-01

    During their differentiation, osteoblasts sequentially express type I collagen, alkaline phosphatase (ALP), and osteocalcin, and then undergo mineral deposition. Among dihydropyridine-type calcium channel blockers, only benidipine stimulated ALP activity of osteoblastic cells derived from neonatal mouse calvaria. To identify the molecular target of benidipine and elucidate the mechanism of action of the drug in osteoblasts, the mouse osteoblastic cell line MC3T3-E1 was used. Benidipine prompted ALP activity and ALP transcription induced by ascorbic acid, and mineral deposition by ascorbic acid and b-glycerophosphate. Benidipine, however, did not change collagen accumulation. MC3T3-E1 cells expressed the L-type Ca channel a1C subunit throughout the differentiation process, and Ca influx by potassium ions and Bay K 8644, an agonist, was strongly attenuated by benidipine. Each one of three structurally different classes of Ca channel blockers, nifedipine, verapamil, and diltiazem stimulated ALP activity, although at much higher concentrations of ca. 100 nM than benidipine, 1 pM. These results suggest that benidipine directly exerts its effect on osteoblasts and promotes osteoblast differentiation after the step of collagen accumulation by blocking the L-type Ca channel. Since benidipine blocked Ca influx more potently than the three other Ca channel blockers, the unique and potent osteoblast differentiating ability of benidipine may be due to its high affinity for Ca channel together with its high membrane retaining ability, as has been previously reported.

  14. Scatter correction for cone-beam computed tomography using moving blocker strips

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Mao, Weihua; Solberg, Timothy

    2011-03-01

    One well-recognized challenge of cone-beam computed tomography (CBCT) is the presence of scatter contamination within the projection images. Scatter degrades the CBCT image quality by decreasing the contrast, introducing shading artifacts and leading to inaccuracies in the reconstructed CT number. We propose a blocker-based approach to simultaneously estimate scatter signal and reconstruct the complete volume within the field of view (FOV) from a single CBCT scan. A physical strip attenuator (i.e., "blocker"), consists of lead strips, is inserted between the x-ray source and the patient. The blocker moves back and forth along z-axis during the gantry rotation. The two-dimensional (2D) scatter fluence is estimated by interpolating the signal from the blocked regions. A modified Feldkamp-Davis-Kress (FDK) algorithm and an iterative reconstruction based on the constraint optimization are used to reconstruct CBCT images from un-blocked projection data after the scatter signal is subtracted. An experimental study is performed to evaluate the performance of the proposed scatter correction scheme. The scatter-induced shading/cupping artifacts are substantially reduced in CBCT using the proposed strategy. In the experimental study using a CatPhan©600 phantom, CT number errors in the selected regions of interest are reduced from 256 to less than 20. The proposed method allows us to simultaneously estimate the scatter signal in projection data, reduce the imaging dose and obtain complete volumetric information within the FOV.

  15. An N-methyl-d-aspartate receptor channel blocker with neuroprotective activity

    PubMed Central

    Tai, Kwok-Keung; Blondelle, Sylvie E.; Ostresh, John M.; Houghten, Richard A.; Montal, Mauricio

    2001-01-01

    Excitotoxicity, resulting from sustained activation of glutamate receptors of the N-methyl-d-aspartate (NMDA) subtype, is considered to play a causative role in the etiology of ischemic stroke and several neurodegenerative diseases. The NMDA receptor is therefore a target for the development of neuroprotective agents. Here, we identify an N-benzylated triamine (denoted as NBTA) as a highly selective and potent NMDA-receptor channel blocker selected by screening a reduced dipeptidomimetic synthetic combinatorial library. NBTA blocks recombinant NMDA receptors expressed in Xenopus laevis oocytes with a mean IC50 of 80 nM; in contrast, it does not block GluR1, a glutamate receptor of the non-NMDA subtype. The blocking activity of NBTA on NMDA receptors exhibits the characteristics of an open-channel blocker: (i) no competition with agonists, (ii) voltage dependence, and (iii) use dependence. Significantly, NBTA protects rodent hippocampal neurons from NMDA receptor, but not kainate receptor-mediated excitotoxic cell death, in agreement with its selective action on the corresponding recombinant receptors. Mutagenesis data indicate that the N site, a key asparagine on the M2 transmembrane segment of the NR1 subunit, is the main determinant of the blocker action. The results highlight the potential of this compound as a neuroprotectant. PMID:11248110

  16. beta-adrenergic receptor gene polymorphisms and beta-blocker treatment outcomes in hypertension.

    PubMed

    Pacanowski, M A; Gong, Y; Cooper-Dehoff, R M; Schork, N J; Shriver, M D; Langaee, T Y; Pepine, C J; Johnson, J A

    2008-12-01

    Numerous studies have demonstrated that beta(1)- and beta(2)-adrenergic receptor gene (ADRB1 and ADRB2) variants influence cardiovascular risk and beta-blocker responses in hypertension and heart failure. We evaluated the relationship between ADRB1 and ADRB2 haplotypes, cardiovascular risk (death, nonfatal myocardial infarction (MI), and nonfatal stroke), and atenolol-based vs. verapamil sustained-release (SR)-based antihypertensive therapy in 5,895 coronary artery disease (CAD) patients. After an average of 2.8 years, death rates were higher in patients carrying the ADRB1 Ser49-Arg389 haplotype (hazard ratio (HR) 3.66, 95% confidence interval (95% CI) 1.68-7.99). This mortality risk was significant in patients randomly assigned to verapamil SR (HR 8.58, 95% CI 2.06-35.8) but not atenolol (HR 2.31, 95% CI 0.82-6.55), suggesting a protective role for the beta-blocker. ADRB2 haplotype associations were divergent within the treatment groups but did not remain significant after adjustment for multiple comparisons. ADRB1 haplotype variation is associated with mortality risk, and beta-blockers may be preferred in subgroups of patients defined by ADRB1 or ADRB2 polymorphisms.

  17. Ab initio ro-vibronic spectroscopy of SiCCl (X{sup ~2}Π)

    SciTech Connect

    Brites, Vincent; Mitrushchenkov, Alexander O.; Léonard, Céline; Peterson, Kirk A.

    2014-07-21

    The full dimensional potential energy surfaces of the {sup 2}A{sup ′} and {sup 2}A{sup ′′} electronic components of X{sup ~2}Π SiCCl have been computed using the explicitly correlated coupled cluster method, UCCSD(T)-F12b, combined with a composite approach taking into account basis set incompleteness, core-valence correlation, scalar relativity, and higher order excitations. The spin-orbit and dipole moment surfaces have also been computed ab initio. The ro-vibronic energy levels and absorption spectrum at 5 K have been determined from variational calculations. The influence of each correction on the fundamental frequencies is discussed. An assignment is proposed for bands observed in the LIF experiment of Smith et al. [J. Chem. Phys. 117, 6446 (2002)]. The overall agreement between the experimental and calculated ro-vibronic levels is better than 7 cm{sup −1} which is comparable with the 10–20 cm{sup −1} resolution of the emission spectrum.

  18. Effects of cefetamet (Ro 15-8074) on Treponema pallidum and experimental syphilis.

    PubMed Central

    Fitzgerald, T J

    1992-01-01

    Cefetamet pivoxil (Ro 15-8075) is a newly developed, expanded-spectrum cephalosporin that is orally active. In vitro, the active form, cefetamet (Ro 15-8074), at a concentration of 0.05 micrograms/ml killed and lysed Treponema pallidum. Rabbit serum did not diminish its effectiveness. The antibiotic rapidly entered the circulation following intramuscular injection into rabbits, attaining its highest levels of 24 to 37 micrograms/ml within 10 to 30 min. Animals were infected intradermally with T. pallidum and then treated with different doses of cefetamet. Accelerated healing was detected following treatment with 15 and 30 mg/kg of body weight. The antibiotic was also effective in killing organisms that had disseminated to distant tissues. In three separate sets of experiments, rabbits were infected with treponemes and then treated with cefetamet intramuscularly at 1, 15, or 30 mg/kg as follows: (i) after lesions had just become clinically apparent, (ii) after lesions were enlarged and well developed, or (iii) prior to the appearance of clinical lesions. Antibiotic effectiveness was determined by sacrificing the animals 1 week after antibiotic treatment and examining splenic tissue for residual, disseminated treponemes. Cefetamet was treponemicidal in all three situations. Maximum effects occurred when the antibiotic was injected before lesions had become clinically apparent (incubation period). These results suggest that cefetamet pivoxil might be useful for treating syphilitic infections. PMID:1622168

  19. Isolated Ro52 Antibodies as Immunological Marker of a Mild Phenotype of Undifferentiated Connective Tissue Diseases

    PubMed Central

    Navarro-Gonzálvez, José Antonio; Rodríguez-Lozano, Beatriz

    2017-01-01

    The term undifferentiated connective tissue disease (UCTD) is used to describe undiagnosed patients that do not fulfill classification criteria for definite connective tissue disease (Systemic Lupus, Systemic Sclerosis, Sjögren Syndrome, and Dermatomyositis/Polymyositis). It is important to find serological markers as predictors of the evolution or severity of these diseases. The objective of this retrospective study was to investigate if there was a milder subgroup of UCTD with a special clinical profile consisting only in the presence of anti-Ro52 autoantibodies. Immunological and clinical records of 62 patients attending the hospital during 30 months were studied. Results showed a target population formed by mostly women, aged between 40 and 80 years at the moment of the study, with a registered age of onset between 40 and 60 years. Speckled pattern was the most frequent pattern found by indirect immunofluorescence. Given the obtained results and keeping in mind possible limitations because of sample size, isolated positive anti-Ro52 autoantibodies seem to lead to a benign effect in terms of evolution of the disease. As a future objective, the follow-up of these patients should be necessary to investigate new clinical symptoms, serological markers, or development of a definite connective tissue disease over time. PMID:28210273

  20. Overlap of Doxycycline Fluorescence with that of the Redox-Sensitive Intracellular Reporter roGFP.

    PubMed

    Khader, Heba; Solodushko, Victor; Al-Mehdi, Abu Bakr; Audia, Jonathon; Fouty, Brian

    2014-03-01

    Tetracycline-inducible systems allow for either suppression or induction of transgene expression to facilitate studies of cell physiology. Doxycycline is a preferred inducer for these gene expression systems due to its membrane permeability; however, the heterocyclic structure of doxycycline exhibits fluorogenic properties that can potentially bias measurement of other fluorochromes. Thus the simultaneous use of tetracycline-inducible systems and fluorescent proteins as reporter genes or as intracellular biosensors may lead to potentially confounding results. Herein, using cells which co-express the ratiometric redox sensitive intracellular reporter, roGFP, and a tetracycline-inducible reporter plasmid encoding the reporter gene, mCherry, as a model system, we describe the overlapping intracellular fluorescent signals between doxycycline and commonly used intracellular fluorescent probes. In our cells, the addition of doxycycline to cells caused a dose- and time-dependent increase in cell fluorescence with 405 nm excitation which overlapped with that of the oxidized configuration of roGFP. Incubating cells in concentrations of doxycycline less than 1 μg/mL and removing doxycycline from the media 60 min before performing experiments eliminated fluorescence interference while still maintaining maximal reporter transgene activation.

  1. RO concentrate minimization by electrodialysis: techno-economic analysis and environmental concerns.

    PubMed

    Zhang, Yang; Ghyselbrecht, Karel; Vanherpe, Ruben; Meesschaert, Boudewijn; Pinoy, Luc; Van der Bruggen, Bart

    2012-09-30

    This paper presents a systematic techno-economical analysis and an environmental impact evaluation of a reverse osmosis (RO) concentrate treatment process using electrodialysis (ED) in view of environmental management of brine discharges. The concentrate originates from a secondary effluent treated by RO. Without any treatment, the concentrate would have to be discharged; this is compared in this study to the costs and benefits of an effective treatment method in a pilot scale ED plant. A technical analysis was done both on lab scale and pilot scale for the determination of operational and maintenance costs for the ED installation at the required conditions of process performance and safety. Subsequently, an economical analysis was done to calculate the cost of the different parts of the ED system. It was shown that an operational cost of 0.19 EUR m(-3) can be achieved, assuming that the ED concentrate is to decarbonated at pH 6.0 to prevent membrane scaling. Finally, environmental impact issues were calculated and discussed for the overall system. Results imply that if renewable energy is applied for the ED power source, CO(2) emission from membrane processes can be much less than from the conventional treatment methods.

  2. Simultaneous manipulation and observation of multiple ro-vibrational eigenstates in solid para-hydrogen

    NASA Astrophysics Data System (ADS)

    Katsuki, Hiroyuki; Ohmori, Kenji

    2016-09-01

    We have experimentally performed the coherent control of delocalized ro-vibrational wave packets (RVWs) of solid para-hydrogen (p-H2) by the wave packet interferometry (WPI) combined with coherent anti-Stokes Raman scattering (CARS). RVWs of solid p-H2 are delocalized in the crystal, and the wave function with wave vector k ˜ 0 is selectively excited via the stimulated Raman process. We have excited the RVW twice by a pair of femtosecond laser pulses with delay controlled by a stabilized Michelson interferometer. Using a broad-band laser pulse, multiple ro-vibrational states can be excited simultaneously. We have observed the time-dependent Ramsey fringe spectra as a function of the inter-pulse delay by a spectrally resolved CARS technique using a narrow-band probe pulse, resolving the different intermediate states. Due to the different fringe oscillation periods among those intermediate states, we can manipulate their amplitude ratio by tuning the inter-pulse delay on the sub-femtosecond time scale. The state-selective manipulation and detection of the CARS signal combined with the WPI is a general and efficient protocol for the control of the interference of multiple quantum states in various quantum systems.

  3. Isolated anti-Ro/SSA thrombocytopenia: a rare feature of neonatal lupus.

    PubMed

    Ayadi, Imene Dahmane; Ben Hamida, Emira; Boukhris, Mohamed Riadh; Bezzine, Ahlem; Chaouachi, Sihem; Marrakchi, Zahra

    2015-01-01

    We report a rare case of isolated thrombocytopenia related to anti-Ro/SSA antibodies. The mother was followed for unlabeled familial thrombocytopenia. The mother had positive anti-Ro/SSA antibodies. She was asymptomatic without skin lesions or other criteria neither of systemic lupus erythematosus nor other connective tissue disease. Pregnancy was uneventful. The postnatal examination was normal. On the first day of life, blood cells count showed thrombocytopenia at 40 x 10(9)/L. Within the second day of life, platelet level dropped to 20 x 10(9)/L. The management of thrombocytopenia included platelet transfusion and human immunoglobulin infusion. On the fifth day of life, there has been a drop in platelet count to 10 x 10(9)/L requiring renewed platelet transfusion and human immunoglobulin infusion. On the 10(th) of life platelets rate was stable around 60 x 10(9)/L. The infant had no evidence of cardiac, dermatologic or hepatobilary involvement initially or throughout follow up.

  4. Tailoring the structure of thin film nanocomposite membranes to achieve seawater RO membrane performance.

    PubMed

    Lind, Mary Laura; Eumine Suk, Daniel; Nguyen, The-Vinh; Hoek, Eric M V

    2010-11-01

    Herein we report on the formation and characterization of pure polyamide thin film composite (TFC) and zeolite-polyamide thin film nanocomposite (TFN) reverse osmosis (RO) membranes. Four different physical-chemical post-treatment combinations were applied after the interfacial polymerization reaction to change the molecular structure of polyamide and zeolite-polyamide thin films. Both TFC and TFN hand-cast membranes were more permeable, hydrophilic, and rough than a commercial seawater RO membrane. Salt rejection by TFN membranes was consistently below that of hand-cast TFC membranes; however, two TFN membranes exhibited 32 g/L NaCl rejections above 99.4%, which was better than the commercial membrane under the test conditions employed. The nearly defect-free TFN films that produced such high rejections were achieved only with wet curing, regardless of other post-treatments. Polyamide films formed in the presence of zeolite nanoparticles were less cross-linked than similarly cast pure polyamide films. At the very low nanoparticle loadings evaluated, differences between pure polyamide and zeolite-polyamide membrane water and salt permeability correlated weakly with extent of cross-linking of the polyamide film, which suggests that defects and molecular-sieving largely govern transport through zeolite-polyamide thin film nanocomposite membranes.

  5. α-Blockers for the Treatment of Chronic Prostatitis/Chronic Pelvic Pain Syndrome: An Update on Current Clinical Evidence

    PubMed Central

    Nickel, J. Curtis; Touma, Naji

    2012-01-01

    The pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is multifactorial, making its treatment difficult. Multimodal therapy including α-adrenergic antagonists (α-blockers), anti-inflammatory agents, and other pain treatments may provide optimal management for CP/CPPS. Although α-blockers are the most prescribed drugs for patients with CP/CPPS, not all studies support their efficacy. A recent meta-analysis of small trials suggested that treatment with α-blockers, possibly in combination with antibacterial agents, is efficacious in relieving symptoms. Third-generation α1A blockers (silodosin, tamsulosin) may provide efficacy as well as reduced cardiovascular side effects. Future research should aim to identify potential biomarkers associated with treatment response. PMID:23526487

  6. An Analysis of Beta-Blocker Administration Pre-and Post-Traumatic Brain Injury with Subanalyses for Head Injury Severity and Myocardial Injury.

    PubMed

    Edavettal, Mathew; Gross, Brian W; Rittenhouse, Katelyn; Alzate, James; Rogers, Amelia; Estrella, Lisa; Miller, Jo Ann; Rogers, Frederick B

    2016-12-01

    A growing body of literature indicates that beta-blocker administration after traumatic brain injury (TBI) is cerebroprotective, limiting secondary injury; however, the effects of preinjury beta blocker status remain poorly understood. We sought to characterize the effects of pre- and postinjury beta-blocker administration on mortality with subanalyses accounting for head injury severity and myocardial injury. In a Level II trauma center, all admissions of patients ≥18 years with a head Abbreviated Injury Scale Score ≥2, Glasgow Coma Scale ≤13 from May 2011 to May 2013 were queried. Demographic, injury-specific, and outcome variables were analyzed using univariate analyses. Subsequent multivariate analyses were conducted to determine adjusted odds of mortality for beta-blocker usage controlling for age, Injury Severity Score, head Abbreviated Injury Scale, arrival Glasgow Coma Scale, ventilator use, and intensive care unit stay. A total of 214 trauma admissions met inclusion criteria: 112 patients had neither pre- nor postinjury beta-blocker usage, 46 patients had preinjury beta-blocker usage, and 94 patients had postinjury beta-blocker usage. Both unadjusted and adjusted odds ratios of preinjury beta-blocker were insignificant with respect to mortality. However, postinjury in-hospital administration of beta blockers was found to significantly in the decrease of mortality in both univariate (P = 0.002) and multivariate analyses (P = 0.001). Our data indicate that beta-blocker administration post-TBI in hospital reduces odds of mortality; however, preinjury beta-blocker usage does not. Additionally, myocardial injury is a useful indicator for beta-blocker administration post-TBI. Further research into which beta blockers confer the best benefits as well as the optimal period of beta-blocker administration post-TBI is recommended.

  7. Transiting exoplanets from the CoRoT space mission. XI. CoRoT-8b: a hot and dense sub-Saturn around a K1 dwarf

    NASA Astrophysics Data System (ADS)

    Bordé, P.; Bouchy, F.; Deleuil, M.; Cabrera, J.; Jorda, L.; Lovis, C.; Csizmadia, S.; Aigrain, S.; Almenara, J. M.; Alonso, R.; Auvergne, M.; Baglin, A.; Barge, P.; Benz, W.; Bonomo, A. S.; Bruntt, H.; Carone, L.; Carpano, S.; Deeg, H.; Dvorak, R.; Erikson, A.; Ferraz-Mello, S.; Fridlund, M.; Gandolfi, D.; Gazzano, J.-C.; Gillon, M.; Guenther, E.; Guillot, T.; Guterman, P.; Hatzes, A.; Havel, M.; Hébrard, G.; Lammer, H.; Léger, A.; Mayor, M.; Mazeh, T.; Moutou, C.; Pätzold, M.; Pepe, F.; Ollivier, M.; Queloz, D.; Rauer, H.; Rouan, D.; Samuel, B.; Santerne, A.; Schneider, J.; Tingley, B.; Udry, S.; Weingrill, J.; Wuchterl, G.

    2010-09-01

    Aims: We report the discovery of CoRoT-8b, a dense small Saturn-class exoplanet that orbits a K1 dwarf in 6.2 days, and we derive its orbital parameters, mass, and radius. Methods: We analyzed two complementary data sets: the photometric transit curve of CoRoT-8b as measured by CoRoT and the radial velocity curve of CoRoT-8 as measured by the HARPS spectrometer. Results: We find that CoRoT-8b is on a circular orbit with a semi-major axis of 0.063 ± 0.001 AU. It has a radius of 0.57 ± 0.02 RJ, a mass of 0.22 ± 0.03 MJ, and therefore a mean density of 1.6 ± 0.1 g cm-3. Conclusions: With 67% of the size of Saturn and 72% of its mass, CoRoT-8b has a density comparable to that of Neptune (1.76 g cm-3). We estimate its content in heavy elements to be 47-63 {M}_⊕, and the mass of its hydrogen-helium envelope to be 7-23 {M}_⊕. At 0.063 AU, the thermal loss of hydrogen of CoRoT-8b should be no more than 0.1% over an assumed integrated lifetime of 3 Ga. Observations made with SOPHIE spectrograph at Observatoire de Haute Provence, France (PNP.07B.MOUT), and the HARPS spectrograph at ESO La Silla Observatory (081.C-0388 and 083.C-0186). The CoRoT space mission, launched on December 27, 2006, has been developed and is operated by the CNES with the contribution of Austria, Belgium, Brasil, ESA, Germany, and Spain.Both data sets are available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/520/A66

  8. Beta Blockers Suppress Dextrose-Induced Endoplasmic Reticulum Stress, Oxidative Stress, and Apoptosis in Human Coronary Artery Endothelial Cells.

    PubMed

    Haas, Michael J; Kurban, William; Shah, Harshit; Onstead-Haas, Luisa; Mooradian, Arshag D

    Beta blockers are known to have favorable effects on endothelial function partly because of their capacity to reduce oxidative stress. To determine whether beta blockers can also prevent dextrose-induced endoplasmic reticulum (ER) stress in addition to their antioxidative effects, human coronary artery endothelial cells and hepatocyte-derived HepG2 cells were treated with 27.5 mM dextrose for 24 hours in the presence of carvedilol (a lipophilic beta blockers with alpha blocking activity), propranolol (a lipophilic nonselective beta blockers), and atenolol (a water-soluble selective beta blockers), and ER stress, oxidative, stress and cell death were measured. ER stress was measured using the placental alkaline phosphatase assay and Western blot analysis of glucose regulated protein 78, c-Jun-N-terminal kinase (JNK), phospho-JNK, eukaryotic initiating factor 2α (eIF2α), and phospho-eIF2α and measurement of X-box binding protein 1 (XBP1) mRNA splicing using reverse transcriptase-polymerase chain reaction. Superoxide (SO) generation was measured using the superoxide-reactive probe 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-A]pyrazin-3-one hydrochloride (MCLA) chemiluminescence. Cell viability was measured by propidium iodide staining method. The ER stress, SO production, and cell death induced by 27.5 mM dextrose were inhibited by all 3 beta blockers tested. The antioxidative and ER stress reducing effects of beta blockers were also observed in HepG2 cells. The salutary effects of beta blockers on endothelial cells in reducing both ER stress and oxidative stress may contribute to the cardioprotective effects of these agents.

  9. Anthracene based compounds as new L-type Ca2+ channel blockers: design, synthesis, and full biological profile.

    PubMed

    Bova, Sergio; Saponara, Simona; Rampa, Angela; Gobbi, Silvia; Cima, Lorenzo; Fusi, Fabio; Sgaragli, Giampietro; Cavalli, Maurizio; de los Rios, Cristobal; Striessnig, Jörg; Bisi, Alessandra

    2009-03-12

    L-Type Ca(2+) channels (LTCCs) play a key role in the regulation of vascular smooth muscle contraction, and substances that interfere with their function (Ca(2+) channel blockers) are widely used in the therapy of hypertension. Here, we report anthracene-maleimide derivatives as new LTCC blockers. Among these, 3, lacking intracellular effects, was investigated in more detail. The results show that 3 binds preferentially to inactivated LTCCs, directly interacting with the pore-forming subunit of the channel.

  10. A Single-Chip Speech Dialogue Module and Its Evaluation on a Personal Robot, PaPeRo-Mini

    NASA Astrophysics Data System (ADS)

    Sato, Miki; Iwasawa, Toru; Sugiyama, Akihiko; Nishizawa, Toshihiro; Takano, Yosuke

    This paper presents a single-chip speech dialogue module and its evaluation on a personal robot. This module is implemented on an application processor that was developed primarily for mobile phones to provide a compact size, low power-consumption, and low cost. It performs speech recognition with preprocessing functions such as direction-of-arrival (DOA) estimation, noise cancellation, beamforming with an array of microphones, and echo cancellation. Text-to-speech (TTS) conversion is also equipped with. Evaluation results obtained on a new personal robot, PaPeRo-mini, which is a scale-down version of PaPeRo, demonstrate an 85% correct rate in DOA estimation, and as much as 54% and 30% higher speech recognition rates in noisy environments and during robot utterances, respectively. These results are shown to be comparable to those obtained by PaPeRo.

  11. Computing Ro in a population with heterogeneity in sexual activity and proportionate mixing using a STM-solver

    NASA Astrophysics Data System (ADS)

    Gutierrez A., Natalia A.

    2014-06-01

    A model to determinate the reproductive basic number, detonated Ro, for the case of population with heterogeneity in sexual activity and proportionate mixing is solved using computer algebra and SMT solvers. Specifically Maple and Z3 were used. The code for the solution of the model was written in Z3-Python, but it can also be played by Z3-SMT-Lib. Ro represents an algebraic synthesis of every epidemiological parameter. Numerical simulations were done to prove the effectiveness of the model and the code. The algebraic structure of Ro suggests the possible control measurements that should be implemented to avoid the propagation of the sexual transmitted diseases. The obtained results are important on the computational epidemiology field. As a future investigation, it is suggested to apply the STM solvers to analyze models for other kinds of epidemic diseases.

  12. Diazepam-induced release of behavior in an extinction procedure: its reversal by Ro 15-1788.

    PubMed

    Thiébot, M H; Childs, M; Soubrié, P; Simon, P

    1983-03-18

    The effects of the benzodiazepine receptor antagonist Ro 15-1788, an imidazobenzodiazepine derivative, were studied with respect to three pharmacological activities exerted by diazepam in rats. Two of these, release of shock-induced suppression of drinking and attenuation of non-reward-induced cessation of responding for food, reflect the anxiolytic property of benzodiazepines. The amnesic-like effect of diazepam was also investigated. Ro 15-1788 (in doses ranging from 4 to 16 mg/kg p.o.) completely reversed diazepam (2 mg/kg)-induced release of behavior in both punishment and non-reward procedures. In contrast, Ro 15-1788 reduced but did not completely abolish diazepam-induced amnesia. These data suggest that the anticonflict and anti-frustration effects of benzodiazepines probably involve similar receptor types which nevertheless differ from those chiefly implicated in the amnesic-like activity of benzodiazepines.

