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Sample records for blocker ro 40-5967

  1. The structurally novel Ca sup 2+ channel blocker Ro 40-5967, which binds to the ( sup 3 H) desmethoxyverapamil receptor, is devoid of the negative inotropic effects of verapamil in normal and failing rat hearts

    SciTech Connect

    Clozel, J.P.; Veniant, M.; Osterrieder, W. )

    1990-06-01

    Ro 40-5967 is a structurally novel Ca{sup 2+} channel blocker that binds to the verapamil-type receptor of cardiac membranes but that has been shown in isolated guinea-pig hearts to be about ten times less potent a negative inotropic agent than verapamil. The goals of the present study were to confirm these findings in vitro in isolated perfused rat hearts as well as in vivo in conscious rats and to compare Ro 40-5967 to verapamil. The effects of Ro 40-5967 and verapamil were tested not only in normal rats, but also in rats with heart failure induced by chronic myocardial infarction. In isolated Langendorff hearts (without heart failure), no decrease of contractility was observed with Ro 40-5967 up to complete AV block. In contrast, verapamil decreased contractility with an IC50 of 100 nM. In isolated, electrically stimulated rat papillary muscles, the IC50 values for the decrease of contractile force were 15,000 and 440 nM for Ro 40-5967 and verapamil, respectively. In vivo, Ro 40-5967 did not decrease left ventricular contractility (as assessed by changes of dP/dt max +) in rats without and with heart failure. In contrast, verapamil was markedly negative inotropic in both conditions.

  2. 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

  3. 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 ...

  4. Beta Blockers

    MedlinePlus

    ... Frishman WH, et al. β-Adrenergic blockers. The Journal of Clinical Hypertension. 2011;13:649. Kaplan NM, et al. Treatment of hypertension: Drug therapy. In: Kaplan's Clinical Hypertension. 11th ed. Philadelphia, ...

  5. H2 blockers

    MedlinePlus

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

  6. Calcium Channel Blockers

    MedlinePlus

    ... calcium channel blockers interact with grapefruit products. References Kaplan NM, et al. Treatment of hypertension: Drug therapy. In: Kaplan's Clinical Hypertension. 11th ed. Philadelphia, Pa.: Wolters Kluwer ...

  7. 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)

  8. 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.

  9. Angiotensin II Receptor Blockers

    MedlinePlus

    ... side effects include: Dizziness Elevated blood potassium level (hyperkalemia) Localized swelling of tissues (angioedema) There have been ... 31, 2016. Townsend RR. Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. http://www.uptodate. ...

  10. 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...

  11. 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

  12. Pharmacogenetics of β-Blockers

    PubMed Central

    Shin, Jaekyu; Johnson, Julie A.

    2009-01-01

    β-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 β-blocker are variable among patients. Results of numerous studies now suggest that genetic polymorphisms may contribute to variability in responses to β-blockers. This review summarizes the pharmacogenetic data for β-blockers in patients with various diseases and discusses the potential implications of β-blocker pharmacogenetics in clinical practice. PMID:17542770

  13. 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.

  14. 46 CFR 111.105-40 - Additional requirements for RO/RO vessels.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Hazardous Locations § 111.105-40 Additional requirements for 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 4-8-4...

  15. 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.

  16. How Do Beta Blocker Drugs Affect Exercise?

    MedlinePlus

    ... Blockers and Physical Activity Interestingly, beta blockers and exercise have some similar effects on the body. “Your blood pressure and heart rate are similarly changed by exercise and beta blockers,” said Gerald Fletcher, M.D., ...

  17. Beta-blockers for hypertension

    PubMed Central

    Wiysonge, Charles S; Bradley, Hazel A; Volmink, Jimmy; Mayosi, Bongani M; Opie, Lionel H

    2017-01-01

    Background Beta-blockers refer to a mixed group of drugs with diverse pharmacodynamic and pharmacokinetic properties. They have shown long-term beneficial effects on mortality and cardiovascular disease (CVD) when used in people with heart failure or acute myocardial infarction. Beta-blockers were thought to have similar beneficial effects when used as first-line therapy for hypertension. However, the benefit of beta-blockers as first-line therapy for hypertension without compelling indications is controversial. This review is an update of a Cochrane Review initially published in 2007 and updated in 2012. Objectives To assess the effects of beta-blockers on morbidity and mortality endpoints in adults with hypertension. Search methods The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to June 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 6), MEDLINE (from 1946), Embase (from 1974), and ClinicalTrials.gov. We checked reference lists of relevant reviews, and reference lists of studies potentially eligible for inclusion in this review, and also searched the the World Health Organization International Clinical Trials Registry Platform on 06 July 2015. Selection criteria Randomised controlled trials (RCTs) of at least one year of duration, which assessed the effects of beta-blockers compared to placebo or other drugs, as first-line therapy for hypertension, on mortality and morbidity in adults. Data collection and analysis We selected studies and extracted data in duplicate, resolving discrepancies by consensus. We expressed study results as risk ratios (RR) with 95% confidence intervals (CI) and conducted fixed-effect or random-effects meta-analyses, as appropriate. We also used GRADE to assess the certainty of the evidence. GRADE classifies the certainty of evidence as high (if we are confident that the true effect lies

  18. RoKSN, a floral repressor, forms protein complexes with RoFD and RoFT to regulate vegetative and reproductive development in rose.

    PubMed

    Randoux, Marie; Davière, Jean-Michel; Jeauffre, Julien; Thouroude, Tatiana; Pierre, Sandrine; Toualbia, Youness; Perrotte, Justine; Reynoird, Jean-Paul; Jammes, Marie-José; Hibrand-Saint Oyant, Laurence; Foucher, Fabrice

    2014-04-01

    FT/TFL1 family members have been known to be involved in the development and flowering in plants. In rose, RoKSN, a TFL1 homologue, is a key regulator of flowering, whose absence causes continuous flowering. Our objectives are to functionally validate RoKSN and to explore its mode of action in rose. We complemented Arabidopsis tfl1 mutants and ectopically expressed RoKSN in a continuous-flowering (CF) rose. Using different protein interaction techniques, we studied RoKSN interactions with RoFD and RoFT and possible competition. In Arabidopsis, RoKSN complemented the tfl1 mutant by rescuing late flowering and indeterminate growth. In CF roses, the ectopic expression of RoKSN led to the absence of flowering. Different branching patterns were observed and some transgenic plants had an increased number of leaflets per leaf. In these transgenic roses, floral activator transcripts decreased. Furthermore, RoKSN was able to interact both with RoFD and the floral activator, RoFT. Protein interaction experiments revealed that RoKSN and RoFT could compete with RoFD for repression and activation of blooming, respectively. We conclude that RoKSN is a floral repressor and is also involved in the vegetative development of rose. RoKSN forms a complex with RoFD and could compete with RoFT for repression of flowering. © 2013 INRA. New Phytologist © 2013 New Phytologist Trust.

  19. 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

  20. 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).

  1. 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) ...

  2. 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.

  3. AST/RO: Submillimeter Astronomy

    NASA Astrophysics Data System (ADS)

    Lane, Adair P.

    1998-05-01

    Submillimeter astronomy can only be pursued from extremely cold and dry sites, where the atmosphere contains a minimal amount of precipitable water. Water vapor measurements at the South Pole, in conjunction with submillimeter skydip measurements, show that the Antarctic Plateau provides the best submillimeter observing conditions on Earth. The 1.7-m diameter telescope of the Antarctic Submillimeter Telescope and Remote Observatory (AST/RO) has been exploiting these conditions for the past 3 years to study atomic carbon (CI) and J=4-3 CO emission in a broad range of physical environments in the Milky Way and Large Magellanic Cloud. We have found from samples of [CI] emission throughout the plane of the Milky Way that [CI] arises primarily in the photodissociated skins of molecular clouds. A detection of the 492 GHz [CI] line in absorption allows the derivation of lower limits for the [CI] column density in cold foreground material in the Galactic disk. Comparison of the absorption data with the low-resolution COBE FIRAS [CI] emission line survey in the Galactic plane indicates that a substantial fraction of the atomic carbon in the interstellar medium has very low excitation and thus may be difficult to detect in emission. Observations of [CI] in the LMC indicate that photodissociation regions are enhanced in this low metallicity system. 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.

  4. β-Blocker pharmacogenetics in heart failure

    PubMed Central

    Shin, Jaekyu

    2009-01-01

    β-Blockers (metoprolol, bisoprolol, and carvedilol) are a cornerstone of heart failure (HF) treatment. However, it is well recognized that responses to a β-blocker are variable among patients with HF. Numerous studies now suggest that genetic polymorphisms may contribute to variability in responses to a β-blocker, including left ventricular ejection fraction improvement, survival, and hospitalization due to HF exacerbation. This review summarizes the pharmacogenetic data for β-blockers in patients with HF and discusses the potential implications of β-blocker pharmacogenetics for HF patients. PMID:18437562

  5. Ro52, Ro60 and La IgG autoantibody levels and Ro52 IgG subclass profiles longitudinally throughout pregnancy in congenital heart block risk pregnancies.

    PubMed

    Strandberg, L; Salomonsson, S; Bremme, K; Sonesson, S- E; Wahren-Herlenius, M

    2006-01-01

    Congenital heart block occurs in fetuses of Ro/SSA and La/SSB positive women. To investigate the stability of maternal autoantibody levels during pregnancy, we followed Ro52, Ro60 and La autoantibody IgG level variation and Ro52 subclass profiles longitudinally in selected congenital heart block risk pregnancies. Serum samples were obtained from 12 Ro/La positive women diagnosed with a systemic rheumatic disease and followed on average 60 months (range two to 84) which included 13 pregnancies. Seven children were affected by neonatal lupus, whereof four developed complete congenital heart block. Serum was also collected from the babies at birth. Ro52, Ro60 and La IgG as well as subclass antibodies were analysed by ELISA using recombinant antigens. Six Ro/La negative rheumatic patients were included as controls for antibody levels during pregnancy. Ro52, Ro60 and La IgG levels decreased progressively from early to late pregnancy, significantly for Ro52 and Ro60 (P < 0.01). No peaks or persistent elevation of antibody levels were noted in any of the CHB risk pregnancies. Ro52 IgG1 antibody levels were significantly higher than IgG2 (P < 0.01), IgG3 (P < 0.01) and IgG4 (P < 0.05) levels in the mothers during pregnancy. Ro52 IgG1 and IgG4 levels decreased significantly from early to late pregnancy (P = 0.02), while levels of IgG2 and IgG3 were low and the decrease was not significant. All IgG subclasses were transferred to the children. We conclude that maternal levels of Ro52, Ro60 and La autoantibodies tended rather to decrease than to increase during pregnancy.

  6. 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

  7. 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%.

  8. [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.

  9. 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.

  10. Azilsartan: Novel Angiotensin Receptor Blocker.

    PubMed

    Dargad, Ramesh R; Parekh, Jai D; Dargad, Rohit R; Kukrety, Shweta

    2016-03-01

    To describe the efficacy and safety profile of the new angiotensin receptor blocker (ARB), "Azilsartan Medoxomil", reviewing data available from both clinical and pre-clinical studies. We completed a review of the English literature from PubMed using the keywords- azilsartan medoxomil, angiotensin receptor blockers (ARB), angiotensin converting enzyme inhibitors (ACEi) and hypertension. Many clinical trials have been conducted comparing the efficacy of azilsartan with other ARB's and also with the ACEi ramipril. The trials have shown azilsartan to be more effective in reducing the mean 24-hour systolic blood pressure compared to its counterparts. Azilsartan is a recently approved ARB and appears to be more efficacious in reducing blood pressure (BP) than the other ARBs with a similar safety and tolerability profile. Azilsartan's very high affinity to and slow dissociation from the angiotensin 1 receptor (AT1R) along with its inverse agonistic properties make it a very good candidate for clinical effects beyond simple BP control, potentially counteracting cardiac hypertrophy, cardiac fibrosis and insulin resistance, together with improved reno-protection and atherosclerotic plaque stabilization.

  11. 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

  12. Cytoplasmic relocation of Daxx induced by Ro52 and FLASH

    PubMed Central

    Tanaka, Makoto; Kamitani, Tetsu

    2010-01-01

    The RING-finger protein Ro52/TRIM21 is known to be an autoantigen and is recognized by anti-Ro/SSA antibodies, which are commonly found in patients with Sjögren's syndrome and systemic lupus erythematosus. We recently showed that Ro52 is an E3 ubiquitin ligase and localizes to cytoplasmic bodies that are highly motile along the microtubule network. To expand our knowledge of Ro52, we searched partners co-operating with Ro52. We performed a yeast two-hybrid screening of a human brain cDNA library with Ro52 as bait. This screening identified several genes encoding Ro52-interacting proteins, including the apoptosis-related proteins, Daxx and FLASH. Further yeast two-hybrid assays revealed that Daxx binds to the B30.2 domain of Ro52 and that FLASH binds to coiled-coil domains of Ro52 through its death-effector domain-recruiting domain. These results suggest that Ro52, Daxx, and FLASH form heteromeric protein complexes. Indeed, this was supported by results of immunoprecipitation experiments in which we found that Daxx is co-immunoprecipitated with Ro52 in the presence of overexpressed FLASH. Importantly, our fluorescence microscopy revealed that, although Daxx is predominantly located in the nucleus, overexpression of both Ro52 and FLASH leads to relocation of Daxx into the cytoplasm. Thus, Ro52 seems to co-operate with FLASH to induce cytoplasmic localization of Daxx in cells. PMID:20697732

  13. TNF blocker drugs modulate human TNF-α-converting enzyme pro-domain shedding induced by autoantibodies.

    PubMed

    Sisto, Margherita; Lisi, Sabrina; Lofrumento, Dario D; Caprio, Simone; Mitolo, Vincenzo; D'Amore, Massimo

    2010-11-01

    Novel biologic therapies targeted against specific components of the immune system, including blockade of TNF-α have revolutionized therapeutic approaches to inflammatory conditions and systemic inhibitors of TNF-α have been approved for the treatment of a wide variety of autoimmune diseases. No studies aimed to elucidate the effects of anti-TNF-α blockers on tumour necrosis factor-α convertase (TACE) expression and activation have yet been published. TACE is the principal protease involved in the activation of pro-TNF-α and is a target for anti-TNF-α therapy. Here we focused on regulation of TACE expression in human salivary gland epithelial cells (SGEC) treated by anti-Ro/SSA autoantibodies (autoAbs), characterizing primary Sjögren's syndrome and on the effect of anti-Ro/SSA autoAbs on TACE pro-domain shedding and activation. To test the hypothesis that anti-TNF-α blocker drugs affect TACE expression, we used Adalimumab and Etanercept to block TNF-α and evaluate the effects of these biological agents on post-translational regulation of TACE. Anti-Ro/SSA autoAbs determines TACE pro-domain shedding suggesting that TACE activity is necessary for the release of TNF-α observed in anti-Ro/SSA autoAbs-stimulated cells. The comparative efficacy analysis of the regulation of TACE activity by Adalimumab and Etanercept revealed that Adalimumab appear to be significantly more efficacious than Etanercept in preventing TACE activation caused by anti-Ro/SSA autoAbs. It is intriguing to consider that regulation of TACE may participate in the pathogenic role of autoantibodies and the modulation of TACE expression by TNF-α antagonists might contribute to the beneficial effect of these drugs in inflammatory and autoimmune diseases. Copyright © 2009 Elsevier GmbH. All rights reserved.

  14. 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

  15. 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.

  16. Use of neuromuscular blockers in Brazil.

    PubMed

    Locks, Giovani de Figueiredo; Cavalcanti, Ismar Lima; Duarte, Nadia Maria Conceição; da Cunha, Rafael Martins; de Almeida, Maria Cristina Simões

    2015-01-01

    The objective of this study was to evaluate how Brazilian anesthesiologists are using neuromuscular blockers, focusing on how they establish the diagnosis of postoperative residual curarization and the incidence of complications associated with the use of neuromuscular blockers. A questionnaire was sent to anesthesiologists inviting them to participate in the study. The online data collection remained open from March 2012 to June 2013. During the study period, 1296 responses were collected. Rocuronium, atracurium, and cisatracurium were the main neuromuscular blockers used in cases of elective surgery. Succinylcholine and rocuronium were the main neuromuscular blockers used in cases of emergency surgery. Less than 15% of anesthesiologists reported the frequent use of neuromuscular function monitors. Only 18% of those involved in the study reported that all workplaces have such a monitor. Most respondents reported using only the clinical criteria to assess whether the patient is recovered from the muscle relaxant. Most respondents also reported always using some form of neuromuscular blockade reversal. The major complications attributed to neuromuscular blockers were residual curarization and prolonged blockade. Eighteen anesthesiologists reported death attributed to neuromuscular blockers. Residual or prolonged blockade is possibly recorded as a result of the high rate of using clinical criteria to diagnose whether the patient has recovered or not from motor block and, as a corollary, the poor use of neuromuscular transmission monitors in daily practice.

  17. β1-Adrenoceptor blocker aggravated ventricular arrhythmia.

    PubMed

    Wang, Yan; Patel, Dimpi; Wang, Dao Wu; Yan, Jiang Tao; Hsia, Henry H; Liu, Hao; Zhao, Chun Xia; Zuo, Hou Juan; Wang, Dao Wen

    2013-11-01

    To assess the impact of β1 -adrenoceptor blockers (β1 -blocker) and isoprenaline on the incidence of idiopathic repetitive ventricular arrhythmia that apparently decreases with preprocedural anxiety. From January 2010 to July 2012, six patients were identified who had idiopathic ventricular arrhythmias that apparently decreased (by greater than 90%) with preprocedural anxiety. The number of ectopic ventricular beats per hour (VPH) was calculated from Holter or telemetry monitoring to assess the ectopic burden. The mean VPH of 24 hours from Holter before admission (VPH-m) was used as baseline (100%) for normalization. β1 -Blockers, isoprenaline, and/or aminophylline were administrated successively on the ward and catheter lab to evaluate their effects on the ventricular arrhythmias. Among 97 consecutive patients with idiopathic ventricular arrhythmias, six had reduction in normalized VPHs in the hour before the scheduled procedure time from (104.6 ± 4.6%) to (2.8 ± 1.6%) possibly due to preprocedural anxiety (P < 0.05), then increased to (97.9 ± 9.7%) during β1 -blocker administration (P < 0.05), then quickly reduced to (1.6 ± 1.0%) during subsequent isoprenaline infusion. Repeated β1 -blocker quickly counteracted the inhibitory effect of isoprenaline, and VPHs increased to (120.9 ± 2.4%) from (1.6 ± 1.0%; P < 0.05). Isoprenaline and β1 -blocker showed similar effects on the arrhythmias in catheter lab. In some patients with structurally normal heart and ventricular arrhythmias there is a marked reduction of arrhythmias associated with preprocedural anxiety. These patients exhibit a reproducible sequence of β1 -blocker aggravation and catecholamine inhibition of ventricular arrhythmias, including both repetitive ventricular premature beats and monomorphic ventricular tachycardia. ©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.

  18. 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

  19. 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.

  20. 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

  1. Exoplanet discoveries with the CoRoT space observatory

    NASA Astrophysics Data System (ADS)

    Lammer, H.; Dvorak, R.; Deleuil, M.; Barge, P.; Deeg, H. J.; Moutou, C.; Erikson, A.; Csizmadia, Sz.; Tingley, B.; Bruntt, H.; Havel, M.; Aigrain, S.; Almenara, J. M.; Alonso, R.; Auvergne, M.; Baglin, A.; Barbieri, M.; Benz, W.; Bonomo, A. S.; Bordé, P.; Bouchy, F.; Cabrera, J.; Carone, L.; Carpano, S.; Ciardi, D.; Ferraz-Mello, S.; Fridlund, M.; Gandolfi, D.; Gazzano, J.-C.; Gillon, M.; Gondoin, P.; Guenther, E.; Guillot, T.; den Hartog, R.; Hasiba, J.; Hatzes, A.; Hidas, M.; Hébrard, G.; Jorda, L.; Kabath, P.; Léger, A.; Lister, T.; Llebaria, A.; Lovis, C.; Mayor, M.; Mazeh, T.; Mura, A.; Ollivier, M.; Ottacher, H.; Pätzold, M.; Pepe, F.; Pont, F.; Queloz, D.; Rabus, M.; Rauer, H.; Rouan, D.; Samuel, B.; Schneider, J.; Shporer, A.; Stecklum, B.; Steller, M.; Street, R.; Udry, S.; Weingrill, J.; Wuchterl, G.

    2010-12-01

    The CoRoT space observatory is a project which is led by the French space agency CNES and leading space research institutes in Austria, Brazil, Belgium, Germany and Spain and also the European Space Agency ESA. CoRoT observed since its launch in December 27, 2006 about 100 000 stars for the exoplanet channel, during 150 days uninterrupted high-precision photometry. Since the The CoRoT-team has several exoplanet candidates which are currently analyzed under its study, we report here the discoveries of nine exoplanets which were observed by CoRoT. Discovered exoplanets such as CoRoT-3b populate the brown dwarf desert and close the gap of measured physical properties between usual gas giants and very low mass stars. CoRoT discoveries extended the known range of planet masses down to about 4.8 Earth-masses (CoRoT-7b) and up to 21 Jupiter masses (CoRoT-3b), the radii to about 1.68 × 0.09 R Earth (CoRoT-7b) and up to the most inflated hot Jupiter with 1.49 × 0.09 R Earth found so far (CoRoT-1b), and the transiting exoplanet with the longest period of 95.274 days (CoRoT-9b). Giant exoplanets have been detected at low metallicity, rapidly rotating and active, spotted stars. Two CoRoT planets have host stars with the lowest content of heavy elements known to show a transit hinting towards a different planethost-star-metallicity relation then the one found by radial-velocity search programs. Finally the properties of the CoRoT-7b prove that rocky planets with a density close to Earth exist outside the Solar System. Finally the detection of the secondary transit of CoRoT-1b at a sensitivity level of 10-5 and the very clear detection of the "super-Earth" CoRoT-7b at 3.5 × 10-4 relative flux are promising evidence that the space observatory is being able to detect even smaller exoplanets with the size of the Earth.

  2. [Beta-adrenergic receptor blocker poisoning].

    PubMed

    Reingardiene, Dagmara

    2007-01-01

    Beta-adrenergic receptor blocking drugs are used in the treatment of hypertension, angina, myocardial infarction, cardiac dysrhythmia, cardiomyopathy, migraine headache, thyrotoxicosis, and glaucoma. beta-adrenergic receptor blocking agents are competitive antagonist at beta(1), beta(2), or both types of adrenergic receptors. Overdoses of beta-adrenergic receptor blockers are uncommon, but are associated with significant morbidity and mortality. This review article discusses the properties of beta-adrenergic receptor blockers, presents the doses of these drugs causing toxicity and doses, after ingestion of which, referral to an emergency department is recommended. Clinical presentation of overdose (the cardiovascular, neurologic manifestations, pulmonary and other complications), diagnosis, and treatment (gastrointestinal decontamination; the usage of atropine, phosphodiesterase inhibitors, glucagon, insulin; indications for cardiac pacing, extracorporeal procedures of drug removal, etc.) are analyzed. In addition, this article focuses on clinical course and prognosis of beta-blocker overdose.

  3. Pharmacogenetics of ophthalmic topical β-blockers

    PubMed Central

    Sidjanin, Duska J; McCarty, Catherine A; Patchett, Richard; Smith, Edward; Wilke, Russell A

    2009-01-01

    Glaucoma is the second leading cause of blindness worldwide. The primary glaucoma risk factor is elevated intraocular pressure. Topical β-blockers are affordable and widely used to lower intraocular pressure. Genetic variability has been postulated to contribute to interpersonal differences in efficacy and safety of topical β-blockers. This review summarizes clinically significant polymorphisms that have been identified in the β-adrenergic receptors (ADRB1, ADRB2 and ADRB3). The implications of polymorphisms in CYP2D6 are also discussed. Although the candidate-gene approach has facilitated significant progress in our understanding of the genetic basis of glaucoma treatment response, most drug responses involve a large number of genes, each containing multiple polymorphisms. Genome-wide association studies may yield a more comprehensive set of polymorphisms associated with glaucoma outcomes. An understanding of the genetic mechanisms associated with variability in individual responses to topical β-blockers may advance individualized treatment at a lower cost. PMID:19266054

  4. 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.

  5. 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.

  6. 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...

  7. 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...

  8. 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.

  9. 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…

  10. 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…

  11. 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…

  12. 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.