  13. Benzodiazepine receptor inverse agonists. beta. -CCM and RO 15-3505 both reverse the anxiolytic effects of ethanol in mice

    SciTech Connect

    Belzung, C.; Misslin, R.; Vogel, E.

    1988-01-01

    The antagonistic effects of the benzodiazepine receptor inverse agonist ..beta..-CCM and of the partial inverse agonist RO 15-3505 on the anxiolytic properties of ethanol in mice confronted with a light/dark choice procedure and with the staircase test were investigated. Both drugs reversed the effects of ethanol on some of the behavioral parameters, but ..beta..-CCM alone elicited anxiogenic intrinsic effects. RO-3505 induced seizures in mice treated with a subconvulsant dose of pentylenetetrazole, the most efficient doses being 3 and 6 mg/kg. These data indicate that ..beta..-CCM and RO 15-3505 can reverse some of the anxiolytic effects of ethanol, acting probably to oppose GABA function via the benzodiazepine receptor.

  14. Impact of alpha- and beta-adrenergic receptor blockers on fractional flow reserve and index of microvascular resistance.

    PubMed

    Barbato, Emanuele; Sarno, Giovanna; Berza, Catalina Trana; Di Gioia, Giuseppe; Bartunek, Jozef; Vanderheyden, Marc; Di Serafino, Luigi; Wijns, William; Trimarco, Bruno; De Bruyne, Bernard

    2014-12-01

    We investigated the effect of β- and α-adrenergic blockers on fractional flow reserve (FFR) and index of microvascular resistance (IMR). In 43 patients (pts) with intermediate stenoses, we measured FFR and IMR before and after nonselective β-blocker propranolol (30 μg/kg, n = 20) and selective β1-blocker metoprolol (40 μg/kg, n = 23) IC; (b) In additional 21 pts after percutaneous coronary intervention (PCI), FFR and IMR were measured before and after α-blocker phentolamine (3 mg) IC. Neither propranolol nor metoprolol changed values of FFR and IMR. Phentolamine slightly decreased FFR (from 0.88 ± 0.05 to 0.87 ± 0.06, p = 0.025) but did not change IMR. FFR decreased from >0.80 to ≤0.80 in 3 pts (14%), but in none, the value decreased to <0.75. β-blockers do not affect FFR and IMR in intermediate stenoses. After PCI, a mild decrease in FFR occurs after α-blockers, though of limited clinical impact.

  15. Modulation of cholinephosphotransferase activity in breast cancer cell lines by Ro5-4864, a peripheral benzodiazepine receptor agonist

    SciTech Connect

    Akech, Jacqueline; Roy, Somdutta Sinha; Das, Salil K. . E-mail: sdas@mmc.edu

    2005-07-22

    Changes in phospholipid and fatty acid profile are hallmarks of cancer progression. Increase in peripheral benzodiazepine receptor expression has been implicated in breast cancer. The benzodiazepine, Ro5-4864, increases cell proliferation in some breast cancer cell lines. Biosynthesis of phosphatidylcholine (PC) has been identified as a marker for cells proliferating at high rates. Cholinephosphotransferase (CPT) is the terminal enzyme for the de novo biosynthesis of PC. We have addressed here whether Ro5-4864 facilitates some cancer causing mechanisms in breast cancer. We report that cell proliferation increases exponentially in aggressive breast cancer cell lines 11-9-1-4 and BT-549 when treated with nanomolar concentrations of Ro5-4864. This increase is seen within 24 h of treatment, consistent with the cell doubling time in these cells. Ro5-4864 also upregulates c-fos expression in breast cancer cell lines 11-9-1-4 and BT-549, while expression in non-tumorigenic cell line MCF-12A was either basal or slightly downregulated. We further examined the expression of the CPT gene in breast cancer (11-9-1-4, BT-549) and non-tumorigenic cell lines (MCF-12A, MCF-12F). We found that the CPT gene is overexpressed in breast cancer cell lines compared to the non-tumorigenic cell lines. Furthermore, the activity of CPT in forming PC is increased in the breast cancer cell lines cultured for 24 h. Additionally, we examined the CPT activity in the presence of nanomolar concentrations of Ro5-4864. Biosynthesis of PC was increased in breast cancer cell lines upon treatment. We therefore propose that Ro5-4864 facilitates PC formation, a process important in membrane biogenesis for proliferating cells.

  16. Efficiently Combining Water Reuse and Desalination through Forward Osmosis—Reverse Osmosis (FO-RO) Hybrids: A Critical Review

    PubMed Central

    Blandin, Gaetan; Verliefde, Arne R.D.; Comas, Joaquim; Rodriguez-Roda, Ignasi; Le-Clech, Pierre

    2016-01-01

    Forward osmosis (FO) is a promising membrane technology to combine seawater desalination and water reuse. More specifically, in a FO-reverse osmosis (RO) hybrid process, high quality water recovered from the wastewater stream is used to dilute seawater before RO treatment. As such, lower desalination energy needs and/or water augmentation can be obtained while delivering safe water for direct potable reuse thanks to the double dense membrane barrier protection. Typically, FO-RO hybrid can be a credible alternative to new desalination facilities or to implementation of stand-alone water reuse schemes. However, apart from the societal (public perception of water reuse for potable application) and water management challenges (proximity of wastewater and desalination plants), FO-RO hybrid has to overcome technical limitation such as low FO permeation flux to become economically attractive. Recent developments (i.e., improved FO membranes, use of pressure assisted osmosis, PAO) demonstrated significant improvement in water flux. However, flux improvement is associated with drawbacks, such as increased fouling behaviour, lower rejection of trace organic compounds (TrOCs) in PAO operation, and limitation in FO membrane mechanical resistance, which need to be better considered. To support successful implementation of FO-RO hybrid in the industry, further work is required regarding up-scaling to apprehend full-scale challenges in term of mass transfer limitation, pressure drop, fouling and cleaning strategies on a module scale. In addition, refined economics assessment is expected to integrate fouling and other maintenance costs/savings of the FO/PAO-RO hybrid systems, as well as cost savings from any treatment step avoided in the water recycling. PMID:27376337

  17. Efficiently Combining Water Reuse and Desalination through Forward Osmosis-Reverse Osmosis (FO-RO) Hybrids: A Critical Review.

    PubMed

    Blandin, Gaetan; Verliefde, Arne R D; Comas, Joaquim; Rodriguez-Roda, Ignasi; Le-Clech, Pierre

    2016-07-01

    Forward osmosis (FO) is a promising membrane technology to combine seawater desalination and water reuse. More specifically, in a FO-reverse osmosis (RO) hybrid process, high quality water recovered from the wastewater stream is used to dilute seawater before RO treatment. As such, lower desalination energy needs and/or water augmentation can be obtained while delivering safe water for direct potable reuse thanks to the double dense membrane barrier protection. Typically, FO-RO hybrid can be a credible alternative to new desalination facilities or to implementation of stand-alone water reuse schemes. However, apart from the societal (public perception of water reuse for potable application) and water management challenges (proximity of wastewater and desalination plants), FO-RO hybrid has to overcome technical limitation such as low FO permeation flux to become economically attractive. Recent developments (i.e., improved FO membranes, use of pressure assisted osmosis, PAO) demonstrated significant improvement in water flux. However, flux improvement is associated with drawbacks, such as increased fouling behaviour, lower rejection of trace organic compounds (TrOCs) in PAO operation, and limitation in FO membrane mechanical resistance, which need to be better considered. To support successful implementation of FO-RO hybrid in the industry, further work is required regarding up-scaling to apprehend full-scale challenges in term of mass transfer limitation, pressure drop, fouling and cleaning strategies on a module scale. In addition, refined economics assessment is expected to integrate fouling and other maintenance costs/savings of the FO/PAO-RO hybrid systems, as well as cost savings from any treatment step avoided in the water recycling.

  18. The PA endonuclease inhibitor RO-7 protects mice from lethal challenge with influenza A or B viruses.

    PubMed

    Jones, Jeremy C; Marathe, Bindumadhav M; Vogel, Peter; Gasser, Rodolfo; Najera, Isabel; Govorkova, Elena A

    2017-02-13

    Current influenza treatment relies on a single class of antiviral drugs, the neuraminidase inhibitors (NAIs), raising concern over the potential emergence of resistant variants and necessitating the development of novel drugs. In recent years, investigational inhibitors targeting the endonuclease activity of the influenza acidic polymerase (PA) protein have yielded encouraging results, although there are only limited data on their in vivo efficacy. Here, we examined the antiviral potential of the PA endonuclease inhibitor RO-7 in prophylactic and therapeutic regimens in BALB/c mice inoculated with influenza A/California/04/2009 (H1N1)pdm09 or B/Brisbane/60/2008 viruses, which represent currently circulating antigenic variants. RO-7 was administered to mice intraperitoneally twice daily at dosages of 6, 15, or 30 mg/kg/day for 5 days, starting 4 h before or 24 or 48 h after virus inoculation, and showed no adverse effects. Prophylactic administration completely protected mice from lethal infection by influenza A or B virus. The level of therapeutic protection conferred depended upon the time of treatment initiation and RO-7 dosage, resulting in 60%-100% and 80%-100% survival with influenza A and B viruses, respectively. RO-7 treatment significantly decreased virus titers in the lung and lessened the extent and severity of lung damage. No PA endonuclease-inhibitor resistance was observed in viruses isolated from lungs of RO-7-treated mice, and the viruses remained susceptible to the drug at nanomolar concentrations in phenotypic assays. These in vivo efficacy results further highlight the potential of RO-7 for development as antiviral therapy for influenza A and B virus infections.

  19. Lichen scléro-atrophique extra-génital: à propos d’un cas

    PubMed Central

    Zemmez, Youssef; Amraoui, Mohammed El; Bouhamidi, Ahmed; Azhari, Jaouad El; Ismaili, Nadia; Benzekri, Laila; Meziane, Mariame; Hassam, Badreddine; Senouci, Karima

    2016-01-01

    Le lichen scléro-atrophique est une dermatose inflammatoire d'évolution chronique, avec un tropisme particulier pour les muqueuses génitales externes, l'atteinte cutanée isolée reste rare. Nous rapportons un cas de lichen scléro-atrophique chez une femme avec atteinte purement cutanée soulignant ainsi l'intérêt d'évoquer ce diagnostic en absence d'une atteinte génitale évidente. PMID:28292152

  20. Renoprotective effect and cost-effectiveness of using benidipine, a calcium channel blocker, to lower the dose of angiotensin receptor blocker in hypertensive patients with albuminuria.

    PubMed

    Saito, Fumio; Fujita, Hirotaka; Takahashi, Atsuhiko; Ichiyama, Izumi; Harasawa, Shinsuke; Oiwa, Kouji; Takahashi, Naoyuki; Otsuka, Yuji; Uchiyama, Takashi; Kanmatsuse, Katsuo; Kushiro, Toshio

    2007-01-01

    In hypertensive patients with chronic renal disease, angiotensin receptor blockers (ARBs) are among the first-line drugs, and calcium channel blockers (CCBs) are recommended as a second line. We examined the effects of two therapeutic strategies using ARBs and benidipine, a CCB, on blood pressure (BP), urinary albumin excretion (UAE), and cost-effectiveness in hypertensive patients with albuminuria. Patients whose BP was 140/90 mmHg or higher despite treatment with low- or medium-dose ARBs were assigned randomly to two groups. In Group A (n=14), the ARB dose was maximized and then benidipine was added until BP targets were reached (<130/85 mmHg). In Group B (n=18), benidipine was administered first and then the ARB dose was increased until BP targets were reached. The BP targets were achieved by ARB alone in 36% of Group A patients and by the addition of benidipine in 83% of Group B patients. Finally, BP decreased in each group, reaching the targets in 93% of Group A patients and 94% of Group B patients after a 4-month therapeutic period. UAE was decreased in both groups after a 4-month therapeutic period compared to the allocation period (-33+/-6% in Group A, -31+/-6% in Group B; p<0.001, respectively). The monthly drug cost was higher (11,426+/-880 vs. 8,955+/-410 yen, p=0.012) and the cost-effectiveness of antihypertensive treatment was lower (p=0.003) in Group A than in Group B. We conclude that the addition of benidipine to low- or medium-dose ARB is, in light of the renal protection and the cost-effectiveness of this approach, a useful therapeutic strategy for controlling BP in hypertensive patients with albuminuria.

  1. Angiotensin Converting-Enzyme Inhibitors, Angiotensin Receptor Blockers, and Calcium Channel Blockers Are Associated with Prolonged Vascular Access Patency in Uremic Patients Undergoing Hemodialysis

    PubMed Central

    Chen, Yu-Wei; Wu, Yu-Te; Lin, Chih-Ching

    2016-01-01

    Background Vascular access failure is a huge burden for patients undergoing hemodialysis. Many efforts have been made to maintain vascular access patency, including pharmacotherapy. Angiotensin converting enzyme inhibitor (ACE-I), angiotensin receptor blocker (ARB), and calcium channel blocker (CCB) are known for their antihypertensive and cardio-protective effects, however, their effects on long-term vascular access patency are still inconclusive. Design, setting, participants and measurements We retrospectively enrolled patients commencing maintenance hemodialysis between January 1, 2000, and December 31, 2006 by using National Health Insurance Research Database in Taiwan. Primary patency was defined as the date of first arteriovenous fistula (AVF) or arteriovenous graft (AVG) creation to the time of access thrombosis or any intervention aimed to maintain or re-establish vascular access patency. Cox proportional hazards models were used to adjust the influences of patient characteristics, co-morbidities and medications. Results Total 42244 patients were enrolled in this study, 37771 (89.4%) used AVF, 4473 (10.6%) used AVG as their first long term dialysis access. ACE-I, ARB, and CCB use were all associated with prolonged primary patency of AVF [hazard ratio (HR) 0.586, 95% confidence interval (CI) 0.557–0.616 for ACE-I use; HR 0.532, CI 0.508–0.556 for ARB use; HR 0.485, CI 0.470–0.501 for CCB use] and AVG (HR 0.557, CI 0.482–0.643 for ACE-I use, HR 0.536, CI 0.467–0.614 for ARB use, HR 0.482, CI 0.442–0.526 for CCB use). Conclusions In our analysis, ACE-I, ARB, and CCB were strongly associated with prolonged primary patency of both AVF and AVG. Further prospective randomized studies are still warranted to prove the causality. PMID:27832203

  2. Comparative effect of angiotensin II type I receptor blockers and calcium channel blockers on laboratory parameters in hypertensive patients with type 2 diabetes

    PubMed Central

    2012-01-01

    Background Both angiotensin II type I receptor blockers (ARBs) and calcium channel blockers (CCBs) are widely used antihypertensive drugs. Many clinical studies have demonstrated and compared the organ-protection effects and adverse events of these drugs. However, few large-scale studies have focused on the effect of these drugs as monotherapy on laboratory parameters. We evaluated and compared the effects of ARB and CCB monotherapy on clinical laboratory parameters in patients with concomitant hypertension and type 2 diabetes mellitus. Methods We used data from the Clinical Data Warehouse of Nihon University School of Medicine obtained between Nov 1, 2004 and July 31, 2011, to identify cohorts of new ARB users (n = 601) and propensity-score matched new CCB users (n = 601), with concomitant mild to moderate hypertension and type 2 diabetes mellitus. We used a multivariate-adjusted regression model to adjust for differences between ARB and CCB users, and compared laboratory parameters including serum levels of triglyceride (TG), total cholesterol (TC), non-fasting blood glucose, hemoglobin A1c (HbA1c), sodium, potassium, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), hemoglobin and hematocrit, and white blood cell (WBC), red blood cell (RBC) and platelet (PLT) counts up to 12 months after the start of ARB or CCB monotherapy. Results We found a significant reduction of serum TC, HbA1c, hemoglobin and hematocrit and RBC count and a significant increase of serum potassium in ARB users, and a reduction of serum TC and hemoglobin in CCB users, from the baseline period to the exposure period. The reductions of RBC count, hemoglobin and hematocrit in ARB users were significantly greater than those in CCB users. The increase of serum potassium in ARB users was significantly greater than that in CCB users. Conclusions Our study suggested that hematological adverse effects and electrolyte imbalance are

  3. Transiting exoplanets from the CoRoT space mission. XXI. CoRoT-19b: a low density planet orbiting an old inactive F9V-star

    NASA Astrophysics Data System (ADS)

    Guenther, E. W.; Díaz, R. F.; Gazzano, J.-C.; Mazeh, T.; Rouan, D.; Gibson, N.; Csizmadia, Sz.; Aigrain, S.; Alonso, R.; Almenara, J. M.; Auvergne, M.; Baglin, A.; Barge, P.; Bonomo, A. S.; Bordé, P.; Bouchy, F.; Bruntt, H.; Cabrera, J.; Carone, L.; Carpano, S.; Cavarroc, C.; Deeg, H. J.; Deleuil, M.; Dreizler, S.; Dvorak, R.; Erikson, A.; Ferraz-Mello, S.; Fridlund, M.; Gandolfi, D.; Gillon, M.; Guillot, T.; Hatzes, A.; Havel, M.; Hébrard, G.; Jehin, E.; Jorda, L.; Lammer, H.; Léger, A.; Moutou, C.; Nortmann, L.; Ollivier, M.; Ofir, A.; Pasternacki, Th.; Pätzold, M.; Parviainen, H.; Queloz, D.; Rauer, H.; Samuel, B.; Santerne, A.; Schneider, J.; Tal-Or, L.; Tingley, B.; Weingrill, J.; Wuchterl, G.

    2012-01-01

    Context. Observations of transiting extrasolar planets are of key importance to our understanding of planets because their mass, radius, and mass density can be determined. These measurements indicate that planets of similar mass can have very different radii. For low-density planets, it is generally assumed that they are inflated owing to their proximity to the host-star. To determine the causes of this inflation, it is necessary to obtain a statistically significant sample of planets with precisely measured masses and radii. Aims: The CoRoT space mission allows us to achieve a very high photometric accuracy. By combining CoRoT data with high-precision radial velocity measurements, we derive precise planetary radii and masses. We report the discovery of CoRoT-19b, a gas-giant planet transiting an old, inactive F9V-type star with a period of four days. Methods: After excluding alternative physical configurations mimicking a planetary transit signal, we determine the radius and mass of the planet by combining CoRoT photometry with high-resolution spectroscopy obtained with the echelle spectrographs SOPHIE, HARPS, FIES, and SANDIFORD. To improve the precision of its ephemeris and the epoch, we observed additional transits with the TRAPPIST and Euler telescopes. Using HARPS spectra obtained during the transit, we then determine the projected angle between the spin of the star and the orbit of the planet. Results: We find that the host star of CoRoT-19b is an inactive F9V-type star close to the end of its main-sequence life. The host star has a mass M∗ = 1.21 ± 0.05 M⊙ and radius R∗ = 1.65 ± 0.04 R⊙. The planet has a mass of MP = 1.11 ± 0.06 MJup and radius of RP = 1.29 ± 0.03 RJup. The resulting bulk density is only ρ = 0.71 ± 0.06 g cm-3, which is much lower than that for Jupiter. Conclusions: The exoplanet CoRoT-19b is an example of a giant planet of almost the same mass as Jupiter but a ≈30% larger radius. The CoRoT space mission, launched on

  4. Revisiting the SAR of the Antischistosomal Aryl Hydantoin (Ro 13-3978)

    PubMed Central

    2016-01-01

    The aryl hydantoin 1 (Ro 13-3978) was identified in the early 1980s as a promising antischistosomal lead compound. However, this series of aryl hydantoins produced antiandrogenic side effects in the host, a not unexpected outcome given their close structural similarity to the antiandrogenic drug nilutamide. Building on the known SAR of this compound series, we now describe a number of analogs of 1 designed to maximize structural diversity guided by incorporation of substructures and functional groups known to diminish ligand–androgen receptor interactions. These analogs had calculated polar surface area (PSA), measured LogD7.4, aqueous kinetic solubility, and estimated plasma protein binding values in ranges predictive of good ADME profiles. The principal SAR insight was that the hydantoin core of 1 is required for high antischistosomal activity. We identified several compounds with high antischistosomal efficacy that were less antiandrogenic than 1. These data provide direction for the ongoing optimization of antischistosomal hydantoins. PMID:27933964

  5. High-efficiency optical coupling single-sideband modulation for OFDM-RoF-PON systems

    NASA Astrophysics Data System (ADS)

    Xue, Xuwei; Ji, Wei; Kang, Zhaoyuan; Huang, Kangrui; Li, Xiao

    2015-12-01

    We report on an OFDM-RoF-PON system based on novel optical coupling single-sideband (O-SSB) modulation for one wavelength carrying one baseband and two radio frequency (RF) signals. The impact of nonlinear distortion consisting of harmonic distortion (HD) and intermodulation distortion (IMD) in this system is theoretically investigated. Transmission over 0 km and 40 km of standard single mode fiber is successfully demonstrated and it is indicated that modulation index 0.6 is more adapted to O-SSB modulation. The error vector magnitude (EVM) of system based on O-SSB modulation after transmission over 40 km is <0.1. For O-SSB modulation, bit error rate (BER) after 40 km transmission is below forward error correction (FEC) limit of 10-3.

  6. Pharmacokinetics of Ro 03-8799 in mice bearing melanosarcoma: comparison with tumors without melanin

    SciTech Connect

    Laurent, F.; Canal, P.; Soula, G.

    1989-04-01

    The pharmacokinetics of Ro 03-8799 has been studied in melanic and non-melanic tumor bearing mice after iv administration of 150 mg/kg. The peak concentration in B16 melanosarcoma tumor reached 152 micrograms/g, that is 7.6-fold higher than the plasma concentration at the same time. This concentration is 3-times greater than that obtained in the tumor of mice bearing non-melanic sarcoma (DB16) or Lewis lung carcinoma (3LL). The exposure of B16 tumor (AUC) is respectively 15-times and 11-times higher than the 3LL and the DB16 ones. These experimental data confirm that this 2-nitro-imidazol compound has an important affinity for melanin and suggest that it might be used as a radiosensitizer for the treatment of malignant melanoma.

  7. Looking for planetary candidates in the CoRoT Long Run LRc10

    NASA Astrophysics Data System (ADS)

    Zannoni, A.; Borsa, F.; Poretti, E.; Lodato, G.; Rainer, M.; Frustagli, G.

    We analysed the public data of the CoRoT Long Run LRc10 looking for planetary candidates. In a first step we removed outliers and trends caused by stellar activity and instrumental problems. Then we applied the Box-fitting Least Squares (BLS) algorithm to detect periodic decreases in luminosity. From all the significative transit detections, we selected the ones that passed different checks. For the 7 planetary candidates found, we applied a new ``ad hoc'' normalization and fitted the orbital parameters, to verify their reliability. Using the stellar temperature information, we could estimate the dimensions that the candidates should have if confirmed. Our research method demonstrated to be sensitive to candidates with hypothetic dimension up to ˜3.5 REarth on stars of mag V≃14.

  8. Variational Calculations of Ro-Vibrational Energy Levels and Transition Intensities for Tetratomic Molecules

    NASA Technical Reports Server (NTRS)

    Schwenke, David W.; Langhoff, Stephen R. (Technical Monitor)

    1995-01-01

    A description is given of an algorithm for computing ro-vibrational energy levels for tetratomic molecules. The expressions required for evaluating transition intensities are also given. The variational principle is used to determine the energy levels and the kinetic energy operator is simple and evaluated exactly. The computational procedure is split up into the determination of one dimensional radial basis functions, the computation of a contracted rotational-bending basis, followed by a final variational step coupling all degrees of freedom. An angular basis is proposed whereby the rotational-bending contraction takes place in three steps. Angular matrix elements of the potential are evaluated by expansion in terms of a suitable basis and the angular integrals are given in a factorized form which simplifies their evaluation. The basis functions in the final variational step have the full permutation symmetries of the identical particles. Sample results are given for HCCH and BH3.

  9. Ro-vibrational averaging of the isotropic hyperfine coupling constant for the methyl radical

    SciTech Connect

    Adam, Ahmad Y.; Jensen, Per; Yachmenev, Andrey; Yurchenko, Sergei N.

    2015-12-28

    We present the first variational calculation of the isotropic hyperfine coupling constant of the carbon-13 atom in the CH{sub 3} radical for temperatures T = 0, 96, and 300 K. It is based on a newly calculated high level ab initio potential energy surface and hyperfine coupling constant surface of CH{sub 3} in the ground electronic state. The ro-vibrational energy levels, expectation values for the coupling constant, and its temperature dependence were calculated variationally by using the methods implemented in the computer program TROVE. Vibrational energies and vibrational and temperature effects for coupling constant are found to be in very good agreement with the available experimental data. We found, in agreement with previous studies, that the vibrational effects constitute about 44% of the constant’s equilibrium value, originating mainly from the large amplitude out-of-plane bending motion and that the temperature effects play a minor role.

  10. A hybrid ED/RO process for TDS reduction of produced waters

    SciTech Connect

    Tsai, S.P.; Datta, R.; Frank, J.R.

    1995-12-31

    Large volumes of produced waters are generated from natural gas production. In the United States the prevailing management practice for produced waters is deep well injection, but this practice is costly. Therefore minimizing the need for deep well injection is desirable. A major treatment issue for produced waters is the reduction of total dissolved solids (TDS), which consist mostly of inorganic salts. A hybrid electrodialysis/reverse-osmosis (ED/RO) treatment process is being developed to concentrate the salts in produced waters and thereby reduce the volume of brine that needs to be managed for disposal. The desalted water can be used beneficially or discharged. In this study, laboratory feasibility experiments were conducted by using produced waters from multiple sites. A novel-membrane configuration approach to prevent fouling and scale formation was developed and demonstrated. Results of laboratory experiments and plans for field demonstration are discussed.

  11. Constructing generalized Cesàro formulas for finite plane strains

    NASA Astrophysics Data System (ADS)

    Georgievskii, D. V.

    2014-05-01

    The problem of finding the displacement vector from a system of nonlinear differential equations which includes displacement gradient components is studied. Expressions on the right side of this system for certain parameter values have the kinematic sense of Lagrange and Euler finite strain tensors. The task is to construct generalized Cesàro formulas for finite strains. The construction of the solution consists of two stages (algebraic and differential), and the second is performed for space whose dimension is greater than or equal to two. An algorithm for the inversion of the original system is proposed, and analytical constructions for the case of two-dimensional space are performed. The problem is solved at the first (algebraic) stage, i.e., an exact analytical expression for the displacement vector components is derived through the known finite strain tensor and an unknown scalar function having the kinematic sense of rotation. Necessary conditions for the existence of this relationship are formulated.

  12. Doppler mapping of four roAp stars with anomalous lithium abundance

    NASA Astrophysics Data System (ADS)

    Polosukhina, N.; Shulyak, D.; Shavrina, A.; Lyashko, D.; Drake, N.; Glagolevsky, Y.; Kudryavtsev, D.; Smirnova, M.

    2014-11-01

    We present the first results from Doppler Imaging of two roAp stars, HD 12098 and HD 60435, that show strong and variable Li lines in their spectra. High-resolution spectra were obtained with the Russian 6-m BTA telescope, and with the HARPS and VLT/UVES instruments at ESO. We derived the surface abundance distribution of Li and Pr and analysed the correlation between the positions of the Li-abundance spots and magnetic field. We compare our results with Doppler Imaging mapping previously obtained for two CP2 stars, HD 83668 and HD 3980, and discuss the common properties of the locations of the ``Li spots'' on the surfaces of magnetic chemically peculiar A-type stars.

  13. The CoRoT and Kepler Revolution in Stellar Variability Studies

    NASA Astrophysics Data System (ADS)

    Degroote, Pieter; Debosscher, Jonas

    2012-04-01

    Space-based observations of variable stars have revolutionized the field of variability studies. Dedicated satellites such as the CoRoT and Kepler missions have duty cycles which are unachievable from the ground, and effectively solve many of the aliasing problems prevalent in ground-based observation campaigns. Moreover, the location above the Earth's atmosphere eliminates a major source of scatter prevalent in observations from the ground. These two major improvements in instrumentation have triggered significant increases in our knowledge of the stars, but in order to reap the full benefits they are also obliging the community to adopt more efficient techniques for handling, analysing and interpreting the vast amounts of new, high-precision data in an effective yet comprehensive manner. This workshop heard an outline of the history and development of asteroseismology, and descriptions of the two space missions (CoRoT and Kepler) which have been foremost in accelerating those recent developments. Informal discussions on numerous points peppered the proceedings, and involved the whole audience at times. The conclusions which the workshop reached have been distilled into a list of seven recommendations (Section 5) for the asteroseismology community to study and absorb. In fact, while addressing activities (such as stellar classification or analysing and modelling light curves) that could be regarded as specific to the community in question, the recommendations include advice on matters such as improving communication, incorporating trans-disciplinary knowledge and involving the non-scientific public that are broad enough to serve as guidelines for the astrophysical community at large.

  14. The CoRoT satellite in flight: description and performance

    NASA Astrophysics Data System (ADS)

    Auvergne, M.; Bodin, P.; Boisnard, L.; Buey, J.-T.; Chaintreuil, S.; Epstein, G.; Jouret, M.; Lam-Trong, T.; Levacher, P.; Magnan, A.; Perez, R.; Plasson, P.; Plesseria, J.; Peter, G.; Steller, M.; Tiphène, D.; Baglin, A.; Agogué, P.; Appourchaux, T.; Barbet, D.; Beaufort, T.; Bellenger, R.; Berlin, R.; Bernardi, P.; Blouin, D.; Boumier, P.; Bonneau, F.; Briet, R.; Butler, B.; Cautain, R.; Chiavassa, F.; Costes, V.; Cuvilho, J.; Cunha-Parro, V.; de Oliveira Fialho, F.; Decaudin, M.; Defise, J.-M.; Djalal, S.; Docclo, A.; Drummond, R.; Dupuis, O.; Exil, G.; Fauré, C.; Gaboriaud, A.; Gamet, P.; Gavalda, P.; Grolleau, E.; Gueguen, L.; Guivarc'h, V.; Guterman, P.; Hasiba, J.; Huntzinger, G.; Hustaix, H.; Imbert, C.; Jeanville, G.; Johlander, B.; Jorda, L.; Journoud, P.; Karioty, F.; Kerjean, L.; Lafond, L.; Lapeyrere, V.; Landiech, P.; Larqué, T.; Laudet, P.; Le Merrer, J.; Leporati, L.; Leruyet, B.; Levieuge, B.; Llebaria, A.; Martin, L.; Mazy, E.; Mesnager, J.-M.; Michel, J.-P.; Moalic, J.-P.; Monjoin, W.; Naudet, D.; Neukirchner, S.; Nguyen-Kim, K.; Ollivier, M.; Orcesi, J.-L.; Ottacher, H.; Oulali, A.; Parisot, J.; Perruchot, S.; Piacentino, A.; Pinheiro da Silva, L.; Platzer, J.; Pontet, B.; Pradines, A.; Quentin, C.; Rohbeck, U.; Rolland, G.; Rollenhagen, F.; Romagnan, R.; Russ, N.; Samadi, R.; Schmidt, R.; Schwartz, N.; Sebbag, I.; Smit, H.; Sunter, W.; Tello, M.; Toulouse, P.; Ulmer, B.; Vandermarcq, O.; Vergnault, E.; Wallner, R.; Waultier, G.; Zanatta, P.

    2009-10-01

    Context: CoRoT is a space telescope dedicated to stellar seismology and the search for extrasolar planets. The mission is led by the CNES in association with French laboratories and has a large international participation. The European Space Agency (ESA), Austria, Belgium, and Germany contribute to the payload, and Spain and Brazil contribute to the ground segment. Development of the spacecraft, which is based on a PROTEUS low earth orbit (LEO) recurrent platform, commenced in October 2000, and the satellite was launched on December 27, 2006. Aims: The instrument and platform characteristics prior to launch have been described in ESA publication (SP-1306). In the present paper we explain the behaviour in flight, based on raw and corrected data. Methods: Five runs have been completed since January 2007. The data used here are essentially those acquired during the commissioning phase and from a long run that lasted 146 days. These enable us to give a complete overview of the instrument and platform behaviour for all environmental conditions. The ground based data processing is not described in detail because the most important method has been published elsewhere. Results: We show that the performance specifications are easily satisfied when the environmental conditions are favourable. Most of the perturbations, hence data corrections, are related to LEO perturbations: high energy particles inside the South Atlantic Anomaly (SAA), eclipses and temperature variations, and line of sight fluctuations due to the attitude control system. Straylight due to the reflected light from the earth, which is controlled by the telescope and baffle design, appears to be negligible. The CoRoT space mission, launched on December 27th 2006, has been developed and is operated by CNES, with contributions from Austria, Belgium, Brazil, ESA, Germany and Spain. Four French laboratories associated with the CNRS (LESIA, LAM, IAS, OMP) collaborate with CNES on the satellite development. The

  15. RoHS regulated substances in mixed plastics from waste electrical and electronic equipment.

    PubMed

    Wäger, Patrick A; Schluep, Mathias; Müller, Esther; Gloor, Rolf

    2012-01-17

    The disposal and recovery of plastics from waste electrical and electronic equipment (WEEE) are of considerable importance, both from an environmental and an economic perspective. This paper presents the results of a study investigating current concentrations of hazardous substances in mixed plastics from WEEE and their implications for an environmentally sound recovery. The study included 53 sampling campaigns for mixed plastics from WEEE. The samples were analyzed with regard to heavy metals (cadmium, chromium, mercury, and lead) and flame retardants (PentaBDE, OctaBDE, DecaBDE, DecaBB) regulated in the RoHS Directive. Besides these substances, other brominated flame retardants known to occur in electronics (HBCD, TBBPA) as well as the total bromine and phosphorus contents were considered. Results show that no mixed plastics fraction from WEEE is completely free from substances regulated in the RoHS Directive. The lowest number and average concentrations were found in flat screen monitors. The highest concentrations were found in mixed plastics from CRT monitors and TVs. Mixed plastics fractions with high average concentrations of heavy metals originate from the treatment of small household appliances (cadmium), ICT equipment (lead), and consumer equipment (lead). Mixed plastics fractions with high average concentrations of brominated flame retardants mainly originate from the treatment of small household appliances for high temperature applications (DecaBDE), CRT monitors (OctaBDE and DecaBDE) and consumer equipment (DecaBDE), in particular CRT TVs (DecaBDE). To avoid a dissipation of hazardous substances into plastics and the environment, it is recommended that mixed plastics from WEEE are subject to a strict quality management.

  16. Presenting new exoplanet candidates for the CoRoT chromatic light curves

    NASA Astrophysics Data System (ADS)

    Boufleur, Rodrigo; Emilio, Marcelo; Andrade, Laerte; Janot-Pacheco, Eduardo; De La Reza, Ramiro

    2015-08-01

    One of the most promising topics of modern Astronomy is the discovery and characterization of extrasolar planets due to its importance for the comprehension of planetary formation and evolution. Missions like MOST (Microvariability and Oscillations of Stars Telescope) (Walker et al., 2003) and especially the satellites dedicated to the search for exoplanets CoRoT (Convection, Rotation and planetary Transits) (Baglin et al., 1998) and Kepler (Borucki et al., 2003) produced a great amount of data and together account for hundreds of new discoveries. An important source of error in the search for planets with light curves obtained from space observatories are the displacements occuring in the data due to external causes. This artificial charge generation phenomenon associated with the data is mainly caused by the impact of high energy particles onto the CCD (Pinheiro da Silva et al. 2008), although other sources of error, not as well known also need to be taken into account. So, an effective analysis of the light curves depends a lot on the mechanisms employed to deal with these phenomena. To perform our research, we developed and applied a different method to fix the light curves, the CDAM (Corot Detrend Algorithm Modified), inspired by the work of Mislis et al. (2012). The paradigms were obtained using the BLS method (Kovács et al., 2002). After a semiautomatic pre-analysis associated with a visual inspection of the planetary transits signatures, we obtained dozens of exoplanet candidates in very good agreement with the literature and also new unpublished cases. We present the study results and characterization of the new cases for the chromatic channel public light curves of the CoRoT satellite.

  17. A 60GHz RoF(radio-over-fiber) transmission system based on PM modulator

    NASA Astrophysics Data System (ADS)

    Wang, Xin; Liu, Yi; Wang, Wen-Ting

    2016-11-01

    As one of the most important applications of microwave photonic ROF (Radio over Fiber) system which combines the advantages of optical communication and wireless communication is a good candidate for broadband mobile Communication In this paper, we built and simulation a 60GHz RoF(Radio-over-Fiber) transmission system based on PM modulator. First, we introduce the PM-IM(Phase modulation to intensity modulation) modulation mechanisms by the breaking the phase balanced approach. This method solves the problem that the constant envelope (phase modulation signal) generated by the phase modulator can not be directly detected by a photo detector. A standard single-mode fiber (SMF) is connected input to the F-P(Fabry-Perot) optical filter, which is to achieve the PM-IM modulation conversion by changing the wavelength of the laser or the frequency of the modulation factor of the F-P optical filter to adapt to different fiber lengths and the signal transmission rate. These two methods which changing the phase relationship between the optical carrier and the optical side band can realize the ideal phase transition to obtain efficient and low loss modulation conversion. Finally, the simulation results show that different fiber lengths and the signal transmission rate configuration of different wavelength of the laser or the frequency of the modulation factor of the F-P optical filter, the BER performance and the eye diagram of the 60GHz RoF transmission system signals have been improved based on these PM-IM modulation methods.

  18. A self-consistent chemically stratified atmosphere model for the roAp star 10 Aquilae

    NASA Astrophysics Data System (ADS)

    Nesvacil, N.; Shulyak, D.; Ryabchikova, T. A.; Kochukhov, O.; Akberov, A.; Weiss, W.

    2013-04-01

    Context. Chemically peculiar A-type (Ap) stars are a subgroup of the CP2 stars that exhibit anomalous overabundances of numerous elements, e.g. Fe, Cr, Sr, and rare earth elements. The pulsating subgroup of Ap stars, the roAp stars, present ideal laboratories to observe and model pulsational signatures, as well as the interplay of the pulsations with strong magnetic fields and vertical abundance gradients. Aims: Based on high-resolution spectroscopic observations and observed stellar energy distributions, we construct a self-consistent model atmosphere for the roAp star 10 Aquilae (HD 176232). It accounts for modulations of the temperature-pressure structure caused by vertical abundance gradients. We demonstrate that such an analysis can be used to determine precisely the fundamental atmospheric parameters required for pulsation modelling. Methods: Average abundances were derived for 56 species. For Mg, Si, Ca, Cr, Fe, Co, Sr, Pr, and Nd, vertical stratification profiles were empirically derived using the DDAFit minimisation routine together with the magnetic spectrum synthesis codeSynthmag. Model atmospheres were computed with the LLmodels code, which accounts for the individual abundances and stratification of chemical elements. Results: For the final model atmosphere, Teff = 7550 K and log (g) = 3.8 were adopted. While Mg, Si, Co, and Cr exhibit steep abundance gradients, Ca, Fe, and Sr showed much wider abundance gradients between logτ5000 = -1.5 and 0.5. Elements Mg and Co were found to be the least stratified, while Ca and Sr showed strong depth variations in abundance of up to ≈ 6 dex. Table 4 and Figs. 10-12 are available in electronic form at http://www.aanda.org

  19. The CoRoT chemical peculiar target star HD 49310

    NASA Astrophysics Data System (ADS)

    Paunzen, E.; Fröhlich, H.-E.; Netopil, M.; Weiss, W. W.; Lüftinger, T.

    2015-02-01

    Context. The magnetic chemically peculiar (CP) stars of the upper main sequence are well-suited laboratories for investigating the influence of local magnetic fields on the stellar surface because they produce inhomogeneities (spots) that can be investigated in detail as the star rotates. Aims: We studied the inhomogeneous surface structure of the CP2 star HD 49310 based on high-quality CoRoT photometry obtained during 25 days. The data have nearly no gaps. This analysis is similar to a spectroscopic Doppler-imaging analysis, but it is not a tomographic method. Methods: We performed detailed light-curve fitting in terms of stationary circular bright spots. Furthermore, we derived astrophysical parameters with which we located HD 49310 within the Hertzsprung-Russell diagram. We also investigated the possible connection of this star to the nearby young open cluster NGC 2264. Results: With a Bayesian technique, we produced a surface map that shows six bright spots. After removing some artefacts, the residuals of the observed and synthetic photometric data are ± 0.123 mmag. The rotational period of the star is P = 1.91909 ± 0.00001 days. Our photometric observations therefore cover about 13 full rotational cycles. Three spots are very large with diameters of ≃ 40deg. The spots are brighter by 40% than the unperturbed stellar photosphere. Conclusions: HD 49310 is a classical silicon (CP2) star with a mass of about 3 M⊙. It is not a member of NGC 2264. Our analysis shows the potential of using high-quality photometric data to analyse the surface structure of CP stars. A comprehensive analysis of similar archival data, preferrably from space missions, would contribute significantly to our understanding of surface phenomena of CP stars and their temporal evolution. The CoRoT space mission was developed and is operated by the French space agency CNES, with participation of ESA's RSSD and Science Programmes, Austria, Belgium, Brazil, Germany, and Spain.

  20. Use of non-selective β-blockers is associated with decreased tumor proliferative indices in early stage breast cancer.

    PubMed

    Montoya, Alexa; Amaya, Clarissa N; Belmont, Andres; Diab, Nabih; Trevino, Richard; Villanueva, Geri; Rains, Steven; Sanchez, Luis A; Badri, Nabeel; Otoukesh, Salman; Khammanivong, Ali; Liss, Danielle; Baca, Sarah T; Aguilera, Renato J; Dickerson, Erin B; Torabi, Alireza; Dwivedi, Alok K; Abbas, Aamer; Chambers, Karinn; Bryan, Brad A; Nahleh, Zeina

    2017-01-24

    Previous studies suggest beta-adrenergic receptor (β-AR) antagonists (β-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of β1-AR and β3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor proliferation. Our analysis revealed that non-selective β-blockers, but not selective β-blockers, reduced tumor proliferation by 66% (p < 0.0001) in early stage breast cancer compared to non-users. We tested the efficacy of propranolol on an early stage breast cancer patient, and quantified the tumor proliferative index before and after treatment, revealing a propranolol-mediated 23% reduction (p = 0.02) in Ki67 positive tumor cells over a three-week period. The anti-proliferative effects of β-blockers were measured in a panel of breast cancer lines, demonstrating that mammary epithelial cells were resistant to propranolol, and that most breast cancer cell lines displayed dose dependent viability decreases following treatment. Selective β-blockers alone or in combination were not as effective as propranolol at reducing breast cancer cell proliferation. Molecular analysis revealed that propranolol treatment of the SK-BR-3 breast cancer line, which showed high sensitivity to beta blockade, led to a reduction in Ki67 protein expression, decreased phosphorylation of the mitogenic signaling regulators p44/42 MAPK, p38 MAPK, JNK, and CREB, increased phosphorylation of the cell survival/apoptosis regulators AKT, p53, and GSK3β. In conclusion, use of non-selective β-blockers in patients with early stage breast cancer may lead to decreased tumor proliferation.

  1. Use of non-selective β-blockers is associated with decreased tumor proliferative indices in early stage breast cancer

    PubMed Central

    Diab, Nabih; Trevino, Richard; Villanueva, Geri; Rains, Steven; Sanchez, Luis A.; Badri, Nabeel; Otoukesh, Salman; Khammanivong, Ali; Liss, Danielle; Baca, Sarah T.; Aguilera, Renato J.; Dickerson, Erin B.; Torabi, Alireza; Dwivedi, Alok K.; Abbas, Aamer; Chambers, Karinn; Bryan, Brad A.; Nahleh, Zeina

    2017-01-01

    Previous studies suggest beta-adrenergic receptor (β-AR) antagonists (β-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of β1-AR and β3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor proliferation. Our analysis revealed that non-selective β-blockers, but not selective β-blockers, reduced tumor proliferation by 66% (p < 0.0001) in early stage breast cancer compared to non-users. We tested the efficacy of propranolol on an early stage breast cancer patient, and quantified the tumor proliferative index before and after treatment, revealing a propranolol-mediated 23% reduction (p = 0.02) in Ki67 positive tumor cells over a three-week period. The anti-proliferative effects of β-blockers were measured in a panel of breast cancer lines, demonstrating that mammary epithelial cells were resistant to propranolol, and that most breast cancer cell lines displayed dose dependent viability decreases following treatment. Selective β-blockers alone or in combination were not as effective as propranolol at reducing breast cancer cell proliferation. Molecular analysis revealed that propranolol treatment of the SK-BR-3 breast cancer line, which showed high sensitivity to beta blockade, led to a reduction in Ki67 protein expression, decreased phosphorylation of the mitogenic signaling regulators p44/42 MAPK, p38 MAPK, JNK, and CREB, increased phosphorylation of the cell survival/apoptosis regulators AKT, p53, and GSK3β. In conclusion, use of non-selective β-blockers in patients with early stage breast cancer may lead to decreased tumor proliferation. PMID:28031536

  2. Effects of a D2 receptor agonist RO 41-9067 alone and with clonidine on sleep parameters in the rat.

    PubMed

    Python, A; de Saint Hilaire, Z; Gaillard, J M

    1996-02-01

    The effects of RO 41-9067, a D2 dopamine receptors agonist, on different sleep parameters were studied in the rat. RO 41-9067 dose dependently decreased paradoxical sleep, and only at the higher dose increased waking during the light period. In contrast, the higher dose of RO 41-9067 increased paradoxical sleep and decreased waking during the dark period. Finally, the combination of RO 41-9067 and clonidine significantly prevent the decrease of total sleep time and paradoxical sleep found after clonidine alone. These results, compared with those of classical D2 dopamine receptors agonists, suggest an action for RO 41-9067 on D2 dopamine receptors depending on the cerebral structure, a different action particularly on the striatum and/or on the structures responsible for paradoxical sleep. An active role for D2 dopamine receptors and an interaction between noradrenergic and dopaminergic systems in the regulation of sleep is proposed.

  3. Incidence of medication error associated with the use of beta-blockers in Pakistan.

    PubMed

    Nesar, Shagufta; Shoaib, Muhammad Harris; Yousuf, Rabia Ismail; Rahim, Najia; Muhammad, Iyad Naeem

    2014-05-01

    Medication errors (ME) are human errors, which are very frequent in cardiovascular patients and result in patient morbidity and mortality. This study was focused to evaluate the quality of prescriptions and to emphasize the placement of clinical pharmacist in health care team. This study was carried out in different outpatient settings of (in) Karachi, Pakistan. The study period was June 2011 till June 2012. Retrospective data was analyzed for the outpatients' prescription of beta blocker drugs. During the study, prescriptions (n=450) were collected from different outpatient settings of (in) Karachi, Pakistan. Prescription containing beta-blockers were analyzed for the essential elements to be mentioned in prescription. Drug-drug interactions were identified by the Micromedex.2.0 Drug-Reax database and severity of medication error was determined by NCCMERP Index. A total of 1627 medication errors were identified in 450 prescriptions. The most frequent error was not mentioning the patient's weight (95%), followed by missing diagnosis (79.4%) and drug-drug interactions (69.5%). Twenty-two prescriptions were placed in the most severe category I (4.88%). Average number of drugs per prescription was 4.76. Significant difference was observed (χ(2)=52.418, p<0.05) using SPSS 19 for those prescription orders having more than 5 drugs with Beta-blockers. This indicates that the errors in prescription such as drug-drug interactions, wrong dose etc. was significantly increased with the number of drugs per prescription. Results showed that medication errors are very frequent in prescription written in outpatient setting of various hospitals and clinics in Karachi. This shows that the irrational prescribing is a common practice in developing countries. Placement of skilled pharmacist in the health care system is the only solution for avoidance of these medication related problems.

  4. Pro-survival function of MEF2 in cardiomyocytes is enhanced by β-blockers

    PubMed Central

    Hashemi, S; Salma, J; Wales, S; McDermott, JC

    2015-01-01

    β1-Adrenergic receptor (β1-AR) stimulation increases apoptosis in cardiomyocytes through activation of cAMP/protein kinase A (PKA) signaling. The myocyte enhancer factor 2 (MEF2) proteins function as important regulators of myocardial gene expression. Previously, we reported that PKA signaling directly represses MEF2 activity. We determined whether (a) MEF2 has a pro-survival function in cardiomyocytes, and (b) whether β-adrenergic/PKA signaling modulates MEF2 function in cardiomyocytes. Initially, we observed that siRNA-mediated gene silencing of MEF2 induces cardiomyocyte apoptosis as indicated by flow cytometry. β1-AR activation by isoproterenol represses MEF2 activity and promotes apoptosis in cultured neonatal cardiomyocytes. Importantly, β1-AR mediated apoptosis was abrogated in cardiomyocytes expressing a PKA-resistant form of MEF2D (S121/190A). We also observed that a β1-blocker, Atenolol, antagonizes isoproterenol-induced apoptosis while concomitantly enhancing MEF2 transcriptional activity. β-AR stimulation modulated MEF2 cellular localization in cardiomyocytes and this effect was reversed by β-blocker treatment. Furthermore, Kruppel-like factor 6, a MEF2 target gene in the heart, functions as a downstream pro-survival factor in cardiomyocytes. Collectively, these data indicate that (a) MEF2 has an important pro-survival role in cardiomyocytes, and (b) β-adrenergic signaling antagonizes the pro-survival function of MEF2 in cardiomyocytes and β-blockers promote it. These observations have important clinical implications that may contribute to novel strategies for preventing cardiomyocyte apoptosis associated with heart pathology. PMID:27551452

  5. Enantiomeric selectivity in adsorption of chiral β-blockers on sludge.

    PubMed

    Sanganyado, Edmond; Fu, Qiuguo; Gan, Jay

    2016-07-01

    Adsorption of weakly basic compounds by sludge is poorly understood, although it has important implications on the distribution and fate of such micropollutants in wastewater effluent and sludge. Additionally, many of these compounds are chiral, and it is likely that their interactions with sludge is stereoselective and that the process may be further modified by surfactants that coexist in these systems. Adsorption of (R) and (S)-enantiomers of five commonly used β-blockers, i.e., acebutolol, atenolol, metoprolol, pindolol and propranolol, on sludge was characterized through batch experiments. Stereoselectivity in adsorption increased with decreases in hydrophobicity of the β-blockers. The enantiomeric fraction (EF) of the amount of acebutolol, atenolol and metoprolol sorbed on sludge were 0.27, 0.55 and 0.32, respectively. Thus, Kd values of the (S)-enantiomers of acebutolol and metoprolol were approximately twice that of the (R)-enantiomer, that is, 109 ± 11 and 57 ± 8 L/kg compared to 52 ± 13 and 22 ± 8 L/kg, respectively. There was no statistically significant difference in Kd values of the enantiomers of pindolol and propranolol, suggesting stereoselectivity in adsorption was likely driven by specific polar interactions rather than hydrophobic interactions. The EF value of atenolol decreased from 0.55 ± 0.03 to 0.44 ± 0.04 after modifying the sludge with Triton X 100. These results suggested that surfactants altered adsorption of β-blockers to sludge, likely by forming ion pair complexes that promote hydrophobic interactions with the solid surfaces.