  13. β-Blocker Continuation After Noncardiac Surgery

    PubMed Central

    Kwon, Steve; Thompson, Rachel; Florence, Michael; Maier, Ronald; McIntyre, Lisa; Rogers, Terry; Farrohki, Ellen; Whiteford, Mark; Flum, David R.

    2014-01-01

    Background Despite limited evidence of effect, β-blocker continuation has become a national quality improvement metric. Objective To determine the effect of β-blocker continuation on outcomes in patients undergoing elective noncardiac surgery. Design, Setting, and Patients The Surgical Care and Outcomes Assessment Program is a Washington quality improvement benchmarking initiative based on clinical data from more than 55 hospitals. Linking Surgical Care and Outcomes Assessment Program data to Washington’s hospital admission and vital status registries, we studied patients undergoing elective colorectal and bariatric surgical procedures at 38 hospitals between January 1, 2008, and December 31, 2009. Main Outcome Measures Mortality, cardiac events, and the combined adverse event of cardiac events and/or mortality. Results Of 8431 patients, 23.5% were taking β-blockers prior to surgery (mean [SD] age, 61.9 [13.7] years; 63.1% were women). Treatment with β-blockers was continued on the day of surgery and during the postoperative period in 66.0% of patients. Continuation of β-blockers both on the day of surgery and postoperatively improved from 57.2% in the first quarter of 2008 to 71.3% in the fourth quarter of 2009 (P value <.001). After adjusting for risk characteristics, failure to continue β-blocker treatment was associated with a nearly 2-fold risk of 90-day combined adverse event (odds ratio, 1.97; 95% CI, 1.19-3.26). The odds were even greater among patients with higher cardiac risk (odds ratio, 5.91; 95% CI, 1.40-25.00). The odds of combined adverse events continued to be elevated 1 year postoperatively (odds ratio, 1.66; 95% CI, 1.08-2.55). Conclusions β-Blocker continuation on the day of and after surgery was associated with fewer cardiac events and lower 90-day mortality. A focus on β-blocker continuation is a worthwhile quality improvement target and should improve patient outcomes. PMID:22249847

  14. Inhibition of myocardial Ca2+ channels by three dihydropyridines with different structural features: potential-dependent blockade by Ro 18-3981.

    PubMed Central

    Holck, M.; Osterrieder, W.

    1987-01-01

    Inhibition of myocardial Ca2+ channels was investigated for three dihydropyridines with different structural features: Ro 18-3981, darodipine (PY 108-068) and nifedipine. Ro 18-3981 contains a sulphamoyl acetyl side-chain. In voltage-clamps experiments with isolated cardiac myocytes of guinea-pig, Ro 18-3981 caused a concentration-dependent inhibition of the Ca2+ current, which was influenced by the membrane holding potential. A markedly greater inhibition by Ro 18-3981 was observed when myocytes were depolarized (to +10 mV) from a holding potential (Vh) of -20 mV (IC50 = 2.3 nm) than at -50 mV (IC50 = 100 nM). The three dihydropyridines caused a concentration-dependent reduction in contractile force of isolated, electrically-stimulated left atria of the guinea-pig. Elevation of the extracellular K+ concentration from 5.9 to 24 mM resulted in a significant reduction in negative inotropic IC50 values for Ro 18-3981 (137 fold), darodipine (8 fold) and nifedipine (20 fold). The affinity of these drugs for the high-affinity (+)-[3H]-PN 200-110 binding site was determined in guinea-pig cardiac membranes. The KD value of Ro 18-3981 (1.0 nM) was similar to the IC50 value for blockade of ICa at a Vh of -20 mV (2.3 nM), i.e. at a level of near-maximal depolarization. Thus, structurally-different dihydropyridines exert potential-dependent inhibition of myocardial Ca2+ channel activity consistent with the modulated receptor hypothesis. These results demonstrate that blockade of myocardial excitation-contraction coupling by Ca2+ entry blockers is also potential-dependent. PMID:2439160

  15. Methylene blue reverses recalcitrant shock in β-blocker and calcium channel blocker overdose.

    PubMed

    Aggarwal, Nidhi; Kupfer, Yizhak; Seneviratne, Chanaka; Tessler, Sidney

    2013-01-18

    β-blocker and calcium channel blocker toxicity generally present with bradycardia and hypotension. A 69-year-old woman presented after a suicide attempt with a β-blocker and calcium channel blocker overdose. Her blood pressure was 69/35 mm Hg and her HR was in the 40s. She was treated with calcium chloride, glucagon, a dextrose-insulin infusion and three vasopressors, but remained hypotensive. She suffered two cardiac arrests and required a transvenous pacemaker. When all interventions failed, she was started on a methylene blue infusion for refractory vasodilatory shock which resulted in a dramatic improvement in her blood pressure. The patient was successfully weaned off all vasopressors and from mechanical ventilation without any end-organ damage.

  16. [Results of an intervention to reduce potentially inappropriate prescriptions of beta blockers and calcium channel blockers].

    PubMed

    Machado-Alba, J E; Giraldo-Giraldo, C; Aguirre Novoa, A

    2016-01-01

    To determine the frequency of simultaneous prescription of β-blockers and calcium channel blockers, notify the cardiovascular risk of these patients to the health care professionals in charge of them, and achieve a reduction in the number of those who use them. Quasi-experimental, prospective study by developing an intervention on medical prescriptions of patients older than 65 years treated between January 1 and July 30, 2014, affiliated to the Health System in 101 cities in Colombia. A total of 43,180 patients received a β-blocker each month, and 14,560 receiving a calcium channel blocker were identified. Educational interventions were performed and an evaluation was made, using sociodemographic and pharmacological variables, on the number of patients that stopped taking any of the two drugs in the following three months. A total of 535 patients, with a mean age 75.8±6.7 years received concomitant β-blockers plus calcium channel blockers. Modification of therapy was achieved in 235 patients (43.9% of users) after 66 educational interventions. In 209 cases (88.9%) one of the two drugs was suspended, and 11.1% changed to other antihypertensive drugs. The variable of being more than 85 years old (OR: 1.93; 95% CI: 1.07-3.50), and receiving concomitant medication with inhibitors of the renin-angiotensin system (OR: 2.16; 95% CI: 1.28-3.65) were associated with increased risk of their doctor changing or stopping the prescription. An improved adherence to recommendations for appropriate use of β-blockers and calcium channel blockers by health service providers was achieved. Intervention programs that reduce potentially inappropriate prescriptions for patients treated for cardiovascular disease should be used more frequently. Copyright © 2015 SECA. Published by Elsevier Espana. All rights reserved.

  17. 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.

  18. 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).

  19. Side Effects of alpha-Blocker Use: Retrograde Ejaculation.

    PubMed

    Kaplan, Steven A

    2009-01-01

    There are currently 5 alpha-blockers that are approved by the US Food and Drug Administration to treat lower urinary tract symptoms (LUTS). The American Urological Association guidelines committee believes that all alpha-blockers are equally effective. However, alpha-blockers differ in their likelihood of causing abnormal ejaculation. This article discusses the effects on ejaculatory function, and specifically retrograde ejaculation, of the currently available alpha-blockers being used to treat men with LUTS due to benign prostatic hyperplasia.

  20. 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

  1. [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.

  2. CoRoT in Brief

    NASA Astrophysics Data System (ADS)

    Boisnard, L.; Auvergne, M.

    2006-11-01

    The CoRoT Space Telescope is an experiment of astronomy dedicated to stellar seismology and search for extrasolar planets. The mission is led by CNES in association with French laboratories and with a significant international participation: ESA (Science Programme and RSSD/ESTEC, Austria, Belgium, Germany contribute to the payload, whereas Spain and Brazil (who has recently joined the project) contribute to the ground segment. Based on a PROTEUS low earth orbit recurrent platform, the spacecraft has been in development since October 2000 for a launch scheduled in Ocotber 2006. It gives an overview of the experiment, explains where the critical scientific requirements are for payload engineering and describes the cost-effective compromises found for high accuracy photometry in low earth orbit. We run through the different families of perturbations due to the interaction between the spacecraft and its environment and illustrate how some noise contributors, which generate spectral lines likely to be misinterpreted as a component of the star signal, are reduced by design, avoided by an appropriate mission profile or corrected after calibration. We focus on the following technical issues: telescope baffling and orbital drift, pointing stability, optoelectronics thermal regulation, light curve processing

  3. Neuromuscular blockers--a means of palliation?

    PubMed

    Hawryluck, L

    2002-06-01

    As we die, our respiratory pattern is altered and we seem to gasp and struggle for each breath. Such gasping is commonly seen as a clear sign of dyspnoea and suffering by families and loved ones, however, it is unclear whether it is perceived at all by the dying person. Narcotics and sedatives do not seem to affect these gasping respirations. In this issue of the Journal of Medical Ethics, we are asked to consider whether the last gasp of a dying patient could be or, perhaps, even should be avoided by administering neuromuscular blockers to palliate dying patients. For many reasons, such as our current failure to alleviate pain and distress, stories of inadequate analgesia and sedation in critically ill paralysed patients and the inability to know the intent-whether to palliate or to euthanise-it would seem that administering neuromuscular blockers should not be ethically permissible.

  4. 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.

  5. 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.

  6. Metric-driven RoSy field design and remeshing.

    PubMed

    Lai, Yu-Kun; Jin, Miao; Xie, Xuexiang; He, Ying; Palacios, Jonathan; Zhang, Eugene; Hu, Shi-Min; Gu, Xianfeng

    2010-01-01

    Designing rotational symmetry fields on surfaces is an important task for a wide range of graphics applications. This work introduces a rigorous and practical approach for automatic N-RoSy field design on arbitrary surfaces with user-defined field topologies. The user has full control of the number, positions, and indexes of the singularities (as long as they are compatible with necessary global constraints), the turning numbers of the loops, and is able to edit the field interactively. We formulate N-RoSy field construction as designing a Riemannian metric such that the holonomy along any loop is compatible with the local symmetry of N-RoSy fields. We prove the compatibility condition using discrete parallel transport. The complexity of N-RoSy field design is caused by curvatures. In our work, we propose to simplify the Riemannian metric to make it flat almost everywhere. This approach greatly simplifies the process and improves the flexibility such that it can design N-RoSy fields with single singularity and mixed-RoSy fields. This approach can also be generalized to construct regular remeshing on surfaces. To demonstrate the effectiveness of our approach, we apply our design system to pen-and-ink sketching and geometry remeshing. Furthermore, based on our remeshing results with high global symmetry, we generate Celtic knots on surfaces directly.

  7. GCM simulated geopotential heights compared to GPS RO data

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

    Accurate, high-quality, global coverage data is required for global climate monitoring. It also provides possibility of additional validation of the general circulation models (GCMs). GPS Radio occultation (GPS RO) measurements have potential of becoming a new benchmark in data acquisition, providing new high-quality profiles of the parameters of the atmosphere, such as the temperature, water vapor pressure, and geopotential heights. In our study we use GPS RO data with a purpose to test global circulation models (GCMs). We study how climate change signal emerges in the GPS RO data and how these signals are reflected in GCM simulations. We use temperature and geopotential height profiles from 2001-2006 CHAMP and 2006-2011 COMIC acquisitions to validate the output from twelve IPCC AR4 GCMs run under A1B SRES scenario. We found that the 2001-2011 trends of the temperature and geopotential height derived from the IPCC AR4 GCMs show the same pattern with trends derived from GPS RO data - warming of the upper troposphere (UT) and cooling of the lower stratosphere (LS). There is some discrepancy between trends in lower troposphere (LT) between models and GPS RO data: some GCMs show decreasing temperature and geopotential height trends while the GPS RO trends are positive. The statistical analysis of these trends will be reported.

  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. 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).

  10. 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

  11. Clinical and laboratory aspects of Ro/SSA-52 autoantibodies.

    PubMed

    Defendenti, Caterina; Atzeni, Fabiola; Spina, Maria Francesca; Grosso, Silvia; Cereda, Aldo; Guercilena, Giacinto; Bollani, Simona; Saibeni, Simone; Puttini, Piercarlo Sarzi

    2011-01-01

    Anti-Ro/SSA antibodies, which were described for the first time in systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS), are the most prevalent extractable nuclear antigen (ENA) specificity identified in laboratories. Two types of anti-Ro/SSA antibodies have been described, anti-SSA-52 kDa (aSSA52) and anti-SSA-60 kDa (aSSA60), each specific to different antigens. Anti-Ro/SSA52 autoantibodies are more frequent than other autoantibodies possibly because of the antigen's accessible and ubiquitous nature. The sites involved and the symptoms associated with these autoantibodies depend on the antigen's structural variability. Isolated congenital complete atrioventricular block (CAVB) shows a close association with maternal anti-Ro/SSA and anti-La/SSB antibodies; the highest relative risks of CAVB are seen in offspring of mothers with antibodies against 52-kDa Ro and 48-kDa La proteins. Anti-Ro/SSA52 antibodies have little impact on adult rheumatic autoimmune diseases or adult cardiac arrhythmias, but the course of autoimmune liver diseases is greatly worsened by their presence, and solid tumours tend to relapse. Their diagnostic role in rheumatic diseases is controversial, although a significant association between isolated anti-Ro/SSA52-kDa positivity and myositis and to a lesser extent with systemic sclerosis (SSc) has been described. However, the majority of the specific diagnosis is mostly based on the simultaneous presence of other autoantibodies that seems diagnostically more relevant.

  12. SU-E-T-218: The IHE-RO Helper Tool: Demonstrating the Connectivity Issues Solved by IHE-RO.

    PubMed

    Kapoor, Rishabh; Yeung, Daniel; Kumar, Sabari Ajay; Alex, Daley; Kapur, Priyanka; Palta, Jatinder

    2012-06-01

    To develop a Web-based application (IHE-RO Helper) to allow comprehensive review of the interconnectivity and interoperability of various radiotherapy devices established through testing sanctioned by the Integrating Healthcare Enterprise-Radiation Oncology (IHE-RO). IHE-RO is an initiative sponsored by ASTRO to improve the way computer based systems in radiation oncology share information using well-defined data exchange standards (DICOM / HL7). At the IHE-RO Connectathon events over the last 4 years, 11 vendors with 14 different products have successfully tested and identified solutions to connectivity problems in treatment planning, simulation and delivery. Because the test results are highly technical, the interconnectivity issues amongst the RT devices may get overlooked by the end users. The IHE-RO helper tool is designed to operate in simple clinical terms with queries and presentations organized based on treatment techniques and clinical features that are familiar to the practitioners. For example, if you are planning to purchase a treatment planning system capable of generating plans (e.g. Stereotactic treatments) and are concerned whether the TPS can successfully transfer such data to your treatment management system (TMS) and subsequently to your treatment delivery system (TDS), the IHE-RO Helper can identify the connectivity requirements and list vendors that have successfully passed an IHE-RO Connectathon and validated their solution to the specific requirements. The IHE-RO helper tool provides a graphical and textual user interface to effectively demonstrate the solved interconnectivity problems between TPS, TMS and TDS. A report is also provided that explains the interconnectivity problems and its solutions. The IHE-RO helper is an effective tool to clearly identify vendor products that are IHE-RO compliant, thereby encourages vendor participation in testing and validation. Such a tool will be invaluable in procurement of new equipment to ensure a

  13. 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.

  14. CoRoT data reduction by example

    NASA Astrophysics Data System (ADS)

    Weingrill, J.

    2015-02-01

    Data reduction techniques published so far for the CoRoT N2 data product were targeted primarily on the detection of extrasolar planets. Since the whole dataset has been released, specific algorithms are required to process the lightcurves from CoRoT correctly. Though only unflagged datapoints must be chosen for scientific processing, some flags might be reconsidered. The reduction of data along with improving the signal-to-noise ratio can be achieved by applying a one dimensional drizzle algorithm. Gaps can be filled by linear interpolated data without harming the frequency spectrum. Magnitudes derived from the CoRoT color channels might be used to derive additional information about the targets. Depending on the needs, various filters in the frequency domain remove either the red noise background or high frequency noise. The autocorrelation function or the least squares periodogram are appropriate methods to identify periodic signals. The methods described here are not strictly limited to CoRoT data but may also be applied on Kepler data or the upcoming PLATO mission. The CoRoT space mission, launched on 2006 December 27, has been developed and is operated by CNES, with the contribution of Austria, Belgium, Brazil, ESA (RSSD and Science Programme), Germany and Spain.

  15. Side Effects of α-Blocker Use: Retrograde Ejaculation

    PubMed Central

    Kaplan, Steven A

    2009-01-01

    There are currently 5 α-blockers that are approved by the US Food and Drug Administration to treat lower urinary tract symptoms (LUTS). The American Urological Association guidelines committee believes that all α-blockers are equally effective. However, α-blockers differ in their likelihood of causing abnormal ejaculation. This article discusses the effects on ejaculatory function, and specifically retrograde ejaculation, of the currently available α-blockers being used to treat men with LUTS due to benign prostatic hyperplasia. PMID:20126607

  16. [Use of neuromuscular blockers in Brazil].

    PubMed

    Locks, Giovani de Figueiredo; Cavalcanti, Ismar Lima; Duarte, Nadia Maria Conceição; Cunha, Rafael Martins da; Almeida, Maria Cristina Simões de

    2015-01-01

    The objective of this study was to evaluate how Brazilian anesthesiologists are using neuromuscular blockers (NMB), focusing on how they establish the diagnosis of postoperative residual curarization and the incidence of complications associated with the use of NMB. A questionnaire was sent to anesthesiologists inviting them to participate in the study. The online data collection remained open from March 2012 to June 2013. During the study period, 1296 responses were collected. Rocuronium, atracurium, and cisatracurium were the main neuromuscular blockers used in cases of elective surgery. Succinylcholine and rocuronium were the main NMB used in cases of emergency surgery. Less than 15% of anesthesiologists reported the frequent use of neuromuscular function monitors. Only 18% of those involved in the study reported that all workplaces have such a monitor. Most respondents reported using only the clinical criteria to assess whether the patient is recovered from the muscle relaxant. Most respondents also reported always using some form of neuromuscular blockade reversal. The major complications attributed to NMB were residual curarization and prolonged blockade. Eighteen anesthesiologists reported death attributed to NMB. Residual or prolonged blockade is possibly recorded as a result of the high rate of using clinical criteria to diagnose whether the patient has recovered or not from motor block and, as a corollary, the poor use of neuromuscular transmission monitors in daily practice.

  17. 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.

  18. 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.

  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. 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.

  1. The opacity mechanism in roAp stars

    NASA Astrophysics Data System (ADS)

    Cunha, Margarida S.; Gough, Douglas

    2001-01-01

    In the present paper we present the first results of work whose main goal is to understand the details of the process of high-order mode excitation in roAp stars. Motivated by the work by Balmforth et al. (1999, 2000), according to which convection might be suppressed in the polar regions of roAp stars, we show that in a radiative region the excitation of high-order pulsations takes place in the region of hydrogen ionization, and is the direct consequence of the abrupt change in the opacity derivative κT = (∂lnκ/∂lnT)ρ in these layers.

  2. The pleiotropic effects of angiotensin receptor blockers.

    PubMed

    Chrysant, Steven G; Chrysant, George S

    2006-04-01

    The angiotensin receptor blockers (ARBs) are very effective and safe antihypertensive drugs. They exert their antihypertensive effect through blockage of the angiotensin II, type 1 receptor and quite possibly through stimulation by angiotensin II of the unoccupied type 2 receptor. Besides hypertension, the ARBs have been found recently to be of value in the treatment of heart failure and diabetic nephropathy. In addition, ARBs have emerged lately as being very effective and perhaps superior to other antihypertensive drugs in the prevention of de novo or recurrent strokes. Other actions that may account for their stroke-protective effects include their antiatherogenic, antidiabetic, antiplatelet aggregating, hypouricemic, and atrial antifibrillatory actions. All these actions make the ARBs a true pleiotropic class of drugs. Each of the foregoing effects will be discussed briefly in this concise review.

  3. 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.

  4. 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.

  5. Should β-blockers still be routine after myocardial infarction?

    PubMed

    Thompson, Peter L

    2013-07-01

    This review will assess whether the 25-year-old evidence base to support routine prescribing of β-blockers after myocardial infarction (MI) is relevant to modern management. The evidence base to support the recommendation for the widespread use of β-blockers after MI was near-finalized in the mid-1980s. Whereas the use of intravenous β-blockers is waning, the routine use of oral β-blockers after MI is still regarded as evidence based. In the past 25 years, the introduction of coronary reperfusion and of effective nonreperfusion therapies has changed the natural history of MI and there have been substantial changes in the definition of MI. The relevance of old clinical trial data collected in patients who bear little resemblance to today's MI patients is questioned. Recent analyses have shown that there is no convincing evidence for the use of β-blockers as first-line therapy in hypertension or in patients with stable coronary heart disease. In contrast, the evidence base for the use of β-blockers in heart failure is strong and contemporary. A rational recommendation for the modern treatment of MI would be to limit the use of β-blockers in the post-MI patient to higher-risk patients with evidence of ongoing ischemia, heart failure, or left ventricular dysfunction. There is no evidence to support the routine use of oral β-blockers in low-risk MI patients.

  6. Beta Blockers for the Prevention of Acute Exacerbations of COPD

    DTIC Science & Technology

    2016-10-01

    known to be triggered by β-blockers or β-blocker withdrawal including myasthenia gravis, periodic hypokalemic paralysis , pheochromocytoma and...Veterans Affairs Hospital, Birmingham, Alabama, USA 4Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San

  7. 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.

  8. 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.

  9. 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

  10. AmeriFlux US-Ro3 Rosemount- G19

    SciTech Connect

    Baker, John; Griffis, Tim

    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.

  11. AmeriFlux US-Ro1 Rosemount- G21

    SciTech Connect

    Baker, John; Griffis, Tim; Griffis, Timothy

    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.

  12. 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…

  13. 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.

  14. 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...

  15. 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...

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. Common and specific associations of anti-SSA/Ro60 and anti-Ro52/TRIM21 antibodies in systemic lupus erythematosus.

    PubMed

    Menéndez, Aurora; Gómez, Jesús; Caminal-Montero, Luis; Díaz-López, José Bernardino; Cabezas-Rodríguez, Iván; Mozo, Lourdes

    2013-01-01

    Little information exists about the association of anti-SSA/Ro60 and anti-Ro52/TRIM21 with systemic lupus erytematosus (SLE) features. In this work, we analysed the associations of both anti-Ro reactivities with clinical and immunological manifestations in 141 SLE patients. Photosensitivity and xerophtalmia/xerostomia were found to be positively associated with both anti-SSA/Ro60 (P = 0.024 and P = 0.019, resp.) and anti-Ro52/TRIM21 (P = 0.026 and P = 0.022, resp.). In contrast, a negative association was detected regarding anti-phospholipid antibodies, anti-SSA/Ro60 having a stronger effect (P = 0.014) than anti-Ro52/TRIM21. Anti-SSA/Ro60 showed a specific positive association with hypocomplementemia (P = 0.041), mainly with low C4 levels (P = 0.008), whereas anti-Ro52/TRIM21 was found to be positively associated with Raynaud's phenomenon (P = 0.026) and cytopenia (P = 0.048) and negatively associated with anti-dsDNA (P = 0.013). Lymphocytes are involved in the relationship between anti-Ro52/TRIM21 and cytopenia since positive patients showed lower cell levels than negative patients (P = 0.036). In conclusion, anti-SSA/Ro60 and anti-Ro52/TRIM21 showed both common and specific associations in SLE. These data thus increase evidence of the different associations of the two anti-Ro specificities even in a particular disease.

  1. Clinical associations of anti-SSA/Ro60 and anti-Ro52/TRIM21 antibodies: Diagnostic utility of their separate detection.

    PubMed

    Menéndez, Aurora; Gómez, Jesús; Escanlar, Esther; Caminal-Montero, Luis; Mozo, Lourdes

    2013-02-01

    Clinical associations of anti-SSA/Ro60 and anti-Ro52/TRIM21 antibodies are not yet fully established. In order to analyse the diagnostic utility of their separate detection, we retrospectively revised the clinical data of 200 anti-SSA/Ro60 and/or anti-Ro52/TRIM21 positive patients identified by line immunoassay during ANA routine detection. Anti-SSA/Ro60 positive patients showed a significantly higher prevalence of autoimmune diseases (AIDs) independently on the presence of anti-Ro52/TRIM21 (OR 3.13, 95% CI 1.10-8.88, p = 0.032). Anti-SSA/Ro60 was independently associated with systemic lupus erythematosus (SLE) when comparing with Sjögren's syndrome (SS) and other systemic AIDs (OR 3.46, 95% CI 1.08-11.06, p = 0.036). The more frequent specificity found in cutaneous lupus erythematosus (CLE) was also anti-SSA/Ro60. In contrast, detection of isolated anti-Ro52/TRIM21 was characteristic of SS (7/35, 20.0%), diffuse cutaneous systemic sclerosis (dcSSc) (3/4, 75.0%), primary biliary cirrhosis (PBC) (4/5, 80.0%) and, specially, of polymyositis/dermatomyositis (PM/DM) (6/6, 100%). In fact, anti-Ro52/TRIM21 was the only antibody detected in 4 out of the 6 PM/DM patients. Malignancies mainly account for the observed high prevalence of mono-specific anti-Ro52/TRIM21 in patients with non-AIDs (10/15, 62.5%). In conclusion, this retrospective study supports the routine distinction of anti-SSA/Ro60 and anti-Ro52/TRIM21 due to their different clinical associations.