  6. Effect of RAAS blockers on adverse clinical outcomes in high CVD risk subjects with atrial fibrillation

    PubMed Central

    Chaugai, Sandip; Sherpa, Lhamo Yanchang; Sepehry, Amir A.; Arima, Hisatomi; Wang, Dao Wen

    2016-01-01

    Abstract Recent studies have demonstrated that atrial fibrillation significantly increases the risk of adverse clinical outcomes in high cardiovascular disease risk subjects. Application of renin–angiotensin–aldosterone system blockers for prevention of recurrence of atrial fibrillation and adverse clinical outcomes in subjects with atrial fibrillation is a theoretically appealing concept. However, results of clinical trials evaluating the effect of renin–angiotensin–aldosterone blockers on adverse clinical outcomes in high cardiovascular disease risk subjects with atrial fibrillation remain inconclusive. A pooled study of 6 randomized controlled trials assessing the efficacy of renin–angiotensin–aldosterone blockers on subjects with atrial fibrillation was performed. A total of 6 randomized controlled trials enrolled a total of 53,510 patients followed for 1 to 5 years. RAAS blockade therapy was associated with 14% reduction in the incidence of heart failure (OR: 0.86, [95%CI: 0.76– 0.97], P=0.018) and 17% reduction in the incidence of CVE (OR: 0.83, [95%CI: 0.70–0.99], P = 0.038). The corresponding decline in absolute risk against heart failure (ARR: 1.4%, [95%CI: 0.2–2.6%], P = 0.018) and CVE (ARR: 3.5%, [95%CI: 0.0–6.9%], P = 0.045) in the AF group was much higher than the non-AF group for heart failure (ARR: 0.4%, [95%CI: 0.0–0.7%], P = 0.057) and CVE (ARR: 1.6%, [95%CI: –0.1% to 3.3%], P = 0.071). No significant effect was noted on all-cause or cardiovascular mortality, stroke, or myocardial infarction. This study suggests that RAAS blockade offers protection against heart failure and cardiovascular events in high cardiovascular disease risk subjects with atrial fibrillation. PMID:27368043

  7. SU-E-I-08: Investigation of Deconvolution Methods for Blocker-Based CBCT Scatter Estimation

    SciTech Connect

    Zhao, C; Jin, M; Ouyang, L; Wang, J

    2015-06-15

    Purpose: To investigate whether deconvolution methods can improve the scatter estimation under different blurring and noise conditions for blocker-based scatter correction methods for cone-beam X-ray computed tomography (CBCT). Methods: An “ideal” projection image with scatter was first simulated for blocker-based CBCT data acquisition by assuming no blurring effect and no noise. The ideal image was then convolved with long-tail point spread functions (PSF) with different widths to mimic the blurring effect from the finite focal spot and detector response. Different levels of noise were also added. Three deconvolution Methods: 1) inverse filtering; 2) Wiener; and 3) Richardson-Lucy, were used to recover the scatter signal in the blocked region. The root mean square error (RMSE) of estimated scatter serves as a quantitative measure for the performance of different methods under different blurring and noise conditions. Results: Due to the blurring effect, the scatter signal in the blocked region is contaminated by the primary signal in the unblocked region. The direct use of the signal in the blocked region to estimate scatter (“direct method”) leads to large RMSE values, which increase with the increased width of PSF and increased noise. The inverse filtering is very sensitive to noise and practically useless. The Wiener and Richardson-Lucy deconvolution methods significantly improve scatter estimation compared to the direct method. For a typical medium PSF and medium noise condition, both methods (∼20 RMSE) can achieve 4-fold improvement over the direct method (∼80 RMSE). The Wiener method deals better with large noise and Richardson-Lucy works better on wide PSF. Conclusion: We investigated several deconvolution methods to recover the scatter signal in the blocked region for blocker-based scatter correction for CBCT. Our simulation results demonstrate that Wiener and Richardson-Lucy deconvolution can significantly improve the scatter estimation

  8. Acrolein-mediated conduction loss is partially restored by K+ channel blockers

    PubMed Central

    Yan, Rui; Page, Jessica C.

    2015-01-01

    Acrolein-mediated myelin damage is thought to be a critical mechanism leading to conduction failure following neurotrauma and neurodegenerative diseases. The exposure and activation of juxtaparanodal voltage-gated K+ channels due to myelin damage leads to conduction block, and K+ channel blockers have long been studied as a means for restoring axonal conduction in spinal cord injury (SCI) and multiple sclerosis (MS). In this study, we have found that 100 μM K+ channel blockers 4-aminopyridine-3-methanol (4-AP-3-MeOH), and to a lesser degree 4-aminopyridine (4-AP), can significantly restore compound action potential (CAP) conduction in spinal cord tissue following acrolein-mediated myelin damage using a well-established ex vivo SCI model. In addition, 4-AP-3-MeOH can effectively restore CAP conduction in acrolein-damaged axons with a range of concentrations from 0.1 to 100 μM. We have also shown that while both compounds at 100 μM showed no preference of small- and large-caliber axons when restoring CAP conduction, 4-AP-3-MeOH, unlike 4-AP, is able to augment CAP amplitude while causing little change in axonal responsiveness measured in refractory periods and response to repetitive stimuli. In a prior study, we show that 4-AP-3-MeOH was able to functionally rescue mechanically injured axons. In this investigation, we conclude that 4-AP-3-MeOH is an effective K+ channel blocker in restoring axonal conduction following both primary (physical) and secondary (chemical) insults. These findings also suggest that 4-AP-3-MeOH is a viable alternative of 4-AP for treating myelin damage and improving function following central nervous system trauma and neurodegenerative diseases. PMID:26581866

  9. Calcium channel blockers in the management of hypertension in the elderly.

    PubMed

    Caballero-Gonzalez, Francisco J

    2015-01-01

    The aging population is rapidly increasing, and is mainly due to medical advances and the control of chronic diseases, with a real worldwide increase in the elderly population. Special emphasis has been placed on the management of hypertension in the geriatric patient, since its long-term benefits have been shown to prevent both cerebral and cardiac infarctions. Calcium channel blockers have been shown to be effective in this condition in the elderly. Their success depends on their mechanism of action, as well as on the physiological changes observed, and on the aging process itself, which include cardiac hypertrophy, calcification of cardiac valves, and a decrease in the excitation-conduction system. There is thickening of the tunica intima of the arteries, and the production of nitric oxide at cellular level decreases with age, along with an increase in endothelin 1, which leads to vascular endothelium dysfunction. In the kidneys, there is a decrease in prostacyclin, endothelial hyperpolarization factor, as well as the Klotho anti-aging protein, which leads to an increase in blood pressure. Calcium channel blocker drugs have been shown to be effective in any age group for the management of hypertension, and are safe in the elderly patients. These drugs block L-type calcium channels, with the long-acting or latest generation dihydropyridines being the most effective of this group. Several studies, including SYST-EUR2, NORDIL, and STOP-2, have demonstrated the effectiveness of these drugs in the geriatric patient. The prescribing of long-acting calcium channel blocker drugs in a single dose is the most recommended. The safety in the use of this drug group has been demonstrated in the treatment of hypertension in the elderly patient, with a level of effectiveness similar to other widely used drugs.

  10. Electrically enhanced microextraction for highly selective transport of three β-blocker drugs.

    PubMed

    Seidi, Shahram; Yamini, Yadollah; Rezazadeh, Maryam

    2011-12-15

    Facilitated transport of three β-blocker drugs including atenolol (ATE), betaxolol (BET) and propranolol (PRO) was investigated under electrical field across a supported liquid membrane (SLM) using phosphoric acid derivatives as selective ion carriers, dissolved in 2-nitro phenyl octyl ether (NPOE). In the presence of di-(2-ethylhexyl) phosphate (DEHP) and tris-(2-ethylhexyl) phosphate (TEHP) in the membrane phase, the three β-blockers showed completely different transport behaviors which enabled highly selective separation of the drugs. Each β-blocker migrated from 3 mL of sample solutions, through a thin layer of specific organic solvent immobilized in the pores of a porous hollow fiber, and into a 15 μL acidic aqueous acceptor solution present inside the lumen of the fiber. The influences of fundamental parameters affecting the transport of target drugs including type of ion carrier for selective separation of each drug and its concentration in the membrane phase, extraction voltage, time of transport, pH of donor and acceptor phases, stirring speed of donor phase and salt effect were studied and optimized. After microextraction process, the extracts were analyzed by high-performance liquid chromatography with ultraviolet detection. Under optimal conditions, ATE was selectively extracted from different saliva samples with recovery of 37%, which corresponded to preconcentration factor of 74. A good linearity was achieved for calibration curve with a coefficient of determination higher than 0.997. Limits of detection and intra-day precision (n=3) were less than 2 μg L(-1) and 8.8%, respectively.

  11. Novel blockers of hyperpolarization-activated current with isoform selectivity in recombinant cells and native tissue.

    PubMed

    Del Lungo, Martina; Melchiorre, Michele; Guandalini, Luca; Sartiani, Laura; Mugelli, Alessandro; Koncz, Istvan; Szel, Tamas; Varro, Andras; Romanelli, Maria Novella; Cerbai, Elisabetta

    2012-05-01

    BACKGROUND AND PURPOSE Selective hyperpolarization activated, cyclic nucleotide-gated channel (HCN) blockers represent an important therapeutic goal due to the wide distribution and multiple functions of these proteins, representing the molecular correlate of f- and h-current (I(f) or I(h) ). Recently, new compounds able to block differentially the homomeric HCN isoforms expressed in HEK293 have been synthesized. In the present work, the electrophysiological and pharmacological properties of these new HCN blockers were characterized and their activities evaluated on native channels. EXPERIMENTAL APPROACH HEK293 cells expressing mHCN1, mHCN2 and hHCN4 isoforms were used to verify channel blockade. Selected compounds were tested on native guinea pig sinoatrial node cells and neurons from mouse dorsal root ganglion (DRG) by patch-clamp recordings and on dog Purkinje fibres by intracellular recordings. KEY RESULTS In HEK293 cells, EC18 was found to be significantly selective for HCN4 and MEL57A for HCN1 at physiological membrane potential. When tested on guinea pig sinoatrial node cells, EC18 (10 µM) maintained its activity, reducing I(f) by 67% at -120 mV, while MEL57A (3 µM) reduced I(f) by 18%. In contrast, in mouse DRG neurons, only MEL57A (30 and 100 µM) significantly reduced I(h) by 60% at -80 mV. In dog cardiac Purkinje fibres, EC18, but not MEL57A, reduced the amplitude and slowed the slope of the spontaneous diastolic depolarization. CONCLUSIONS Our results have identified novel and highly selective HCN isoform blockers, EC18 and MEL57A; the selectivity found in recombinant system was maintained in various tissues expressing different HCN isoforms.

  12. Comparative effects of sodium channel blockers in short term rat whole embryo culture

    SciTech Connect

    Nilsson, Mats F; Sköld, Anna-Carin; Ericson, Ann-Christin; Annas, Anita; Villar, Rodrigo Palma; Cebers, Gvido; Hellmold, Heike; Gustafson, Anne-Lee; Webster, William S

    2013-10-15

    This study was undertaken to examine the effect on the rat embryonic heart of two experimental drugs (AZA and AZB) which are known to block the sodium channel Nav1.5, the hERG potassium channel and the L-type calcium channel. The sodium channel blockers bupivacaine, lidocaine, and the L-type calcium channel blocker nifedipine were used as reference substances. The experimental model was the gestational day (GD) 13 rat embryo cultured in vitro. In this model the embryonic heart activity can be directly observed, recorded and analyzed using computer assisted image analysis as it responds to the addition of test drugs. The effect on the heart was studied for a range of concentrations and for a duration up to 3 h. The results showed that AZA and AZB caused a concentration-dependent bradycardia of the embryonic heart and at high concentrations heart block. These effects were reversible on washout. In terms of potency to cause bradycardia the compounds were ranked AZB > bupivacaine > AZA > lidocaine > nifedipine. Comparison with results from previous studies with more specific ion channel blockers suggests that the primary effect of AZA and AZB was sodium channel blockage. The study shows that the short-term rat whole embryo culture (WEC) is a suitable system to detect substances hazardous to the embryonic heart. - Highlights: • Study of the effect of sodium channel blocking drugs on embryonic heart function • We used a modified method rat whole embryo culture with image analysis. • The drugs tested caused a concentration dependent bradycardia and heart block. • The effect of drugs acting on multiple ion channels is difficult to predict. • This method may be used to detect cardiotoxicity in prenatal development.

  13. A real-time screening assay for GIRK1/4 channel blockers.

    PubMed

    Walsh, Kenneth B

    2010-12-01

    The cardiac acetylcholine-activated K(+) channel (I(K,Ach)) represents a novel target for drug therapy in the treatment of atrial fibrillation (AF). This channel is a member of the G-protein-coupled inward rectifier K(+) (GIRK) channel superfamily and is composed of the GIRK1/4 (Kir3.1 and Kir3.4) subunits. The goal of this study was to develop a cell-based screening assay for identifying new blockers of the GIRK1/4 channel. The mouse atrial HL-1 cell line, expressing the GIRK1/4 channel, was plated in 96-well plate format, loaded with the fluorescent membrane potential-sensitive dye bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC(4)(3)) and measured using a fluorescent imaging plate reader (FLIPR). Application of the muscarinic agonist carbachol to the cells caused a rapid, time-dependent decrease in the fluorescent signal, indicative of K(+) efflux through the GIRK1/4 channel (carbachol vs. control solution, Z' factor = 0.5-0.6). The GIRK1/4 channel fluorescent signal was blocked by BaCl(2) and enhanced by increasing the driving force for K(+) across the cell membrane. To test the utility of the assay for screening GIRK1/4 channel blockers, cells were treated with a small compound library of Na(+) and K(+) channel modulators. Analogues of amiloride and propafenone were identified as channel blockers at concentrations less than 1 µM. Thus, the GIRK1/4 channel assay may be used in the development of new and selective agents for treating AF.

  14. Experts Consensus Recommendations for the Management of Calcium Channel Blocker Poisoning in Adults

    PubMed Central

    Anseeuw, Kurt; Cantrell, Frank Lee; Gilchrist, Ian C.; Hantson, Philippe; Bailey, Benoit; Lavergne, Valéry; Gosselin, Sophie; Kerns, William; Laliberté, Martin; Lavonas, Eric J.; Juurlink, David N.; Muscedere, John; Yang, Chen-Chang; Sinuff, Tasnim; Rieder, Michael; Mégarbane, Bruno

    2017-01-01

    Objective: To provide a management approach for adults with calcium channel blocker poisoning. Data Sources, Study Selection, and Data Extraction: Following the Appraisal of Guidelines for Research & Evaluation II instrument, initial voting statements were constructed based on summaries outlining the evidence, risks, and benefits. Data Synthesis: We recommend 1) for asymptomatic patients, observation and consideration of decontamination following a potentially toxic calcium channel blocker ingestion (1D); 2) as first-line therapies (prioritized based on desired effect), IV calcium (1D), high-dose insulin therapy (1D–2D), and norepinephrine and/or epinephrine (1D). We also suggest dobutamine or epinephrine in the presence of cardiogenic shock (2D) and atropine in the presence of symptomatic bradycardia or conduction disturbance (2D); 3) in patients refractory to the first-line treatments, we suggest incremental doses of high-dose insulin therapy if myocardial dysfunction is present (2D), IV lipid-emulsion therapy (2D), and using a pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block without significant alteration in cardiac inotropism (2D); 4) in patients with refractory shock or who are periarrest, we recommend incremental doses of high-dose insulin (1D) and IV lipid-emulsion therapy (1D) if not already tried. We suggest venoarterial extracorporeal membrane oxygenation, if available, when refractory shock has a significant cardiogenic component (2D), and using pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block in the absence of myocardial dysfunction (2D) if not already tried; 5) in patients with cardiac arrest, we recommend IV calcium in addition to the standard advanced cardiac life-support (1D), lipid-emulsion therapy (1D), and we suggest venoarterial extracorporeal membrane oxygenation if available (2D). Conclusion: We offer recommendations for the stepwise management of calcium channel blocker

  15. Acrolein-mediated conduction loss is partially restored by K⁺ channel blockers.

    PubMed

    Yan, Rui; Page, Jessica C; Shi, Riyi

    2016-02-01

    Acrolein-mediated myelin damage is thought to be a critical mechanism leading to conduction failure following neurotrauma and neurodegenerative diseases. The exposure and activation of juxtaparanodal voltage-gated K(+) channels due to myelin damage leads to conduction block, and K(+) channel blockers have long been studied as a means for restoring axonal conduction in spinal cord injury (SCI) and multiple sclerosis (MS). In this study, we have found that 100 μM K(+) channel blockers 4-aminopyridine-3-methanol (4-AP-3-MeOH), and to a lesser degree 4-aminopyridine (4-AP), can significantly restore compound action potential (CAP) conduction in spinal cord tissue following acrolein-mediated myelin damage using a well-established ex vivo SCI model. In addition, 4-AP-3-MeOH can effectively restore CAP conduction in acrolein-damaged axons with a range of concentrations from 0.1 to 100 μM. We have also shown that while both compounds at 100 μM showed no preference of small- and large-caliber axons when restoring CAP conduction, 4-AP-3-MeOH, unlike 4-AP, is able to augment CAP amplitude while causing little change in axonal responsiveness measured in refractory periods and response to repetitive stimuli. In a prior study, we show that 4-AP-3-MeOH was able to functionally rescue mechanically injured axons. In this investigation, we conclude that 4-AP-3-MeOH is an effective K(+) channel blocker in restoring axonal conduction following both primary (physical) and secondary (chemical) insults. These findings also suggest that 4-AP-3-MeOH is a viable alternative of 4-AP for treating myelin damage and improving function following central nervous system trauma and neurodegenerative diseases.

  16. Temporal Spectral Analysis of Be stars observed with CoRoT satellite

    NASA Astrophysics Data System (ADS)

    Emilio, Marcelo; Janot Pacheco, Eduardo; Andrade, Laerte

    . Nevertheless, to measure frequencies with great accuracy in stars requires both high photometric precision and high time-frequency resolution. The CoRoT (Convection, Rotation and planetary Transits) satellite opens for the first time in history the possibility of fulfilling this goal. CoRoT is an experiment of astronomy dedicated to seismology and the detection of extrasolar planet transits. It was launched on December 2006 in an inertial polar orbit at an altitude of 897 mathrm{km}. The instrument is fed by a phi=27 textrm{cm} telescope. Its scientific program is three-fold consisting of: (1) The seismology core program (SISMO), which concerns the seismic study of ˜10 bright (6RoT ID 102761769 observed by CoRoT satellite. We found two close frequencies related to the .CoRoT ID 102761769 star. They are 2.465 c d(-1) (28.5 mathrm{mu Hz}) and 2.441 c d(-1) (28.2 mathrm{mu Hz}). The precision to which those frequencies were found is 0.018 c d(-1) (0.2 mathrm{mu Hz}). The projected stellar rotation was estimated to be 120 km s(-1) from the Fourier transform of spectral lines. If CoRoT-ID 102761769 is a typical Galactic Be star it rotates near the critical velocity. The critical rotation frequency of a typical B5-6 star is about 3.5 c d(-1) (40.5 mathrm{mu Hz}), which implies that the above frequencies are really caused by stellar pulsations rather than star's rotation. HD 171219 frequencies 1.113, 1.130, 1.146 c * d(-1) form a triplet with the

  17. Jumping the nuclear envelop barrier: Improving polyplex-mediated gene transfection efficiency by a selective CDK1 inhibitor RO-3306.

    PubMed

    Zhou, Xuefei; Liu, Xiangrui; Zhao, Bingxiang; Liu, Xin; Zhu, Dingcheng; Qiu, Nasha; Zhou, Quan; Piao, Ying; Zhou, Zhuxian; Tang, Jianbin; Shen, Youqing

    2016-07-28

    Successful transfection of plasmid DNA (pDNA) requires intranuclear internalization of pDNA effectively and the nuclear envelope appears to be one of the critical intracellular barriers for polymer mediated pDNA delivery. Polyethylenimine (PEI), as the classic cationic polymer, compact the negatively charged pDNA tightly and make up stable polyplexes. The polyplexes are too large to enter the nuclear through nuclear pores and it is believed that the nuclear envelope breakdown in mitosis could facilitate the nuclear entry of polyplexes. To jump the nuclear envelope barrier, we used a selective and reversible CDK1 inhibitor RO-3306 to control the G2/M transition of the cell cycle and increased the proportion of mitotic cells which have disappeared nuclear envelope during transfection. Herein, we show that RO-3306 remarkably increases the transfection efficiency of PEI polyplexes through enhanced nuclear localization of PEI and pDNA. However, RO-3306 is less effective to the charge-reversal polymer poly[(2-acryloyl)ethyl(p-boronic acid benzyl)diethylammonium bromide] (B-PDEAEA) which responses to cellular stimuli and releases free pDNA in cytoplasm. Our findings not only offer new opportunities for improving non-viral based gene delivery but also provide theoretical support for the rational design of novel functional polymers for gene delivery. We also report current data showing that RO-3306 synergizes TRAIL gene induced apoptosis in cancer cells.

  18. 77 FR 1707 - National Toxicology Program (NTP) Final Process for Preparation of the Report on Carcinogens (RoC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ... available on the NTP Web site ( http://ntp.niehs.nih.gov/go/rocprocess ) or by contacting Dr. Ruth Lunn (see...) on December 15, 2011 ( http://ntp.niehs.nih.gov/go/9741 ). The NTP now announces the final process....gov/go/rocprocess ) or by contacting Dr. Lunn (see ADDRESSES). Background Information on the RoC...

  19. Behaviour of RO98pHt polyamide membrane in reverse osmosis and low reverse osmosis conditions for phenol removal.

    PubMed

    Hidalgo, A M; León, G; Gómez, M; Murcia, M D; Gómez, E; Gómez, J L

    2011-10-01

    Phenolic compounds and their derivatives are very common pollutants in wastewaters. Among the methods described for their removal, pressure-driven membrane processes are considered as a reliable alternative. Our research group has previously studied phenol removal in reverse osmosis (RO) conditions and obtained very low rejection percentages. Subsequently, when low reverse osmosis (LRO) conditions were studied, the organic rejection percentages improved. To further our knowledge in this respect, the main objective of this work was to study the behaviour of the polyamide thin-film composite membrane RO98pHt used for phenol removal in RO and LRO conditions. The influence of different operating pressures, phenol feed concentrations and pH on permeate flux and phenol rejection was studied. Low reverse osmosis conditions led to higher phenol rejection percentages in all the assayed conditions, suggesting that other factors related to the molecular characteristics of the organic molecules, such as solubility, acidity and hydrogen bonding capacity, play an important role in the rejection percentage attained. As expected, permeate flux was greater in RO conditions.

  20. The CoRoT-GES Collaboration: Improving red giants spectroscopic surface gravitity and abundances with asteroseismology

    NASA Astrophysics Data System (ADS)

    Valentini, M.; Chiappini, C.; Miglio, A.; Montalbán, J.; Rodrigues, T.; Mosser, B.; Anders, F.; the CoRoT RG Group; GES Consortium, the

    2016-09-01

    Nowadays large spectroscopic surveys, like the Gaia-ESO Survey (GES), provide unique stellar databases for better investigating the formation and evolution of our Galaxy. Great attention must be paid to the accuracy of the basic stellar properties derived: large uncertainties in stellar parameters lead to large uncertainties in abundances, distances and ages. Asteroseismology has a key role in this context: when seismic information is combined with information derived from spectroscopic analysis, highly precise constraints on distances, masses, extinction and ages of red giants can be obtained. In the light of this promising joint action, we started the CoRoT-GES collaboration. We present a set of 1111 CoRoT stars, observed by GES from December 2011 to July 2014, these stars belong to the CoRoT field LRc01, pointing at the inner Galactic disk. Among these stars, 534 have reliable global seismic parameters. By combining seismic informations and spectroscopy, we derived precise stellar parameters, ages, kinematic and orbital parameters and detailed element abundances for this sample of stars. We also show that, thanks to asteroseismology, we are able to obtain a higher precision than what can be achieved by the standard spectroscopic means. This sample of CoRoT red giants, spanning Galactocentric distances from 5 to 8 kpc and a wide age interval (1-13 Gyr), provides us a representative sample for the inner disk population.

  1. Measuring E(GSH) and H2O2 with roGFP2-based redox probes.

    PubMed

    Morgan, Bruce; Sobotta, Mirko C; Dick, Tobias P

    2011-12-01

    Redox biochemistry plays an important role in a wide range of cellular events. However, investigation of cellular redox processes is complicated by the large number of cellular redox couples, which are often not in equilibrium with one another and can vary significantly between subcellular compartments and cell types. Further, it is becoming increasingly clear that different redox systems convey different biological information; thus it makes little sense to talk of an overall "cellular redox state". To gain a more differentiated understanding of cellular redox biology, quantitative, redox couple-specific, in vivo measurements are necessary. Unfortunately our ability to investigate specific redox couples or redox-reactive molecules with the necessary degree of spatiotemporal resolution is very limited. The development of genetically encoded redox biosensors offers a promising new way to investigate redox biology. Recently developed redox-sensitive green fluorescent proteins (roGFPs), genetically fused to redox-active proteins, allow rapid equilibration of the roGFP moiety with a specific redox couple. Two probes based on this principle are now available: Grx1-roGFP2 for the measurement of glutathione redox potential (E(GSH)) and roGFP2-Orp1 for measuring changes in H(2)O(2) concentration. Here we provide a detailed protocol for the use of these probes in both yeast and mammalian systems using either plate-reader- or microscopy-based measurements.

  2. Downregulation of (3H)Ro5-4864 binding sites after exposure to peripheral-type benzodiazepines in vitro

    SciTech Connect

    Johnson, M.D.; Wang, J.K.; Morgan, J.I.; Spector, S.

    1986-09-01

    Peripheral-type benzodiazepine (BZD) binding sites undergo a rapid and pronounced downregulation after exposure to these compounds in vitro. Friend erythroleukemia cells were incubated with micromolar concentrations of BZD after which they were washed thoroughly and the binding of the specific peripheral-type BZD radioligand (/sup 3/H)Ro5-4864 was determined. Exposure to the peripheral-type BZD Ro7-3351 decreased the number of (/sup 3/H)Ro5-4864 binding sites from 324 to 41 fmol/10(6) cells with no change in affinity. Downregulation appears to require active cellular processes because it is blocked when exposure to BZD is at 4/sup 0/C rather than at 37/sup 0/C. Furthermore, whereas (/sup 3/H)Ro5-4864 binding is decreased substantially in membrane preparations made from downregulated cells, it is not altered when membrane preparations from control cells are exposed to BZD. The time course of downregulation is quite rapid, as it occurs within minutes. In contrast, the return of sites requires days and there is a close relationship between return of sites and growth of new cells. The ability of BZDs to downregulate correlates more closely with affinity for the peripheral-type site than with biological activity. The ability to undergo downregulation is characteristic of receptors and its occurrence suggests that peripheral-type BZD binding sites are functional receptors.

  3. Finest light curve details, physical parameters, and period fluctuations of CoRoT RR Lyrae stars

    NASA Astrophysics Data System (ADS)

    Benkő, J. M.; Szabó, R.; Derekas, A.; Sódor, Á.

    2016-12-01

    The CoRoT satellite supplied the scientific community with a huge data base of variable stars. Among them the RR Lyrae stars have intensively been discussed in numerous papers in the last few years, but the latest runs have not been checked to find RR Lyrae stars up to now. Our main goal was to fill this gap and complete the CoRoT RR Lyrae sample. We found nine unstudied RR Lyrae stars. Seven of them are new discoveries. We identified three new Blazhko stars. The Blazhko effect shows non-strictly repetitive nature for all stars. The frequency spectrum of the Blazhko star CoRoT 104948132 contains second overtone frequency with the highest known period ratio. The harmonic amplitude and phase declines with the harmonic order were studied for non-Blazhko stars. We found a period dependent but similar shape amplitude decline for all stars. We discovered significant random period fluctuation for one of the two oversampled target, CM Ori. After a successful transformation of the CoRoT band parameters to the Johnson V values we estimated the basic physical properties such as mass, luminosity, metallicity. The sample can be divided into two subgroups with respect to the metallicity but otherwise the physical parameters are in the canonical range of RR Lyrae stars.

  4. Beneficial phosphate recovery from reverse osmosis (RO) concentrate of an integrated membrane system using polymeric ligand exchanger (PLE).

    PubMed

    Kumar, Manish; Badruzzaman, Mohammad; Adham, Samer; Oppenheimer, Joan

    2007-05-01

    Phosphorus (P) discharge to surface water is a major environmental problem. Wastewater treatment is targeted towards removal of this nutrient to prevent degradation of surface water. Integrated membrane systems (IMS) are increasingly being considered for wastewater reclamation, and provide excellent removal of P compounds. However, reverse osmosis (RO), which forms an integral part of these IMSs, concentrates most dissolved substances including P-species such as phosphates in the RO waste stream. In this study, removal of phosphate from this stream using polymeric ligand exchange (PLE) resins was investigated. Further, the possibility of phosphate recovery through struvite (MgNH(4)PO(4).6H(2)O) precipitation was tested. Struvite has been promoted as a slow release fertilizer in recent years. This study demonstrates that PLEs can be successfully used to remove phosphate from RO-concentrate, and to recover more than 85% of the adsorbed phosphorus from the exhausted media and precipitated as a beneficial product (struvite). The approach, presented in this study, suggests advantages of providing economic benefit from a waste product (RO) while avoiding phosphorus discharge to the environment.

  5. Global chemical reactivity parameters for several chiral beta-blockers from the Density Functional Theory viewpoint

    PubMed Central

    TALMACIU, MONA MARIA; BODOKI, EDE; OPREAN, RADU

    2016-01-01

    Background and aim Beta-adrenergic antagonists have been established as first line treatment in the medical management of hypertension, acute coronary syndrome and other cardiovascular diseases, as well as for the prevention of initial episodes of gastrointestinal bleeding in patients with cirrhosis and esophageal varices, glaucoma, and have recently become the main form of treatment of infantile hemangiomas. The aim of the present study is to calculate for 14 beta-blockers several quantum chemical descriptors in order to interpret various molecular properties such as electronic structure, conformation, reactivity, in the interest of determining how such descriptors could have an impact on our understanding of the experimental observations and describing various aspects of chemical binding of beta-blockers in terms of these descriptors. Methods The 2D chemical structures of the beta-blockers (14 molecules with one stereogenic center) were cleaned in 3D, their geometry was preoptimized using the software MOPAC2012, by PM6 method, and then further refined using standard settings in MOE; HOMO and LUMO descriptors were calculated using semi-empirical molecular orbital methods AM1, MNDO and PM3, for the lowest energy conformers and the quantum chemical descriptors (HLG, electronegativity, chemical potential, hardness and softness, electrophilicity) were then calculated. Results According to HOMO-LUMO gap and the chemical hardness the most stable compounds are alprenolol, bisoprolol and esmolol. The softness values calculated for the study molecules revolve around 0.100. Propranolol, sotalol and timolol have among the highest electrophilicity index of the studied beta-blocker molecules. Results obtained from calculations showed that acebutolol, atenolol, timolol and sotalol have the highest values for the electronegativity index. Conclusions The future aim is to determine whether it is possible to find a valid correlation between these descriptors and the physicochemical

  6. Development of a highly cardioselective ultra short-acting beta-blocker, ONO-1101.

    PubMed

    Iguchi, S; Iwamura, H; Nishizaki, M; Hayashi, A; Senokuchi, K; Kobayashi, K; Sakaki, K; Hachiya, K; Ichioka, Y; Kawamura, M

    1992-06-01

    A novel, highly cardioselective ultra short-acting beta-blocker, ONO-1101, has been developed for application in the emergency treatment of tachycardia and better control of heart rate in surgery. This agent is approximately nine times more potent in beta-blocking activity in vivo and eight times more cardioselective in vitro than esmolol. This beta-blocking drug has a short duration of activity, enabling rapid recovery after cessation of administration if side effects occur. It can be used safely in patients suffering from acute heart disease and represents a major therapeutic advance in the treatment of heart disease.

  7. Treating the Host Response to Ebola Virus Disease with Generic Statins and Angiotensin Receptor Blockers

    PubMed Central

    Jacobson, Jeffrey R.; Rordam, Ole Martin; Opal, Steven M.

    2015-01-01

    ABSTRACT Treatments targeting the Ebola virus may eventually be shown to work, but they will not have an impact on overall Ebola mortality in West Africa. Endothelial dysfunction is responsible for the fluid and electrolyte imbalances seen in Ebola patients. Because inexpensive generic statins and angiotensin receptor blockers restore endothelial barrier integrity, they can be used to treat the host response in these patients. In Sierra Leone, approximately 100 Ebola patients were treated with this combination, and reports indicate that survival was greatly improved. PMID:26106080

  8. Synthesis and biological evaluation of oxazole derivatives as T-type calcium channel blockers.

    PubMed

    Lee, Jie Eun; Koh, Hun Yeong; Seo, Seon Hee; Baek, Yi Yeon; Rhim, Hyewhon; Cho, Yong Seo; Choo, Hyunah; Pae, Ae Nim

    2010-07-15

    T-type calcium channel is one of therapeutic targets for the treatment of cardiovascular diseases and neuropathic pain. In this study, as a part of our ongoing efforts to develop potent T-type calcium channel blockers, we designed oxazole derivatives substituted with arylpiperazinylalkylamines. The oxazoles were synthesized in a convenient convergent synthetic method, and biologically evaluated against alpha(1G) (Ca(V)3.1) T-type calcium channel. Among total 41 oxazole compounds synthesized, the most active one was the compound 10-35 with an IC(50) value of 0.65 microM, which is comparable with that of mibefradil.

  9. PRISMA-combined α-blockers and antimuscarinics for ureteral stent-related symptoms

    PubMed Central

    Zhang, Yu-ming; Chu, Pei; Wang, Wen-jin

    2017-01-01

    Abstract Background: As a monotherpay, a-blockers and anti-muscarinics are both efficacy for ureteral stent-related symptoms (SRS). The aim of the study was to systematically evaluate their efficacy of a combination therapy for SRS. Methods: Relevant studies investigating α-blockers and/or anti-muscarinics for SRS were identified though searching online databases including PubMed, EMBASE, Cochrane Library, and other sources up to March 2016. The RevMan software was used for data analysis, and senesitivity analysis and inverted funnel plot were also adopted. Results: Seven randomized controlled trials (RCTs) and 1 prospective controlled trial including 545 patients were selected. Compared with α-blockers, the combination group achieved significant improvements in total International Prostate Symptom Score (IPSS) [–3.93 (2.89, 4.96), P < 0.00001], obstructive subscore [–1.29 (0.68, 1.89), P < 0.0001], irritative subscore [–2.93 (2.18, 3.68), P < 0.00001], and quality of life score [–0.99 (0.42, 1.55), P < 0.001]. Compared with antimuscarinics, there were also significant differences in total IPSS [–3.49 (2.43, 4.55), P < 0.00001], obstructive subscore [–1.40 (0.78, 2.01), P < 0.00001], irritative subscore [–2.10 (1.30, 2.90), P < 0.00001], and quality of life score [–1.18 (0.58, 1.80), P < 0.001] in favor of combination group. No significant difference was found in the visual analog pain score and the urinary symptoms score in Ureteral Stent Symptom Questionnaire (USSQ). No significant difference in complications was found. Conclusions: Current analysis shows significant advantages of combination therapy compared with monotherapy of α-blockers or antimuscarinics alone mainly based on IPSS. More RCTs adopting validated USSQ as outcome measures are warranted to support the finding. PMID:28207522

  10. Real role of β-blockers in regression of left ventricular mass in hypertension patients

    PubMed Central

    Xing, FuWei; Chen, Jialin; Zhao, BinLiang; Jiang, Jingzhou; Tang, Anli; Chen, Yili

    2017-01-01

    Abstract Background: Left ventricular hypertrophy (LVH) is commonly present in patients with hypertension (HT). According to the expert consensus document from American, angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blockers (ARBs) were recommended as 1st-line therapeutic drugs. However, none noticed the different efficacy between fat-soluble and selective β1-receptor blockers (FS-β-B) and other β-blockers on regression of LVH before. The aim of this analysis was to compare the efficacy of FS-β-B with the other 4 different classes of antihypertensive drugs (ACEI, ARBs, calcium channel blockers [CCBs], and diuretics) on regression of LVH. Methods: Relative trials were identified in the PubMed, Web of Science, OVID EBM Reviews and Cochrane databases, and the relevant papers were examined. We performed both traditional and Bayesian meta-analysis of randomized controlled trials (RCTs) about the regression of LVH. Sensitivity analysis and regression analysis were performed to explore possible sources of heterogeneity. Inconsistency analysis was performed to check whether the analysis of the trials in the network was indeed consistent. Results: A total of 41 RCTs involving 2566 patients with HT and LVH were included in this analysis. Bayesian network meta-analysis indicated no statistically significant differences between these groups: FS-β-B and ACEI (MD, −7.09; 95% CI, −14.99, 1.27); FS-β-B and ARB (MD, −2.66; 95% Cl, −12.02, 6.31). Although FS-β-B showed greater efficacy when compared with diuretic (MD, 13.04; 95% CI, 3.38, 22.59) or CCB (MD, 10.90; 95% CI, 1.98, 19.49). The probabilities of being among the most efficacious treatments were: FS-β-B (72%), ARB (27%), ACEI (0.01%), CCB (0.00%), and diuretic (0.00%). Conclusion: Evidence from our analysis reveals that FS-β-B have potential to become 1st-line therapeutic drugs in HT and LVH patients. However, the real efficacy of FS-β-B on regression of LVH should be confirmed by

  11. Management of beta-adrenergic blocker and calcium channel antagonist toxicity.

    PubMed

    Kerns, William

    2007-05-01

    State-of-the-art therapy for beta-adrenergic receptor blocker and calcium channel antagonist toxicity is reviewed in the light of new insights into drug-induced shock. A brief discussion of pathophysiology, including cardiac, hemodynamic, and metabolic effects of cardiac drug toxicity, provides a foundation for understanding the basis of therapy. The major focus of this review is a critical evaluation of antidotal use of calcium, glucagon, catecholamines, insulin-euglycemia, and other novel therapies based on investigational studies and cumulative clinical experience.

  12. Intraoperative Extracorporeal Carbon Dioxide Removal During Apneic Oxygenation with an EZ-Blocker in Tracheal Surgery.

    PubMed

    Rispoli, Marco; Nespoli, Moana Rossella; Mattiacci, Dario Maria; Esposito, Marianna; Corcione, Antonio; Buono, Salvatore

    2016-06-01

    Tracheal surgery requires continued innovation to manage the anesthetic during an open airway phase. A common approach is apneic oxygenation with continuous oxygen flow, but the lack of effective ventilation causes hypercapnia, with respiratory acidosis. We used extracorporeal carbon dioxide removal for intraoperative decapneization during apneic oxygenation in a 64-year-old woman who was scheduled for tracheal surgery because of tracheal stenosis caused by long-term intubation. Our findings demonstrate that even after 40 minutes of total apnea, using an EZ-blocker for oxygenation and external decapneization, hemodynamic and gas exchange variables never demonstrated any dangerous alterations.

  13. Two functionally distinct subsites for the binding of internal blockers to the pore of voltage-activated K+ channels

    PubMed Central

    Baukrowitz, Thomas; Yellen, Gary

    1996-01-01

    Many blockers of Na+ and K+ channels act by blocking the pore from the intracellular side. For Shaker K+ channels, such intracellular blockers vary in their functional effect on slow (C-type) inactivation: Some blockers interfere with C-type inactivation, whereas others do not. These functional differences can be explained by supposing that there are two overlapping “subsites” for blocker binding, only one of which inhibits C-type inactivation through an allosteric effect. We find that the ability to bind to these subsites depends on specific structural characteristics of the blockers, and correlates with the effect of mutations in two distinct regions of the channel protein. These interactions are important because they affect the ability of blockers to produce use-dependent inhibition. PMID:8917595

  14. The expression of RoTat 1.2 variable surface glycoprotein (VSG) in Trypanosoma evansi and T. equiperdum.

    PubMed

    Claes, F; Verloo, D; De Waal, D T; Majiwa, P A O; Baltz, T; Goddeeris, B M; Büscher, P

    2003-10-20

    In order to define whether the variable antigenic type RoTat 1.2 is restricted to Trypansoma evansi and could be used as antigen in serological tests to differentiate T. evansi from Trypansoma equiperdum, the appearance of RoTat 1.2-specific antibodies in rabbits, experimentally infected with T. evansi and T. equiperdum, respectively, was analyzed. Ten strains of T. evansi and 11 strains of T. equiperdum originating from Asia, Europe, Africa and Latin America were tested. Rabbit pre-infection sera and sera of days 7, 14, 25, 35 post-infection (p.i.) were analyzed for the presence of antibodies reactive with RoTat 1.2 in immune trypanolysis, ELISA/T. evansi and CATT/T. evansi. Within the duration of the infection (maximum 35 days), all T. evansi as well as 9 out of 11 T. equiperdum infected rabbits became positive in all these tests. The rabbits infected with T. equiperdum OVI (South Africa) and BoTat 1.1 (Morocco) remained negative in the immune trypanolysis test although the latter rabbit became positive in the CATT/T. evansi and ELISA/T. evansi. On the contrary, both rabbits were positive in immune trypanolysis when tested against their respective infecting population. From these data, we conclude that most T. equiperdum strains express isoVATs of RoTat 1.2. This explains, in part, why antibody tests based on T. evansi RoTat 1.2 cannot reliably distinguish between infections caused by T. evansi and those caused by T. equiperdum unless it can be proven that most described T. equiperdum are actually misclassified T. evansi.

  15. Water reuse: >90% water yield in MBR/RO through concentrate recycling and CO2 addition as scaling control.

    PubMed

    Joss, Adriano; Baenninger, Claudia; Foa, Paolo; Koepke, Stephan; Krauss, Martin; McArdell, Christa S; Rottermann, Karin; Wei, Yuansong; Zapata, Ana; Siegrist, Hansruedi

    2011-11-15

    Over 1.5 years continuous piloting of a municipal wastewater plant upgraded with a double membrane system (ca. 0.6 m(3) d(-1) of product water produced) have demonstrated the feasibility of achieving high water quality with a water yield of 90% by combining a membrane bioreactor (MBR) with a submerged ultrafiltration membrane followed by a reverse osmosis membrane (RO). The novelty of the proposed treatment scheme consists of the appropriate conditioning of MBR effluent prior to the RO and in recycling the RO concentrates back to the biological unit. All the 15 pharmaceuticals measured in the influent municipal sewage were retained below 100 ng L(-1), a proposed quality parameter, and mostly below detection limits of 10 ng L(-1). The mass balance of the micropollutants shows that these are either degraded or discharged with the excess concentrate, while only minor quantities were found in the excess sludge. The micropollutant load in the concentrate can be significantly reduced by ozonation. A low treated water salinity (<10 mM inorganic salts; 280 ± 70 μS cm(-1)) also confirms that the resulting product has a high water quality. Solids precipitation and inorganic scaling are effectively mitigated by lowering the pH in the RO feed water with CO(2) conditioning, while the concentrate from the RO is recycled to the biological unit where CO(2) is stripped by aeration. This causes precipitation to occur in the bioreactor bulk, where it is much less of a process issue. SiO(2) is the sole exception. Equilibrium modeling of precipitation reactions confirms the effectiveness of this scaling-mitigation approach for CaCO(3) precipitation, calcium phosphate and sulfate minerals.

  16. Low-amplitude variations detected by CoRoT in the B8IIIe star HD 175869

    NASA Astrophysics Data System (ADS)

    Gutiérrez-Soto, J.; Floquet, M.; Samadi, R.; Neiner, C.; Garrido, R.; Fabregat, J.; Frémat, Y.; Diago, P. D.; Huat, A.-L.; Leroy, B.; Emilio, M.; Hubert, A.-M.; Andrade, O. Thizy L.; de Batz, B.; Janot-Pacheco, E.; Espinosa Lara, F.; Martayan, C.; Semaan, T.; Suso, J.; Auvergne, M.; Chaintreuil, S.; Michel, E.; Catala, C.

    2009-10-01

    Context: The origin of the short-term variability in Be stars remains a matter of controversy. Pulsations and rotational modulation are the components of the favored hypothesis. Aims: We present our analysis of CoRoT data of the B8IIIe star HD 175869 observed during the first short run in the center direction (SRC1). Methods: We review both the instrumental effects visible in the CoRoT light curve and the analysis methods used by the CoRoT Be team. We applied these methods to the CoRoT light curve of the star HD 175869. A search for line-profile variations in the spectroscopic data was also performed. We also searched for a magnetic field, by applying the LSD technique to spectropolarimetric data. Results: The light curve exhibits low-amplitude variations of the order of 300 μmag with a double wave shape. A frequency within the range determined for the rotational frequency and 6 of its harmonics are detected. The main frequency and its first harmonic exhibit amplitude variations of a few days. Other significant frequencies of low-amplitude from 25 to a few μmag are also found. The analysis of line profiles from ground-based spectroscopic data does not detect any variation. In addition, no Zeeman signature was found. Conclusions: Inhomogeneities caused by stellar activity in or just above the photosphere are proposed to produce the photometric variability detected by CoRoT in the Be star HD 175869. The hypothesis that non-radial pulsations are the origin of these variations cannot be excluded.

  17. Comparative clustering analysis of variable stars in the Hipparcos, OGLE Large Magellanic Cloud, and CoRoT exoplanet databases

    NASA Astrophysics Data System (ADS)

    Sarro, L. M.; Debosscher, J.; Aerts, C.; López, M.

    2009-10-01

    Context: Discovery of new variability classes in large surveys using multivariate statistics techniques such as clustering, relies heavily on the correct understanding of the distribution of known classes as point processes in parameter space. Aims: Our objective is to analyze the correspondence between the classical stellar variability types and the clusters found in the distribution of light curve parameters and colour indices of stars in the CoRoT exoplanet sample. The final aim is to help in the identification on new types of variability by first identifying the well known variables in the CoRoT sample. Methods: We apply unsupervised classification algorithms to identify clusters of variable stars from modes of the probability density distribution. We use reference variability databases (Hipparcos and OGLE) as a framework to calibrate the clustering methodology. Furthermore, we use the results from supervised classification methods to interpret the resulting clusters. Results: We interpret the clusters in the Hipparcos and OGLE LMC databases in terms of large-amplitude radial pulsators in the classical instability strip and of various types of eclipsing binaries. The Hipparcos data also provide clear distributions for low-amplitude nonradial pulsators. We show that the preselection of targets for the CoRoT exoplanet programme results in a completely different probability density landscape than the OGLE data, the interpretation of which involves mainly classes of low-amplitude variability in main-sequence stars. Our findings will be incorporated to improve the supervised classification used in the CoRoT catalogue production, once the existence of new classes or subtypes will be confirmed from complementary spectroscopic observations. The CoRoT space mission was developed and is operated by the French space agency CNES, with participation of ESA's RSSD and Science Programmes, Austria, Belgium, Brazil, Germany, and Spain.

  18. Influence of the previous use of β-blockers on the early clinical course of acute coronary syndromes.

    PubMed

    Garcia-Rubira, Juan Carlos; Almendro-Delia, Manuel; Calvo-Taracido, Manuel; Blanco-Ponce, Emilia; Bastos-Amador, Pablo; Reina-Toral, Antonio; Calvo-Jambrina, Roman; Cruz-Fernández, José Maria; Garcia-Alcántara, Angel; Hidalgo-Urbano, Rafael

    2015-10-01

    Recent studies have recently questioned the current role of β-blockers in myocardial infarction. Our purpose is to analyze the influence of the previous use of β-blockers on the early course of patients admitted because of acute coronary syndrome (ACS). We analyzed the data of 37.359 patients included in the ARIAM-Andalucia Registry. Of them, 7759 (20.8%) were previously receiving β-blockers. BB patients were older, more often female, had more risk factors and vascular disease, and less often had an ST-elevation myocardial infarction. In the unadjusted analysis, BB patients less often had ventricular fibrillation or atrioventricular block, and more often a Killip classification >1, and no difference of in-hospital mortality (5.7 vs 5.6%). After logistic regression analysis and propensity score matching, no differences in complications or mortality (odds ratio 0.997, 95% confidence interval 0.882-1.128) were found in relationship to previous β-blockers. In conclusion, we find that the previous administration of β-blockers is not an independent predictor of the early prognosis of ACS.

  19. Effects of beta-adrenergic blockers with different ancillary properties on lipid peroxidation in hyperthyroid rat cardiac muscle.

    PubMed

    Asayama, K; Dobashi, K; Hayashibe, H; Kato, K

    1989-10-01

    To determine whether beta-blockade protects rat heart against thyroxine (T4)-induced accelelation of lipid peroxidation, in vivo effects of 3 beta-blockers with different ancillary properties on the mitochondrial oxidative enzyme, antioxidant enzymes and lipid peroxide were investigated. The rats were rendered hyperthyroid by adding T4 to their drinking water for 3 weeks and were treated simultaneously with either carteolol (a blocker with partial agonist activity; 30 mg/kg/day), atenolol (50 mg/kg/day) or arotinolol (a blocker with weak alpha-blocking action; 50 mg/kg/day). The T4-induced tachycardia was alleviated completely by either atenolol or arotinolol, but only partially by carteolol. Cytochrome c oxidase activity in the heart muscle was increased by T4 with a parallel increase in manganese (mitochondrial) superoxide dismutase. Atenolol, but neither carteolol nor arotinolol, suppressed this increase. Similarly, the T4-induced acceleration of lipid peroxidation was suppressed by atenolol alone. Glutathione peroxidase was markedly decreased, and both copper zinc (cytosolic) superoxide dismutase and catalase were also decreased or tended to be decreased by T4. The levels of these 3 enzymes were only minimally affected by the beta-blocker treatments. These results suggest that beta-blockade suppresses mitochondrial hypermetabolism and protects heart muscle against oxidative stress in hyperthyroidism, and that the ancillary properties of beta-blockers such as partial agonist activity and alpha-blocking action negate the protection.

  20. Meta-analysis of the efficacy and safety of adding an angiotensin receptor blocker (ARB) to a calcium channel blocker (CCB) following ineffective CCB monotherapy

    PubMed Central

    Ma, Jin; Wang, Xiao-Yan; Hu, Zhi-De; Zhou, Zhi-Rui; Schoenhagen, Paul

    2015-01-01

    Background We conducted this meta-analysis to systematically review and analyze the clinical benefits of angiotensin receptor blocker (ARB) combined with calcium channel blocker (CCB) following ineffective CCB monotherapy. Methods PubMed was searched for articles published until August 2015. Randomized controlled trials (RCTs) evaluating the clinical benefits of ARB combined with CCB following ineffective CCB monotherapy were included. The primary efficacy endpoint of the studies was normal rate of blood pressure, the secondary efficacy endpoints were the response rate and change in blood pressure from baseline. The safety endpoint of the studies was incidence of adverse events. Differences are expressed as relative risks (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and weighted mean differences (WMDs) with 95% CIs for continuous outcomes. Heterogeneity across studies was tested by using the I2 statistic. Results Seven RCTs were included and had sample sizes ranging from 185 to 1,183 subjects (total: 3,909 subjects). The pooled analysis showed that the on-target rate of hypertension treatment was significantly higher in the amlodipine + ARB group than in the amlodipine monotherapy group (RR =1.59; 95% CI, 1.31–1.91; P<0.01). The response rate of systolic blood pressure (SBP) (RR =1.28; 95% CI, 1.04–1.58; P<0.01) and diastolic blood pressure (DBP) (RR =1.27; 95% CI, 1.12–1.44; P=0.04) were significantly higher in the amlodipine + ARB group than in the amlodipine monotherapy group. The change in SBP (RR =−3.56; 95% CI, −7.76–0.63; P=0.10) and DBP (RR =−3.03; 95% CI, −6.51–0.45; P=0.09) were higher in hypertensive patients receiving amlodipine + ARB but the difference did not reach statistical significance. ARB + amlodipine treatment carried a lower risk of adverse events relative to amlodipine monotherapy (RR =0.88; 95% CI, 0.80-0.96; P<0.01). Conclusions The results of our meta-analysis demonstrate that adding an ARB to CCB

  1. Blue blocker glasses impede the capacity of bright light to suppress melatonin production.

    PubMed

    Sasseville, Alexandre; Paquet, Nathalie; Sévigny, Jean; Hébert, Marc

    2006-08-01

    Blocking morning light exposure with dark goggles can contribute to the adjustment to night work but these glasses are incompatible with driving. Recently, it was discovered that the biological clock is most sensitive to short wavelengths (blue light). Therefore, we tested the hypothesis that cutting the blue portion of the light spectrum with orange lens glasses (blue blockers) would prevent the light-induced melatonin suppression, a test broadly used as an indirect assessment of the circadian clock sensitivity. Fourteen normal subjects were exposed at night to a 60 min bright light pulse (1300 lx behind filters) between 01:00 and 02:00 hr while wearing orange lens glasses (experimental condition) or grey lens glasses (control condition). The amount of salivary melatonin change observed during the light pulse was compared with a melatonin baseline obtained the night before. Although both glasses transmitted the same illuminance (1300 lx) but at an irradiance 25% higher for the orange lens (408 microW/cm2) compared with the grey lens (327 microW/cm2), a non-significant increase of 6% (95% CI, -20% to 9%) was observed with the orange lens whereas a significant (P < 0.05) reduction of 46% (95% CI, 35-57%) was observed with the grey lens. Blue blockers represent an elegant means to prevent the light-induced melatonin suppression. Further studies are needed to show that these glasses, which are suitable for driving, could facilitate adaptation to night work.

  2. Bean amylase inhibitor and other carbohydrate absorption blockers: effects on diabesity and general health.

    PubMed

    Preuss, Harry G

    2009-06-01

    Many believe that excessive intake of refined carbohydrates (CHO) plays a major role in the development of obesity/overweight, type 2 diabetes mellitus and insulin resistance, a collection of events commonly referred to as "diabesity," and have sought natural means to overcome these linked perturbations. As a first approach, planned diets with low portions of refined CHO have become popular. However, these diets do not satisfy everyone; and many are concerned over replacing CHO with more fats. As a second option, addition of soluble fiber to the diet can slow absorption of refined CHO, i.e., lower the glycemic index of foods and overcome or at least ameliorate many of the adverse reactions resulting from increased refined CHO ingestion. Unfortunately, the general public does not favor diets high in fiber content, and various fibers can lead to gastrointestinal problems such as gas and diarrhea. A third choice to favorably influence CHO absorption is to use natural dietary supplements that block or slow CHO absorption in the gastrointestinal tract via inhibiting enzymes necessary for CHO absorption -amylase and alpha-glucosidases. Although a number of natural supplements with anti-amylase activity have been recognized, the most studied and favored one is white kidney bean extract. Animal and human studies clearly show that this agent works in vivo and has clinical utility. This paper reviews many aspects of diabesity and the use of "carb blockers" to prevent and ameliorate the situation. In many respects, carb blockers mimic the beneficial effects of fibers.