  2. Common and Specific Associations of Anti-SSA/Ro60 and Anti-Ro52/TRIM21 Antibodies in Systemic Lupus Erythematosus

    PubMed Central

    Menéndez, Aurora; Gómez, Jesús; Caminal-Montero, Luis; Díaz-López, José Bernardino; Cabezas-Rodríguez, Iván; Mozo, Lourdes

    2013-01-01

    Little information exists about the association of anti-SSA/Ro60 and anti-Ro52/TRIM21 with systemic lupus erytematosus (SLE) features. In this work, we analysed the associations of both anti-Ro reactivities with clinical and immunological manifestations in 141 SLE patients. Photosensitivity and xerophtalmia/xerostomia were found to be positively associated with both anti-SSA/Ro60 (P = 0.024 and P = 0.019, resp.) and anti-Ro52/TRIM21 (P = 0.026 and P = 0.022, resp.). In contrast, a negative association was detected regarding anti-phospholipid antibodies, anti-SSA/Ro60 having a stronger effect (P = 0.014) than anti-Ro52/TRIM21. Anti-SSA/Ro60 showed a specific positive association with hypocomplementemia (P = 0.041), mainly with low C4 levels (P = 0.008), whereas anti-Ro52/TRIM21 was found to be positively associated with Raynaud's phenomenon (P = 0.026) and cytopenia (P = 0.048) and negatively associated with anti-dsDNA (P = 0.013). Lymphocytes are involved in the relationship between anti-Ro52/TRIM21 and cytopenia since positive patients showed lower cell levels than negative patients (P = 0.036). In conclusion, anti-SSA/Ro60 and anti-Ro52/TRIM21 showed both common and specific associations in SLE. These data thus increase evidence of the different associations of the two anti-Ro specificities even in a particular disease. PMID:24294139

  3. 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

  4. 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.

  5. Impact of Combination Glaucoma Therapies on β-Blocker Exposure.

    PubMed

    Xu, Kunyong; Campbell, Erica de L P; Gill, Sudeep S; Nesdole, Robert; Campbell, Robert J

    2017-02-01

    β-adrenergic receptor antagonists (β-blockers) used in the treatment of glaucoma are an often-overlooked source of systemic adverse events. Ophthalmic timolol has been associated with severe systemic adverse events including numerous cases resulting in death. In recent years the number of fixed-dose combination therapies for glaucoma has grown rapidly, and among available combination therapies only the nonselective β-blocker timolol is used as the β-blocker component. A population-based study was conducted in Ontario, Canada between January 1, 2001 and December 31, 2012 to assess the shift to combination therapies in the management of glaucoma, and to investigate the impact of this shift on the relative use of selective and nonselective β-blockers in patients with this disease. Between 2001 and 2012 timolol (nonselective β-blocker) use grew at an average annual rate of 2.2% (P<0.0001), whereas betaxolol (selective β-blocker) use declined by 14.1% per year (P<0.0001). These changes in the relative use of betaxolol and timolol coincided with changes in the relative use of combination and single-drug therapies. Over the study period, the use of β-blockers as single-drug therapy decreased by 7.7% annually (P<0.0001). In contrast, the use of combination therapies containing a β-blocker increased by 7.6% annually (P<0.0001). The introduction of fixed combination glaucoma therapies has been associated with a significant shift to greater use of nonselective β-blockers. In vulnerable older populations, this may have an important impact on patient safety that warrants further study.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. Chronotropic incompentence and functional capacity in chronic heart failure: no role of β-blockers and β-blocker dose.

    PubMed

    Magrì, Damiano; Palermo, Pietro; Cauti, Filippo M; Contini, Mauro; Farina, Stefania; Cattadori, Gaia; Apostolo, Anna; Salvioni, Elisabetta; Magini, Alessandra; Vignati, Carlo; Alimento, Marina; Sciomer, Susanna; Bussotti, Maurizio; Agostoni, Piergiuseppe

    2012-04-01

    To assess the effect of chronotropic incompetence on functional capacity in chronic heart failure (CHF) patients, as evaluated as NYHA and peak oxygen consumption (pVO(2) ), focusing on the presence and dose of β-blocker treatment. Nine hundred and sixty-seven consecutive CHF patients were evaluated, 328 of whom were discarded because they failed to meet the study criteria. Of the 639 analyzed, 90 were not treated with β-blockers whereas the other 549 were. The latter were further subdivided in high (n = 184) and low (n = 365) β-blockers daily dose group in accordance with an arbitrary cut-off of 25 mg for carvedilol and of 5 mg for bisoprolol. Failure to achieve 80% of the percentage of maximum age predicted peak heart rate (%Max PHR) or of HR reserve (%HRR) constituted chronotropic incompetence. No differences were found in NYHA or pVO2 between patients with and without β-blockers and, similarly, between high and low β-blocker dose groups. Twenty and sixty-nine percent of not β-blocked patients showed chronotropic incompetence according to %Max PHR and %HRR, respectively, whereas this prevalence rose to 61% and 84% in those on β-blocker therapy. Patients taking β-blockers without chronotropic incompetence, as inferable from both %Max PHR and %HRR, showed higher NYHA and pVO2 regardless of drug dose, whereas, in not β-blocked patients, only %HRR revealed a difference in functional capacity. At multivariable analysis, HR increase during exercise (ΔHR) was the variable most strongly associated to pVO2 (β: 0.572; SE: 0.008; P < 0.0001) and NYHA class (β: -0.499; SE: 0.001; P < 0.0001). ΔHR is a powerful predictor of CHF severity regardless of the presence of β-blocker therapy and of β-blocker daily dose. © 2010 Blackwell Publishing Ltd.

  11. Solubilization of saikosaponin a by ginsenoside Ro biosurfactant in aqueous solution: mesoscopic simulation.

    PubMed

    Dai, Xingxing; Shi, Xinyuan; Wang, Yuguang; Qiao, Yanjiang

    2012-10-15

    Ginsenoside Ro (Ro), a natural anionic biosurfactant derived from ginseng, has been found to markedly increase the solubility of saikosaponin a (SSa), which is the active ingredient of Radix Bupleuri. SSa is minimally soluble in water. To determine the mechanism by which Ro solubilizes SSa, the self-assembly behavior of Ro and the phase behavior of blended Ro and SSa systems were studied by mesoscopic dynamics (MesoDyn) and dissipative particle dynamics (DPD) simulations. The simulation results show that Ro can form vesicles via the closure of oblate membranes. At low concentrations, SSa molecules are solubilized in the palisade layer of the Ro vesicles. At high concentrations, they interact with Ro molecules to form mixed vesicles with Ro adsorbing on the surfaces of the vesicles. The evaluation of the SSa solubilization process reveals that, at low concentrations, Ro aggregates preferentially to form vesicles, which then absorb SSa into themselves. However, at high concentrations, SSa first self-aggregates and then dissolves. This is because the solubilization behavior of Ro shifts the precipitation-dissolution equilibrium in the direction of dissolution. These results of the simulations are consistent with those of transmission electron microscopy (TEM) and dynamic light scattering (DLS). Copyright © 2012 Elsevier Inc. All rights reserved.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. Discoveries in the Atmospheres of roAp Stars

    NASA Astrophysics Data System (ADS)

    Kurtz, D. W.; Freyhammer, L. M.; Elkin, V. G.; Mathys, G.

    2007-11-01

    We have obtained a large amount of data on over 40 roAp stars and potential roAp stars with the Ultraviolet and Visual Echelle Spectrograph (UVES) on the VLT with time resolution typically around 1 min and radial velocity precision as high as 1 m s-1. Abundance stratification caused by atomic diffusion in the presence of strong global magnetic fields gives promise of three-dimensional maps of the pulsation amplitude and phase, and of the abundance distributions of many ions that may provide the strongest observational tests of atomic diffusion theory. Studies of individual spectral lines and of line profile variability sample the observable atmospheres of roAp stars from continuum optical depth τ5000~1 to as high as τ5000~10-5, revealing fascinating new pulsational behaviour not observed in other types of pulsating stars, including, inter alia, line profile variability in rare earth elements lines interpreted by as evidence for shock waves in the high atmosphere of these stars, an intriguing range of line bisector shapes, and a new pulsational diagnostic for resolved Zeeman components for the most strongly magnetic stars.

  17. 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.

  18. 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.

  19. 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...

  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. Reninoma Masked by the Use of an Angiotensin Receptor Blocker.

    PubMed

    Kim, Min Jung; Kim, Joo Hui; Kim, Il Young; Lee, Dong Won; Lee, Soo Bong

    2016-11-01

    Reninoma is a tumor that secretes excessive renin and is a rare cause of secondary hypertension. We report a case of reninoma with delayed diagnosis in a 33-year-old woman taking an angiotensin receptor blocker. During angiotensin receptor blocker medication, she had exhibited no electrolyte abnormality. The angiotensin receptor blocker was stopped for pregnancy planning purposes, and subsequent hypokalemia was observed. Abdominal computed tomography showed an enhanced round mass in the right kidney. Right partial nephrectomy was performed and the renal mass was removed. Histologic findings confirmed a diagnosis of reninoma. The patient's blood pressure and serum potassium remained normal after surgery. Diagnosis of reninoma might be delayed in patients taking angiotensin receptor blockers because they can mask hypokalemia due to reninoma.

  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. Incoherent blocker soliton interactions in Kerr waveguide arrays.

    PubMed

    Meier, J; Stegeman, G I; Christodoulides, D N; Morandotti, R; Salamo, G; Yang, H; Sorel, M; Silberberg, Y; Aitchison, J S

    2005-12-01

    We have observed the incoherent interaction between a highly confined (blocker) soliton and wide, moving signal beams of a different wavelength in a one-dimensional discrete Kerr medium. Digital switching of the blocker solitons to successive adjacent channels was measured with increasing signal power via both one and two cascaded interactions in an AlGaAs waveguide array, operations equivalent to a reconfigurable three-output router.

  4. Stereochemical comparison of nebivolol with other beta-blockers.

    PubMed

    Siebert, Carsten D; Hänsicke, André; Nagel, Thomas

    2008-02-01

    beta-Blockers are widely used in the treatment of cardiovascular disease and act by antagonizing the effects of adrenaline (epinephrine) and noradrenaline (norepinephrine) on beta-adrenergic receptors. All beta-blockers currently used in the treatment of cardiovascular disease contain at least one chiral center and, while most are marketed as racemates, their cardiac antihypertensive activity generally resides in the S-enantiomer. Nebivolol is a third generation beta-blocker that is highly selective for the beta(1)-adrenoceptor. The nebivolol molecule contains four chiral centers and is marketed as a racemate of (+)-nebivolol (SRRR-configuration) and (-)-nebivolol (RSSS-configuration). Nebivolol differs from all other beta-blockers with a hydroxypropanolamine substructure in that its cardiac antihypertensive activity resides in the R-enantiomer at the hydroxy group, whereas all other beta-blockers have antihypertensive activity in the S-enantiomer. Two of the four chiral centers in nebivolol are part of a ring structure and the increased rigidity of this structure may be related to nebivolol's divergence from the standard pharmacophore model of beta-blockers.

  5. [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.

  6. Anti-Ro52 Autoantibodies from Patients with Sjögren's Syndrome Inhibit the Ro52 E3 Ligase Activity by Blocking the E3/E2 Interface*

    PubMed Central

    Espinosa, Alexander; Hennig, Janosch; Ambrosi, Aurélie; Anandapadmanaban, Madhanagopal; Abelius, Martina Sandberg; Sheng, Yi; Nyberg, Filippa; Arrowsmith, Cheryl H.; Sunnerhagen, Maria; Wahren-Herlenius, Marie

    2011-01-01

    Ro52 (TRIM21) is an E3 ligase of the tripartite motif family that negatively regulates proinflammatory cytokine production by ubiquitinating transcription factors of the interferon regulatory factor family. Autoantibodies to Ro52 are present in patients with lupus and Sjögren's syndrome, but it is not known if these autoantibodies affect the function of Ro52. To address this question, the requirements for Ro52 E3 ligase activity were first analyzed in detail. Scanning a panel of E2 ubiquitin-conjugating enzymes, we found that UBE2D1–4 and UBE2E1–2 supported the E3 ligase activity of Ro52 and that the E3 ligase activity of Ro52 was dependent on its RING domain. We also found that the N-terminal extensions in the class III E2 enzymes affected their interaction with Ro52. Although the N-terminal extension in UBE2E3 made this E2 enzyme unable to function together with Ro52, the N-terminal extensions in UBE2E1 and UBE2E2 allowed for a functional interaction with Ro52. Anti-Ro52-positive patient sera and affinity-purified anti-RING domain autoantibodies inhibited the E3 activity of Ro52 in ubiquitination assays. Using NMR, limited proteolysis, ELISA, and Ro52 mutants, we mapped the interactions between Ro52, UBE2E1, and anti-Ro52 autoantibodies. We found that anti-Ro52 autoantibodies inhibited the E3 ligase activity of Ro52 by sterically blocking the E2/E3 interaction between Ro52 and UBE2E1. Our data suggest that anti-Ro52 autoantibodies binding the RING domain of Ro52 may be actively involved in the pathogenesis of rheumatic autoimmune disease by inhibiting Ro52-mediated ubiquitination. PMID:21862588

  7. 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.

  8. Anti-SLA/LP alone or in combination with anti-Ro52 and fine specificity of anti-Ro52 antibodies in patients with autoimmune hepatitis.

    PubMed

    Zachou, Kalliopi; Gampeta, Stella; Gatselis, Nikolaos K; Oikonomou, Katerina; Goulis, John; Manoussakis, Menelaos N; Renaudineau, Yves; Bogdanos, Dimitrios P; Dalekos, George N

    2015-02-01

    Antibodies (Abs) to soluble liver antigen/liver pancreas (anti-SLA/LP) are considered markers of worse prognosis and outcome in patients with autoimmune hepatitis (AIH) although this assumption has recently been attributed to their frequent co-expression with Abs against Ro52 (anti-Ro52). To assess the clinical significance of anti-SLA/LP Abs alone or in combination with anti-Ro52 in AIH patients and determine the immunodominant Ro52 epitopes according to the anti-SLA/LP status. Twenty-three anti-SLA/LP-positive and 106 anti-SLA/LP-negative AIH patients were included. Anti-SLA/LP were determined by ELISA using recombinant antigen, and confirmed by immunoblot using cytosolic rat liver fraction or HuH-7 extract. Anti-Ro52 Abs were determined by ELISA using recombinant antigen. Epitope mapping was assessed by ELISA using overlapping peptides covering the whole Ro52 protein in 26 AIH patients and 12 patients with Sjögren's syndrome. Anti-SLA/LP positivity was not associated with the clinical, laboratory or histological characteristics of AIH patients. Treatment response, corticosteroid withdrawal, relapse after stopping treatment and outcome, were not associated with the presence of anti-SLA/LP, anti-Ro52 or double reactivity. Moreover, Ro52 epitope mapping revealed new epitopes unique for AIH and independent from anti-SLA/LP positivity. Neither anti-SLA/LP nor anti-Ro52 Abs or their combination could specify a distinct group of AIH patients in terms of clinical characteristics, treatment response and outcome. Further studies are needed to clarify whether the newly discovered immunodominant epitopes of Ro52 antigen which were associated specifically with AIH have any clinical or pathogenetic significance in AIH. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Azilsartan medoxomil: a new Angiotensin receptor blocker.

    PubMed

    Zaiken, Kathy; Cheng, Judy W M

    2011-11-01

    Azilsartan medoxomil is an angiotensin receptor blocker, approved on February 25, 2011 by the US Food and Drug Administration (FDA) for hypertension management. The purpose of this study was to review the pharmacology, pharmacokinetics, efficacy, safety profile, and role of azilsartan for hypertension management. Peer-reviewed clinical trials, review articles, and relevant treatment guidelines were identified from MEDLINE and Current Contents (both 1966 to August 31, 2011) using the search terms azilsartan, TAK-491, TAK-536, pharmacology, pharmacokinetics, pharmacodynamics, pharmacoeconomics, and cost-effectiveness. The FDA Web site and manufacturer prescribing information were also reviewed to identify other relevant information. Compared with olmesartan 40 mg daily, azilsartan 80 mg reduced mean systolic blood pressure (SBP) by an additional 2.1 mm Hg (P = 0.038), whereas azilsartan 40 mg was noninferior to olmesartan 40 mg. Azilsartan 40 mg or 80 mg added to chlorthalidone 25 mg daily significantly reduced SBP to a greater extent than did chlorthalidone alone (P < 0.05), but there was no difference between azilsartan 40 mg and 80 mg (40 mg: -31.72 mm Hg; 80 mg: -31.3 mm Hg [P > 0.05]). When coadministered with amlodipine 5 mg daily, both azilsartan 40 mg and 80 mg + amlodipine decreased SBP significantly more than amlodipine alone (amlodipine: -13.6 mm Hg; with azilsartan 40 mg: -24.79 mm Hg; with azilsartan 80 mg: -24.51 mm Hg [P < 0.05]). Compared with ramipril 10 mg daily, both azilsartan 40 mg and 80 mg resulted in significantly (P < 0.001) greater reductions in mean SBP (-20.63 and -21.24 mm Hg, respectively; ramipril: -12.22 mm Hg). The most common adverse events reported were dizziness (4%), dyslipidemia (3.3%), and diarrhea (2%). At the recommended dose of 80 mg once daily, azilsartan is reported to be an efficacious BP-lowering agent. With once-daily dosing and a favorable side-effect profile, azilsartan is an attractive option for the treatment of

  10. Ocular beta-blockers in glaucoma management. Clinical pharmacological aspects.

    PubMed

    Brooks, A M; Gillies, W E

    1992-01-01

    Topical beta-blockers reduce the intraocular pressure (IOP) by blockade of sympathetic nerve endings in the ciliary epithelium causing a fall in aqueous humour production. Two types of topical beta-blockers are available for use in glaucoma: nonselective, which block both beta 1- and beta 2-adrenoceptors; and cardioselective, which block only beta 1-receptors. Of the beta-Blockers commercially available, timolol, levobunolol, metipranolol and carteolol are nonselective, and betaxolol is cardioselective. Twice-daily timolol is probably the most effective agent in lowering IOP, although levobunolol is equally effective and can be used once daily with little difference in effect. Carteolol is used twice daily and any theoretical advantage in diminished side effects conferred by its partial beta-agonist activity compared with timolol has not been fully substantiated. Metipranolol is effective twice daily and does not have partial beta-agonist activity. Betaxolol has an effect comparable to timolol in lowering IOP, but is less effective in some patients. beta-Blockers can be used with other antiglaucoma medications, but their combined action with epinephrine (adrenaline) is suspect, particularly in the case of the nonselective beta-blockers, and the effect should be assessed in patients on an individual basis. Local stinging can be a problem in some patients with betaxolol. The most serious side effects of beta-blockers are the exacerbation of chronic obstructive airways disease with nonselective agents and the precipitation of bronchospasm in some patients. Betaxolol seems relatively free of adverse respiratory effects, although this may be dose-related and extreme caution should still be exercised in patients with any history of respiratory illness. Because of the lower risk of precipitating side effects, betaxolol is probably the beta-blocker of first choice for use in glaucoma; timolol or levobunolol are reserved for patients who do not respond satisfactorily to

  11. 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.

  12. 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.

  13. Arrhythmogenic effects of anti-Ro/SSA antibodies on the adult heart: more than expected?

    PubMed

    Lazzerini, Pietro Enea; Capecchi, Pier Leopoldo; Acampa, Maurizio; Selvi, Enrico; Guideri, Francesca; Bisogno, Stefania; Rossi, Pier Carlo; Galeazzi, Mauro; Pasini, Franco Laghi

    2009-09-01

    The arrhythmogenicity of anti-Ro/SSA antibodies for the foetal heart and their crucial role in the development of congenital heart block is now well established, representing a paradigmatic model of passively acquired autoimmunity. Recently, intriguing data suggest that also the adult heart may represent a possible target of anti-Ro/SSA antibody-mediated autoimmune injury. The prolongation of the QTc interval, possibly resulting from a direct inhibitory interaction between the anti-Ro/SSA antibodies and the potassium current I(Kr) in the heart seems the abnormality more frequently observed in adults with anti-Ro/SSA-positive CTD. Although the possibility that anti-Ro/SSA positivity may be considered a risk factor for arrhythmic sudden death in adults has not been demonstrated as yet, preliminary data suggest a relationship among anti-Ro/SSA antibodies, QTc prolongation, and the prevalence of ventricular arrhythmias, also life threatening, in adult patients.

  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. 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

  16. 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.

  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. Anti-Ro/SSA antibodies in rheumatoid arthritis: clinical and immunologic associations.

    PubMed

    Cavazzana, I; Franceschini, F; Quinzanini, M; Manera, C; Del Papa, N; Maglione, W; Comina, D; Radice, A; Sinico, R A; Cattaneo, R

    2006-01-01

    To assess the prevalence of anti-Ro/SSA in RA and to analyse clinical and serological features of anti-Ro/SSA positive patients with RA. 195 consecutive patients affected by RA were studied by counterimmunoelectrophoresis and ELISA for the detection of anti-Ro/SSA antibodies. Anti-Ro were found in 12 patients, with a prevalence of 6%. These 12 patients were pooled with other 15 patients known to have anti-Ro/SSA antibodies and RA, in order to evaluate their clinical and laboratory features. Anti-Ro positive patients showed a common pattern of joint involvement at onset and a comparable progression of disease compared to anti-Ro negative subjects. In addition, extra-articular manifestations (such as xerophthalmia, xerostomia, scleritis, oral ulcers and amyloidosis) and peculiar autoantibody profile (hypergammaglobulinemia, anti-dsDNA and AMA) were found significantly associated to anti-Ro/SSA positivity. Even though DMARDs withdrawals were more frequently detected in anti-Ro/SSA patients, especially when using gold salts, no statistical difference between the two groups was detected. In addition, anti-TNFalpha treatment did not cause further progression of autoimmunity neither on laboratory nor on clinical ground. Anti-Ro/SSA can be detected in about 6% of patients affected by RA. These patients presented a peculiar clinical picture characterised by extra-articular manifestations some of which are known to be anti-Ro/SSA correlated, while others are more disease-specific (amyloidosis, episcleritis). Anti-Ro/SSA are significantly associated with other autoantibodies not specific for RA such as anti-dsDNA and AMA. Treatment with anti-TNF drugs did not cause further progression of autoimmunity neither on laboratory nor on clinical ground.

  19. Experimental Study of Advanced Treatment of Coking Wastewater Using MBR-RO Combined Process

    NASA Astrophysics Data System (ADS)

    Zhang, Lei; Hwang, Jiannyang; Leng, Ting; Xue, Gaifeng; Chang, Hongbing

    A membrane bioreactor-reverse osmosis (MBR-RO) combined process was used for advanced treatment of coking wastewater from secondary biological treatment. MBR and RO units' treatment efficiency for the pollution removal were conducted, and effects of raw water conductivity and trans-membrane pressure on water yield and desalination rate in RO unit were investigated in detail. The experimental results proved that MBR-RO combined process ran steadily with good treatment effect, which could obtain stable effluent water quality and met the requirement of "Design Criterion of the Industrial Circulating Cooling Water Treatment" (GB 50050-2007).

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. The CoRoT Mission - Status and Preliminary Results

    NASA Astrophysics Data System (ADS)

    Fridlund, M.

    2007-08-01

    The CoRoT (Convection, Rotation and planetary Transits) space mission is the first dedicated space mission designed to search for exo-planets akin to our own. It is a joint effort by France, Austria Belgium, Brazil, Germany, Spain and the European Space Agency. It is specifically designed to search for exo-planets much smaller than hitherto discovered. It was launched in December 2006 on a mission lasting not less than 3 years. Verification and first operations have proven the mission to superceed all expectations. This is of course most relevant in the fact that planets as small as our own Earth are detectable. In this presentation we describe the experiences of the first 6 mo0nths of the mission, the actual status of the mission, the supporting ground based program, and what we expect in the near future. After giving examples of data relevant to the topic of this session, we turn to describing the expected impact of the results of CoRoT on future endeavours such as KEPLER, Extremely Large Telescopes (ELT's) and ultimately Darwin.