  3. Comparison of annual cost between brand and generic ocular beta-adrenergic blockers.

    PubMed

    Ikeda, Hiroaki; Tsukamoto, Hidetoshi; Sawa, Akihiro; Sugimoto, Ayako; Mishima, Hiromu; Kihira, Kenji

    2005-05-01

    We conducted a study of the annual cost of various ophthalmic products used in Japan for treating glaucoma including six of brands and generic ocular beta-adrenergic blockers (38 products). The total number of drops in one bottle of each solution was counted drop by drop. The cost per drop was calculated by dividing the government-controlled standard prices by the total number of drops in one bottle. The annual cost of ophthalmic solution was calculated by multiplying the cost per drop by the number of drops typically used per day. The total number of drops of the ophthalmic solutions in one bottle ranged from 108 to 168. The yearly cost of the beta-adrenergic blockers studied ranged widely, from yen 5392 to yen 27236. Differences in the total number of drops and the usage effect on the annual cost of ophthalmic solutions were found. The annual cost depended on not only the price of the products but also on the total number of drops in one bottle and the usage. Annual cost data may be helpful in selecting ophthalmic products for treating glaucoma in Japan.

  4. Non-additive interactions between mitochondrial complex IV blockers and hypoxia in rat carotid body responses

    PubMed Central

    Donnelly, David F; Kim, Insook; Mulligan, Eileen M; Carroll, John L

    2013-01-01

    The metabolic hypothesis of carotid body chemoreceptor hypoxia transduction proposes an impairment of ATP production as the signal for activation. We hypothesized that mitochondrial complex IV blockers and hypoxia would act synergistically in exciting afferent nerve activity. Following a pretreatment with low dosage sodium cyanide (10-20μM), the hypoxia-induced nerve response was significantly reduced along with hypoxia-induced catecholamine release. However, in isolated glomus cells, the intracellular calcium response was enhanced as initially predicted. This suggests a cyanide-mediated impairment in the step between the glomus cell intracellular calcium rise and neurotransmitter release from secretory vesicles. Administration of a PKC blocker largely reversed the inhibitory actions of cyanide on the neural response. We conclude that the expected synergism between cyanide and hypoxia occurs at the level of glomus cell intracellular calcium but not at downstream steps due to a PKC-dependent inhibition of secretion. This suggests that at least one regulatory step beyond the glomus cell calcium response may modulate the magnitude of chemoreceptor responsiveness. PMID:24096081

  5. Effects of calcium channel blockers on cloned cardiac K+ channels IKr and IKs.

    PubMed

    Chouabe, C; Drici, M D; Romey, G; Barhanin, J

    2000-01-01

    Cloned HERG and KvLQT1-IsK K+ channels have been expressed in mammalian cells and assayed as a target for calcium channel blockers. These channels generate the rapid and slow components of the cardiac delayed rectifier K+ current, and mutations can affect them that lead to long QT syndromes. HERG is blocked by bepridil (EC50 = 0.55 microM), verapamil (EC50 = 0.83 microM) and mibefradil (EC50 = 1.43 microM), whereas nitrendipine and diltiazem have negligible effects. Steady-state activation and inactivation parameters are shifted to more negative values in the presence of the blockers. Similarly, KvLQT1-IsK is inhibited by bepridil (EC50 = 10.0 microM) and mibefradil (EC50 = 11.8 microM), whilst being insensitive to nitrendipine, diltiazem or verapamil. This work may help to understand the mechanisms of action of verapamil in certain ventricular tachycardias as well as some of the deleterious adverse cardiac events associated with bepridil and mibefradil.

  6. Chiral Recognition Mechanisms of four β-Blockers by HPLC with Amylose Chiral Stationary Phase

    PubMed Central

    Wang, Dongmei; Li, Fang; Jiang, Zhen; Yu, Li; Guo, Xingjie

    2014-01-01

    The high performance liquid chromatography (HPLC) enantioseparation of four β-blocking agents metoprolol, bisoprolol, propranolol and atenolol was performed on amylose tris-(3,5-dimethylphenylcarbamate) chiral stationary phase using n-hexane-ethanol-diethylamine (DEA) as the mobile phase and related chiral recognition mechanisms were discussed. Enantiomeric separation of the four β-blockers was a result of more than one type of interaction between solutes and CSP. Besides hydrogen bonding, there was another type interaction that was independent of solvent polarity and responsible for enantiomeric selectivity, such as - interactions. Both the groups close to the chiral centers and the substituent groups on the phenyl rings, which were far away from the chiral centers, could contribute to the good separation. The separations of the four β-blocker enantiomers were all enthalpy driven process. In the range of 293–308K (20–35 ℃), as the temperature increased, the retention as well as the resolution decreased. The molecular size rather than concentration of the alcohol modifiers affected the resolution and retention. PMID:25237340

  7. [Treatment of arrhythmia in coronary patients and hypertensives with beta blockers and Depasan retard].

    PubMed

    Kandziora, J

    1981-05-14

    In the ambulatory of an internal specialist a number of patients suffering from angina pectoris or hypertonia together with arrhythmic troubles received an initial treatment with beta-blockers over a period of 21 days. In cases in which arrhythmia persisted after this initial period the treatment was continued for another 21 days with the addition of Depasan retard in function of a second medicament. This combined treatment in form of an open study was extended to a total number of 50 patients presenting ventricular extrasystolia in 45 cases and in 5 cases absolute arrhythmia in addition to the main disease. Treatment with Depasan retard showed good or satisfactory results in 39 out of 45 patients suffering from ventricular extrasystoles, whilst no effect could be obtained in the 5 cases with absolute arrhythmia. No signs of incompatibility or unwanted interactions were observed in the course of this open study. Based on these results it can be concluded that Depasan retard should be recommended in those cases where on account of persistent arrhythmical troubles and especially extrasystoles, during a treatment with beta-blockers in patients suffering from angina pectoris or hypertonia, and additional treatment with anti-arrhythmical medicaments appears to be indicated.

  8. Inhibition of purified lysosomal phospholipase A1 by beta-adrenoceptor blockers.

    PubMed

    Pappu, A S; Yazaki, P J; Hostetler, K Y

    1985-02-15

    Inhibition of rat liver lysosomal phospholipases is one of the main events that leads to accumulation of tissue phospholipids during drug-induced phospholipidosis. Drug inhibition of lysosomal phospholipase A may occur by direct effects of drugs on the enzyme (or substrate) or by drug-induced increases in intralysosomal pH. Although beta-adrenoceptor blockers have not been reported to cause lipid storage, they do inhibit lysosomal phospholipase A. To investigate the structural requirements for drug inhibition, we studied the effects of six beta-adrenoceptor blockers on purified rat liver lysosomal phospholipase A1. The agents studied include: propranolol, timolol, metoprolol, practolol, atenolol and the combined alpha and beta adrenoceptor blocking agent, labetalol. The drugs varied by two logs in their abilities to inhibit phospholipase A1 activity. The relative inhibitory potencies were propranolol greater than labetalol much greater than timolol greater than metoprolol much greater than practolol greater than atenolol. Our studies identify drug hydrophobicity as a key determinant for phospholipase A1 inhibition. A strong negative correlation was noted between the octanol/water partition coefficients and IC50 for phospholipase inhibition (r = -0.91). The ability of propranolol to inhibit phospholipase A1 was identical for the d, l and the d and l stereoisomers.

  9. Characterization of Novel Cannabinoid Based T-Type Calcium Channel Blockers with Analgesic Effects

    PubMed Central

    2015-01-01

    Low-voltage-activated (T-type) calcium channels are important regulators of the transmission of nociceptive information in the primary afferent pathway and finding ligands that modulate these channels is a key focus of the drug discovery field. Recently, we characterized a set of novel compounds with mixed cannabinoid receptor/T-type channel blocking activity and examined their analgesic effects in animal models of pain. Here, we have built on these previous findings and synthesized a new series of small organic compounds. We then screened them using whole-cell voltage clamp techniques to identify the most potent T-type calcium channel inhibitors. The two most potent blockers (compounds 9 and 10) were then characterized using radioligand binding assays to determine their affinity for CB1 and CB2 receptors. The structure–activity relationship and optimization studies have led to the discovery of a new T-type calcium channel blocker, compound 9. Compound 9 was efficacious in mediating analgesia in mouse models of acute inflammatory pain and in reducing tactile allodynia in the partial nerve ligation model. This compound was shown to be ineffective in Cav3.2 T-type calcium channel null mice at therapeutically relevant concentrations, and it caused no significant motor deficits in open field tests. Taken together, our data reveal a novel class of compounds whose physiological and therapeutic actions are mediated through block of Cav3.2 calcium channels. PMID:25314588

  10. Differential effects of K(+) channel blockers on frequency-dependent action potential broadening in supraoptic neurons.

    PubMed

    Hlubek, M D; Cobbett, P

    2000-09-15

    Recordings were made from magnocellular neuroendocrine cells dissociated from the supraoptic nucleus of the adult guinea pig to determine the role of voltage gated K(+) channels in controlling the duration of action potentials and in mediating frequency-dependent action potential broadening exhibited by these neurons. The K(+) channel blockers charybdotoxin (ChTx), tetraethylammonium (TEA), and 4-aminopyridine (4-AP) increased the duration of individual action potentials indicating that multiple types of K(+) channel are important in controlling action potential duration. The effect of these K(+) channel blockers was almost completely reversed by simultaneous blockade of voltage gated Ca(2+) channels with Cd(2+). Frequency-dependent action potential broadening was exhibited by these neurons during trains of action potentials elicited by membrane depolarizing current pulses presented at 10 Hz but not at 1 Hz. 4-AP but not ChTx or TEA inhibited frequency-dependent action potential broadening indicating that frequency-dependent action potential broadening is dependent on increasing steady-state inactivation of A-type K(+) channels (which are blocked by 4-AP). A model of differential contributions of voltage gated K(+) channels and voltage gated Ca(2+) channels to frequency-dependent action potential broadening, in which an increase of Ca(2+) current during each successive action potential is permitted as a result of the increasing steady-state inactivation of A-type K(+) channels, is presented.

  11. Simultaneous determination of beta-blockers in human plasma using liquid chromatography-tandem mass spectrometry.

    PubMed

    Umezawa, Hironobu; Lee, Xiao-Pen; Arima, Yoshiko; Hasegawa, Chika; Izawa, Hikaru; Kumazawa, Takeshi; Sato, Keizo

    2008-07-01

    A detailed procedure for the analysis of four beta-blockers, acebutolol, labetalol, metoprolol and propranolol, in human plasma by high-performance liquid chromatography (LC)-tandem mass spectrometry (MS-MS) using an MSpak GF column, which enables direct injection of crude plasma samples, is presented. Protein and/or macromolecule matrix compounds were eluted first from the column, while the drugs were retained on the polymer stationary phase of the MSpak GF column. The analytes retained on the column were then eluted into an acetonitrile-rich mobile phase using a gradient separation technique. All drugs showed base peak ions due to [M + H]+ ions by LC-MS with positive ion electrospray ionization, and the product ions were produced from each [M + H]+ ion by LC-MS-MS. Quantification was performed by selected reaction monitoring. The recoveries of the four beta-blockers spiked into plasma were 73.5-89.9%. The regression equations for all compounds showed excellent linearity in the range 10-1000 ng/mL of plasma, with the exception of propranolol (10-800 ng/mL). The limits of detection and quantification for each drug were 1-3 and 10 ng/mL, respectively, of plasma. The intra- and inter-day coefficients of variation for all drugs in plasma were not greater than 10.9%.

  12. Substituted Indazoles as Nav1.7 Blockers for the Treatment of Pain.

    PubMed

    Frost, Jennifer M; DeGoey, David A; Shi, Lei; Gum, Rebecca J; Fricano, Meagan M; Lundgaard, Greta L; El-Kouhen, Odile F; Hsieh, Gin C; Neelands, Torben; Matulenko, Mark A; Daanen, Jerome F; Pai, Madhavi; Ghoreishi-Haack, Nayereh; Zhan, Cenchen; Zhang, Xu-Feng; Kort, Michael E

    2016-04-14

    The genetic validation for the role of the Nav1.7 voltage-gated ion channel in pain signaling pathways makes it an appealing target for the potential development of new pain drugs. The utility of nonselective Nav blockers is often limited due to adverse cardiovascular and CNS side effects. We sought more selective Nav1.7 blockers with oral activity, improved selectivity, and good druglike properties. The work described herein focused on a series of 3- and 4-substituted indazoles. SAR studies of 3-substituted indazoles yielded analog 7 which demonstrated good in vitro and in vivo activity but poor rat pharmacokinetics. Optimization of 4-substituted indazoles yielded two compounds, 27 and 48, that exhibited good in vitro and in vivo activity with improved rat pharmacokinetic profiles. Both 27 and 48 demonstrated robust activity in the acute rat monoiodoacetate-induced osteoarthritis model of pain, and subchronic dosing of 48 showed a shift to a lower EC50 over 7 days.

  13. Acute effect of calcium blocker on renal hemodynamics in diabetic spontaneously hypertensive rat.

    PubMed

    Kaizu, K; Ling, Q Y; Uriu, K; Ikeda, M; Eto, S

    1995-01-01

    This study was done to examine the acute effect of a calcium channel blocker on renal hemodynamics in the diabetic spontaneously hypertensive rat (SHR). Streptozotocin was used to induce diabetes, and barnidipine (B) was used as a calcium blocker. Renal blood flow (RBF) and glomerular filtration rate (GFR) were measured by a clearance method with paraaminohypurate (PAH) and inulin, respectively. Rats were divided into two groups: nondiabetic SHR, N-SHR; diabetic SHR, DM-SHR. B increased RBF in N-SHR (7.44 +/- 1.99 versus 8.50 +/- 1.97 mL/min/g.kw) while there was no change in DM-SHR. B reduced renovascular resistance (RVR) in DM-SHR and N-SHR. B increased GFR in N-SHR (1.15 +/- 0.24 versus 1.34 +/- 0.25 mL/min/g.kw), in spite of no changes in DM-SHR. B did not modify filtration fraction (FF) in both groups. These results indicate (1) in SHR, B exerts beneficial effects on hypertensive renal damage by reducing mean arterial pressure (MAP), RVR, RBF, and GFR; (2) in diabetic SHR, B is less effective in restoring renal hyperfiltration in spite of reducing RVR.

  14. Calcium channel blockers as potential therapeutics for obesity-associated autophagy defects and fatty liver pathologies.

    PubMed

    Park, Hwan-Woo; Lee, Jun Hee

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD), typically associated with overnutrition and obesity, is one of the most common liver diseases both in the US and worldwide. During obesity and NAFLD, lipotoxic injuries to hepatocytes can provoke formation of protein inclusions consisting of SQSTM1/p62 and ubiquitinated proteins. It has been suggested that autophagy deregulation during obesity contributes to protein inclusion formation and progression of other liver pathologies including insulin resistance, steatohepatitis, and hepatocellular carcinoma. To examine how lipotoxicity and obesity affect autophagy, we established an in vitro system where cultured HepG2 cells exhibit prominent accumulation of SQSTM1 and ubiquitinated proteins in insoluble inclusion bodies upon treatment with saturated fatty acids. Using this system and a mouse model of obesity, we have determined that obesity induces chronic elevation of cytosolic calcium levels in hepatocytes, which interferes with the fusion between autophagosomes and lysosomes. Intriguingly, pharmacological inhibition of calcium channels using the FDA-approved drug verapamil successfully restores autophagic flux and suppresses protein inclusions, not only in HepG2 cells but also in mouse liver. Verapamil also reduces hepatic lipid droplet accumulation, insulin resistance and steatohepatitis, suggesting that calcium channel blockers can be used for correction of general NAFLD pathologies. Indeed, there have been a number of clinical observations in which beneficial effects of calcium channel blockers against obesity-associated metabolic pathologies are observed in humans and animal models.

  15. Predictors of response to TNF blockers in patients with polyarticular psoriatic arthritis.

    PubMed

    Carvalho, Pedro David; Duarte, Cátia; Vieira-Sousa, Elsa; Cunha-Miranda, Luís; Avila-Ribeiro, Pedro; Santos, Helena; Bernardes, Miguel; Santos, Maria José; Cerqueira, Marcos; Mateus, Margarida; Nero, Patrícia; Águeda, Ana; Silva, José António Pereira da; Machado, Pedro

    2017-01-01

    Psoriatic arthritis (PsA) is a chronic inflammatory rheumatic disease with a broad clinical spectrum. PsA can affect the axial skeleton, peripheral joints, entheses, synovial sheaths of tendons, skin, nails and extra-articular organs. Tumour necrosis factor alpha blockers (TNF blockers) were a breakthrough development in the treatment of PsA. Identifying predictors of response to biological therapies in patients with PsA is of utmost importance, especially in view of the costs and potential side effects of these agents. The aims of the present study were to determine baseline predictive factors of response to biological therapies, at 3 and 6 months, in PsA patients with polyarticular involvement (with or without axial involvement). Data were collected from the Rheumatic Diseases Portuguese Register (Reuma.pt). Eligible patients had to be anti-TNF-naive at baseline and to have at least 3 months of follow-up after the beginning of TNF blocker therapy. Only patients with information on at least one of the response measures (at 3 or 6 months of follow-up) were included in the analysis. Univariable logistic regression analysis of potential baseline predictors of European League Against Rheumatism (EULAR) good clinical response, EULAR good/moderate response, 28-joint Disease Activity Score with three variables including the erythrocyte sedimentation rate (DAS28-3V-ESR) remission and Health Assessment Questionnaire (HAQ) response were performed. Multivariable logistic regression using a forward selection procedure was used until the best-fit model was obtained, taking confounding effects into account. A total of 180 patients were eligible for the study (mean age 52 years, 54% women). In multivariable analysis at 3 months, females were less likely to attain a good EULAR response [OR=0.082 (95% CI=0.024, 0.278)], a DAS28-3V-ESR remission [OR=0.083 (95% CI=0.017, 0.416)], a moderate or good EULAR response [OR=0.091 (95% CI=0.011, 0.091)] and a HAQ response [OR=0.074 (95% CI

  16. The potential anticancer effect of beta-blockers and the genetic variations involved in the interindividual difference.

    PubMed

    He, Ruo-Hui; He, Yi-Jing; Tang, Yong-Jun; Zhou, Hong-Hao; McLeod, Howard L; Liu, Jie

    2016-01-01

    β-ARs are extensively spread in different tissues of our body, which could be activated by neurotransmitters norepinephrine and epinephrine to mediate physiological function and abnormal states including cancer. Recently, β-AR blockers could have significant implications in cancer therapy. But the precise molecular mechanisms are far from being fully understood. Through identifying the β-AR system signal pathways relevant to cancer, we can understand the mechanisms of β-blockers used for cancer treatment. What's more, retrospective clinical data made β-blockers jump out of the traditional field of cardiovascular disease and strengthened our confidence in cancer therapy. At last, genetic studies of β-adrenergic system offered crucial genes to analyze the effects of polymorphisms on cancer susceptibility, therapy response and prognosis of cancer patients.

  17. Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate.

    PubMed

    Ivanov, Vadim; Ivanova, Svetlana; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

    2016-01-01

    Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth

  18. Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate

    PubMed Central

    Ivanov, Vadim; Ivanova, Svetlana; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

    2016-01-01

    Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth

  19. The intrinsic and interactive effects of RO 15-4513 and ethanol on locomotor activity, body temperature, and blood glucose concentration

    SciTech Connect

    Wood, A.L.; Healey, P.A.; Menendez, J.A.; Verne, S.L.; Atrens, D.M. )

    1989-01-01

    The ability of the putative ethanol antagonist RO 15-4513 to antagonize ethanol-induced hypoactivity, hypothermia and hyperglycemia was investigated in rats. Although RO 15-4513 produced hypoactivity by itself, it attenuated ethanol-induced hypoactivity. This antagonism suggests that ethanol-induced hypoactivity is mediated by the GABA-benzodiazepine receptor complex which is thought to be the site of action of RO 15-4513. In contrast, although RO 15-4513 produced hypothermia by itself, it had no significant effect on ethanol-induced hypothermia. This suggests that the hypothermic effect of ethanol is not mediated by the GABA-benzodiazepine receptor complex. The fact that RO 15-4513, ethanol and the vehicle all produced hyperglycemia suggests a common stress effect and does not permit any firm conclusions to be drawn as to the interaction between ethanol and RO 15-4513 in modulating glycemic responses. These data indicate that the ethanol antagonism of RO 15-4513 is primarily confined to ethanol's behavioral effects and that ethanol's behavioral and physiological effects are mediated by neurochemically distinct mechanisms.

  20. Receptor binding characterization of the benzodiazepine radioligand sup 125 I-Ro16-0154: Potential probe for SPECT (Single Photon Emission Computed Tomography) brain imaging

    SciTech Connect

    Johnson, E.W.; Woods, S.W.; Zoghbi, S.; Baldwin, R.M.; Innis, R.B. ); McBride, B.J. )

    1990-01-01

    The binding of an iodinated benzodiazepine (BZ) radioligand has been characterized, particularly in regard to its potential use as a neuroreceptor brain imaging agent with SPECT (Single Photon Emission Computed Tomography). Ro16-0154 is an iodine-containing BZ antagonist and a close analog of Ro15-1788. In tissue homogenates prepared from human and monkey brain, the binding of {sup 125}I-labeled Ro16-0154 was saturable, of high affinity, and had high ratios of specific to non-specific binding. Physiological concentrations of NaCl enhanced specific binding approximately 15% compared to buffer without this salt. Kinetic studies of association and dissociation demonstrated a temperature dependent decrease in affinity with increasing temperature. Drug displacement studies confirmed that {sup 125}I-Ro16-0154 binds to the central type BZ receptor: binding is virtually identical to that of {sup 3}H-Ro15-1788 except that {sup 125}I-Ro16-0154 shows an almost 10 fold higher affinity at 37{degree}C. These in vitro results suggest that {sup 123}I-labeled Ro16-0154 shows promise as a selective, high affinity SPECT probe of the brain's BZ receptor.

  1. Effects of different alpha-1 adrenoceptor blockers on proximal urethral function using in vivo isovolumetric pressure changes.

    PubMed

    Yamaguchi, Takanori; Nagano, Masashi; Osada, Yukio

    2005-10-01

    The effects of different alpha-1 adrenoceptor blockers on the urethra and the cardiovascular system were evaluated using an in vivo isovolumetric intra-urethral pressure model in New Zealand white rabbits. The urethra of anesthetized male rabbits was cannulated through the bladder and secured at the vesico-urethral junction. The distal side of urethra under the pubic bone was also closed to allow measurement of the intra-urethral pressure. Both the intra-urethral pressure and the femoral arterial pressure were monitored. The effects of five different alpha-1 adrenoceptor blockers on the increases in both the intra-urethral pressure and blood pressure induced by phenylephrine were then examined. The inhibition rate of the alpha-1 adrenoceptor blockers prazosin, bunazosin, terazosin, alfuzosin and tamsulosin on the increase in intra-urethral pressure caused as a result of contraction by phenylephrine was 87.5 +/- 4.5% (mean +/- S.E.), 88.0 +/- 7.2%, 86.2 +/- 6.2%, 81.4 +/- 4.8% and 92.5 +/- 5.0% respectively. The potency ranking of these alpha-1 adrenoceptor blockers was tamsulosin > bunazosin > prazosin > terazosin > alfuzosin. Their inhibition rate of the arterial pressure increase induced by phenylephrine was 81.9 +/- 5.0%, 86.2 +/- 5.9%, 76.0 +/- 6.0%, 63.6 +/- 5.7% and 58.0 +/- 5.2% respectively, with a potency ranking of bunazosin > prazosin > terazosin > alfuzosin > tamsulosin. We therefore conclude that the alpha-1 adrenoceptor blockers bunazosin and prazosin have a more potent action on both the urethra and the vascular system. However, tamsulosin and alfuzosin displayed a marked blockade of the increased urethral pressure induced by phenylephrine, with much less of a blockade of arterial pressure. In the present study, tamsulosin has been shown to be the most sensitive and powerful of the alpha-1 adrenoceptor blockers on urethral smooth muscle.

  2. CNS-related (side-)effects of beta-blockers with special reference to mechanisms of action.

    PubMed

    Koella, W P

    1985-01-01

    beta-Adrenoreceptor antagonists are liable to produce behavioural side-effects such as drowsiness, fatigue, lethargy, sleep disorders, nightmares, depressive moods, and hallucinations. These undesirable actions indicate that beta-blockers affect not only peripheral autonomic activity but also some central nervous mechanisms. In experimental animals beta-blockers have been found to reduce spontaneous motor activity, to counteract isolation-, lesion-, stimulation- and amphetamine-induced hyperactivity, and to produce slow-wave and paradoxical sleep disturbances. Furthermore, central effects such as tranquilizing influences are used for the treatment of conditions such as anxiety. Several different mechanisms of action could be responsible for these CNS effects: Centrally mediated specific actions on centrally located beta-adrenergic receptors, known to exist downstream from, and at the terminals of, 'vigilance-enhancing' central noradrenergic pathways. Centrally mediated specific actions on centrally located receptors of the non-adrenergic type; an affinity of some beta-blockers towards 5-HT-receptors is well documented. Centrally mediated non-specific actions on centrally located neurones, owing to the membrane-stabilizing effects of beta-blockers. Peripherally mediated actions whereby beta-blockers induce changes in the autonomic activity in the periphery, which are relayed to the CNS to induce changes in activity of a variety of central systems. It can be assumed that with any one of the beta-blockers all these mechanisms come into play, yet with varying degrees depending on characteristics of the drugs such as lipophilicity and hydrophilicity, the ratio of antagonist versus (partial) agonist properties, affinity to 'alien' receptor sites, strength of membrane-stabilizing activity, stereospecific affinity, and potency.

  3. T Cell Subset and Stimulation Strength-Dependent Modulation of T Cell Activation by Kv1.3 Blockers

    PubMed Central

    Fung-Leung, Wai-Ping; Edwards, Wilson; Liu, Yi; Ngo, Karen; Angsana, Julianty; Castro, Glenda; Wu, Nancy; Liu, Xuejun; Swanson, Ronald V.; Wickenden, Alan D.

    2017-01-01

    Kv1.3 is a voltage-gated potassium channel expressed on T cells that plays an important role in T cell activation. Previous studies have shown that blocking Kv1.3 channels in human T cells during activation results in reduced calcium entry, cytokine production, and proliferation. The aim of the present study was to further explore the effects of Kv1.3 blockers on the response of different human T cell subsets under various stimulation conditions. Our studies show that, unlike the immune suppressor cyclosporine A, the inhibitory effect of Kv1.3 blockers was partial and stimulation strength dependent, with reduced inhibitory efficacy on T cells under strengthened anti-CD3/CD28 stimulations. T cell responses to allergens including house dust mites and ragweed were partially reduced by Kv1.3 blockers. The effect of Kv1.3 inhibition was dependent on T cell subsets, with stronger effects on CCR7- effector memory compared to CCR7+ central memory CD4 T cells. Calcium entry studies also revealed a population of CD4 T cells resistant to Kv1.3 blockade. Activation of CD4 T cells was accompanied with an increase in Kv1.3 currents but Kv1.3 transcripts were found to be reduced, suggesting a posttranscriptional mechanism in the regulation of Kv1.3 activities. In summary, Kv1.3 blockers inhibit T cell activation in a manner that is highly dependent on the T cell identity and stimulation strength, These findings suggest that Kv1.3 blockers inhibit T cells in a unique, conditional manner, further refining our understanding of the therapeutic potential of Kv1.3 blockers. PMID:28107393

  4. Impact of oral beta-blocker therapy on mortality after primary percutaneous coronary intervention for Killip class 1 myocardial infarction.