  7. A New Mapping Function Based on GNSS-RO observations

    NASA Astrophysics Data System (ADS)

    Benedetto, Catia; Rosciano, Elisa; Vespe, Francesco; Vizziello, Giuseppe

    2015-04-01

    The coordinates of a static Global Navigation Satellite System (GNSS) station placed on the ground are estimated together with the delay suffered by the incoming satellite signals through the atmosphere. The tropospheric delay (TD) is shaped as the product of the zenith delay (ZTD) times a mapping function (MF) depending on the sine of elevation angles. In processing chain, ZTD is just estimated together with the coordinates; while the MF is modelled apart, in an independent way, by using atmospheric profiles retrieved with balloon observations ( RAOB) as done for the Niell MF (1996) or provided by climate or Numerical Weather Prediction (NWP) models as in the Vienna MFs. The several space missions devoted to GNSS-RO (e.g. COSMIC-FORMOSAT, METOP, CHAMP, GRACE end others) are providing a huge amount of data which makes worthwhile to be attempted the reconstruction of a new mapping function based on such kind of data. Thus we have built the "Matera" MF ( MTMF) based just on GNSS-RO observations. The new MTMF will be applied to a network of EUREF GNSS stations in the Mediterranean area. Formal errors and repeatability of ZTD and coordinates estimated with the MTMF will be compared with those achieved applying other MF. In validation activities we plan to use the Bernese software.

  8. Neuroprotective effects of blockers for T-type calcium channels

    PubMed Central

    Wildburger, Norelle C; Lin-Ye, Avary; Baird, Michelle A; Lei, Debin; Bao, Jianxin

    2009-01-01

    Cognitive and functional decline with age is correlated with deregulation of intracellular calcium, which can lead to neuronal death in the brain. Previous studies have found protective effects of various calcium channel blockers in pathological conditions. However, little has been done to explore possible protective effects of blockers for T-type calcium channels, which forms a family of FDA approved anti-epileptic drugs. In this study, we found that neurons showed an increase in viability after treatment with either L-type or T-type calcium channel antagonists. The family of low-voltage activated, or T-type calcium channels, comprise of three members (Cav3.1, Cav3.2, and Cav3.3) based on their respective main pore-forming alpha subunits: α1G, α1H, and α1I. Among these three subunits, α1H is highly expressed in hippocampus and certain cortical regions. However, T-type calcium channel blockers can protect neurons derived from α1H-/- mice, suggesting that neuroprotection demonstrated by these drugs is not through the α1H subunit. In addition, blockers for T-type calcium channels were not able to confer any protection to neurons in long-term cultures, while blockers of L-type calcium channels could protect neurons. These data indicate a new function of blockers for T-type calcium channels, and also suggest different mechanisms to regulate neuronal survival by calcium signaling pathways. Thus, our findings have important implications in the development of new treatment for age-related neurodegenerative disorders. PMID:19863782

  9. Neuroprotective effects of blockers for T-type calcium channels.

    PubMed

    Wildburger, Norelle C; Lin-Ye, Avary; Baird, Michelle A; Lei, Debin; Bao, Jianxin

    2009-10-28

    Cognitive and functional decline with age is correlated with deregulation of intracellular calcium, which can lead to neuronal death in the brain. Previous studies have found protective effects of various calcium channel blockers in pathological conditions. However, little has been done to explore possible protective effects of blockers for T-type calcium channels, which forms a family of FDA approved anti-epileptic drugs. In this study, we found that neurons showed an increase in viability after treatment with either L-type or T-type calcium channel antagonists. The family of low-voltage activated, or T-type calcium channels, comprise of three members (Cav3.1, Cav3.2, and Cav3.3) based on their respective main pore-forming alpha subunits: alpha1G, alpha1H, and alpha1I. Among these three subunits, alpha1H is highly expressed in hippocampus and certain cortical regions. However, T-type calcium channel blockers can protect neurons derived from alpha1H-/- mice, suggesting that neuroprotection demonstrated by these drugs is not through the alpha1H subunit. In addition, blockers for T-type calcium channels were not able to confer any protection to neurons in long-term cultures, while blockers of L-type calcium channels could protect neurons. These data indicate a new function of blockers for T-type calcium channels, and also suggest different mechanisms to regulate neuronal survival by calcium signaling pathways. Thus, our findings have important implications in the development of new treatment for age-related neurodegenerative disorders.

  10. Anti-SSA/Ro52 autoantibodies in scleroderma: results of an observational, cross-sectional study.

    PubMed

    Sánchez-Montalvá, A; Fernández-Luque, A; Simeón, C P; Fonollosa-Plà, V; Marín, A; Guillén, A; Vilardell, M

    2014-01-01

    To date, the diagnostic utility of anti-SSA/Ro52 autoantibodies in scleroderma and the association of them with certain clinical manifestations, particularly inflammatory myositis, are still controversial. This paper aims to assess the correlation between the presence of anti-SSA/Ro52 antibodies and the demographic, clinical and prognosis characteristics of patients with systemic sclerosis (SSc). This is a retrospective, cross-sectional and observational study in patients with SSc. Baseline demographic and clinical characteristics were recorded. Presence of anti-SSA/Ro52, anti-SSA/Ro, anti-SSB/La, snRNP/Sm, anti-centromere, anti-Scl-70 and anti-PM-Scl were analysed by immunoblot, and antinuclear antibodies (ANA) by indirect immunofluorescence. Statistical analysis was performed with PASW Statics 18 software. A total of 132 consecutive patients with analysis of anti-SSA/Ro52 antibodies were selected from a Spanish cohort of 408 patients with SSc, 87.1% of them being women. About half of patients had the limited form (51.5%), followed by diffused form (18.9%), sclerosis sine scleroderma (22.7%), and pre-scleroderma (6.8%). Prevalence of anti-SSA/Ro52 was 35.6%. No association between anti-SSA/Ro52 and clinical manifestations was found, while detection of anti-SSA/Ro52 was significantly associated with the presence of anti-Ro. The results of our study show that anti-SSA/Ro52 antibodies are often found in SSc patients. No clinical manifestations, including inflammatory myopathy, were related with anti-SSA/Ro antibodies.

  11. 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.

  12. The CoRoT transit candidate catalog

    NASA Astrophysics Data System (ADS)

    Aigrain, S.; Deleuil, M.

    2013-09-01

    We present a full catalog of all the candidate transiting planets identified by the CoRoT space mission during its first 5 years of operations, including homogeneously derived transit parameters, validation diagnostics and a summary of the outcome of follow-up observations, where available.The catalog includes confirmed planets, clear false alarms (mainly blended or grazing eclipsing binaries), but also dozens of unconfirmed cases, where the follow-up was either inconclusive (hot stars, fast rotators) or incomplete (owing to limited telescope time and the relatively faint nature of the CoRoT targets). The catalog is intended primarily as a resource for the community, for example as a starting point for completeness and population studies. The candidate detection and selection processes have evolved significantly over the course of the mission. Several teams independently analyse the light curves from each observing run, searching for transits and providing ranked candidate lists, which are subsequently merged and ranked manually. This enables the use of some specialist methods, which are better suited to the detection of only certain types of transits, but makes it difficult to provide an overall assessment of the sensitivity of the mission to transits of different depths and periods. However, we note the transit search methods used by the different teams have gradually converged since launch, and there are now fewer teams actively involved in the transit search, with more overlap between the resulting candidate lists. For each CoRoT observing run, one team member coordinates the selection of candidates for followup, with input from the other team members. The set of criteria used to perform this selection have also evolved over the years, becoming more homogeneous. In particular, the light curve fitting tools used to produce the transit parameters and other diagnostics, which are included in the present catalog, are now routinely used to validate candidates and

  13. 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

  14. endo-Cyclization of unsaturated RO2 radicals from the gas-phase ozonolysis of cyclohexadienes.

    PubMed

    Richters, Stefanie; Pfeifle, Mark; Olzmann, Matthias; Berndt, Torsten

    2017-04-06

    Unsaturated RO2 radicals from the ozonolysis of cyclodienes can readily undergo an endo-cyclization step under atmospheric conditions forming a new ring-containing RO2 radical after further O2 addition. This path represents an extension of the atmospheric autoxidation scheme forming highly oxidized multifunctional organic compounds (HOMs). HOMs play an important role for Earth's organic aerosol burden.

  15. 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

  16. [alpha-Neurotoxins and alpha-conotoxins--nicotinic cholinoreceptor blockers].

    PubMed

    Utkin, Iu N; Kasheverov, I E; Tsetlin, V I

    1999-11-01

    The review is devoted to the competitive blockers of different nicotinic acetylcholine receptors, alpha-neurotoxins from snake venoms, and alpha-conotoxins from marine snails of the Conidae family. The relationship between the structure and function of these toxins is discussed. Recent data on the mechanism of alpha-neurotoxin and alpha-conotoxin interaction with the nicotinic acetylcholine receptor are presented.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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...

  2. [The results of treating aphakic glaucoma with beta-blockers].

    PubMed

    Kartasheva, E A; Pimneva, I V

    1999-01-01

    Treatment of patients with aphakia and increased intraocular pressure by beta-blockers is sufficiently effective. Instillations of these agents decreases ophthalmic tone in patients with aphakia combined with primary glaucoma and in those with aphakic glaucoma. Intraocular pressure decreased in 70% patients and the effect persisted for at least 3 months in the majority of cases.

  3. 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...

  4. 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.

  5. Developing Memory Reconsolidation Blockers as Novel PTSD Treatments

    DTIC Science & Technology

    2010-06-01

    has produced the original finding that the anti-progesterone and glucocorticoid receptor antagonist mifepristone , when administered systemically...further original discovery that the beta-adrenergic blocker propranolol blocks this mifepristone effect. We have produced the further original...as powerful as mifepristone . We have produced the further original discovery that post- reactivation rapamycin reduces synaptic strength underlying

  6. [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.

  7. High Flux, Fouling Resistant Membranes for RO Pretreatment

    DTIC Science & Technology

    2010-07-30

    technology and manufacture a hollow‐fiber  module that may be used for pretreatment to the  reverse   osmosis  unit in the Navy  desalination  system...project objective is to develop low‐maintenance, high‐flux, low‐fouling water filtration modules for  reverse   osmosis  (RO) pre‐treatment in order to... Reverse   Osmosis  unit (NSRO) where  cartridge filters are the pretreatment prior to single pass  reverse   osmosis .  The NSRO system was  designed in the

  8. 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

  9. Arrhythmogenicity of Anti-Ro/SSA Antibodies in Patients With Torsades de Pointes.

    PubMed

    Lazzerini, Pietro Enea; Yue, Yuankun; Srivastava, Ujala; Fabris, Frank; Capecchi, Pier Leopoldo; Bertolozzi, Iacopo; Bacarelli, Maria Romana; Morozzi, Gabriella; Acampa, Maurizio; Natale, Mariarita; El-Sherif, Nabil; Galeazzi, Mauro; Laghi-Pasini, Franco; Boutjdir, Mohamed

    2016-04-01

    In patients with autoimmune disease, anti-Ro/SSA antibodies (anti-Ro/SSA) are responsible for a novel autoimmune-associated long-QT syndrome by targeting the hERG potassium channel and inhibiting the related current (IKr). Because anti-Ro/SSA are also present in a significant proportion of healthy subjects and may be associated with torsades de pointes (TdP) arrhythmia, we tested the hypothesis that anti-Ro/SSA may represent a silent risk factor in patients developing TdP. Twenty-five consecutive patients who experienced TdP were prospectively collected independent of ongoing therapies and concomitant diseases. Anti-Ro/SSA were detected by fluoroenzyme immunoassay, immuno-Western blotting, and line-blot immunoassay. Purified IgGs from anti-Ro/SSA-positive and anti-Ro/SSA-negative patients were tested on IKr using HEK293 cells stably expressing the hERG channel. As expected, in TdP patients, many known corrected QT interval-prolonging risk factors were simultaneously present, including hypokalemia that was the most common (52%). Anti-Ro/SSA were present in 60% of the subjects, mostly the anti-Ro/SSA-52-kD subtype detected by immuno-Western blotting only. A history of autoimmune disease was found in only 2 of anti-Ro/SSA-positive patients. Experimental data demonstrated that purified anti-Ro/SSA-positive IgGs significantly inhibited IKr and cross reacted with hERG-channel proteins. Moreover, anti-Ro/SSA-positive sera exhibited high reactivity with a peptide corresponding to the hERG-channel pore-forming region. Anti-Ro/SSA may represent a clinically silent novel risk factor for TdP development via an autoimmune-mediated electrophysiological interference with the hERG channel. We propose that TdP patients may benefit from specific anti-Ro/SSA testing even in the absence of autoimmune diseases as immunomodulating therapies may be effective in shortening corrected QT interval and reducing TdP recurrence risk. © 2016 American Heart Association, Inc.

  10. Transiting exoplanets from the CoRoT space mission. XXVI. CoRoT-24: a transiting multiplanet system

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

    We present the discovery of a candidate multiply transiting system, the first one found in the CoRoT mission. Two transit-like features with periods of 5.11 and 11.76 d are detected in the CoRoT light curve around a main sequence K1V star of r = 15.1. If the features are due to transiting planets around the same star, these would correspond to objects of 3.7 ± 0.4 and 5.0 ± 0.5 R⊕ , respectively. Several radial velocities serve to provide an upper limit of 5.7 M⊕ for the 5.11 d signal and to tentatively measure a mass of 28+11-11 M⊕ for the object transiting with a 11.76 d period. These measurements imply low density objects, with a significant gaseous envelope. The detailed analysis of the photometric and spectroscopic data serves to estimate the probability that the observations are caused by transiting Neptune-sized planets as much as over 26 times higher than a blend scenario involving only one transiting planet and as much as over 900 times higher than a scenario involving two blends and no planets. The radial velocities show a long-term modulation that might be attributed to a 1.5 MJup planet orbiting at 1.8 AU from the host, but more data are required to determine the precise orbital parameters of this companion. The CoRoT space mission, launched on 27 December 2006, has been developed and is operated by the CNES, with the contribution of Austria, Belgium, Brazil, ESA (RSSD and Science Program), Germany, and Spain. Some of the observations were made with the HARPS spectrograph at ESO La Silla Observatory (184.C-0639) and with the HIRES spectrograph at the Keck Telescope (N035Hr, N143Hr 260 and N095Hr). Partly based on observations obtained at ESO Paranal Observatory, Chile (086.C-0235(A) and B).Tables 2-4 and Fig. 12 are available in electronic form at http://www.aanda.org

  11. Aryl hydantoin Ro 13-3978, a broad-spectrum antischistosomal

    PubMed Central

    Keiser, Jennifer; Panic, Gordana; Vargas, Mireille; Wang, Chunkai; Dong, Yuxiang; Gautam, Nagsen; Vennerstrom, Jonathan L.

    2015-01-01

    Objectives Praziquantel is the only drug available for the treatment of schistosomiasis and the state of the exhausted drug discovery pipeline is alarming. We restarted investigations on the abandoned antischistosomal Ro 13-3978, an aryl hydantoin discovered in the early 1980s by Hoffmann La-Roche. Methods Newly transformed schistosomula and adult Schistosoma mansoni were studied in the presence of Ro 13-3978 in vitro. The metabolic stability of Ro 13-3978 was determined in vitro using human and mouse liver S9 fractions. Dose–response relationship, stage specificity, hepatic shift and scanning electron microscopy studies were carried out in S. mansoni-infected mice. In addition, efficacy experiments were conducted in rodents infected with Echinostoma caproni and Fasciola hepatica as well as in S. mansoni-infected immunocompromised nude (Foxn1nu) mice. Results Ro 13-3978 showed minor in vitro activity and no damage to the tegument was found. No cytotoxicity was detected for Ro 13-3978. Ro 13-3978 was metabolically stable. ED50 values of 138.9 and 14.6 mg/kg were calculated for the treatment of juvenile and adult S. mansoni infections, respectively, with a single oral dose of Ro 13-3978. SEM studies revealed severe damage to the worms 48 h post-treatment of infected mice. A single oral dose of Ro 13-3978 (100 mg/kg) administered to S. mansoni-infected (Foxn1nu) mice reduced the worm burden by 88%. Ro 13-3978 was not active against E. caproni and F. hepatica in vivo. Conclusions Ro 13-3978 has excellent antischistosomal properties in vivo. Structure–activity relationship studies with the aryl hydantoins have been launched in order to elucidate active pharmacophores, further investigate the mechanism of action and to identify a derivative with minimal antiandrogenic effects. PMID:25691324

  12. Intracellular calcium changes induced by the endozepine triakontatetraneuropeptide in human polymorphonuclear leukocytes: role of protein kinase C and effect of calcium channel blockers.

    PubMed

    Marino, Franca; Cosentino, Marco; Ferrari, Marco; Cattaneo, Simona; Frigo, Giuseppina; Fietta, Anna M; Lecchini, Sergio; Frigo, Gian Mario

    2004-06-30

    BACKGROUND: The endozepine triakontatetraneuropeptide (TTN) induces intracellular calcium ([Ca++]i) changes followed by activation in human polymorphonuclear leukocytes (PMNs). The present study was undertaken to investigate the role of protein kinase (PK) C in the modulation of the response to TTN by human PMNs, and to examine the pharmacology of TTN-induced Ca++ entry through the plasma membrane of these cells. RESULTS: The PKC activator 12-O-tetradecanoylphorbol-13-acetate (PMA) concentration-dependently inhibited TTN-induced [Ca++]i rise, and this effect was reverted by the PKC inhibitors rottlerin (partially) and Ro 32-0432 (completely). PMA also inhibited TTN-induced IL-8 mRNA expression. In the absence of PMA, however, rottlerin (but not Ro 32-0432) per se partially inhibited TTN-induced [Ca++]i rise. The response of [Ca++]i to TTN was also sensitive to mibefradil and flunarizine (T-type Ca++-channel blockers), but not to nifedipine, verapamil (L-type) or omega-conotoxin GVIA (N-type). In agreement with this observation, PCR analysis showed the expression in human PMNs of the mRNA for all the alpha1 subunits of T-type Ca++ channels (namely, alpha1G, alpha1H, and alpha1I). CONCLUSIONS: In human PMNs TTN activates PKC-modulated pathways leading to Ca++ entry possibly through T-type Ca++ channels.

  13. Intracellular calcium changes induced by the endozepine triakontatetraneuropeptide in human polymorphonuclear leukocytes: role of protein kinase C and effect of calcium channel blockers

    PubMed Central

    Marino, Franca; Cosentino, Marco; Ferrari, Marco; Cattaneo, Simona; Frigo, Giuseppina; Fietta, Anna M; Lecchini, Sergio; Frigo, Gian Mario

    2004-01-01

    Background The endozepine triakontatetraneuropeptide (TTN) induces intracellular calcium ([Ca++]i) changes followed by activation in human polymorphonuclear leukocytes (PMNs). The present study was undertaken to investigate the role of protein kinase (PK) C in the modulation of the response to TTN by human PMNs, and to examine the pharmacology of TTN-induced Ca++ entry through the plasma membrane of these cells. Results The PKC activator 12-O-tetradecanoylphorbol-13-acetate (PMA) concentration-dependently inhibited TTN-induced [Ca++]i rise, and this effect was reverted by the PKC inhibitors rottlerin (partially) and Ro 32-0432 (completely). PMA also inhibited TTN-induced IL-8 mRNA expression. In the absence of PMA, however, rottlerin (but not Ro 32-0432) per se partially inhibited TTN-induced [Ca++]i rise. The response of [Ca++]i to TTN was also sensitive to mibefradil and flunarizine (T-type Ca++-channel blockers), but not to nifedipine, verapamil (L-type) or ω-conotoxin GVIA (N-type). In agreement with this observation, PCR analysis showed the expression in human PMNs of the mRNA for all the α1 subunits of T-type Ca++ channels (namely, α1G, α1H, and α1I). Conclusions In human PMNs TTN activates PKC-modulated pathways leading to Ca++ entry possibly through T-type Ca++ channels. PMID:15228623

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

    NASA Astrophysics Data System (ADS)

    COROT Team

    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 Baikonour. 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 "transit" 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 by

  15. Angiotensin II receptor blocker-based therapy in Japanese elderly, high-risk, hypertensive patients.

    PubMed

    Ogawa, Hisao; Kim-Mitsuyama, Shokei; Matsui, Kunihiko; Jinnouchi, Tomio; Jinnouchi, Hideaki; Arakawa, Kikuo

    2012-10-01

    It is unknown whether high-dose angiotensin II receptor blocker therapy or angiotensin II receptor blocker + calcium channel blocker combination therapy is better in elderly hypertensive patients with high cardiovascular risk. The objective of the study was to compare the efficacy of these treatments in elderly, high-risk Japanese hypertensive patients. The OlmeSartan and Calcium Antagonists Randomized (OSCAR) study was a multicenter, prospective, randomized, open-label, blinded-end point study of 1164 hypertensive patients aged 65 to 84 years with type 2 diabetes or cardiovascular disease. Patients with uncontrolled hypertension during treatment with olmesartan 20 mg/d were randomly assigned to receive 40 mg/d olmesartan (high-dose angiotensin II receptor blocker) or a calcium channel blocker + 20 mg/d olmesartan (angiotensin II receptor blocker + calcium channel blocker). The primary end point was a composite of cardiovascular events and noncardiovascular death. During a 3-year follow-up, blood pressure was significantly lower in the angiotensin II receptor blocker + calcium channel blocker group than in the high-dose angiotensin II receptor blocker group. Mean blood pressure at 36 months was 135.0/74.3 mm Hg in the high-dose angiotensin II receptor blocker group and 132.6/72.6 mm Hg in the angiotensin II receptor blocker + calcium channel blocker group. More primary end points occurred in the high-dose angiotensin II receptor blocker group than in the angiotensin II receptor blocker + calcium channel blocker group (58 vs 48 events, hazard ratio [HR], 1.31, 95% confidence interval, 0.89-1.92; P=.17). In patients with cardiovascular disease at baseline, more primary events occurred in the high-dose angiotensin II receptor blocker group (HR, 1.63, P=.03); in contrast, fewer events were observed in the subgroup without cardiovascular disease (HR, 0.52, P=.14). This treatment-by-subgroup interaction was significant (P=.02). The angiotensin II receptor blocker and

  16. Adverse effects of neuromuscular blockers and their antagonists.

    PubMed

    Naguib, M; Magboul, M M

    1998-06-01

    Among all the drugs used for general anesthesia, neuromuscular blockers appear to play a prominent role in the incidence of severe adverse reactions. It now seems likely that most serious adverse drug reactions occurring during anesthesia are immunological in type. The frequency of life-threatening anaphylactic or anaphylactoid reactions occurring during anesthesia has been estimated to be between 1 in 1000 and 1 in 25,000 anesthetic procedures, with the neuromuscular blockers being involved in 80% of cases. The mortality from such serious reactions is reported to be in the range of 3.4 to 6%. The highly immunogenic drug, suxamethonium chloride (succinylcholine), was found to be the most hazardous agent. Drug-specific immunoglobulin E antibodies to suxamethonium chloride and other neuromuscular blockers have been demonstrated. This sensitivity to neuromuscular blockers seems to be a long-lasting phenomenon. During anesthesia, the clinical features of an allergic reaction are often masked. Tachycardia and circulatory collapse may be the only signs of an allergic reaction, and they are easily misdiagnosed. Bronchospasm is reported to be present in about 40% of cases. Successful management of these patients includes stabilisation during the acute reaction and avoidance of future reactions. The latter is based on the identification of the causative drug and potentially cross-reacting compounds. The use of suxamethonium chloride is associated with many other adverse effects, such as fasciculations, myalgia, potassium release, changes in the heart rate, increases in intragastric and intraocular pressures, and malignant hyperthermia. Because of the dangers of hyperkalemic cardiac arrest suxamethonium chloride administration in children with unrecognised muscular dystrophy, there have now been moves to limit the use of this drug in children. Although neuromuscular blockers are designed to specifically block nicotinic cholinergic receptors at the neuromuscular junction

  17. Anti-SSA Ro52/Ro60 antibody testing by immunodot could help the diagnosis of Sjogren's syndrome in the absence of anti-SSA/SSB antibodies by ELISA.

    PubMed

    Mekinian, Arsène; Nicaise-Roland, Pascale; Chollet-Martin, Sylvie; Fain, Olivier; Crestani, Bruno

    2013-12-01

    The objective of this study was to assess the diagnostic value of anti-Ro52/60 antibodies by immunodot in patients with suspected SS. All patients between 2008 and 2012 with suspected SS without anti-SSA/SSB antibodies by ELISA and who had a determination of anti-SSA (Ro52/Ro60) antibodies by immunodot (Euroimmun, Germany) were retrospectively analysed. Eighty-four patients (median age 62 years; males 35 cases) were included. Forty-five patients had associated interstitial lung disease (ILD). American-European Consensus Group (AECG) criteria for SS were fulfilled in 10 patients (12%) with a positive salivary gland biopsy, and among them 2 patients had anti-Ro52 antibodies by dot (20%). Among 74 patients with a negative salivary gland biopsy, 16 (22%) had anti-Ro52/60 antibodies and 10 (14%) fulfilled AECG criteria when including Ro52/60 antibodies. A comparison of patients with and without anti-Ro52/60 antibodies revealed no differences, except gamma globulin levels and more frequent steroid use in patients with anti-Ro52/60 antibodies (P < 0.05). In 45 patients with ILD and dry eye/mouth syndrome, 10 (22%) had positive anti-Ro52/60 antibodies. In these patients 2 (4%) fulfilled AECG criteria without anti-Ro52/60 antibodies vs 4 (8%) patients if anti-Ro52/60 antibodies were included. In patients with dry eye/mouth syndrome without anti-SSA/SSB antibodies by ELISA, the detection of anti-Ro52/Ro60 antibodies by dot could help in the diagnosis of SS. In patients with ILD, the lower frequency of a Chisholm score ≥3 enhances the interest of anti-Ro52/Ro60 screening.

  18. Tumor-infiltrating CD45RO(+) Memory T Lymphocytes Predict Favorable Clinical Outcome in Solid Tumors.

    PubMed

    Hu, Guoming; Wang, Shimin

    2017-09-04

    The prognostic role of tumor-infiltrating CD45RO(+) memory T lymphocytes (CD45RO(+) T cells) in human solid tumors remains controversial. Herein, we conducted a meta-analysis including 25 published studies with 4720 patients identified from PubMed and EBSCO to assess the prognostic impact of tumor-infiltrating CD45RO(+) T cells in human solid tumors. We found that CD45RO(+) T cell infiltration was significantly associated with improved overall survival (OS) and disease-free survival (DFS) in all types of solid tumors. In stratified analyses, CD45RO(+) T cell infiltration significantly improved 1-year, 3-year and 5-year OS in colorectal, gastric and esophageal cancer, but only 5-year OS in hepatocellular carcinoma. And these cells were positively associated with 1-year, 3-year and 5-year DFS in hepatocellular, colorectal and esophageal cancer. In addition, high density of intratumoral CD45RO(+) T cells inversely correlated with TNM stage of solid tumor. In conclusion, CD45RO(+) memory T lymphocyte infiltration leads to a favorable clinical outcome in solid tumors, implicating that it is a valuable biomarker for prognostic prediction for human solid malignances.

  19. Experimental results from RO-PRO: a next generation system for low-energy desalination.

    PubMed

    Achilli, Andrea; Prante, Jeri L; Hancock, Nathan T; Maxwell, Eric B; Childress, Amy E

    2014-06-03

    A pilot system was designed and constructed to evaluate reverse osmosis (RO) energy reduction that can be achieved using pressure-retarded osmosis (PRO). The RO-PRO experimental system is the first known system to utilize energy from a volume of water transferred from atmospheric pressure to elevated pressure across a semipermeable membrane to prepressurize RO feedwater. In other words, the system demonstrated that pressure could be exchanged between PRO and RO subsystems. Additionally, the first experimental power density data for a RO-PRO system is now available. Average experimental power densities for the RO-PRO system ranged from 1.1 to 2.3 W/m2. This is higher than previous river-to-sea PRO pilot systems (1.5 W/m2) and closer to the goal of 5 W/m2 that would make PRO an economically feasible technology. Furthermore, isolated PRO system testing was performed to evaluate PRO element performance with higher cross-flow velocities and power densities exceeding 8 W/m2 were achieved with a 28 g/L NaCl draw solution. From this empirical data, inferences for future system performance can be drawn that indicate future RO-PRO systems may reduce the specific energy requirements for desalination by ∼1 kWh/m3.

  20. 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.

  1. 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.

  2. 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.

  3. [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.

  4. 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

  5. Stability of high-dose insulin in normal saline bags for treatment of calcium channel blocker and beta blocker overdose.

    PubMed

    Laskey, Dayne; Vadlapatla, Rajesh; Hart, Katherine

    2016-11-01

    High-dose insulin has become a first-line therapy for treating severe calcium channel blocker and beta blocker toxicity. Insulin infusions used to treat other conditions (e.g., diabetic ketoacidosis) may be used, but this may lead to pulmonary compromise due to fluid volume overload. An obvious solution would be to use a more concentrated insulin infusion; however, data describing the stability of insulin in polyvinyl chloride bags at concentrations >1 unit/mL are not readily available. To determine the stability of insulin at 16 units/mL in 0.9% saline solution. Eight-hundred units of regular insulin (8 mL from a stock vial containing 100 units/mL) were added to 42 mL of 0.9% saline solution in a polyvinyl chloride bag to make a final concentration of 16 units/mL. Two bags were stored at 4 °C (refrigerated) and two at 25 °C (room temperature). Samples were withdrawn and tested for insulin concentration periodically over 14 days. Concentrated regular insulin in a polyvinyl chloride bag remained within 90% of equilibrium concentration at all time points, indicating the 16 units/mL concentration was sufficiently stable both refrigerated and at room temperature for 14 days. Administration of high-dose insulin can cause fluid volume overload when using traditional insulin formulations. The 16 units/mL concentration allows for the treatment of a patient with severe calcium channel blocker or beta blocker toxicity for a reasonable period of time without administering excessive fluid. Insulin at a concentration of 16 units/mL is stable for 14 days, the maximum timeframe currently allowed under US Pharmacopeia rules for compounding of sterile preparations. This stability data will allow institutions to issue beyond-use dating for intravenous fluids containing concentrated insulin and used for treating beta blocker and calcium channel blocker toxicity.

  6. 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.

  7. Calcium channel blockers for acute traumatic brain injury.

    PubMed

    Langham, J; Goldfrad, C; Teasdale, G; Shaw, D; Rowan, K

    2003-01-01

    Acute traumatic brain injury is a major cause of death and disability. Calcium channel blockers (calcium antagonists) have been used in an attempt to prevent cerebral vasospasm after injury, maintain blood flow to the brain, and so prevent further damage. To estimate the effects of calcium channel blockers in patients with acute traumatic brain injury, and in a subgroup of brain injury patients with traumatic subarachnoid haemorrhage. Handsearching and electronic searching for randomised controlled trials. Randomised controlled trials in patients with all levels of severity of clinically diagnosed acute traumatic brain injury. Two reviewers independently assessed the identified studies for eligibility and extracted data from each study. Summary odds ratios were calculated using the Mantel-Haenszel method. Six RCTs were identified as eligible for inclusion in the systematic review. The effect of calcium channel blockers on the risk of death was reported in five of the RCTs. The pooled odds ratio (OR) for the five studies was 0.91 (95% confidence interval [95%CI] 0.70-1.17). For the four RCTs that reported death and severe disability (unfavourable outcome), the pooled odds ratio was 0.85 (95%CI 0.68-1.07). In the two RCTs which reported the risk of death in a subgroup of traumatic subarachnoid haemorrhage patients, the pooled odds ratio was 0.59 (95%CI 0.37-0.94). Three RCTs reported death and severe disability as an outcome in this subgroup, and the pooled odds ratio was 0.67 (95%CI 0.46-0.98). This systematic review of randomised controlled trials of calcium channel blockers in acute traumatic head injury patients shows that considerable uncertainty remains over their effects. The effect of nimodipine in a subgroup of brain injury patients with subarachnoid haemorrhage shows a beneficial effect, though the increase in adverse reactions suffered by the intervention group may mean that the drug is harmful for some patients.

  8. Topical beta blockers in asthmatic patients-is it safe?

    PubMed

    Kaiserman, Igor; Fendyur, Anna; Vinker, Shlomo

    2009-07-01

    To investigate the use of topical ocular anti-glaucoma medications by glaucomatous patients with obstructive pulmonary disease and their effect on related hospitalizations and emergency room visits. We followed the electronic medical records of all the members in a district of the largest health maintenance organization in Israel (the "central district" of Clalit Health Services) older than 20 years (317,469 members); 6597 of them were on chronic topical anti-glaucoma treatment of which 693 (10.5%) suffered from obstructive pulmonary disease (OPD). In a historical cohort study, we documented all anti-glaucoma prescriptions filled in the district between January 1, 2001, and December 31, 2003, and all emergency room (ER) visits and hospitalizations in internal medicine, geriatric, or pulmonology departments. The rate of hospitalization and emergency room visits during treatment with each anti-glaucoma medication. Five hundred forty-four glaucomatous OPD patients (78.5%) were treated with topical beta-blockers, but only 169 (31.1%) of them received a cardio-selective beta-blocker (betaxolol). Patients treated with betaxolol each received more prescriptions per year than patients treated with timolol (p < 0.0001). Patients on topical betaxolol or timolol had 23.1 and 20.7 hospitalization days as well as 7.3 and 6.1 emergency room visits per 100 treatments per year, respectively, compared to a mean of 10 hospitalization days (p < 0.0001) and 5.0 ER visits for patients on non-beta-blocker anti-glaucoma medications. A majority of glaucomatous patients with obstructive pulmonary disease were treated with topical beta-blockers, mostly non-cardioselective (timolol). Those patients were more prone to be hospitalized or visit the emergency room while on the medication.

  9. 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.

  10. Serotonin uptake blockers and the treatment of alcoholism.

    PubMed

    Gorelick, D A

    1989-01-01

    There is growing research and clinical interest in the role of brain serotonin in regulating alcohol consumption, based on two lines of evidence: negative correlations between brain serotonin levels and spontaneous alcohol consumption in rodents, and decreased alcohol intake produced by drug-induced increases in brain serotonin activity in rodents and humans. Specific blockers of neuronal serotonin uptake, such as citalopram, fluoxetine, and zimelidine, are the major drugs used in such studies. More than a dozen studies have consistently found that such specific serotonin uptake blockers reduce alcohol preference and intake in rodents, whereas nonspecific monoamine uptake blockers (e.g., amitriptyline, doxepin) do not. The effect begins within 1 hr of administration, wears off within several days of stopping drug, and often shows tolerance after 4-10 days of daily administration (the opposite time course from antidepressant action in humans). In four human, double-blind, placebo-controlled studies, citalopram (40 mg but not 20 mg daily), fluoxetine (80 mg daily), and zimelidine (200 mg more than 300 mg daily) significantly reduced alcohol intake 10-26% in social drinkers, early problem drinkers, and chronic alcoholics. The effect occurred within a few days, wore off within several days of stopping drug, and lasted throughout the 2-4 weeks of drug administration, except that in the fluoxetine study with chronic alcoholics the effect was significant only during the first week. The reduced alcohol intake was not due to sedation, antidepression, or antianxiety effects, or an aversive drug-alcohol interaction, but could be explained in part by decreased appetitive behavior (two studies found that subjects lost weight) or a conditioned (taste) aversion to alcohol promoted by serotonin (as occurs in animals). Further research is also needed to clarify the neuropharmacological mechanism of action, since the alcohol intake-reducing effects in rodents are not blocked by

  11. 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

  12. 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.

  13. 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

  14. 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

  15. Retention of β blockers on native titania stationary phase.

    PubMed

    El Debs, Racha; Abi Jaoudé, Maguy; Morin, Nicolas; Miege, Cécile; Randon, Jérôme

    2011-08-01

    In recent years, metal oxides such as titania have been commercially available as chromatographic beds that can potentially be used to achieve novel separations of polar compounds. For example β blockers, which are more often encountered in environmental sciences, have a wide range of polarity, and their basic character leads to difficult sample treatment and separation on conventional silica-based sorbents. The contribution of titania to the selective analysis of nine β blockers was evaluated in terms of retention mechanisms observed in hydrophilic interaction LC using acetonitrile/water mobile phases with various additives. The mobile phase additives enabled to control the β blocker charge as well as the titania surface charge. Depending on their respective ionic state, various retention mechanisms were identified at low water contents (<40%), including mainly adsorption mixed with hydrophilic interaction LC partition, ion exchange and ion exclusion. An unexpected retention was also observed for high water content and high pH, changing the selectivity of the support. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. The role of Angiotensin receptor blocker and calcium channel blocker combination therapy in treating hypertension: focus on recent studies.

    PubMed

    Chrysant, Steven G

    2010-01-01

    Hypertension remains a significant health problem, affecting approximately 30% of the US population. Of these, only 36.8% have BP controlled to recommended levels of <140/90 mmHg for uncomplicated hypertension and <130/80 mmHg for patients with diabetes mellitus or renal disease. For those with uncontrolled hypertension, the risk of diabetes, renal disease, stroke, and cardiovascular disease is increased. Therapeutic options for the treatment of hypertension include several major classes of drugs: diuretics, β-adrenoceptor antagonists (β-blockers), ACE inhibitors, angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]), renin inhibitors, calcium channel blockers, and central sympatholytics, alone or in combination. Guidelines recommend thiazide diuretics as preferred first-line monotherapy. However, only 50% of patients will respond adequately to this therapy and the rest will require two or more antihypertensive agents to achieve BP goals. Clinical evidence demonstrates that some drugs have advantages when used in combination rather than as monotherapy. Drugs that block the renin-angiotensin-aldosterone system not only provide BP control but may also provide vascular protection and are metabolically neutral. This is a concise review of the safety and efficacy of ARBs in combination with amlodipine for the treatment of hypertension, with focus on the telmisartan-amlodipine combination. A MEDLINE search of the English literature from 2006 to 2009 of amlodipine in combination with ARBs revealed six publications, which are included in this review.

  1. 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

  2. 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

  3. 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.

  4. Nonvariational Orbital Optimization Techniques for the AP1roG Wave Function.

    PubMed

    Boguslawski, Katharina; Tecmer, Paweł; Bultinck, Patrick; De Baerdemacker, Stijn; Van Neck, Dimitri; Ayers, Paul W

    2014-11-11

    We introduce new nonvariational orbital optimization schemes for the antisymmetric product of one-reference orbital geminal (AP1roG) wave function (also known as pair-coupled cluster doubles) that are extensions to our recently proposed projected seniority-two (PS2-AP1roG) orbital optimization method [ J. Chem. Phys. 2014 , 140 , 214114 )]. These approaches represent less stringent approximations to the PS2-AP1roG ansatz and prove to be more robust approximations to the variational orbital optimization scheme than PS2-AP1roG. The performance of the proposed orbital optimization techniques is illustrated for a number of well-known multireference problems: the insertion of Be into H2, the automerization process of cyclobutadiene, the stability of the monocyclic form of pyridyne, and the aromatic stability of benzene.

  5. Anti-Ro/SSA antibodies are associated with severe mitral valve regurgitation in patients with systemic lupus erythematosus.

    PubMed

    Higuera-Ortiz, Violeta; Mora-Arias, Tania; Castillo-Martinez, Diana; Amezcua-Guerra, Luis M

    2017-05-01

    To assess whether anti-Ro/SSA antibodies are associated with cardiac valve disease in lupus. A single-center, medical chart review was performed. Lupus patients were divided according to its anti-Ro/SSA status and subgroups were compared for valvular abnormalities and other characteristics. Dependence of anti-Ro/SSA reactivity to anti-Ro52/TRIM21 antibodies was also evaluated. Eighty-nine lupus patients were analyzed. The most common valvular abnormalities were tricuspid (60%), mitral (41%) and pulmonary (14%) regurgitation. Thirty-six patients were positive and 53 negative for anti-Ro/SSA antibodies. In patients positive to anti-Ro/SSA, a difference was noted for anti-dsDNA (67 versus 45%; p = 0.04) and anti-La/SSB (19 versus 2%; p = 0.004) antibodies. An association between anti-Ro/SSA antibodies and severe mitral regurgitation was observed; indeed, 4/15 patients with anti-Ro/SSA and mitral regurgitation had severe forms of valvulopathy as compared to only 1/22 patients with mitral regurgitation but negative to such antibody (27 versus 5%; p = 0.02). Anti-Ro/SSA antibodies significantly elevated the risk of severe mitral regurgitation (OR = 5). Anti-Ro52/TRIM21 levels (103 ± 29 versus 42 ± 43 U/mL; p = 0.03) and anti-Ro52/TRIM21: anti-Ro/SSA ratios (0.88 ± 0.02 versus 0.35 ± 0.37; p = 0.03) were higher in patients with mitral valve regurgitation than in those with no valvulopathy. Anti-Ro/SSA antibodies, mainly against Ro52/TRIM21 antigens, may be pathologically involved in lupus-associated mitral valve regurgitation.

  6. 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

  7. 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

  8. 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.

  9. Association of anti-Ro/SSA antibody with response to biologics in patients with rheumatoid arthritis.

    PubMed

    Hagiwara, Shinya; Tsuboi, Hiroto; Honda, Fumika; Takahashi, Hidenori; Kurata, Izumi; Ohyama, Ayako; Yagishita, Mizuki; Abe, Saori; Kurashima, Yuko; Kaneko, Syunta; Kawaguchi, Hoshimi; Takahashi, Hiroyuki; Ebe, Hiroshi; Yokosawa, Masahiro; Asashima, Hiromitsu; Hirota, Tomoya; Umeda, Naoto; Kondo, Yuya; Matsumoto, Isao; Sumida, Takayuki

    2016-11-01

    To compare the effectiveness of three different biologics in anti-Ro/SSA antibody-positive and antibody-negative patients with rheumatoid arthritis (RA). The study subjects were 110 biologics naïve patients with RA who started treatment with biologics and examined for anti-Ro/SSA antibody between December 2003 and March 2014. For patients treated with intravenous infliximab (IFX), tocilizumab (TCZ), or abatacept (ABT), we compared the clinical characteristics and changes in composite disease activity index, such as DAS28, SDAI, and CDAI, for 12 months in anti-Ro/SSA antibody-positive and antibody-negative patients. We examined 59 patients (nine were positive and 50 were negative for anti-Ro/SSA antibody) treated with IFX, 27 patients (5 positive and 22 negative) treated with TCZ, and 24 patients (13 positive and 11 negative) treated with ABT. For patients treated with IFX, parameters of disease activity did not change significantly from baseline in anti-Ro/SSA antibody-positive patients, whereas they improved in antibody-negative patients. On the other hand, treatment with TCZ and ABT significantly decreased disease activity, relative to baseline, in both anti-Ro/SSA antibody-positive and antibody-negative patients. Anti-Ro/SSA antibody-positive patients treated with IFX showed higher frequency of HACA and seroconversion of ANA, and lower serum TGF-β levels. Positivity to anti-Ro/SSA in RA seems to confer resistance to IFX via production of HACA and ANA, and low serum TGF-β levels, but not to TCZ and ABT.

  10. The generalizability of trial data; a comparison of beta-blocker trial participants with a prospective cohort of women taking beta-blockers in pregnancy.

    PubMed

    Magee, L A; Bull, S B; Koren, G; Logan, A

    2001-02-01

    To evaluate the generalizability of randomized controlled trial (RCT) data to obstetric practice, using the example of beta-blocker therapy. Descriptive comparison of characteristics of participants, interventions, and outcomes assessed between a meta-analysis of trials of beta-blocker therapy in pregnancy, and a prospective cohort of beta-blocker exposed callers to Motherisk, a Teratology Information Service. 72 women (cohort) and 34 trials with 2474 participants (meta-analysis) were compared. The generalizability of trials was limited by an inadequate description of maternal demographics and indications for beta-blockers, and a focus on the effectiveness of beta-blockers as antihypertensives rather than on reproductive risks. Some of these limitations could be rectified. Others cannot, such as evaluation of teratogenicity (for ethical reasons) or all indications for a drug (for practical reasons). Reference to observational literature is, and will likely remain, necessary to address the 'harm' side of the therapeutic equation in pregnancy.

  11. CoRoT-7b: SUPER-EARTH OR SUPER-Io?

    SciTech Connect

    Barnes, Rory; Kaib, Nathan A.; Raymond, Sean N.; Greenberg, Richard; Jackson, Brian

    2010-02-01

    CoRoT-7b, a planet about 70% larger than the Earth orbiting a Sun-like star, is the first-discovered rocky exoplanet, and hence has been dubbed a 'super-Earth'. Some initial studies suggested that since the planet is so close to its host star, it receives enough insolation to partially melt its surface. However, these past studies failed to take into consideration the role that tides may play in this system. Even if the planet's eccentricity has always been zero, we show that tidal decay of the semimajor axis could have been large enough that the planet formed on a wider orbit which received less insolation. Moreover, CoRoT-7b could be tidally heated at a rate that dominates its geophysics and drives extreme volcanism. In this case, CoRoT-7b is a 'super-Io' that, like Jupiter's volcanic moon, is dominated by volcanism and rapid resurfacing. Such heating could occur with an eccentricity of just 10{sup -5}. This small value could be driven by CoRoT-7c if its own eccentricity is larger than {approx}10{sup -4}. CoRoT-7b may be the first of a class of planetary super-Ios likely to be revealed by the CoRoT and Kepler spacecraft.

  12. 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.

  13. 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.

  14. 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

  15. Calcium channel blockers enhance sac shrinkage after endovascular aneurysm repair.

    PubMed

    Bailey, Marc A; Sohrabi, Soroush; Flood, Karen; Griffin, Kathryn J; Rashid, S Tawqeer; Johnson, Anne B; Baxter, Paul D; Patel, Jai V; Scott, D Julian A

    2012-06-01

    Sac shrinkage is a surrogate marker of success after endovascular aneurysm repair (EVAR). We set out to determine if any common cardioprotective medications had a beneficial effect on sac shrinkage. This retrospective observational study took place at Leeds Vascular Institute, a tertiary vascular unit in the Northern United Kingdom. The cohort comprised 149 patients undergoing EVAR between January 1, 2005, and December 31, 2008. Medication use was recorded at intervention (verified at study completion in 33 patients), and patients were monitored for 2 years. The main outcome measures were the effect of medication on sac shrinkage as determined by percentage change in maximal idealized cross-sectional area of the aneurysm at 1 month, 6 months, 1 year, and 2 years by linear regression model, in addition to 2-year endoleak and death rates determined by a binary logistic regression model. After exclusions, 112 patients, who were a median age of 78 years (interquartile range, 78-83 years), remained for analysis. The median Glasgow Aneurysm Score was 85 (interquartile range, 79-92). At 2 years, mortality was 13.4%, endoleak developed in 37.5%, and significant endoleak developed in 14.3%. Patients taking a calcium channel blocker had enhanced sac shrinkage, compared with those not taking a calcium channel blocker, by 6.6% at 6 months (-3.0% to 16.3%, P = .09), 12.3% at 1 year (2.9% to 21.7%, P = .008), and 13.1% at 2 years (0.005% to 26.2%, P = .007) independent of other medication use, graft type, endoleak development, or death. Enhanced sac shrinkage occurred after EVAR in patients taking calcium channel blockers. This warrants further study in other centers and at the molecular level. Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  16. Beta-Blockers for Exams Identify Students at High Risk of Psychiatric Morbidity.

    PubMed

    Butt, Jawad H; Dalsgaard, Søren; Torp-Pedersen, Christian; Køber, Lars; Gislason, Gunnar H; Kruuse, Christina; Fosbøl, Emil L

    2017-04-01

    Beta-blockers relieve the autonomic symptoms of exam-related anxiety and may be beneficial in exam-related and performance anxiety, but knowledge on related psychiatric outcomes is unknown. We hypothesized that beta-blocker therapy for exam-related anxiety identifies young students at risk of later psychiatric events. Using Danish nationwide administrative registries, we studied healthy students aged 14-30 years (1996-2012) with a first-time claimed prescription for a beta-blocker during the exam period (May-June); students who were prescribed a beta-blocker for medical reasons were excluded. We matched these students on age, sex, and time of year to healthy and study active controls with no use of beta-blockers. Risk of incident use of antidepressants, incident use of other psychotropic medications, and suicide attempts was examined by cumulative incidence curves for unadjusted associations and multivariable cause-specific Cox proportional hazard analyses for adjusted hazard ratios (HRs). We identified 12,147 healthy students with exam-related beta-blocker use and 12,147 matched healthy students with no current or prior use of beta-blockers (median age, 19 years; 80.3% women). Among all healthy students, 0.14% had a first-time prescription for a beta-blocker during the exam period with the highest proportion among students aged 19 years (0.39%). Eighty-one percent of the students filled only that single prescription for a beta-blocker during follow-up. During follow-up, 2225 (18.3%) beta-blocker users and 1400 (11.5%) nonbeta-blocker users were prescribed an antidepressant (p < 0.0001); 1225 (10.1%) beta-blocker users and 658 (5.4%) nonbeta-blocker users were prescribed a psychotropic drug (p < 0.0001); and 16 (0.13%) beta-blocker users and 6 (0.05%) nonbeta-blocker users attempted suicide (p = 0.03). Exam-related beta-blocker use was associated with an increased risk of antidepressant use (adjusted HRs, 1.68 [95% confidence intervals (CIs), 1

  17. 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.