    PubMed

    Hioki, Hirofumi; Motoki, Hirohiko; Izawa, Atsushi; Kashima, Yuichirou; Miura, Takashi; Ebisawa, Souichirou; Tomita, Takeshi; Miyashita, Yusuke; Koyama, Jun; Ikeda, Uichi

    2016-05-01

    The use of beta-blockers therapy has been recommended to reduce mortality in patients with left ventricular dysfunction after acute myocardial infarction (AMI). Primary percutaneous coronary intervention (PCI), which has become the mainstay of treatment for AMI, is associated with a lower mortality than fibrinolysis. The benefits of beta-blockers after primary PCI in AMI patients without pump failure are unclear. We hypothesized that oral beta-blocker therapy after primary PCI might reduce the mortality in AMI patients without pump failure. The assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction (ALPS-AMI) study was a multi-center study that enrolled 508 AMI patients to compare the efficacy of hydrophilic and lipophilic statins in secondary prevention after myocardial infarction. We prospectively tracked cardiovascular events for 3 years in 444 ALPS-AMI patients (median age 66 years; 18.2 % women) who had Killip class 1 on admission and were discharged alive. The primary endpoint was all-cause mortality. The 3-year follow-up was completed in 413 patients (93.0 %). During this follow-up, 21 patients (4.7 %) died. In Kaplan-Meier analysis, patients on beta-blockers had a significantly lower incidence of all-cause mortality (2.7 vs. 7.3 %, log-rank p = 0.025). After adjusting for the calculated propensity score for using beta-blockers, their use remained an independent predictor of all-cause mortality (hazard ratio 0.309; 95 % confidence interval 0.116-0.824; p = 0.019). In the statin era, the use of beta-blocker therapy after primary PCI is associated with lower mortality in AMI patients with Killip class 1 on admission.

  5. SDN based millimetre wave radio over fiber (RoF) network

    NASA Astrophysics Data System (ADS)

    Amate, Ahmed; Milosavljevic, Milos; Kourtessis, Pandelis; Robinson, Matthew; Senior, John M.

    2015-01-01

    This paper introduces software-defined, millimeter Wave (mm-Wave) networks with Radio over Fiber (RoF) for the delivery of gigabit connectivity required to develop fifth generation (5G) mobile. This network will enable an effective open access system allowing providers to manage and lease the infrastructure to service providers through unbundling new business models. Exploiting the inherited benefits of RoF, complete base station functionalities are centralized at the edges of the metro and aggregation network, leaving remote radio heads (RRHs) with only tunable filtering and amplification. A Software Defined Network (SDN) Central Controller (SCC) is responsible for managing the resource across several mm-Wave Radio Access Networks (RANs) providing a global view of the several network segments. This ensures flexible resource allocation for reduced overall latency and increased throughput. The SDN based mm-Wave RAN also allows for inter edge node communication. Therefore, certain packets can be routed between different RANs supported by the same edge node, reducing latency. System level simulations of the complete network have shown significant improvement of the overall throughput and SINR for wireless users by providing effective resource allocation and coordination among interfering cells. A new Coordinated Multipoint (CoMP) algorithm exploiting the benefits of the SCC global network view for reduced delay in control message exchange is presented, accounting for a minimum packet delay and limited Channel State Information (CSI) in a Long Term Evolution-Advanced (LTE-A), Cloud RAN (CRAN) configuration. The algorithm does not require detailed CSI feedback from UEs but it rather considers UE location (determined by the eNB) as the required parameter. UE throughput in the target sector is represented using a Cumulative Distributive Function (CDF). The drawn characteristics suggest that there is a significant 60% improvement in UE cell edge throughput following the

  6. Chemistry of silica scale mitigation for RO desalination with particular reference to remote operations.

    PubMed

    Milne, Nicholas A; O'Reilly, Tom; Sanciolo, Peter; Ostarcevic, Eddy; Beighton, Mark; Taylor, Kelvin; Mullett, Mark; Tarquin, Anthony J; Gray, Stephen R

    2014-11-15

    Silica scaling in reverse osmosis of groundwater is a significant issue in water stressed areas due to the limitations that scaling imposes on water recovery. While calcium and magnesium scaling potential can be significantly reduced by the use of ion exchange or other softening processes, the silica scaling potential typically remains. Improving the recovery of reverse osmosis by limiting the potential for silica scale is important in ensuring maximum water recovery. This is particularly important for mining and natural gas industries that are located in remote regions. The remote nature of these sites imposes three major restrictions on the silica scale mitigation process. Firstly, the generation of poorly dewaterable sludges must be avoided. Also, the quality of any reverse osmosis (RO) permeate must be able to meet the end use requirements, particularly for boilers. Finally, silica removal should not impact upon other potentially useful or valuable components within the brine, and should not make the disposal of the unusable waste brine components more difficult. Reduction of scaling potential can be achieved in three main ways: operating RO at high pH after hardness has been removed, operating at low pH, and reducing the silica concentration either in pretreatment or by using an interstage technique. Operating at high pH has the initial requirement of hardness removal to prevent scaling and this could be an issue on some sites. Hardness removal operations that use ion exchange resins may be challenged by water chemistry and the operational costs associated with high chemical regeneration costs. Operating at low pH may be more desirable than high pH operation as this can help to reduce the risk of scale formation from calcium or magnesium salts. The drawback comes from the cost of acid, particularly for high-alkalinity waters. There are numerous silica removal techniques including chemical dosing of lime, or aluminium or iron salts, electrocoagulation

  7. AST/RO Observations of CO J=7-6 Emission from the Galactic Center

    NASA Astrophysics Data System (ADS)

    Kim, S.; Martin, C. L.; Stark, A. A.; Lane, A. P.

    2000-12-01

    We present a map of the Galactic Center region in the CO J=7-6 transition observed with the Antarctic Submillimeter Telescope and Remote Observatory (AST/RO) located at Amundsen-Scott South Pole Station. Emission from the 809 GHz J=7-6 transition of 12CO was mapped over the region -2.7 < l < 3.6, -1.0 < b < 1.0, on a 1' grid with a spatial resolution of ~ 85''. The CO J=4-3 and [CI] emissions from this region have been mapped with AST/RO by Martin et al. (2001) and Ojha et al. (2000). These two spectral lines are distributed throughout the Galactic Center region in a manner almost identical to that of CO J=1-0; the CO(4-3)/ CO(1-0) line ratio and the [CI]/CO line ratios are remarkably uniform across a wide variety of Galactic Center features. In contrast, the CO J=7-6 emission from the Galactic Center region is confined to the Sgr A and Sgr B2 complexes. The implication is that the photon-dominated regions surrounding the Galactic Center are remarkably similar in mean density and kinetic temperature at n = 3000 cm-3 and T = 35 K, except for the two special regions Sgr A and Sgr B2, which are denser. The CO(7-6)/CO(4-3) line temperature ratios near Sgr B2 are similar to those observed in the nuclear region of the starburst galaxy M82 (Mao et al. 2000), while the CO(7-6)/CO(4-3) line temperature ratios around Sgr A are a factor of three lower than those near Sgr B2. The CO(7-6)/CO(4-3) line ratio in the Galactic Center region as a whole is at least an order of magnitude less than that in a comparable region near the center of M82. This research was supported in part by the National Science Foundation under a cooperative agreement with the Center for Astrophysical Research in Antarctica (CARA), grant number NSF OPP 89-20223. CARA is a National Science Foundation Science and Technology Center.

  8. Disentangling planetary and stellar activity features in the CoRoT-2 light curve

    NASA Astrophysics Data System (ADS)

    Bruno, G.; Deleuil, M.; Almenara, J.-M.; Barros, S. C. C.; Lanza, A. F.; Montalto, M.; Boisse, I.; Santerne, A.; Lagrange, A.-M.; Meunier, N.

    2016-11-01

    Aims: Stellar activity is an important source of systematic errors and uncertainties in the characterization of exoplanets. Most of the techniques used to correct for this activity focus on an ad hoc data reduction. Methods: We have developed a software for the combined fit of transits and stellar activity features in high-precision long-duration photometry. Our aim is to take advantage of the modelling to derive correct stellar and planetary parameters, even in the case of strong stellar activity. Results: We use an analytic approach to model the light curve. The code KSint, modified by adding the evolution of active regions, is implemented into our Bayesian modelling package PASTIS. The code is then applied to the light curve of CoRoT-2. The light curve is divided in segments to reduce the number of free parameters needed by the fit. We perform a Markov chain Monte Carlo analysis in two ways. In the first, we perform a global and independent modelling of each segment of the light curve, transits are not normalized and are fitted together with the activity features, and occulted features are taken into account during the transit fit. In the second, we normalize the transits with a model of the non-occulted activity features, and then we apply a standard transit fit, which does not take the occulted features into account. Conclusions: Our model recovers the activity features coverage of the stellar surface and different rotation periods for different features. We find variations in the transit parameters of different segments and show that they are likely due to the division applied to the light curve. Neglecting stellar activity or even only bright spots while normalizing the transits yields a 1.2σ larger and 2.3σ smaller transit depth, respectively. The stellar density also presents up to 2.5σ differences depending on the normalization technique. Our analysis confirms the inflated radius of the planet (1.475 ± 0.031RJ) found by other authors. We show that

  9. Variational Calculations of IR Ro-Vibrational Spectra for Nitric Acid

    NASA Astrophysics Data System (ADS)

    Pavlyuchko, A. I.; Yurchenko, S. N.; Tennyson, J.

    2013-09-01

    To model the atmospheric composition of the potentially habitable planets, it is essential to have comprehensive data on the spectroscopic properties of the main molecular absorbers. This is especially true in the infrared region which is dominated by transitions of polyatomic molecules [1]. Nitric acid (HNO3) is an important constituent of the Earth atmosphere where it is a prominent bio-signature. Here we present simulations of the absorption spectra for HNO3. We have developed a variational method to solve the ro-vibrational Schrödinger equation for a general polyatomic molecule. The ro-vibrational Hamiltonian is given by [2] where the internal curvilinear vibrational coordinates qi are used to represent the displacements of the bond lengths and bond angles, ?ij(q) are elements of the matrix of the kinematic coefficients, t is the determinant of this matrix, 'a are the Euler angles, and μab(q) is the inverse matrix of the tensor of inertia. The potential energy function, V (q), is given by a fourthorder polynomial expansion in terms of Morse variables xi = 1 - e-iqi for the stretching coordinates and xi = qi for the bending coordinates. The dipole moment of the molecule is presented in the form of a Taylor series of the 2nd order in terms of qi. The parameters of the potential energy and the dipole moment functions of HNO3 were calculated by the quantum chemical method at the CCSD(T)/aug-cc-pVQZ level of theory. With this potential energy function, agreement between the calculated and experimental fundamental frequencies of vibrations is within 5 cm -1. The harmonic part of the potential function was then optimized by fitting to the experimental fundamental frequencies and used to simulate the IR spectra of HNO3. The results are in good agreement with the experimental data. The figure shows an example of the simulated spectra of HNO3 in the area of the strong Fermi resonance between the -5 and 2-9 bands along with an experimental counterpart. The resulting

  10. The roAp star α Circinus as seen by BRITE-Constellation

    NASA Astrophysics Data System (ADS)

    Weiss, W. W.; Fröhlich, H.-E.; Pigulski, A.; Popowicz, A.; Huber, D.; Kuschnig, R.; Moffat, A. F. J.; Matthews, J. M.; Saio, H.; Schwarzenberg-Czerny, A.; Grant, C. C.; Koudelka, O.; Lüftinger, T.; Rucinski, S. M.; Wade, G. A.; Alves, J.; Guedel, M.; Handler, G.; Mochnacki, St.; Orleanski, P.; Pablo, B.; Pamyatnykh, A.; Ramiaramanantsoa, T.; Rowe, J.; Whittaker, G.; Zawistowski, T.; Zocłońska, E.; Zwintz, K.

    2016-04-01

    We report on an analysis of high-precision, multi-colour photometric observations of the rapidly-oscillating Ap (roAp) star α Cir. These observations were obtained with the BRITE-Constellation, which is a coordinated mission of five nanosatellites that collects continuous millimagnitude-precision photometry of dozens of bright stars for up to 180 days at a time in two colours (≈Johnson B and R). BRITE stands for BRight Target Explorer. The object α Cir is the brightest roAp star and an ideal target for such investigations, facilitating the determination of oscillation frequencies with high resolution. This star is bright enough for complementary interferometry and time-resolved spectroscopy. Four BRITE satellites observed α Cir for146 d or 33 rotational cycles. Phasing the photometry according to the 4.4790 d rotational period reveals qualitatively different light variations in the two photometric bands. The phased red-band photometry is in good agreement with previously-published WIRE data, showing a light curve symmetric about phase 0.5 with a strong contribution from the first harmonic. The phased blue-lband data, in contrast, show an essentially sinusoidal variation. We model both light curves with Bayesian Photometric Imaging, which suggests the presence of two large-scale, photometrically bright (relative to the surrounding photosphere) spots. We also examine the high-frequency pulsation spectrum as encoded in the BRITE photometry. Our analysis establishes the stability of the main pulsation frequency over the last ≈20 yr, confirms the presence of frequency f7, which was not detected (or the mode not excited) prior to 2006, and excludes quadrupolar modes for the main pulsation frequency. Based on data collected by the BRITE-Constellation satellite mission, built, launched and operated thanks to support from the Austrian Aeronautics and Space Agency, the University of Vienna, the Canadian Space Agency (CSA), the Foundation for Polish Science

  11. Standardization of vitrinite reflectance measurements in shale petroleum systems: How accurate are my Ro data?

    USGS Publications Warehouse

    Hackley, Paul C.

    2014-01-01

    Vitrinite reflectance generally is considered the most robust thermal maturity parameter available for application to hydrocarbon exploration and petroleum system evaluation. However, until 2011 there was no standardized methodology available to provide guidelines for vitrinite reflectance measurements in shale. Efforts to correct this deficiency resulted in publication of ASTM D7708-11: Standard test method for microscopical determination of the reflectance of vitrinite dispersed in sedimentary rocks. In 2012-2013, an interlaboratory exercise was conducted to establish precision limits for the measurement technique. Six samples, representing a wide variety of shale, were tested in duplicate by 28 analysts in 22 laboratories from 14 countries. Samples ranged from immature to overmature (Ro 0.31-1.53%), from organic-rich to organic-lean (1-22 wt.% total organic carbon), and contained Type I (lacustrine), Type II (marine), and Type III (terrestrial) kerogens. Repeatability values (difference between repetitive results from same operator, same conditions) ranged from 0.03-0.11% absolute reflectance, whereas reproducibility values (difference between results obtained on same test material by different operators, different laboratories) ranged from 0.12-0.54% absolute reflectance. Repeatability and reproducibility degraded consistently with increasing maturity and decreasing organic content. However, samples with terrestrial kerogens (Type III) fell off this trend, showing improved levels of reproducibility due to higher vitrinite content and improved ease of identification. Operators did not consistently meet the reporting requirements of the test method, indicating that a common reporting template is required to improve data quality. The most difficult problem encountered was the petrographic distinction of solid bitumens and low-reflecting inert macerals from vitrinite when vitrinite occurred with reflectance ranges overlapping the other components. Discussion among

  12. Inhibitory Effects of Cytosolic Ca2+ Concentration by Ginsenoside Ro Are Dependent on Phosphorylation of IP3RI and Dephosphorylation of ERK in Human Platelets

    PubMed Central

    Kwon, Hyuk-Woo; Shin, Jung-Hae; Lee, Dong-Ha; Park, Hwa-Jin

    2015-01-01

    Intracellular Ca2+ ([Ca2+]i) is platelet aggregation-inducing molecule and is involved in activation of aggregation associated molecules. This study was carried out to understand the Ca2+-antagonistic effect of ginsenoside Ro (G-Ro), an oleanane-type saponin in Panax ginseng. G-Ro, without affecting leakage of lactate dehydrogenase, dose-dependently inhibited thrombin-induced platelet aggregation, and the half maximal inhibitory concentration was approximately 155 μM. G-Ro inhibited strongly thrombin-elevated [Ca2+]i, which was strongly increased by A-kinase inhibitor Rp-8-Br-cAMPS compared to G-kinase inhibitor Rp-8-Br-cGMPS. G-Ro increased the level of cAMP and subsequently elevated the phosphorylation of inositol 1, 4, 5-triphosphate receptor I (IP3RI) (Ser1756) to inhibit [Ca2+]i mobilization in thrombin-induced platelet aggregation. Phosphorylation of IP3RI (Ser1756) by G-Ro was decreased by PKA inhibitor Rp-8-Br-cAMPS. In addition, G-Ro inhibited thrombin-induced phosphorylation of ERK 2 (42 kDa), indicating inhibition of Ca2+ influx across plasma membrane. We demonstrate that G-Ro upregulates cAMP-dependent IP3RI (Ser1756) phosphorylation and downregulates phosphorylation of ERK 2 (42 kDa) to decrease thrombin-elevated [Ca2+]i, which contributes to inhibition of ATP and serotonin release, and p-selectin expression. These results indicate that G-Ro in Panax ginseng is a beneficial novel Ca2+-antagonistic compound and may prevent platelet aggregation-mediated thrombotic disease. PMID:26355658

  13. Isolation and characterization of a cDNA clone encoding the 60-kD component of the human SS-A/Ro ribonucleoprotein autoantigen.

    PubMed Central

    Ben-Chetrit, E; Gandy, B J; Tan, E M; Sullivan, K F

    1989-01-01

    SS-A/Ro is a nucleocytoplasmic ribonucleoprotein (RNP) particle that is a common target of autoimmune response in Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). Previously, SS-A/Ro has been shown to be composed of at least two polypeptide antigens of 60 and 52 kD noncovalently associated with a set of small RNAs, designated Y1-Y5. A serum from an SS patient was selected to screen a lambda gt11 cDNA library constructed from human T cell lymphoblastic leukemia (MOLT-4) mRNA. An immunoreactive clone was isolated that possessed a 1.8-kb cDNA insert. In vitro transcription and translation of the cDNA resulted in the synthesis of a 57.5-kD polypeptide which was specifically immunoprecipitated by SS-A/Ro antisera. The identity of the cDNA encoded protein as the 60-kD SS-A/Ro antigen was established by proteolytic peptide mapping of the cDNA-encoded protein and the 60-kD HeLa cell antigen. The sequence of the cDNA shows that the 60-kD SS-A/Ro protein possesses both RNA binding protein consensus sequences and a single zinc-finger motif. Recombinant SS-A/Ro antigen produced in bacteria proved to be a sensitive and specific reagent for detection of anti-SS-A/Ro antibodies in patient sera. The availability of the 60-kD SS-A/Ro cDNA will enable detailed analysis of the molecular structure and function of the SS-A/Ro RNP particle and its role in autoimmune pathology. Images PMID:2649513

  14. Astrobiology Road Mapping (AstRoMap) - A project within FP7 of the European Commission: First results

    NASA Astrophysics Data System (ADS)

    Gomez-Gomez, Felipe; Capria, Maria Teresa; Palomba, Ernesto; Walter, Nicolas; Rettberg, Petra; Muller, Christian; Horneck, Gerda

    AstRoMap (Astrobiology and Planetary Exploration Road Mapping) is a funded project formulated in the 5th Call of the European Commission FP7 framework. The main objectives of the AstRoMap are: 1. Identify the main astrobiology issues to be addressed by Europe in the next decades in relation with space exploration 2. Identify potential mission concepts that would allow addressing these issues 3. Identify the technology developments required to enable these missions 4. Provide a prioritized roadmap integrating science and technology activities as well as ground-based approach 5. Map scientific knowledge related to astrobiology in Europe To reach those objectives, AstRoMap is executed within the following steps: 1. Community consultation. In order to map the European astrobiology landscape and to provide a collaborative networking platform for this community, the AstRoMap project hosts a database of scientists (European and beyond) interested in astrobiology and planetary exploration (see: http://www.astromap.eu/database.html). It reflects the demography and the research and teaching activities of the astrobiology community, as well as their professional profiles and involvement in astrobiology projects. Considering future aspects of astrobiology in Europe, the need for more astrobiology-dedicated funding programmes at the EU level, especially for cross-disciplinary groups, was stressed. This might eventually lead to the creation of a European laboratory of Astrobiology, or even of a European Astrobiology Institute. 2. Workshops organisation. On the basis of the feedbacks from the community consultation, the potential participants and interesting topics are being identified to take part in the following workshops: 1-. Origin of organic compounds, steps to life; 2. Physico-chemical boundary conditions for habitability 3. Biosignatures as facilitating life detection 4. Origin of the Solar system 3. Astrobiology road-mapping. Based on the results and major conclusions

  15. Effects of the selective protein kinase C inhibitor, Ro 31-7549, on the proliferation of cultured mouse epidermal keratinocytes.

    PubMed

    Bollag, W B; Ducote, J; Harmon, C S

    1993-03-01

    We have investigated the effects of Ro 31-7549, a selective protein kinase C (PKC) inhibitor, on DNA synthesis and proliferation in two primary mouse epidermal keratinocyte culture systems. In differentiating keratinocytes incubated in medium containing 10% serum and high calcium (approximately 0.5 mM), Ro 31-7549 blocked the inhibitory effect of the phorbol ester 12-0-tetradecanoyl-13-acetate (TPA) (a PKC activator) on keratinocyte DNA synthesis at 24 h [50% maximal response concentration (EC50) = 1 microM], consistent with inhibition of PKC-mediated differentiation. Continuous treatment of the differentiative culture system with the PKC inhibitor resulted in a marked (fourfold) stimulation of [3H]thymidine incorporation at day 7 of exposure, with an EC50 of 0.25 microM. The potencies of these effects of Ro 31-7549 are comparable to that reported for inhibition of TPA-induced platelet 47-kD protein phosphorylation [50% inhibitory concentration (IC50) = 4.4 microM]. The time course of [3H]thymidine incorporation indicated that Ro 31-7549 did not directly stimulate DNA synthesis but instead prevented the loss of proliferative capacity associated with continued culture in this medium. Maximal stimulation (2.6 times) of DNA synthesis was observed on day 4, whereas DNA synthesis at day 1 was unaffected. In a highly proliferative culture system using serum-free medium containing 25 microM calcium, TPA dose-dependently inhibited proliferation with an IC50 of approximately 0.3 mM. This antiproliferative effect of TPA was largely reversed by 0.1 microM Ro 31-7549. In the proliferative culture system, 0.75 microM Ro 31-7549 also essentially reversed the inhibition of proliferation caused by switching to high (1.0 mM) calcium. These results suggest that the loss of proliferative capacity in differentiating epidermal keratinocyte cultures may be mediated, at least in part, by PKC.

  16. Revisiting CoRoT RR Lyrae stars: detection of period doubling and temporal variation of additional frequencies

    NASA Astrophysics Data System (ADS)

    Szabó, R.; Benkő, J. M.; Paparó, M.; Chapellier, E.; Poretti, E.; Baglin, A.; Weiss, W. W.; Kolenberg, K.; Guggenberger, E.; Le Borgne, J.-F.

    2014-10-01

    Context. High-precision, space-based photometric missions like CoRoT and Kepler have revealed new and surprising phenomena in classical variable stars. Such discoveries were the period doubling in RR Lyrae stars and the frequent occurrence of additional periodicities some of which can be explained by radial overtone modes, but others are discordant with the radial eigenfrequency spectrum. Aims: We search for signs of period doubling in CoRoT RR Lyrae stars. The occurrence of this dynamical effect in modulated RR Lyrae stars might help us to gain more information about the mysterious Blazhko effect. The temporal variability of the additional frequencies in representatives of all subtypes of RR Lyrae stars is also investigated. Methods: We preprocess CoRoT light curves by applying trend and jump correction and outlier removal. Standard Fourier technique is used to analyze the frequency content of our targets and follow the time-dependent phenomena. Results: The most comprehensive collection of CoRoT RR Lyrae stars, including new discoveries is presented and analyzed. We found alternating maxima and in some cases half-integer frequencies in four CoRoT Blazhko RR Lyrae stars, as clear signs of the presence of period doubling. This reinforces that period doubling is an important ingredient for understanding the Blazhko effect - a premise we derived previously from the Kepler RR Lyrae sample. As expected, period doubling is detectable only for short time intervals in most modulated RRab stars. Our results show that the temporal variability of the additional frequencies in all RR Lyrae subtypes is ubiquitous. The ephemeral nature and the highly variable amplitude of these variations suggest a complex underlying dynamics of and an intricate interplay between radial and possibly nonradial modes in RR Lyrae stars. The omnipresence of additional modes in all types of RR Lyrae - except in non-modulated RRab stars - implies that asteroseismology of these objects should be

  17. Accretion dynamics and disk evolution in NGC 2264: a study based on CoRoT photometric observations

    NASA Astrophysics Data System (ADS)

    Alencar, S. H. P.; Teixeira, P. S.; Guimarães, M. M.; McGinnis, P. T.; Gameiro, J. F.; Bouvier, J.; Aigrain, S.; Flaccomio, E.; Favata, F.

    2010-09-01

    Context. The young cluster NGC 2264 was observed with the CoRoT satellite for 23 days uninterruptedly in March 2008 with unprecedented photometric accuracy. We present the first results of our analysis of the accreting population belonging to the cluster as observed by CoRoT. Aims: We search for possible light curve variability of the same nature as that observed in the classical T Tauri star AA Tau, which was attributed to a magnetically controlled inner disk warp. The inner warp dynamics is supposed to be directly associated with the interaction between the stellar magnetic field and the inner disk region. Methods: We analyzed the CoRoT light curves of 83 previously known classical T Tauri stars that belong to NGC 2264 classifying them according to their light-curve morphology. We also studied the CoRoT light-curve morphology as a function of a Spitzer-based classification of the star-disk systems. Results: The classification derived on the basis of the CoRoT light-curve morphology agrees very well with the Spitzer IRAC-based classification of the systems. The percentage of AA Tau-like light curves decreases as the inner disk dissipates, from 40% ± 10% in systems with thick inner disks to 36% ± 16% in systems with anemic disks and zero in naked photosphere systems. Indeed, 91% ± 29% of the CTTS with naked photospheres exhibit pure spot-like variability, while only 18% ± 7% of the thick disk systems do so, presumably those seen at low inclination and thus free of variable obscuration. Conclusions: AA Tau-like light curves are found to be fairly common, with a frequency of at least ~30 to 40% in young stars with inner dusty disks. The temporal evolution of the light curves indicates that the structure of the inner disk warp, located close to the corotation radius and responsible for the obscuration episodes, varies over a timescale of a few (~1-3) rotational periods. This probably reflects the highly dynamical nature of the star-disk magnetospheric interaction

  18. ACT‐ONE ‐ ACTION at last on cancer cachexia by adapting a novel action beta‐blocker

    PubMed Central

    Laviano, Alessandro

    2016-01-01

    Abstract Novel action beta‐blockers combine many different pharmacological effects. The espindolol exhibits effects through β and central 5‐HT1α receptors to demonstrate pro‐anabolic, anti‐catabolic, and appetite‐stimulating actions. In the ACT‐ONE trial, espindolol reversed weight loss and improved handgrip strength in patients with cachexia due to non‐small cell lung cancer or colorectal cancer. With this trial, another frontier of cachexia management is in sight. Nonetheless, more efficacy and safety data is needed before new therapeutic indications for novel action beta‐blockers can be endorsed. PMID:27625919

  19. Binding modes of noncompetitive GABA-channel blockers revisited using engineered affinity-labeling reactions combined with new docking studies.

    PubMed

    Charon, Sébastien; Taly, Antoine; Rodrigo, Jordi; Perret, Philippe; Goeldner, Maurice

    2011-04-13

    The binding modes of noncompetitive GABA(A)-channel blockers were re-examined taking into account the recent description of the 3D structure of prokaryotic pentameric ligand-gated ion channels, which provided access to new mammalian or insect GABA receptor models, emphasizing their transmembrane portion. Two putative binding modes were deciphered for this class of compounds, including the insecticide fipronil, located nearby either the intra- or the extracellular part of the membrane, respectively. These results are in full agreement with previously described affinity-labeling reactions performed with GABA(A) noncompetitive blockers (Perret et al. J. Biol. Chem.1999, 274, 25350-25354).

  20. ACT-ONE - ACTION at last on cancer cachexia by adapting a novel action beta-blocker.

    PubMed

    Lainscak, Mitja; Laviano, Alessandro

    2016-09-01

    Novel action beta-blockers combine many different pharmacological effects. The espindolol exhibits effects through β and central 5-HT1α receptors to demonstrate pro-anabolic, anti-catabolic, and appetite-stimulating actions. In the ACT-ONE trial, espindolol reversed weight loss and improved handgrip strength in patients with cachexia due to non-small cell lung cancer or colorectal cancer. With this trial, another frontier of cachexia management is in sight. Nonetheless, more efficacy and safety data is needed before new therapeutic indications for novel action beta-blockers can be endorsed.

  1. [Effect of calcium channel blockers on developing nervous syndrome of high pressure and nitrogen narcosis in mice].

    PubMed

    Sledkov, A I

    1997-01-01

    In the experiments conducted on mice which prior to compression in a heliox environment have been injected the blockers of various types of calcium channels (flunarezine, verapramil and nifedipine) as well as bemethyl (actoprotector) and oxymethacye (antioxidant) there escaped detection of noticeable effect of these drugs on developing the high pressure nervous syndrome (HPNS). On exposure to the hyperbaric nitrogen-oxygen environment verapromil (phenylalkulamine blocker of L-type calcium channels) had a protection effect with respect to a convulsive component of the nitrogen narcosis.

  2. Heart rate recovery improvement in patients following acute myocardial infarction: exercise training, β-blocker therapy or both.

    PubMed

    Medeiros, Wladimir M; de Luca, Fabio A; de Figueredo Júnior, Alcides R; Mendes, Felipe A R; Gun, Carlos

    2017-04-12

    Heart rate recovery (HRR) is a strong mortality predictor. Exercise training (ET) and β-blocker therapy have significant impact on the HRR of patients following myocardial infarction (MI). However, the combination of ET and β-blocker therapy, as well as its effectiveness in patients with a more compromised HRR (≤12 bpm), has been under-studied. Male patients (n = 64) post-MI were divided: Training + β-blocker (n = 19), Training (n = 15), β-blocker (n = 11) and Control (n = 19). Participants performed an ergometric test before and after 3 months of intervention. HRR was obtained during 5 min of recovery and corrected by the cardiac reserve (HRRcorrCR ). Compared to pre-intervention, HRRcorrCR was significantly increased during the 1st and 2nd minutes of recovery in the Training + β-blocker group (70·5% and 37·5%, respectively; P<0·05). A significant improvement, lasting from the 1st to the 4th minute of recovery, was also observed in the Training group (47%, 50%, 25% and 8·7%, respectively; P<0·05). In contrast, the β-blocker group showed a reduction in HRRcorrCR during the 2nd and 3rd minutes of recovery (-21·2% and -16·3%, respectively; P<0·05). In addition, interventions involving ET (Training + βb, Training) were significantly more effective in patients with a pre-intervention HRR ≤ 12 bpm than for patients with HRR > 12 bpm. Combination of β-blocker therapy with ET does not compromise the effect of training and instead promotes HRR and aerobic capacity improvement. In addition, this combination is particularly beneficial for individuals presenting with a more compromised HRR. However, chronic administration of β-blocker therapy alone did not promote improvement in HRR or aerobic capacity.

  3. Otilonium: a potent blocker of neuronal nicotinic ACh receptors in bovine chromaffin cells.

    PubMed Central

    Gandía, L.; Villarroya, M.; Lara, B.; Olmos, V.; Gilabert, J. A.; López, M. G.; Martínez-Sierra, R.; Borges, R.; García, A. G.

    1996-01-01

    1. Otilonium, a clinically useful spasmolytic, behaves as a potent blocker of neuronal nicotinic acetylcholine receptors (AChR) as well as a mild wide-spectrum Ca2+ channel blocker in bovine adrenal chromaffin cells. 2. 45Ca2+ uptake into chromaffin cells stimulated with high K+ (70 mM, 1 min) was blocked by otilonium with an IC50 of 7.6 microM. The drug inhibited the 45Ca2+ uptake stimulated by the nicotinic AChR agonist, dimethylphenylpiperazinium (DMPP) with a 79 fold higher potency (IC50 = 0.096 microM). 3. Whole-cell Ba2+ currents (IBa) through Ca2+ channels of voltage-clamped chromaffin cells were blocked by otilonium with an IC50 of 6.4 microM, very close to that of K(+)-evoked 45Ca2+ uptake. Blockade developed in 10-20 s, almost as a single step and was rapidly and almost fully reversible. 4. Whole-cell nicotinic AChR-mediated currents (250 ms pulses of 100 microM DMPP) applied at 30 s intervals were blocked by otilonium in a concentration-dependent manner, showing an IC50 of 0.36 microM. Blockade was induced in a step-wise manner. Wash out of otilonium allowed a slow recovery of the current, also in discrete steps. 5. In experiments with recordings in the same cells of whole-cell IDMPP, Na+ currents (INa) and Ca2+ currents (ICa), 1 microM otilonium blocked 87% IDMPP, 7% INa and 13% ICa. 6. Otilonium inhibited the K(+)-evoked catecholamine secretory response of superfused bovine chromaffin cells with an IC50 of 10 microM, very close to the IC50 for blockade of K(+)-induced 45Ca2+ uptake and IBa. 7. Otilonium inhibited the secretory responses induced by 10 s pulses of 50 microM DMPP with an IC50 of 7.4 nM. Hexamethonium blocked the DMPP-evoked responses with an IC50 of 29.8 microM, 4,000 fold higher than that of otilonium. 8. In conclusion, otilonium is a potent blocker of nicotinic AChR-mediated responses. The drugs also blocked various subtypes of neuronal voltage-dependent Ca2+ channels at a considerably lower potency. Na+ channels were unaffected by

  4. New RO TFC Membranes by Interfacial Polymerization in n-Dodecane with Various co-Solvents

    PubMed Central

    Al-Hobaib, Abdullah Sulaiman; Al-Suhybani, Mohammed Sulaiman; Al-Sheetan, Khalid Mohammed; Mousa, Hasan; Shaik, Mohammed Rafi

    2016-01-01

    The objective of this research is to prepare and characterize a new and highly efficient polyamide TFC RO membrane by interfacial polymerization in dodecane solvent mixed with co-solvents. Three co-solvents were tested namely; acetone, ethyl acetate, and diethyl ether of concentration of 0.5, 1, 2, 3, and 5 wt %. The modified membranes were characterized by SEM, EDX, AFM and contact angle techniques. The results showed that addition of co-solvent results in a decrease in the roughness, pore size and thickness of the produced membranes. However, as the concentration of the co-solvent increases the pore size of the membranes gets larger. Among the three co-solvents tested, acetone was found to result in membranes with the largest pore size and contact angle followed by diethyl ether then ethyl acetate. Measured contact angle increases as the concentration of the co-solvent increases reaching a constant value except for ethyl acetate where it was found to drop. Investigating flux and salt rejection by the formulated membranes showed that higher flux was attained when acetone was used as a co-solvent followed by diethyl ether then ethyl acetate. However, the highest salt rejection was achieved with diethyl ether. PMID:27136591

  5. AST/RO Observations of CO (J=7-6) Emission in NGC 6334

    NASA Astrophysics Data System (ADS)

    Kim, S.; Lane, A. P.; Stark, A. A.; Martin, C. L.; Narayanan, D.; Yan, M.

    2002-05-01

    We present maps of the massive, southern star-forming region NGC6334 in the CO (J=7-6), CO (J=4-3), and 809 GHz [CI] transitions. These lines were observed with the Antarctic Submillimeter Telescope and Remote Observatory (AST/RO) located at Amundsen-Scott South Pole Station. We find two high-excitation CO components on either side of the X-ray emission peak mapped with ASCA (Sekimoto et al. 2000). Our Large Velocity Gradient (LVG) excitation analysis of the line intensity ratios indicates that the photon-dominated regions in NGC6334 have densities of n(H2) ~ 10(3.9-4.2) cm-3 and kinetic temperatures of T{ k} ~ 25-55 K. With these physical parameters in conjunction with our previously observed 492 GHz [CI] line map, we will discuss a thermal chemical photodissociation model of gas clouds around star forming sites in NGC 6334. This research was supported by the National Science Foundation under a cooperative agreement with the Center for Astrophysical Research in Antarctica (CARA), grant NSF OPP 89-20223. CARA is a National Science Foundation Science and Technology Center.

  6. New RO TFC Membranes by Interfacial Polymerization in n-Dodecane with Various co-Solvents.

    PubMed

    Al-Hobaib, Abdullah Sulaiman; Al-Suhybani, Mohammed Sulaiman; Al-Sheetan, Khalid Mohammed; Mousa, Hasan; Shaik, Mohammed Rafi

    2016-04-29

    The objective of this research is to prepare and characterize a new and highly efficient polyamide TFC RO membrane by interfacial polymerization in dodecane solvent mixed with co-solvents. Three co-solvents were tested namely; acetone, ethyl acetate, and diethyl ether of concentration of 0.5, 1, 2, 3, and 5 wt %. The modified membranes were characterized by SEM, EDX, AFM and contact angle techniques. The results showed that addition of co-solvent results in a decrease in the roughness, pore size and thickness of the produced membranes. However, as the concentration of the co-solvent increases the pore size of the membranes gets larger. Among the three co-solvents tested, acetone was found to result in membranes with the largest pore size and contact angle followed by diethyl ether then ethyl acetate. Measured contact angle increases as the concentration of the co-solvent increases reaching a constant value except for ethyl acetate where it was found to drop. Investigating flux and salt rejection by the formulated membranes showed that higher flux was attained when acetone was used as a co-solvent followed by diethyl ether then ethyl acetate. However, the highest salt rejection was achieved with diethyl ether.

  7. The ro-vibrational `conveyor belt' for all-optical lasing during laser filamentation in Nitrogen

    NASA Astrophysics Data System (ADS)

    Ivanov, Misha; Richter, Maria; Morales, Felipe; Smirnova, Olga

    2016-05-01

    Inducing and controlling lasing in the open air is an intriguing challenge. Recent experiments on laser filamentation in the air have demonstrated generation of population inversion and lasing on the 391 nm line in the nitrogen ion, which corresponds to the transition between its second excited B2Σu+ and the ground X2Σg+ electronic states. Importantly, lasing at this transition appears to be a very general effect, arising during filamentation of virtually any incident radiation, from visible to mid-infrared. We analyze the possible mechanisms that can be responsible for the generation of the population inversion between the B2Σu+ and X2Σg+ states of N2+,focusing on the interplay between tunnel ionization of neutral nitrogen to different electronic states, ultrafast laser driven electronic excitations in the ion, molecular vibrations, laser induced alignment and rotations. We show how the strong laser field creates a ro-vibrational `conveyor belt' carrying the population away from the ground electronic state X2Σg+ and enabling population inversion in B2Σu+ . We show that this mechanism is robust with respect to the incident laser wavelength, and analyze its optimization with respect to the fundamental wavelength and pulse duration.

  8. Thermal maturity patterns in New York State using CAI and %Ro

    USGS Publications Warehouse

    Weary, D.J.; Ryder, R.T.; Nyahay, R.E.

    2001-01-01

    New conodont alteration index (CAI) and vitrinite reflectance (%Ro) data collected from drill holes in the Appalachian basin of New York State allow refinement of thermal maturity maps for Ordovician and Devonian rocks. CAI isotherms on the new maps show a pattern that approximates that published by Harris et al. (1978) in eastern and western New York, but it differs in central New York, where the isotherms are shifted markedly westward by more than 100 km and are more tightly grouped. This close grouping of isograds reflects a steeper thermal gradient than previously noted by Harris et al. (1978) and agrees closely with the abrupt west-to-east increase in thermal maturity across New York noted by Johnsson (1986). These data show, in concordance with previous studies, that thermal maturity levels in these rocks are higher than can be explained by simple burial heating beneath the present thickness of overburden. The Ordovician and Devonian rocks of the Appalachian Basin in New York must have been buried by very thick post-Devonian sediments (4-6 km suggested by Sarwar and Friedman 1995) or were exposed to a higher-than-normal geothermal flux caused by crustal extension, or a combination of the two.

  9. Synergies of CoRoT asteroseismology and APOGEE spectroscopy -- Applications to Galactic Archaeology

    NASA Astrophysics Data System (ADS)

    Anders, Friedrich; Chiappini, Cristina; Silva Rodrigues, Thaíse; Miglio, Andrea; Montalbàn, Josefina; Mosser, Benoit; Girardi, Leo; Valentini, Marica; Steinmetz, Matthias

    2015-08-01

    We present the first coherent dataset of 678 solar-like oscillating CoRoT red-giant stars located in two fields of the Galactic disc which have been followed up spectroscopically by the Apache Point Observatory Galactic Evolution Experiment (APOGEE).For the first time in a homogeneous analysis, ages and chemical abundance patterns of field stars have been measured over a largeradial range of the Milky Way's disc (4.5 kpc

  10. Detecting planets in Kepler lightcurves using methods developed for CoRoT.

    NASA Astrophysics Data System (ADS)

    Grziwa, S.; Korth, J.; Pätzold, M.

    2011-10-01

    Launched in March 2009, Kepler is the second space telescope dedicated to the search for extrasolar planets. NASA released 150.000 lightcurves to the public in 2010 and announced that Kepler has found 1.235 candidates. The Rhenish Institute for Environmental Research (RIU-PF) is one of the detection groups from the CoRoT space mission. RIU-PF developed the software package EXOTRANS for the detection of transits in stellar lightcurves. EXOTRANS is designed for the fast automated processing of huge amounts of data and was easily adapted to the analysis of Kepler lightcurves. The use of different techniques and philosophies helps to find more candidates and to rule out others. We present the analysis of the Kepler lightcurves with EXOTRANS. Results of our filter (trend, harmonic) and detection (dcBLS) techniques are compared with the techniques used by Kepler (PDC, TPS). The different approaches to rule out false positives are discussed and additional candidates found by EXOTRANS are presented.

  11. A European Roadmap for Research in Astrobiology - The AstRoMap Roadmap

    NASA Astrophysics Data System (ADS)

    Gómez, F.; Walter, N.; Horneck, G.; Muller, C.; Rettberg, P.; Capria, M.; Palomba, E.

    2015-10-01

    AstRoMap (Astrobiology Road Mapping activity-www.astromap-eu.org) is a collaborative project which will provide the European Planetary Science Community with a road map in astrobiology. The goals of the project have been: (i) to pose big questions related to astrobiology; and (ii) the identification of experiments, new technology and/or those space missions to be developed in future programs and which could answer those big questions. This collaborative infrastructure includes the organization of expert panels and international workshops in order to discuss about those big questions and the science objectives by the community to be addressed. The main deliverable will be a Roadmap document. The project is steered by a consortium of six European and national research institutes and associations: -­- Centro de Astrobiologica (INTACSIC), Spain -­- European Science Foundation, France -­- Association pour un Réseau Européen d'Exo/Astrobiology (EANA), France -­- B-USOC, Belgium -­- Deutsches Zentrum für Luft- und Raumfahrt (DLR), Germany -­- National Institute for Astrophysics (INAF), ItalyOrigin and evolution of planetary systems -­- Origin of organic compounds in space -­- Rock-water-carbon interactions, organic synthesis, and steps to life -­- Life and habitability on Earth and in Space -­- -­- Biosignatures as facilitating life detection The key topics will focus on a limited number of strategic scientific objectives to be addressed in the next 20 years by European astrobiologists, and suggest research activities for future development.

  12. Toward black-box-type full- and reduced-dimensional variational (ro)vibrational computations

    NASA Astrophysics Data System (ADS)

    Mátyus, Edit; Czakó, Gábor; Császár, Attila G.

    2009-04-01

    A black-box-type algorithm is presented for the variational computation of energy levels and wave functions using a (ro)vibrational Hamiltonian expressed in an arbitrarily chosen body-fixed frame and in any set of internal coordinates of full or reduced vibrational dimensionality. To make the required numerical work feasible, matrix representation of the operators is constructed using a discrete variable representation (DVR). The favorable properties of DVR are exploited in the straightforward and numerically exact inclusion of any representation of the potential and the kinetic energy including the G matrix and the extrapotential term. In this algorithm there is no need for an a priori analytic derivation of the kinetic energy operator, as all of its matrix elements at each grid point are computed numerically either in a full- or a reduced-dimensional model. Due to the simple and straightforward definition of reduced-dimensional models within this approach, a fully anharmonic variational treatment of large, otherwise intractable molecular systems becomes available. In the computer code based on the above algorithm, there is no inherent limitation for the maximally coupled number of vibrational degrees of freedom. However, in practice current personal computers allow the treatment of about nine fully coupled vibrational dimensions. Computation of vibrational band origins of full and reduced dimensions showing the advantages and limitations of the algorithm and the related computer code are presented for the water, ammonia, and methane molecules.

  13. A FFT Method for the Quasiclassical Selection of Initial Ro-Vibrational States of Triatomic Molecules

    NASA Technical Reports Server (NTRS)

    Eaker, Charles W.; Schwenke, David W.; Langhoff, Stephen R. (Technical Monitor)

    1995-01-01

    This paper describes the use of an exact fast Fourier transform (FFT) method to prepare specified vibrational-rotational states of triatomic molecules. The method determines the Fourier coefficients needed to describe the coordinates and momenta of a vibrating-rotating triatomic molecule. Once the Fourier coefficients of a particular state are determined, it is possible to easily generate as many random sets of initial cartesian coordinates and momenta as desired. All the members of each set will correspond to the particular vibrational-rotational state selected. For example, in the case of the ground vibrational state of a non-rotating water molecule, the calculated actions of 100 sets of initial conditions produced actions within 0.001 h(bar) of the specified quantization values and energies within 5 cm(sup -1) of the semiclassical eigenvalue. The numerical procedure is straightforward for states in which all the fundamental frequencies are independent. However for states for which the fundamental frequencies become commensurate (resonance states), there are additional complications. In these cases it is necessary to determine a new set of "fundamental" frequencies and to modify the quantization conditions. Once these adjustments are made, good results are obtained for resonance states. The major problems are in labelling the large number of Fourier coefficients and the presence of regions of chaotic motion. Results are presented for the vibrational states of H2O and HCN and the ro-vibrational states of H2O.

  14. KIC 7582608: a new Kepler roAp star with frequency variability

    NASA Astrophysics Data System (ADS)

    Holdsworth, D. L.; Smalley, B.; Kurtz, D. W.; Southworth, J.; Cunha, M. S.; Clubb, K. I.

    2015-09-01

    We analyse the fifth roAp star reported in the Kepler field, KIC 7582608, discovered with the SuperWASP project. The object shows a high frequency pulsation at 181.7324d-1 (P = 7.9 min) with an amplitude of 1.45 mmag, and low frequency rotational modulation corresponding to a period of 20.4339 d. Spectral analysis confirms the Ap nature of the target, with characteristic lines of rare earth elements present. From our spectral observations we derive a lower limit on the mean magnetic field modulus of =3.05 ± 0.23 kG. Long Cadence Kepler observations show a frequency quintuplet split by the rotational period of the star, typical for an oblique pulsator. We suggest the star is a quadrupole pulsator with a geometry such that i ~ 66° and β ~ 33°. We detect frequency variations of the pulsation in both the WASP and Kepler data sets on many time scales. Linear, non-adiabatic stability modelling allows us to constrain a region on the HR diagram where the pulsations are unstable, an area consistent with observations.

  15. RoPEUS: A New Robust Algorithm for Static Positioning in Ultrasonic Systems

    PubMed Central

    Prieto, José Carlos; Croux, Christophe; Jiménez, Antonio Ramón

    2009-01-01

    A well known problem for precise positioning in real environments is the presence of outliers in the measurement sample. Its importance is even bigger in ultrasound based systems since this technology needs a direct line of sight between emitters and receivers. Standard techniques for outlier detection in range based systems do not usually employ robust algorithms, failing when multiple outliers are present. The direct application of standard robust regression algorithms fails in static positioning (where only the current measurement sample is considered) in real ultrasound based systems mainly due to the limited number of measurements and the geometry effects. This paper presents a new robust algorithm, called RoPEUS, based on MM estimation, that follows a typical two-step strategy: 1) a high breakdown point algorithm to obtain a clean sample, and 2) a refinement algorithm to increase the accuracy of the solution. The main modifications proposed to the standard MM robust algorithm are a built in check of partial solutions in the first step (rejecting bad geometries) and the off-line calculation of the scale of the measurements. The algorithm is tested with real samples obtained with the 3D-LOCUS ultrasound localization system in an ideal environment without obstacles. These measurements are corrupted with typical outlying patterns to numerically evaluate the algorithm performance with respect to the standard parity space algorithm. The algorithm proves to be robust under single or multiple outliers, providing similar accuracy figures in all cases. PMID:22408522

  16. A Study of Ro-vibrational OH Emission from Herbig Ae/Be Stars

    NASA Astrophysics Data System (ADS)

    Brittain, Sean D.; Najita, Joan R.; Carr, John S.; Ádámkovics, Máté; Reynolds, Nickalas

    2016-10-01

    We present a study of ro-vibrational OH and CO emission from 21 disks around Herbig Ae/Be stars. We find that the OH and CO luminosities are proportional over a wide range of stellar ultraviolet luminosities. The OH and CO line profiles are also similar, indicating that they arise from roughly the same radial region of the disk. The CO and OH emission are both correlated with the far-ultraviolet luminosity of the stars, while the polycyclic aromatic hydrocarbon (PAH) luminosity is correlated with the longer wavelength ultraviolet luminosity of the stars. Although disk flaring affects the PAH luminosity, it is not a factor in the luminosity of the OH and CO emission. These properties are consistent with models of UV-irradiated disk atmospheres. We also find that the transition disks in our sample, which have large optically thin inner regions, have lower OH and CO luminosities than non-transition disk sources with similar ultraviolet luminosities. This result, while tentative given the small sample size, is consistent with the interpretation that transition disks lack a gaseous disk close to the star.

  17. Pole STAR: An 810 GHz Array Receiver for AST/RO

    NASA Astrophysics Data System (ADS)

    Groppi, C.; Walker, C.; Hungerford, A.; Kulesa, C.; Jacobs, K.; Kooi, J.

    We are constructing a 4-channel receiver at 810 GHz for use on the Antarctic Submillimeter Telescope and Remote Observatory located at the South Pole (AST/RO). The 810 GHz mixers and junctions for the array are being provided by KOSMA. The mixers are housed in a hybrid cryostat located in a warm Coude' room just below the 1.7 m telescope. A pair of parabolic mirrors will be used to reimage the telescope's focal plane through a Martin-Puplett LO diplexer onto a 2x2 array of lenses. The lenses efficiently couple the telescope to each mixer's corrugated feedhorn. The SIS junction is matched to the waveguide by an on-chip tuner and a single, fixed backshort. The 1-2 GHz IF output of each mixer is fed into a low-noise, balanced, HEMT amplifier. All bias signals are provided by a computer controlled bias system, which is fully optically isolated from the control computer. This system provides automated adjustment and optimization of bias levels with web based monitoring. The IF outputs are further processed at room temperature and fed into a 4-channel array AOS constructed by KOSMA. A Gunn oscillator (J. Carlstrom) and multiplier (Erickson & Narayanan) are used to drive the array.

  18. The changing phases of extrasolar planet CoRoT-1b.

    PubMed

    Snellen, Ignas A G; de Mooij, Ernst J W; Albrecht, Simon

    2009-05-28

    Hot Jupiters are a class of extrasolar planet that orbit their parent stars at very short distances. They are expected to be tidally locked, which can lead to a large temperature difference between their daysides and nightsides. Infrared observations of eclipsing systems have yielded dayside temperatures for a number of transiting planets. The day-night contrast of the transiting extrasolar planet HD 189733b was 'mapped' using infrared observations. It is expected that the contrast between the daysides and nightsides of hot Jupiters is much higher at visual wavelengths, shorter than that of the peak emission, and could be further enhanced by reflected stellar light. Here we report the analysis of optical photometric data obtained over 36 planetary orbits of the transiting hot Jupiter CoRoT-1b. The data are consistent with the nightside hemisphere of the planet being entirely black, with the dayside flux dominating the optical phase curve. This means that at optical wavelengths the planet's phase variation is just as we see it for the interior planets in the Solar System. The data allow for only a small fraction of reflected light, corresponding to a geometric albedo of <0.20.

  19. Massive spectroscopic analysis of the stellar populations in three of the CoRoT/Exoplanet fields

    NASA Astrophysics Data System (ADS)

    Gazzano, J.-C.; Deleuil, M.; de Laverny, P.; Kordopatis, G.; Moutou, C.; Recio-Blanco, A.; Bijaoui, A.; Bouchy, F.; Ordenovic, C