  18. [Vasoprotective effects of statins and angiotensin II blockers in atherothrombosis].

    PubMed

    Egido, J; Ruiz-Ortega, M; Muñoz-García, B; Martín-Ventura, J L; Blanco-Colio, L M

    2005-01-01

    Cardiovascular disease, including atherothrombosis, is the most frequent cause of mortality in the Western World. In the last years, major advances have been made in the pathogenesis of this disease. Currently, the drugs most widely used are the inhibitors of the HMG-CoA reductase (statins) and the antihypertensive drugs, mainly angiotensin II blockers. The first group has been shown to be effective on cardiovascular disease due to atherothrombosis, and the second group on hypertensive disease. Nevertheless, recent data suggest that these two situations can improve with the concomitant use of both drugs.

  19. 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.

  20. [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.

  1. 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

  2. Beta-blockers and depression in elderly hypertension patients in primary care.

    PubMed

    Ringoir, Lianne; Pedersen, Susanne S; Widdershoven, Jos W M G; Pouwer, Francois; Keyzer, Josephine M L; Romeijnders, Arnold C; Pop, Victor J M

    2014-06-01

    Previous findings regarding a possible association between beta-blocker use and depression are mixed. To our knowledge there have been no studies investigating the association of beta-blockers with depression in primary care hypertension patients without previous myocardial infarction. The aim of this study was to determine the relation between lipophilic beta-blocker use and depression in elderly primary care patients with hypertension. This was a cross-sectional study in primary care practices located in the South of The Netherlands. Primary care hypertension patients without previous myocardial infarction or heart failure (n=573), aged between 60 and 85 years (mean age=70±6.6), were included. All patients underwent a structured interview that included a self-report questionnaire to assess depression (PHQ-9), which was divided in four groups (PHQ-9 score of 0, 1--3, 4--8, 9 or higher). A PHQ-9 score of 0 was more prevalent in non-beta-blocker users versus lipophilic beta-blocker users (46% versus 35%), a PHQ-9 score of 4--8 was less prevalent in non-beta-blocker users as compared with lipophilic beta-blocker users (14% versus 25%). A chi-squared test showed that lipophilic beta-blocker users as compared to non-beta-blockers users were more likely to be in a higher depression category. Ordinal regression showed a significant relationship between use of lipophilic beta-blockers and depression (OR=1.60, 95% CI=1.08--2.36) when adjusting for potential confounders. Our findings show that primary care hypertension patients who use a lipophilic beta-blocker are more likely to have higher depression scores than those who do not use a lipophilic beta-blocker.

  3. Outcomes of β-blocker use in pulmonary arterial hypertension: a propensity-matched analysis.

    PubMed

    Bandyopadhyay, Debabrata; Bajaj, Navkaranbir S; Zein, Joe; Minai, Omar A; Dweik, Raed A

    2015-09-01

    The utility and safety of β-blockers in pulmonary hypertension is controversial. Anecdotal reports suggest that β-blockers may be harmful in these patients. The aim of our study was to evaluate outcomes of β-blocker use in pulmonary hypertension.We reviewed patients from our pulmonary hypertension registry between 2000 and 2011. Patients who continued to use β-blockers were compared to those who never used β-blockers for all-cause mortality, time to clinical worsening events, defined as death, lung transplantation and hospitalisation due to pulmonary hypertension. We also evaluated the effect of β-blockers on 6-min walking distance and New York Heart Association (NYHA) functional class.133 patients used β-blockers and 375 patients never used β-blockers. Mean±sd age was 57±16 years and the median follow-up period was 78 months. Propensity-matched analysis showed that the adjusted odds ratio (95% CI) for mortality with β-blocker use was 1.13 (0.69-1.82) and for clinical worsening events was 0.96 (0.55-1.68). No significant difference was noted in probability of survival and time to clinical worsening events. Patients on β-blockers walked a shorter distance on follow-up 6 min walk test; follow-up NYHA class was similar between groups.Pulmonary hypertension patients receiving β-blockers had a similar survival and time to clinical worsening events compared to patients not receiving them. Functional outcomes were similar, although β-blocker use was associated with a tendency towards shorter walking distance. Copyright ©ERS 2015.

  4. The Beneficial Effect of Beta-Blockers in Patients With Cirrhosis, Portal Hypertension and Ascites.

    PubMed

    Aday, Ariel W; Mayo, Marlyn J; Elliott, Alan; Rockey, Don C

    2016-02-01

    Patients with cirrhosis and portal hypertensive complications have reduced survival. As such, it has been suggested that nonselective beta-blocker therapy in patients with advanced ascites is harmful. The aim of this study was, therefore, to determine the risk of mortality in patients with cirrhosis and ascites taking nonselective beta-blocker therapy for the prevention of variceal hemorrhage. This study was a retrospective analysis of 2,419 patients with cirrhosis and portal hypertension admitted to Parkland Memorial Hospital (a university-affiliated county teaching hospital) from 2003-2010. Patients were subdivided into those with varices only, ascites only and those with both varices and ascites. The primary outcome measure for this study was all-cause in-hospital mortality. Overall, 68 of 1,039 (6.5%) patients taking beta-blockers died during their hospitalization, while 223 of 1,380 (16.2%) patients not taking beta-blockers died (P < 0.001). Beta-blocker use was also assessed in specific cohorts; mortality was 21.1% in patients with severe ascites with varices who were not taking beta-blockers compared with 8.9% in patients who were taking beta-blockers (P = 0.05). Overall, fewer patients taking beta-blockers died compared with those not taking beta-blockers in patients with varices only (6.4% versus 12.1%) and those with ascites with or without varices (6.6% versus 18.1%) (P < 0.001). Mortality was lower in patients with cirrhosis and portal hypertension taking nonselective beta-blockers than in those not taking beta-blockers. The use of nonselective beta-blockers provided a significant survival benefit in patients with all grades of ascites, including those with severe ascites. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  5. β-Blocker use and incidence of chronic obstructive pulmonary disease exacerbations.

    PubMed

    Farland, Michelle Z; Peters, Cassey J; Williams, Juli D; Bielak, Kenneth M; Heidel, R Eric; Ray, Shaunta' M

    2013-05-01

    β-Adrenergic antagonist (β-blocker) use in patients with chronic obstructive pulmonary disease (COPD) has been avoided as a result of potential risk of pulmonary adverse effects. However, recent studies indicate that β-blocker use in patients with COPD can decrease outpatient visits and either decrease or have no effect on the number of hospitalizations. Long-term treatment with β-blockers has been shown to increase survival and decrease exacerbations in patients with COPD. To assess the impact of β-blocker use on the incidence of exacerbations in patients with COPD. In a retrospective cohort study of patients with COPD from 2 academic primary care practice sites who were seen in 2010, patients were identified using International Classification of Diseases, 9th revision, Clinical Modification codes for COPD and reviewing active medication lists for COPD-specific medications (tiotropium). Patients were classified as either a β-blocker user or a nonuser. Primary outcomes were incidence and severity of COPD exacerbations. Secondary outcomes included COPD exacerbations distinguished by β-blocker cardioselectivity and all-cause hospitalizations. The study enrolled 412 patients. Of those, 166 patients were β-blocker users and 246 were β-blocker nonusers. β-Blocker users were less likely to have a COPD exacerbation (OR 0.61, 95% CI 0.40-0.93) and had fewer mild exacerbations (OR 0.56; 95% CI 0.34-0.89). There was no significant difference in COPD exacerbations based on β-blocker cardioselectivity (OR 0.84, 95% CI 0.38-1.83). When controlled for, using a backwards stepwise logistic regression, β-blocker use was a variable in the model that predicted exacerbations but alone was not statistically significant (adjusted OR 0.62, 95% CI 0.39-1.01). Patients with COPD prescribed a β-blocker were significantly less likely to have a COPD exacerbation and had fewer mild COPD exacerbations.

  6. 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.

  7. 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.

  8. Relation of Sensory Peripheral Neuropathy in Sjögren Syndrome to anti-Ro/SSA

    PubMed Central

    Scofield, Amanda K.; Radfar, Lida; Ice, John; Vista, Evan; Anaya, Juan-Manuel; Houston, Glen; Lewis, David; Stone, Donald U.; Chodosh, James; Hefner, Kimberly; Lessard, Christopher J.; Moser, Kathy L.; Scofield, R. Hal

    2013-01-01

    Background Sjögren syndrome is a common, chronic autoimmune disease that typically produces inflammation and poor function of the salivary and lacrimal glands. Other organs can be affected, including the nervous system. Sensory peripheral neuropathy is a common manifestation of the disease. Methods Eight-eight patients attending a dry eyes-dry mouth clinic were classified as primary Sjögren syndrome and underwent a neurological examination. Anti-Ro (or SSA) and anti-La (or SSB) were determined using immunodiffusion as well as Inno-Lia and BioPlex ANA screen. Serum vitamin B12 levels were determined using an enzyme-linked microtiter plate assay. Results Twenty-seven (31%) of the 88 patients had peripheral neuropathy as defined by loss of light touch, proprioception or vibratory sensation. Anti-Ro and anti-La were found by immunodiffusion in 12 patients, and 8 of these 12 had neuropathy (χ2=8.46, p=0.0036, odds ratio = 6.0 compared to those without precipitating anti-Ro and anti-La). Of the 27 patients with only anti-Ro by immunodiffusion, 13 (48.1%) of these had neuropathy (χ2 =5.587, p=0.018 compared to those without anti-Ro). There was no relationship of the other, more sensitive measures of anti-Ro and anti-La to neuropathy. In addition, we found no association of serum vitamin B12 levels to neuropathy among these patients with Sjögren syndrome. Conclusion Sensory peripheral neuropathy is common among patients with Sjögren syndrome, and is associated with the presence of anti-Ro and anti-La when determined by immunodiffusion. PMID:22955477

  9. 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

  10. Evaluation of Skin Permeation of β-blockers for Topical Drug Delivery

    PubMed Central

    Chantasart, Doungdaw; Hao, Jinsong; Li, S. Kevin

    2013-01-01

    Purpose β-Blockers have recently become the main form of treatment of infantile hemangiomas. Due to the potential systemic adverse effects of β-blockers, topical skin treatment of the drugs is preferred. However, the effect and mechanism of dosage form pH upon skin permeation of these weak bases is not well understood. To develop an effective topical skin delivery system for the β-blockers, the present study evaluated skin permeation of β-blockers propranolol, betaxolol, timolol, and atenolol. Methods Experiments were performed in side-by-side diffusion cells with human epidermal membrane (HEM) in vitro to determine the effect of donor solution pH upon the permeation of the β-blockers across HEM. Results The apparent permeability coefficients of HEM for the β-blockers increased with their lipophilicity, suggesting the HEM lipoidal pathway as the main permeation mechanism of the β-blockers. The pH in the donor solution was a major factor influencing HEM permeation for the β-blockers with a 2- to 4-fold increase in the permeability coefficient per pH unit increase. This permeability versus pH relationship was found to deviate from theoretical predictions, possibly due to the effective stratum corneum pH being different from the pH in the donor solution. Conclusions The present results suggest the possibility of topical treatment of hemangioma using β-blockers. PMID:23208385

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. Open-channel blockers of the NMDA receptor complex.

    PubMed

    Albensi, Benedict C; Ilkanich, Erin

    2004-11-01

    A variety of compounds have been shown to limit or prevent excitotoxicity by blocking N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission. However, many first-generation NMDA antagonists did not live up to clinical expectations in trials of acute brain injury because of the manifestation of multiple side effects. In spite of this, development of NMDA antagonists continues, where some of the newer agents block excitotoxicity through alternative mechanisms. For example, blockers selective to the NR2B subunit or agents that block metabotropic glutamate receptors or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors are currently under investigation. Several years ago, the arylalkylamine spider toxins were demonstrated to function as open-channel blockers similar to memantine, which was very recently approved by the U.S. FDA for use in patients with Alzheimer's dementia. With this said, programs focusing on NMDA antagonism via alternative mechanisms may still hold promise for treating acute injury and even chronic forms of dementia.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. The end stage of dialysis access: femoral graft or HeRO vascular access device.

    PubMed

    Kudlaty, Elizabeth A; Pan, Jeanne; Allemang, Matthew T; Kendrick, Daniel E; Kashyap, Vikram S; Wong, Virginia L

    2015-01-01

    Maintaining and establishing vascular access in end-stage renal disease (ESRD) patients is complicated when they are poor candidates for traditional upper extremity access. Our objective was to compare our experience with 2 alternative dialysis accesses, the femoral arteriovenous graft (fAVG) and the Hemodialysis Reliable Outflow (HeRO), in patients with limited remaining options. A single institution, retrospective review of ESRD patients with fAVG or HeRO placed between May 2009 and February 2013 was performed. Adult patients were selected by reviewing all arteriovenous grafts placed at a single institution. Patient demographics, medical history, access characteristics, and outcomes were recorded from both institutional and dialysis center databases. Data were evaluated using Fisher's exact test, unpaired t-test for continuous variables, log-rank test, and univariate analysis. A total of 56 accesses in 43 unique patients met these criteria: 35 fAVG and 21 HeRO; with 1 HeRO patient lost immediately to follow-up. Clinical variables were similar except the HeRO group had more diabetic patients (60% HeRO, 22.9% fAVG; P = 0.01). The average number of years on hemodialysis was 7.0 ± 1.0 for fAVG and 5.7 ± 0.9 for HeRO (P = 0.41). Primary patency was 40.5%, 18.7%, and 14.9% for fAVG and 29.0%, 29.0%, and 0% for HeRO at 6 months, 12 months, and 2 years (P = 0.67), respectively. Assisted primary patency was also similar, with 43.8%, 29.4%, and 13.8% for fAVG and 34.8%, 34.8%, and 17.4% for HeRO at 6 months, 12 months, and 2 years (P = 0.81), respectively. Secondary patency was 62.6%, 50.6%, 19.3% for fAVG and 68.0%, 53.5%, 38.3% for HeRO at 6 months, 12 months, and 2 years (P = 0.69), respectively. Average number of interventions to maintain patency for fAVG was 1.1 ± 1.47 and 1.65 ± 2.52 for HeRO (P = 0.35). Infectious complications occurred in 29% of fAVG and 15% of HeRO (P = 0.33). Patients who received either fAVG or HeRO experience poor access patency. ESRD

  1. Linc-RoR promotes c-Myc expression through hnRNP I and AUF1

    PubMed Central

    Huang, Jianguo; Zhang, Ali; Ho, Tsui-Ting; Zhang, Ziqiang; Zhou, Nanjiang; Ding, Xianfeng; Zhang, Xu; Xu, Min; Mo, Yin-Yuan

    2016-01-01

    Linc-RoR was originally identified to be a regulator for induced pluripotent stem cells in humans and it has also been implicated in tumorigenesis. However, the underlying mechanism of Linc-RoR-mediated gene expression in cancer is poorly understood. The present study demonstrates that Linc-RoR plays an oncogenic role in part through regulation of c-Myc expression. Linc-RoR knockout (KO) suppresses cell proliferation and tumor growth. In particular, Linc-RoR KO causes a significant decrease in c-Myc whereas re-expression of Linc-RoR in the KO cells restores the level of c-Myc. Mechanistically, Linc-RoR interacts with heterogeneous nuclear ribonucleoprotein (hnRNP) I and AU-rich element RNA-binding protein 1 (AUF1), respectively, with an opposite consequence to their interaction with c-Myc mRNA. While Linc-RoR is required for hnRNP I to bind to c-Myc mRNA, interaction of Linc-RoR with AUF1 inhibits AUF1 to bind to c-Myc mRNA. As a result, Linc-RoR may contribute to the increased stability of c-Myc mRNA. Although hnRNP I and AUF1 can interact with many RNA species and regulate their functions, with involvement of Linc-RoR they would be able to selectively regulate mRNA stability of specific genes such as c-Myc. Together, these results support a role for Linc-RoR in c-Myc expression in part by specifically enhancing its mRNA stability, leading to cell proliferation and tumorigenesis. PMID:26656491

  2. 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.

  3. Transpiration Rate for Chile Peppers Irrigated with Brackish Groundwater and ro Concentrate

    NASA Astrophysics Data System (ADS)

    Shukla, M. K.; Baath, G.

    2016-12-01

    Fresh water availability is declining in most of the semi-arid and arid regions across the world including southwestern United States. Use of marginal quality groundwater has been increasing for sustaining agriculture in these arid regions. Reverse Osmosis (RO) can treat brackish groundwater but the possibility of using RO concentrate for irrigation needs further exploration. This greenhouse study evaluates the transpiration rate, water use, leaching fraction and yield responses of five selected chile pepper (Capsicum annuum) cultivars irrigated with natural brackish groundwater and RO concentrate. The four saline water treatments used for irrigation were tap water of EC 0.6 (control), ground water of EC 3 and 5 dS/m and RO concentrate of EC 8 dS/m. The transpiration of all chile peppers cultivars decreased and leaching fraction increased with increasing irrigation water salinity. Based on the water use efficiency (WUEY) of selected chile pepper cultivars, brackish water of EC ≤ 3 dS/m can be used for irrigation. The average yield of chile peppers was stable up to a saturated soil paste extract electrical conductivity (ECe) of about 2 dS/m, although further increases in ECe resulted in an exponential yield decline. This study showed that yield reductions in chile peppers irrigated with Ca rich brackish groundwater were less than those reported using NaCl dominant saline solution studies. Environmentally safe reuse of RO concentrate could stimulate implementation of inland desalination in water scarce areas and increase greenhouse chile pepper cultivation.

  4. 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.

  5. 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.

  6. Anti-Ro/SSA antibodies and cardiac arrhythmias in the adult: facts and hypotheses.

    PubMed

    Lazzerini, P E; Capecchi, P L; Laghi-Pasini, F

    2010-09-01

    It is well established that the passive trans-placental passage of anti-Ro/SSA antibodies from mother to foetus is associated with the risk to develop an uncommon syndrome named neonatal lupus (NLE), where the congenital heart block represents the most severe clinical feature. Recent evidence demonstrated that also adult heart, classically considered invulnerable to the anti-Ro/SSA antibodies, may represent a target of the arrhythmogenicity of these autoantibodies. In particular, the prolongation of the QTc interval appears the most frequent abnormality observed in adults with circulating anti-Ro/SSA antibodies, with some data suggesting an association with an increased risk of ventricular arrhythmias, also life threatening. Moreover, even though the association between anti-Ro/SSA antibodies and conduction disturbances is undoubtedly less evident in adults than in infants, from the accurate dissection of the literature data the possibility arises that sometimes also the adult cardiac conduction tissue may be affected by such antibodies. The exact arrhythmogenic mechanisms involved in foetus/newborns and adults, respectively, have not been completely clarified as yet. However, increasing evidence suggests that anti-Ro/SSA antibodies may trigger rhythm disturbances through an inhibiting cross-reaction with several cardiac ionic channels, particularly the calcium channels (L-type and T-type), but also the potassium channel hERG, whose different expression and involvement in the cardiac electrophysiology during lifespan might account for the occurrence of age-related differences.

  7. The Novel Gamma Secretase Inhibitor RO4929097 Reduces the Tumor Initiating Potential of Melanoma

    PubMed Central

    Segura, Miguel F.; Medicherla, Ratna; Haimovic, Adele; Menendez, Silvia; Shang, Shulian; Pavlick, Anna; Shao, Yongzhao; Darvishian, Farbod; Boylan, John F.; Osman, Iman; Hernando, Eva

    2011-01-01

    Several reports have demonstrated a role for aberrant NOTCH signaling in melanoma genesis and progression, prompting us to explore if targeting this pathway is a valid therapeutic approach against melanoma. We targeted NOTCH signaling using RO4929097, a novel inhibitor of gamma secretase, which is a key component of the enzymatic complex that cleaves and activates NOTCH. The effects of RO4929097 on the oncogenic and stem cell properties of a panel of melanoma cell lines were tested both in vitro and in vivo, using xenograft models. In human primary melanoma cell lines, RO4929097 decreased the levels of NOTCH transcriptional target HES1. This was accompanied by reduced proliferation and impaired ability to form colonies in soft agar and to organize in tridimensional spheres. Moreover, RO4929097 affected the growth of human primary melanoma xenograft in NOD/SCID/IL2gammaR-/- mice and inhibited subsequent tumor formation in a serial xenotransplantation model, suggesting that inhibition of NOTCH signaling suppresses the tumor initiating potential of melanoma cells. In addition, RO4929097 decreased tumor volume and blocked the invasive growth pattern of metastatic melanoma cell lines in vivo. Finally, increased gene expression of NOTCH signaling components correlated with shorter post recurrence survival in metastatic melanoma cases. Our data support NOTCH inhibition as a promising therapeutic strategy against melanoma. PMID:21980408

  8. Foulant Analysis of Three RO Membranes Used in Treating Simulated Brackish Water of the Iraqi Marshes

    PubMed Central

    Sachit, Dawood Eisa; Veenstra, John N.

    2017-01-01

    In this work, three different types of Reverse Osmosis (RO) (Thin-Film Composite (SE), Cellulose Acetate (CE), and Polyamide (AD)) were used to perform foulant analysis (autopsy) study on the deposited materials from three different simulated brackish surface feed waters. The brackish surface water qualities represented the water quality in Iraqi marshes. The main foulants from the simulated feed waters were characterized by using Scanning Electron Microscope (SEM) images and Energy-Dispersive X-ray Spectroscopy (EDXS) spectra. The effect of feed water temperatures (37 °C and 11 °C) on the formation of the fouled material deposited on the membrane surface was examined in this study. Also, pretreatment by a 0.1 micron microfiltration (MF) membrane of the simulated feed water in advance of the RO membrane on the precipitated material on the membrane surface was investigated. Finally, Fourier Transform Infrared Spectroscopy (FTIR) analysis was used to identify the functional groups of the organic matter deposited on the RO membrane surfaces. The SEM images and EDSX spectra suggested that the fouled material was mainly organic matter, and the major crystal deposited on the RO membrane was calcium carbonate (CaCO3). The FTIR spectra of the fouled RO membranes suggested that the constituents of the fouled material included aliphatic and aromatic compounds. PMID:28406468

  9. RO-ILS: Radiation Oncology Incident Learning System: A report from the first year of experience.

    PubMed

    Hoopes, David J; Dicker, Adam P; Eads, Nadine L; Ezzell, Gary A; Fraass, Benedick A; Kwiatkowski, Theresa M; Lash, Kathy; Patton, Gregory A; Piotrowski, Tom; Tomlinson, Cindy; Ford, Eric C

    2015-01-01

    Incident learning is a critical tool to improve patient safety. The Patient Safety and Quality Improvement Act of 2005 established essential legal protections to allow for the collection and analysis of medical incidents nationwide. Working with a federally listed patient safety organization (PSO), the American Society for Radiation Oncology and the American Association of Physicists in Medicine established RO-ILS: Radiation Oncology Incident Learning System (RO-ILS). This paper provides an overview of the RO-ILS background, development, structure, and workflow, as well as examples of preliminary data and lessons learned. RO-ILS is actively collecting, analyzing, and reporting patient safety events. As of February 24, 2015, 46 institutions have signed contracts with Clarity PSO, with 33 contracts pending. Of these, 27 sites have entered 739 patient safety events into local database space, with 358 events (48%) pushed to the national database. To establish an optimal safety culture, radiation oncology departments should establish formal systems for incident learning that include participation in a nationwide incident learning program such as RO-ILS. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  10. Risk of Cardiovascular Events in Patients With Diabetes Mellitus on β-Blockers.

    PubMed

    Tsujimoto, Tetsuro; Sugiyama, Takehiro; Shapiro, Martin F; Noda, Mitsuhiko; Kajio, Hiroshi

    2017-07-01

    Although the use of β-blockers may help in achieving maximum effects of intensive glycemic control because of a decrease in the adverse effects after severe hypoglycemia, they pose a potential risk for the occurrence of severe hypoglycemia. This study aimed to evaluate whether the use of β-blockers is effective in patients with diabetes mellitus and whether its use is associated with the occurrence of severe hypoglycemia. Using the ACCORD trial (Action to Control Cardiovascular Risk in Diabetes) data, we performed Cox proportional hazards analyses with a propensity score adjustment. The primary outcome was the first occurrence of a cardiovascular event during the study period, which included nonfatal myocardial infarction, unstable angina, nonfatal stroke, and cardiovascular death. The mean follow-up periods (±SD) were 4.6±1.6 years in patients on β-blockers (n=2527) and 4.7±1.6 years in those not on β-blockers (n=2527). The cardiovascular event rate was significantly higher in patients on β-blockers than in those not on β-blockers (hazard ratio, 1.46; 95% confidence interval, 1.24-1.72; P<0.001). In patients with coronary heart disease or heart failure, the cumulative event rate for cardiovascular events was also significantly higher in those on β-blockers than in those not on β-blockers (hazard ratio, 1.27; 95% confidence interval, 1.02-1.60; P=0.03). The incidence of severe hypoglycemia was significantly higher in patients on β-blockers than in those not on β-blockers (hazard ratio, 1.30; 95% confidence interval, 1.03-1.64; P=0.02). In conclusion, the use of β-blockers in patients with diabetes mellitus was associated with an increased risk for cardiovascular events. © 2017 The Authors.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. A simple method for the biochemical purification of Ro/SS-A antigen.

    PubMed

    Wu, D H; Tavoni, A; Garzelli, C; Neri, R; Vitali, C; Bombardieri, S

    1989-07-26

    In the present study, Ro/SS-A antigen has been isolated from human spleen by a two-step procedure. In the first step most of the non-antigenic material was removed by means of ammonium sulphate precipitation and ion exchange chromatography. The final purification was obtained by passing the Ro/SS-A-containing fractions twice through a Mono Q ion exchange fast protein liquid chromatography (FPLC) column. The purified antigen showed identical immunoreactivity with crude material on CIE and was composed of two polypeptides with a molecular weight of approximately 60,000 and 55,000 respectively on SDS-PAGE, both reacting on Western blotting with a panel of anti-Ro/SS-A antisera. This system permits milligrams of highly purified antigen to be obtained from grams of human spleen.

  16. 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.

  17. Planets and stellar activity: hide and seek in the CoRoT-7 system

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

    Since the discovery of the transiting super-Earth CoRoT-7b, several investigations have yielded different results for the number and masses of planets present in the system, mainly owing to the star's high level of activity. We re-observed CoRoT-7 in 2012 January with both HARPS and CoRoT, so that we now have the benefit of simultaneous radial-velocity and photometric data. This allows us to use the off-transit variations in the star's light curve to estimate the radial-velocity variations induced by the suppression of convective blueshift and the flux blocked by starspots. To account for activity-related effects in the radial velocities which do not have a photometric signature, we also include an additional activity term in the radial-velocity model, which we treat as a Gaussian process with the same covariance properties (and hence the same frequency structure) as the light curve. Our 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 measure the masses of planets b and c to be 4.73 ± 0.95 and 13.56 ± 1.08 M⊕, respectively. The density of CoRoT-7b is (6.61 ± 1.72)(Rp/1.58 R⊕)-3 g cm-3, which is compatible with a rocky composition. We search for evidence of an additional planet d, identified by previous authors with a period close to 9 d. We are not able to confirm the existence of a planet with this orbital period, which is close to the second harmonic of the stellar rotation at ˜7.9 d. Using Bayesian model selection, we find that a model with two planets plus activity-induced variations is most favoured.

  18. 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

  19. 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.

  20. 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).

  1. A Review on the Hemodialysis Reliable Outflow (HeRO) Graft for Haemodialysis Vascular Access.

    PubMed

    Al Shakarchi, J; Houston, J G; Jones, R G; Inston, N

    2015-07-01

    With improved dialysis survival there are increasing numbers of patients who have exhausted definitive access options due to central venous stenosis and are maintaining dialysis on a central venous catheter. The Hemodialysis Reliable Outflow (HeRO) allows an alternative by providing a definitive access solution. The aim of this study is to systematically review the published outcomes of the HeRO graft and discuss the role in complex haemodialysis patients. Electronic databases were searched for studies assessing the use of the HeRO graft for dialysis in accordance with PRISMA published up to December 31 2014. The primary outcomes for this study were 1-year primary and secondary patency rates. Secondary outcomes were rates of dialysis access associated steal syndrome, HeRO-related bacteraemia rates and rates of interventions. Following strict inclusion/exclusion criteria, eight studies including 409 patients were included in our review. Primary and secondary pooled patency rates in this complex cohort of dialysis patients were found to be 21.9% (9.6-37.2%) and 59.4% (39.4-78%). The rate of dialysis access associated steal syndrome was low at 6.3% (1-14.7%) as was the range of HeRO-related bacteraemia (0.13-0.7 events per 1000 days). This literature review shows that the HeRO graft is an acceptable option for complex dialysis patients who are catheter dependent. Owing to device availability, published data are predominantly North American and further longer-term studies in other populations may be necessary. In this challenging patient group, randomized controlled trials are required to allow comparisons with alternative access options. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  2. 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

  3. 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.

  4. Tolerability to beta-blocker therapy among heart failure patients in clinical practice.

    PubMed

    Butler, Javed; Khadim, Ghazanfar; Belue, Rhonda; Chomsky, Don; Dittus, Robert S; Griffin, Marie; Wilson, John R

    2003-06-01

    Although beta-blockers were well-tolerated by heart failure (HF) patients in clinical trials, tolerability of these drugs in a general population of HF patients is not well-described. We studied a total of 308 encounters with beta-blockers therapy in 268 ambulatory HF patients. Side effects and frequency and predictors of discontinuation of therapy were studied. Independent predictors of discontinuation were assessed. Weight gain (59%), fatigue (56%), dizziness (41%), and dyspnea (29%) were the most common side effects. Fifty-one patients (19%) were discontinued on therapy with any 1 particular beta-blocker. Fatigue (30%) and hypotension (28%) were the most common reasons for discontinuation. Forty (78%) of these were given a trial with a different beta-blocker. Of these, 22 (55%) attempts with a different beta-blocker were tolerated. Thus the overall absolute discontinuation rate was only 7% for patients who were given a trial with different beta-blockers or 11% for the entire study population. Independent predictors of discontinuation of therapy included advanced symptoms, nonischemic etiology, history of pulmonary disease, and higher diuretic doses. Side effects with beta-blockers in a general population of HF patients are common; however, with changes in medical management, most patients can tolerate them eventually. In case of intolerance to one kind, a trial with a different beta-blocker is indicated.

  5. 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.

  6. Current status of β-blockers for the treatment of hypertension: an update.

    PubMed

    Chrysant, S G; Chrysant, G S

    2012-05-01

    β-Adrenoceptor blockers (β-blockers) are one of the oldest classes of cardiovascular drugs still in use. Several short- and long-term clinical outcomes studies have demonstrated their effectiveness and safety for the treatment of hypertension, coronary artery disease, myocardial infarction, heart failure and sudden cardiac death. Due to their safety and efficacy, β-blockers have been recommended by several national and international committees as first-line therapy of hypertension. However, despite their proven benefits, their use as first-line treatment for hypertension has come under criticism lately. Because of these recent developments, several authors have recommended that β-blockers no longer be used as first-line therapy for hypertension. In this review, evidence-based information will be presented, which will demonstrate that β-blockers are an effective and safe class of antihypertensive and cardiovascular drugs for most patients with the exception of black and elderly hypertensive patients in whom the β-blockers are less effective compared to other classes of drugs. In addition, evidence will be presented from several major meta-analyses that β-blockers are equally effective in reducing blood pressure and cardiovascular complications. This review will also discuss differences in the mechanism of action of older and newer (third-generation) β-blockers and provide evidence that newer agents should be preferred over the older ones in the treatment of hypertensive patients with certain comorbidities. Copyright 2012 Prous Science, S.A.U. or its licensors. All rights reserved.

  7. Combining other antihypertensive drugs with β-blockers in hypertension: a focus on safety and tolerability.

    PubMed

    Richards, Tiffany R; Tobe, Sheldon W

    2014-05-01

    Combining multiple classes of antihypertensive drugs together is one of the most important factors for achieving blood pressure control in most hypertensive patients. The benefits of combination therapy in comparison with monotherapy include: a synergistic enhancement of each drug's hypertensive effects and a potential reduction of side effects if each drug is used at a lower dose. Although long-acting dihydropyridine calcium channel blockers and β-blockers are a good fit for combination therapy, because of the risk of atrioventricular block and bradycardia, the combination of verapamil and β-blockers is not advised. In addition, the combination of higher-dose diltiazem and β-blockers is also not advised. β-blockers and diuretic agents as initial lone combination therapy are not the preferred combination to be used in uncomplicated hypertension. Using an angiotensin-converting enzyme inhibitor as initial combination therapy with most β-blockers is not recommended because of a lack of antihypertensive efficacy. Nebivolol, however, appears different in this regard and might provide an opportunity for combining these 2 classes of agents with proven cardiovascular benefits for better blood pressure control. Adding an α-blocker to a β-blocker is an effective combination. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  8. 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.

  9. 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.

  10. Evaluation of β-blocker gel and effect of dosing volume for topical delivery.

    PubMed

    Zhang, Qian; Chantasart, Doungdaw; Li, S Kevin

    2015-05-01

    Although topical administration of β-blockers is desired because of the improved therapeutic efficacy and reduced systemic adverse effects compared with systemic administration in the treatment of infantile hemangioma, the permeation of β-blockers across skin under finite dose conditions has not been systematically studied and an effective topical β-blocker formulation for skin application is not available. The present study evaluated the permeation of β-blockers propranolol, betaxolol, and timolol across human epidermal membrane (HEM) from a topical gel in Franz diffusion cells in vitro under various dosing conditions. The effects of occlusion and dosing volume on percutaneous absorption of β-blockers from the gel were studied. The permeation data were compared with those of finite dose diffusion theory. The results showed that skin permeation of β-blockers generally could be enhanced two to three times by skin occlusion. The cumulative amounts of β-blockers permeated across HEM increased with increasing dosing volume. An adequate fit was obtained between the theoretical curve and experimental permeation data, indicating that the experimental results of the gel are consistent with finite dose diffusion theory. In conclusion, the findings suggest the feasibility of using topical gels of β-blockers for infantile hemangioma treatment and topical application with skin occlusion is preferred. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  11. Neuromuscular blockers in surgery and intensive care, Part 1.

    PubMed

    McManus, M C

    2001-12-01

    The historical development, pharmacology, pharmacodynamics, pharmacokinetics, clinical applications, pharmacologic basis for selection, adverse effects, and cost of neuromuscular blockers (NMBs) are discussed. The first NMB to be used was tubocurarine. During neurotransmission, acetylcholine is synthesized, stored in vesicles at the neuromuscular junction, released into the synapse, and bound to nicotinic receptors in the muscle end plate. For muscle contraction to occur, the impulse generated in a neuron's cell body must create an action potential that is chemically transmitted across the synapse. The postsynaptic nicotinic receptor at the neuromuscular junction is the major site of action of depolarizing and nondepolarizing NMBs. All NMBs have the potential for cross-reactivity at other nicotinic and muscarinic sites. Drug interactions most commonly occur between NMBs and inhalation anesthetics, certain antimicrobials, calcium-channel blockers, and anticholinesterases. When selecting an NMB, an agent's onset and duration of action must be considered. NMBs can be used on a short-term or long-term basis. Apart from cost, the choice of an NMB is made on the basis of its adverse-reaction profile, pharmacokinetics, and indications for use. Monitoring tools, their use, the rationale for their use, and the interpretation of the results they provide are unique. The patterns of peripheral nerve stimulation vary and elicit different characteristics of nondepolarizing neuromuscular blockade. The effectiveness of reversal agents is proportional to the degree of blockade. The mechanism of action of anticholinesterases involves inhibition of acetylcholinesterase. The expensive NMBs should be conserved for use in surgery, while the cheaper, long-acting [corrected] agents should be used in the intensive care unit. An understanding of the pharmacology, pharmacodynamics, and pharmacokinetics of NMBs will help health care providers gain expertise in the selection and use of these

  12. Neuromuscular blockers in surgery and intensive care, Part 2.

    PubMed

    McManus, M C

    2001-12-15

    The historical development, pharmacology, pharmacodynamics, pharmacokinetics, clinical applications, pharmacologic basis for selection, adverse effects, and cost of neuromuscular blockers (NMBs) are discussed. The first NMB to be used was tubocurarine. During neurotransmission, acetylcholine is synthesized, stored in vesicles at the neuromuscular junction, released into the synapse, and bound to nicotinic receptors in the muscle end plate. For muscle contraction to occur, the impulse generated in a neuron's cell body must create an action potential that is chemically transmitted across the synapse. The postsynaptic nicotinic receptor at the neuromuscular junction is the major site of action of depolarizing and nondepolarizing NMBs. All NMBs have the potential for cross-reactivity at other nicotinic and muscarinic sites. Drug interactions most commonly occur between NMBs and inhalation anesthetics, certain antimicrobials, calcium-channel blockers, and anticholinesterases. When selecting an NMB, an agent's onset and duration of action must be considered. NMBs can be used on a short-term or long-term basis. Apart from cost, the choice of an NMB is made on the basis of its adverse-reaction profile, pharmacokinetics, and indications for use. Monitoring tools, their use, the rationale for their use, and the interpretation of the results they provide are unique. The patterns of peripheral nerve stimulation vary and elicit different characteristics of nondepolarizing neuromuscular blockade. The effectiveness of reversal agents is proportional to the degree of blockade. The mechanism of action of anticholinesterases involves inhibition of acetylcholinesterase. The expensive NMBs should be conserved for use in surgery, while the cheaper, long-acting [corrected] agents should be used in the intensive care unit. An understanding of the pharmacology, pharmacodynamics, and pharmacokinetics of NMBs will help health care providers gain expertise in the selection and use of these

  13. 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

  14. Azilsartan: a newly approved angiotensin II receptor blocker.

    PubMed

    Lam, Sum

    2011-01-01

    Hypertension is a common chronic disease that leads to significant cardiovascular morbidity and mortality. Blood pressure control is essential to prevent end-organ complications, such as stroke, myocardial infarction, heart failure, or kidney disease. Azilsartan is the eighth angiotensin II receptor blocker approved for the management of hypertension, alone or in combination with other agents. At the approved dosage, it reduces systolic blood pressure by 12 to 15 mm Hg and diastolic blood pressure by 7 to 8 mm Hg. A higher dose of azilsartan (80 mg) was superior to valsartan 320 mg or olmesartan 40 mg in lowering systolic blood pressure in short-term studies. Additional blood pressure reduction is expected when azilsartan is used adjunctively with a diuretic. However, the effects of azilsartan on cardiovascular morbidity or mortality are still lacking. Azilsartan is well tolerated; the most common side effects are headache and diarrhea. No cases of hyperkalemia have been reported in 6-week clinical trials. Worsening of renal function and hypotension should be monitored, particularly in those with baseline risk factors. It is unknown whether azilsartan would join angiotensin-converting enzyme inhibitors and other angiotensin receptor blockers as the preferred hypertensive agents for end-organ protection. At this time, azilsartan should be considered as an alternative agent for mild-to-moderate hypertension, or as an adjunctive therapy when preferred agents fail to maintain optimal blood pressure control. It is also an option for those patients who have contraindications or cannot tolerate other antihypertensive agents, including dry cough induced by angiotensin-converting enzyme inhibitors.

  15. Transiting exoplanets from the CoRoT space mission. XVIII. CoRoT-18b: a massive hot Jupiter on a prograde, nearly aligned orbit

    NASA Astrophysics Data System (ADS)

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

    2011-09-01

    We report the detection of CoRoT-18b, a massive hot Jupiter transiting in front of its host star with a period of 1.9000693 ± 0.0000028 days. This planet was discovered thanks to photometric data secured with the CoRoT satellite combined with spectroscopic and photometric ground-based follow-up observations. The planet has a mass Mp = 3.47 ± 0.38 MJup, a radius Rp = 1.31 ± 0.18 RJup, and a density ρp = 2.2 ± 0.8 g cm-3. It orbits a G9V star with a mass M⋆ = 0.95 ± 0.15 M⊙, a radius R⋆ = 1.00 ± 0.13 R⊙, and arotation period Prot = 5.4 ± 0.4 days. The age of the system remains uncertain, with stellar evolution models pointing either to a few tens Ma or several Ga, while gyrochronology and lithium abundance point towards ages of a few hundred Ma. This mismatch potentially points to a problem in our understanding of the evolution of young stars, with possibly significant implications for stellar physics and the interpretation of inferred sizes of exoplanets around young stars. We detected the Rossiter-McLaughlin anomaly in the CoRoT-18 system thanks to the spectroscopic observation of a transit. We measured the obliquity ψ = 20° ± 20° (sky-projected value λ = -10° ± 20°), indicating that the planet orbits in the same way as the star is rotating and that this prograde orbit is nearly aligned with the stellar equator. The CoRoT space mission, launched on 2006 December 27, has been developed and is operated by CNES, with the contribution of Austria, Belgium, Brazil, ESA (RSSD and Science Programme), Germany and Spain.Table 2 is available in electronic form at http://www.aanda.org

  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. 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.

  18. 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.

  19. 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

  20. How to separate the low amplitude delta Scuti variation in CoRoT data unambigousely?

    NASA Astrophysics Data System (ADS)

    Benko, Jozsef M.; Paparo, Margit

    2015-08-01

    Rich regular frequency patterns were found in the Fourier spectra of low-amplitude Delta Scuti stars observed by CoRoT satellite. The CoRoT observations are, however, influenced by the disturbing effect of the SAA. The effect is marginal for high amplitude variable stars but it could be dangerous in the case of low amplitude variables, especially if the frequency range of the intrinsic variation overlaps the instrumental frequencies. Systematic tests were carried out both on synthetic and real data. Our aim was to determine a limit amplitude above which we were sure that the frequency pattern belonged to the stars.

  1. Galactic Archaeology with CoRoT and APOGEE: Creating mock observations from a chemodynamical model

    NASA Astrophysics Data System (ADS)

    Anders, F.; Chiappini, C.; Rodrigues, T. S.; Piffl, T.; Mosser, B.; Miglio, A.; Montalbán, J.; Girardi, L.; Minchev, I.; Valentini, M.; Steinmetz, M.

    2016-09-01

    In a companion paper, we have presented the combined asteroseismic-spectroscopic dataset obtained from CoRoT light curves and APOGEE infra-red spectra for 606 solar-like oscillating red giants in two fields of the Galactic disc (CoRoGEE). We have measured chemical abundance patterns, distances, and ages of these field stars which are spread over a large radial range of the Milky Way's disc. Here we show how to simulate this dataset using a chemodynamical Galaxy model. We also demonstrate how the observation procedure influences the accuracy of our estimated ages.

  2. 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.

  3. Anti-Ro/SSA antibodies and cardiac rhythm disturbances: Present and future perspectives.

    PubMed

    Santos-Pardo, Irene; Villuendas, Roger; Salvador-Corres, Iñaki; Martínez-Morillo, Melania; Olivé, Alejandro; Bayes-Genis, Antoni

    2015-04-01

    Several case reports, small case series, and original research papers have recently suggested that the action of certain auto-antibodies related to connective tissue diseases may be responsible for significant cardiac rhythm disturbances in adults. The relationship between anti-Ro/SSA antibodies and congenital complete atrioventricular block is well recognized in the fetal heart. Herein we review the emerging evidences of the link to increased levels of anti-Ro/SSA antibodies with rhythm disorders of unknown origin in the adult. Confirmation of this distinct etiology may eventually be the basis for new therapies. Copyright © 2014. Published by Elsevier Ireland Ltd.

  4. Beta2-glycoprotein-I and Protection from Anti-SSA/Ro 60 Associated Cardiac Manifestations of Neonatal Lupus

    PubMed Central

    Reed, Joanne H.; Clancy, Robert M.; Purcell, Anthony W.; Kim, Mimi Y.; Gordon, Tom P.; Buyon, Jill P.

    2011-01-01

    One mechanism to molecularly explain the strong association of maternal anti-Ro60 antibodies with cardiac disease in neonatal lupus (NL) is that these antibodies initiate injury by binding to apoptotic cardiomyocytes in the fetal heart. Previous studies have demonstrated that beta2-glycoprotein I (β2GPI) interacts with Ro60 on the surface of apoptotic Jurkat cells and prevents binding of anti-Ro60 IgG. Accordingly, the current study was initiated to test two complementary hypotheses a) competition between β2GPI and maternal anti-Ro60 antibodies for binding apoptotic induced surface translocated Ro60 occurs on human fetal cardiomyocytes and b) circulating levels of β2GPI influence injury in anti-Ro60 exposed fetuses. Initial flow cytometry experiments conducted on apoptotic human fetal cardiomyocytes demonstrated dose-dependent binding of β2GPI. In competitive inhibition experiments, β2GPI prevented opsonisation of apoptotic cardiomyocytes by maternal anti-Ro60 IgG. ELISA was used to quantify β2GPI in umbilical cord blood from 97 neonates exposed to anti-Ro60 antibodies, 53 with cardiac NL and 44 with no cardiac disease. β2GPI levels were significantly lower in neonates with cardiac NL. Plasmin-mediated cleavage of β2GPI prevented binding to Ro60 and promoted the formation of pathogenic anti-Ro60 IgG-apoptotic cardiomyocyte complexes. In aggregate these data suggest that intact β2GPI in the fetal circulation may be a novel cardioprotective factor in anti-Ro60-exposed pregnancies. PMID:21602492

  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. The potential systemic effect of topically applied beta-blockers in glaucoma therapy.

    PubMed

    Taniguchi, T; Kitazawa, Y

    1997-04-01

    Although topical beta-blockers are generally tolerated, they can produce significant systemic side effects. The systemic side effects of nonselective beta-blockers (eg, timolol, carteolol) are primarily related to the cardiovascular (beta 1-adrenergic) and respiratory (beta 2-adrenergic) systems. Carteolol has intrinsic sympathomimetic activity, which theoretically reduces the risk of adverse effects through beta blockade. It has been reported that topical timolol and carteolol unfavorably alter the lipid profile and that the effects of carteolol are less pronounced than those of timolol. Topical beta-blockers are associated with systemic events, not only acting by themselves, but also interacting with other drugs (eg, quinidine) administered orally or intravenously. To reduce systemic absorption and adverse effects, new preparations of beta-blockers, such as timolol gellan, have been developed. We should always bear in mind the potential systemic effects of topically applied beta-blockers in glaucoma therapy.

  7. 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

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

    PubMed

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

    2013-06-01

    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. 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). 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. Hypertrophic cardiomyopathy not treated with β-blockers is accompanied by prolonged baroreflex delay. The use of β-blockers normalizes this delay. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  9. 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.

  10. Economic benefits associated with beta blocker persistence in the treatment of hypertension: a retrospective database analysis.

    PubMed

    Chen, Stephanie; Swallow, Elyse; Li, Nanxin; Faust, Elizabeth; Kelley, Caroline; Xie, Jipan; Wu, Eric

    2015-04-01

    To assess the association between medical costs and persistence with beta blockers among hypertensive patients, and to quantify persistence related medical cost differences with nebivolol, which is associated with improved tolerability, versus other beta blockers. Adults who initiated hypertension treatment with a beta blocker were identified from the MarketScan * claims database (2008-2012). Patients were classified based on their first beta blocker use: nebivolol, atenolol, carvedilol, metoprolol, and other beta blockers. Patients with compelling indications for atenolol, carvedilol or metoprolol (acute coronary syndrome and congestive heart failure) were excluded. Patients enrolled in health maintenance organization or capitated point of service insurance plans were also excluded. Persistence was defined as continuous use of the index drug (<60 day gap). The average effect of persistence on medical costs (2012 USD) was estimated using generalized linear models (GLMs). Regression estimates were used to predict medical cost differences associated with persistence between nebivolol and the other cohorts. A total of 587,424 hypertensive patients met the inclusion criteria. Each additional month of persistence with any one beta blocker was associated with $152.51 in all-cause medical cost savings; continuous treatment for 1 year was associated with $1585.98 in all-cause medical cost savings. Patients treated with nebivolol had longer persistence during the 1 year study period (median: 315 days) than all other beta blockers (median: 156-292 days). Longer persistence with nebivolol translated into $305.74 all-cause medical cost savings relative to all other beta blockers. The results may not be generalizable to hypertensive patients with acute coronary syndrome or congestive heart failure. Longer persistence with beta blockers for the treatment of hypertension was associated with lower medical costs. There may be greater cost savings due to better persistence with

  11. 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.

  12. Synergistic antinociceptive effect of a calcium channel blocker and a TRPV1 blocker in an acute pain model in mice.

    PubMed

    Palhares, Manuella R; Silva, Juliana F; Rezende, Marcio Junior S; Santos, Duana C; Silva-Junior, Cláudio A; Borges, Márcia H; Ferreira, Juliano; Gomez, Marcus V; Castro-Junior, Célio J

    2017-08-01

    Extensive evidence supports a role for voltage-gated calcium channels (VGCC) and TRPV1 receptors in pain transmission and modulation. We investigated the profile of analgesic interaction between Phα1β toxin (a VGCC blocker) and SB366791 (selective TRPV1 antagonist) in a model of acute pain induced by capsaicin. Changes in body temperature induced by combination regimens were also evaluated. Isobolographic approach with a fixed dose-ratio of combined drugs was used to determine whether antinociceptive interaction of Phα1β and SB366791 are subadditive, additive or synergic. Body temperature was obtained by thermal infrared imaging. Phα1β and SB366791 interact in a synergistic manner to cause antinociception. We found an interaction index (α) of 0.07 for Phα1β and SB366791 when these drugs were injected together intraplantarly, which indicates that in vivo interaction between these drugs is greater than additive interaction. Synergism also occurred when intraplantar SB366791 was administered simultaneously with intrathecal Phα1β (interaction index α=0.06) suggesting a 15 fold rise in potency on the analgesic effect of these drugs when they are added together. It was observed no significant alterations in body temperature of animals treated with this combination regimen. Our data reveal that Phα1β toxin potentiates in 15 fold the antinociceptive action of the TRPV1 blocker SB366791. Therefore, lower doses of these drugs are required to achieve antinociceptive effects when these agents are given in combination. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. 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

  14. The human long non-coding RNA-RoR is a p53 repressor in response to DNA damage

    PubMed Central

    Zhang, Ali; Zhou, Nanjiang; Huang, Jianguo; Liu, Qian; Fukuda, Koji; Ma, Ding; Lu, Zhaohui; Bai, Cunxue; Watabe, Kounosuke; Mo, Yin-Yuan

    2013-01-01

    It is well known that upon stress, the level of the tumor suppressor p53 is remarkably elevated. However, despite extensive studies, the underlying mechanism involving important inter-players for stress-induced p53 regulation is still not fully understood. We present evidence that the human lincRNA-RoR (RoR) is a strong negative regulator of p53. Unlike MDM2 that causes p53 degradation through the ubiquitin-proteasome pathway, RoR suppresses p53 translation through direct interaction with the heterogeneous nuclear ribonucleoprotein I (hnRNP I). Importantly, a 28-base RoR sequence carrying hnRNP I binding motifs is essential and sufficient for p53 repression. We further show that RoR inhibits p53-mediated cell cycle arrest and apoptosis. Finally, we demonstrate a RoR-p53 autoregulatory feedback loop where p53 transcriptionally induces RoR expression. Together, these results suggest that the RoR-hnRNP I-p53 axis may constitute an additional surveillance network for the cell to better respond to various stresses. PMID:23208419

  15. 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.

  16. 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.

  17. Oral beta-blockers for mild to moderate hypertension during pregnancy.

    PubMed

    Magee, L A; Duley, L

    2000-01-01

    Hypertension is a common complication of pregnancy. Antihypertensive drugs are widely used in the belief these will improve outcome for both the woman (such as decreasing the risk of stroke or eclampsia) and her baby (such as decreasing the risk of preterm birth and its complications). Beta-blockers are a popular choice of antihypertensive agent during pregnancy; other choices include methyldopa and calcium channel blockers. The aim of this review is to assess whether oral beta-blockers are overall better than placebo, or no beta-blocker, for women with mild-moderate hypertension during pregnancy, and to assess whether oral beta-blockers have any advantages over other antihypertensive agents for women with mild-moderate hypertension during pregnancy. Both maternal outcomes (e.g., the incidence of severe hypertension) and perinatal outcomes (e.g., mortality) were of interest. Register of trials maintained by the Cochrane Pregnancy and Childbirth Group, MEDLINE 1966-97, bibliographies of retrieved papers, personal files. Date of last search: June 2000. Trials comparing beta-blockers with (i) placebo or no therapy, or (ii) other antihypertensive agents, for women with mild-moderate pregnancy hypertension (i.e., blood pressure under 170 mm Hg systolic, or 110 mm Hg diastolic). All data were extracted independently by two investigators, who were not blinded to outcome or other trial characteristics. Whenever possible, missing data were obtained by personal communication with authors. Discrepancies were resolved by discussion. The overview was divided into two comparisons: (i) beta-blockers versus placebo or no therapy, and (ii) beta-blockers versus other antihypertensives. Twenty-seven trials, involving just under 2400 women, are included in this review. Fourteen trials (1516 women) compared beta-blockers with placebo/no beta blocker. Oral beta-blockers decrease the risk of severe hypertension (relative risk (RR) 0.37, 95% confidence interval (CI) 0.26-0.53) and the

  18. 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.

  19. 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

  20. Erratum dans le numéro de mai-juin 1988

    NASA Astrophysics Data System (ADS)

    Erratum dans le numéro de mai-juin 1988: Dans l'article sur les étoiles à baryum: p. 74, 2e colonne (après la première formule), il faut lire «A est la masse atomique» au lieu de «nombre atomique»

  1. 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

  2. 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.

  3. 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,…

  4. Comparative in vitro activity of Ro 09-1428, a novel cephalosporin with a catechol moiety.

    PubMed

    Qadri, S M; Ayub, A; Ueno, Y; Saldin, H

    1992-01-01

    The in vitro activity of Ro 09-1428, a new parenteral cephalosporin, was compared with that of other beta-lactams and aminoglycosides in 1230 clinical isolates from 1028 consecutive patients. Using an agar dilution method, the drugs were tested against 625 isolates of Enterobacteriaceae, 68 Pseudomonas aeruginosa, 36 Xanthomonas maltophilia, 20 Aeromonas hydrophila, 54 Acinetobacter, 373 staphylococci, and 54 strains of enterococci. More than 98% of Enterobacteriaceae were susceptible to Ro 09-1428, with a minimal inhibitory concentration of less than 0.03 to 4.0 micrograms/ml. Ro 09-1428 also inhibited 99% and 72% of the clinical isolates of P aeruginosa and X maltophilia, respectively. All isolates of methicillin-susceptible Staphylococcus aureus (MSSA) were susceptible to this cephalosporin. However, only 46% of the 54 strains of enterococci exhibited in vitro susceptibility. Ro 09-1428 was found to be superior or comparable to most penicillins, cephalosporins, and aminoglycosides against both gram-negative bacteria and MSSA.

  5. 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

  6. 77 FR 33127 - Airworthiness Directives; HPH s. r.o. Sailplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-05

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; HPH s. r.o. Sailplanes AGENCY: Federal Aviation Administration (FAA), Department of Transportation (DOT). ACTION: Notice... continuing airworthiness information (MCAI) originated by an aviation authority of another country to...

  7. Highly Oxidized RO2 Radicals and Consecutive Products from the Ozonolysis of Three Sesquiterpenes.

    PubMed

    Richters, Stefanie; Herrmann, Hartmut; Berndt, Torsten

    2016-03-01

    The formation of highly oxidized multifunctional organic compounds (HOMs) from the ozonolysis of three sesquiterpenes, α-cedrene, β-caryophyllene, and α-humulene, was investigated for the first time. Sesquiterpenes contribute 2.4% to the global carbon emission of biogenic volatile organic compounds (BVOCs) and can be responsible for up to 70% of the regional BVOC emissions. HOMs were detected with chemical ionization-atmospheric pressure interface-time-of-flight mass spectrometry and nitrate and acetate ionization. Acetate ions were more sensitive toward highly oxidized RO2 radicals containing a single hydroperoxide moiety. Under the chosen reaction conditions, product formation was dominated by highly oxidized RO2 radicals which react with NO, NO2, HO2, and other RO2 radicals under atmospheric conditions. The ozonolysis of sesquiterpenes resulted in molar HOM yields of 0.6% for α-cedrene (acetate), 1.8% for β-caryophyllene (acetate), and 1.4% for α-humulene (nitrate) afflicted with an uncertainty factor of 2. Molar yields of highly oxidized RO2 radicals were identical with HOM yields measuring the corresponding closed-shell products. HOM formation from ozonolysis of α-cedrene was explained by an autoxidation mechanism initiated by ozone attack at the double bond similar to that found in the ozonolysis of cyclohexene and limonene.

  8. 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.

  9. HD 12098 a new far-northern roAp star

    NASA Astrophysics Data System (ADS)

    Girish, V.; Joshi, S.; Seetha, S.; Ashoka, B. N.; Martinez, P.; Chaubey, U. S.; Gupta, S. K.; Kurtz, D. W.; Sagar, R.

    2001-09-01

    The rapidly oscillating Ap (roAp) stars are cool, magnetic, chemically peculiar stars which pulsate in non-radial p-modes in the period range 4-16 min and have Johnson B amplitudes less than 8 mmag. "The NainiTal-Cape survey" to search for and study new roAp stars in the northern hemisphere was initiated in 1998 in collaboration between ISAC & UPSO from India and SAAO & UCT from South Africa. HD12098 is the first roAp star discovered in this survey and also the first far northern hemisphere roAp star. During the initial observations the star showed modulation in the pulsation amplitude indicating the multi-periodicity of pulsations. The multi-periodicity may be either due to the excitation of different modes or due to the rotation of the star. In order to resolve these frequencies HD12098 was observed extensively in October 2000. The preliminary results of these observations are presented here.

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

    PubMed

    Guerreso, Kelsey; Conner, Edward Alexander

    2016-01-01

    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. 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. 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.

  12. 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.

  13. 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

  14. Ro/SSA autoantibody-positive pregnancy: reactions to serial fetal Doppler echocardiographic surveillance.

    PubMed

    Tingström, J; Hjelmstedt, A; Welin Henriksson, E; Sonesson, S-E; Wahren-Herlenius, M

    2015-12-01

    The risk for congenital heart block (CHB) associated with maternal Ro/SSA autoantibodies is low, but the possibility of treating early stages of disease has seen the introduction of Doppler echocardiographic surveillance programs with serial examinations during the CHB susceptibility weeks of pregnancy. The aim of the present study was to understand how Ro/SSA autoantibody-positive women having undergone Doppler echocardiographic surveillance programs and giving birth to children without CHB experienced their pregnancy and frequent ultrasound examinations. A validated questionnaire based on data from an interview-study was distributed to Ro/SSA-positive women supervised with Doppler examinations during their pregnancy (n = 100). The response rate was 79%. The majority of the women (61%) reported that the increased number of ultrasound examinations influenced their pregnancy, but in a positive way, with qualified information and additional support from health care personnel in conjunction with the examinations. Further, the visits to the clinic provided opportunities to see the ultrasound picture of the expected infant. However, one-third of the women also reported stress in relation to the examinations. Fetal echocardiographic surveillance holds many and predominantly positive effects for Ro/SSA-positive women during pregnancy in addition to the medical advantages. © The Author(s) 2015.

  15. 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

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

    PubMed

    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. Our

  17. 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

  18. [The life of Dr. RO Kishun, a reflection of modern Korean medical history of the borders].

    PubMed

    Shin, Young-Jeon; Park, Se-Hong

    2009-06-01

    RO Kishun was born on February 2, 1893 in Ongjin County, Hwanghae Province of Joseon Korea. He graduated from the Medical Training Center, a campus associated with the Joseon Government-General Hospital, in 1915, and from Kyushu Imperial University School of Medicine in 1917. He continued his medical study at the university in 1929, majoring in biochemistry, and earned a doctorate in medicine in 1932. Dr. RO, one of the earliest pioneers in Korean biochemistry, was active in his research, publishing four studies in the Japanese Journal of Biochemistry between 1931 and 1932. After returning from Japan in 1932, Dr. RO opened a medical practice in Mokpo and Busan, port cities situated on the southern tip of Korea. Later in 1936, he moved north to Manchuria (northeast China) to practice medicine at the International Hospital in Mukden (present-day Shenyang). He also served as president of Tumen Public Hospital between 1942 and 1946. When Japan signed unconditional surrender bringing World War II to an end, Dr. RO relocated to Yanbian and began providing medical training to ethnic Koreans. In October 1946, he was appointed dean of the First Branch School of China Medical University in Longjing, and in October 1948 the first dean of Yanbian Medical School, the predecessor of Yanbian University College of Medicine. Dr. RO dedicated his life to medical practice, teaching and training students, and mentoring younger faculty. A brilliant clinician, he also inspired and helped his colleagues with his outstanding ability to diagnose and treat patients. He was one of the founding members of Yanbian University College of Medicine. RO Kishun died on June 7, 1957 at age 64. Ethnic Koreans hailed him as Sinui (literally, the physician of God), and a bronze statue of himself was erected in front of the medical college in 1988. Dr. RO's life brings modern historians' attention to the issue of determining geographical territories and nationality, in that his life unfolded at the

  19. [Detection of anti-SSA/Ro antibody by ELISA, double immunodiffusion, and immunoblotting: a comparative study].

    PubMed

    Tong, Sheng-quan; Shi, Qun; Wen, Xiao-hong; Gan, Xiao-dan; Shi, Yan-ping; Zhao, Yan; Zeng, Xiao-feng; Zhang, Feng-chun; Dong, Yi

    2006-09-19

    To compare the specificity and sensitivity of ELISA, double immunodiffusion (ID), and immunoblotting (IB) in detection of anti-SSA/Ro antibodies in the sera of patients with connective tissue disease (CTD). ELISA, double ID, and IB were used to detect the serum levels of anti-SSA/Ro antibodies in 7736 patients undergoing screening of CTD, 122 healthy blood donors, and 166 CTD patients positive in antinuclear antibody (ANA) and/or anti-extractable nuclear antigen (ENA). (1) The sera of the 122 healthy blood donors were all negative in anti-SSA/Ro antibodies by these three methods. (2) 1085 of the 7736 sera undergoing screening of CTD were positive in the anti-SSA/R0 antibody of the relative molecular quantity of 52,000. Ninety-two of the 1085 patient, ANA and/or anti-ENA negative, were all confirmed by ELISA and ID to be negative in anti-SSA/R0 antibodies. And 993 of these 1085 patients were positive in ANA and/or anti-ENA antibody, 917 of which were shown to be anti-SSA/R0 antibodies positive by ELISA (92.3%, 917/993), and 860 of which were shown to be anti-SSA/R0 antibodies positive by ID (86.6%, 860/993). (3) The prevalence rates of anti-SSA/Ro antibodies in the 166 CTD patients detected by ELISA, ID, and IB respectively were 76.5% (127/166), 65.1% (108/166), and 49.4% (82/166) respectively. (4) 127 of the 166 sera of the CTD group were anti-SSA/Ro antibody positive By ELISA, and 108 of the 166 sera were anti-SSA/R0 antibody positive by ID, with a coincidence rate of ELISA and ID of 88.6% (147/166), and there was a significant difference in positive rate of anti-SSA/Ro antibody between these two methods (P < 0.001). 81 of the 166 CTD sera were anti-SSA/Ro antibody positive with a positive rate of 63.8%. The coincidence rate of ID and IB was 75.9% (126/166) and there was a significant difference in positive rate of anti-SSA/Ro antibody between ID and IB methods too (P < 0.001). (5) Spearman's rank correlation study showed that the correlation coefficient between

  20. 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.

  1. 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

  2. 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

  3. [Neonatal lupus and maternofetal transmission of anti-SSA/Ro and anti-SSB/La antibodies].

    PubMed

    Feki, S; Turki, A; Frikha, F; Hachicha, H; Walha, L; Gargouri, A; Bahloul, Z; Masmoudi, H

    2015-02-01

    Neonatal lupus (NL) is a rare syndrome caused by placental transfer of maternal anti-SSA/Ro (60 and 52kDa) or anti-SSB/La antibodies. The aim of this study was to evaluate the clinical and biological profile of NL at the neonatal unit of Sfax, Tunisia, over a 10-year period. Six mother-NB pairs (two sets of twins and two sisters) had positive ANA by transplacental transmission during the study period. The ANA pattern was speckled and the NBs' sera titer was half that of their mothers'. Anti-SSA, anti-Ro52, and anti-SSB were found in 100%, 33%, and 50% of the mothers' sera, respectively. The transmission of anti-SSA was observed in four pregnancies out of six, anti-Ro52 in two pregnancies out of two, and anti-SSB in one pregnancy out of three. The patients' clinical records showed that two NBs had a congenital heart block: one with anti-SSA, whose mother had Sjögren syndrome, and another with anti-SSA, anti-SSB, anti-Ro52, and anti-mitochondrial antibodies (M2 type), whose mother had no diagnosis at the child's birth (cutaneous erythema and positive ANA with the same profile). Cutaneous signs (erythema, petechia) were described in three NBs out of six. The two sets of fraternal twins had cutaneous signs with the same ANA titer and profile (no anti-SSA transmission from their mother with lupus and anti-phospholipid syndrome). The two sisters' (two pregnancies 3 years apart) mother had Sjögren syndrome, one of them had heart block with positive anti-SSA, and the other was asymptomatic with anti-SSA and anti-Ro52. The same mother had a history of three pregnancies with two NBs who died of heart block. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  4. Prolonged corrected QT interval in anti-Ro/SSA-positive adults with systemic lupus erythematosus.

    PubMed

    Bourré-Tessier, Josiane; Clarke, Ann E; Huynh, Thao; Bernatsky, Sasha; Joseph, Lawrence; Belisle, Patrick; Pineau, Christian A

    2011-07-01

    To examine whether anti-Ro/SSA antibodies are associated with an increased risk of corrected QT (QTc) prolongation, and to study the stability of this relationship over time. Patients fulfilling the American College of Rheumatology (ACR) criteria for systemic lupus erythematosus (SLE) were invited to undergo a 12-lead resting electrocardiogram (EKG) in the pilot phase of our project, performed between February 2002 and March 2005. The same study population was used to perform a second similar analysis with a larger sample between April 2005 and May 2007. Multivariate logistic regression models were fit to estimate the cross-sectional association between anti-Ro/SSA and other demographic and clinical variables on QTc prolongation. The other potentially associated factors examined included age, sex, disease duration, lupus activity (Systemic Lupus Erythematosus Disease Activity Index 2000 update), damage (Systemic Lupus International Collaborating Clinics/ACR Damage Index), potassium and magnesium levels, and medications with the potential to prolong the QTc interval. Cross-sectional analysis of the pilot data (n = 150 patients) showed an association of prolonged QTc with the presence of anti-Ro/SSA (adjusted odds ratio [OR] 12.6; 95% confidence interval [95% CI] 2.3, 70.7). In the second larger study (n = 278), the association was replicated, with a narrower 95% CI (adjusted OR 5.1; 95% CI 1.5, 17.4). In the 118 patients with 2 EKG assessments, the results were consistent over time. Anti-Ro/SSA was associated with QTc prolongation in both our pilot data and a larger SLE cohort sample. Patients positive for anti-Ro/SSA may benefit from EKG testing and appropriate counseling should be considered for those identified with QTc prolongation. Copyright © 2011 by the American College of Rheumatology.

  5. Effect of beta blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study.

    PubMed

    Short, Philip M; Lipworth, Samuel I W; Elder, Douglas H J; Schembri, Stuart; Lipworth, Brian J

    2011-05-10

    To examine the effect of β blockers in the management of chronic obstructive pulmonary disease (COPD), assessing their effect on mortality, hospital admissions, and exacerbations of COPD when added to established treatment for COPD. Retrospective cohort study using a disease specific database of COPD patients (TARDIS) linked to the Scottish morbidity records of acute hospital admissions, the Tayside community pharmacy prescription records, and the General Register Office for Scotland death registry. Tayside, Scotland (2001-2010) Population 5977 patients aged >50 years with a diagnosis of COPD. Hazard ratios for all cause mortality, emergency oral corticosteroid use, and respiratory related hospital admissions calculated through Cox proportional hazard regression after correction for influential covariates. Mean follow-up was 4.35 years, mean age at diagnosis was 69.1 years, and 88% of β blockers used were cardioselective. There was a 22% overall reduction in all cause mortality with β blocker use. Furthermore, there were additive benefits of β blockers on all cause mortality at all treatment steps for COPD. Compared with controls (given only inhaled therapy with either short acting β agonists or short acting antimuscarinics), the adjusted hazard ratio for all cause mortality was 0.28 (95% CI 0.21 to 0.39) for treatment with inhaled corticosteroid, long acting β agonist, and long acting antimuscarinic plus β blocker versus 0.43 (0.38 to 0.48) without β blocker. There were similar trends showing additive benefits of β blockers in reducing oral corticosteroid use and hospital admissions due to respiratory disease. β blockers had no deleterious impact on lung function at all treatment steps when given in conjunction with either a long acting β agonist or antimuscarinic agent β blockers may reduce mortality and COPD exacerbations when added to established inhaled stepwise therapy for COPD, independently of overt cardiovascular disease and cardiac drugs, and

  6. Effect of β blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study

    PubMed Central

    Short, Philip M; Elder, Douglas H J; Schembri, Stuart

    2011-01-01

    Objective To examine the effect of β blockers in the management of chronic obstructive pulmonary disease (COPD), assessing their effect on mortality, hospital admissions, and exacerbations of COPD when added to established treatment for COPD. Design Retrospective cohort study using a disease specific database of COPD patients (TARDIS) linked to the Scottish morbidity records of acute hospital admissions, the Tayside community pharmacy prescription records, and the General Register Office for Scotland death registry. Setting Tayside, Scotland (2001–2010) Population 5977 patients aged >50 years with a diagnosis of COPD. Main outcome measures Hazard ratios for all cause mortality, emergency oral corticosteroid use, and respiratory related hospital admissions calculated through Cox proportional hazard regression after correction for influential covariates. Results Mean follow-up was 4.35 years, mean age at diagnosis was 69.1 years, and 88% of β blockers used were cardioselective. There was a 22% overall reduction in all cause mortality with β blocker use. Furthermore, there were additive benefits of β blockers on all cause mortality at all treatment steps for COPD. Compared with controls (given only inhaled therapy with either short acting β agonists or short acting antimuscarinics), the adjusted hazard ratio for all cause mortality was 0.28 (95% CI 0.21 to 0.39) for treatment with inhaled corticosteroid, long acting β agonist, and long acting antimuscarinic plus β blocker versus 0.43 (0.38 to 0.48) without β blocker. There were similar trends showing additive benefits of β blockers in reducing oral corticosteroid use and hospital admissions due to respiratory disease. β blockers had no deleterious impact on lung function at all treatment steps when given in conjunction with either a long acting β agonist or antimuscarinic agent Conclusions β blockers may reduce mortality and COPD exacerbations when added to established inhaled stepwise therapy for COPD

  7. The impact of an algorithm on the optimization of beta-blockers after cardiac surgery.

    PubMed

    Fellahi, Jean-Luc; Fornier, William; Fischer, Marc-Olivier; Bohadana, Dan; Gerard, Jean-Louis; Hanouz, Jean-Luc

    2015-02-01

    To evaluate the impact of a simple written algorithm of early postoperative beta-blocker administration on daily practices. A prospective, single center observational study. A 16-bed cardiac surgical intensive care unit in a university teaching hospital. One hundred twenty-five consecutive adult patients chronically treated with beta-blockers and scheduled for conventional cardiac surgery. Two successive 4-month phases: Phase 1 = uncontrolled early postoperative beta-blocker administration (n = 73) and phase 2 = beta-blocker administration by an institutional written algorithm using incremental doses of bisoprolol and/or esmolol (n = 52). The main endpoint was the number of patients receiving beta-blockers on the morning of postoperative day 1. Secondary endpoints were the number of patients receiving beta-blockers on the morning of postoperative day 1 and reaching the targeted therapeutic goal and the incidence of postoperative atrial fibrillation in the intensive care unit. A 79% increase in the number of patients receiving beta-blockers on the morning of postoperative day 1 (42% v 75%, p<0.001) was observed during the second phase of the study. The number of patients receiving beta-blockers on the morning of postoperative day 1 and reaching the targeted therapeutic goal was increased significantly by 127% (33% v 75%, p<0.001). The incidence of atrial fibrillation was similar between both phases of the study: 37% versus 31%, p = 0.567. A simple written algorithm markedly improved early postoperative continuation of beta-blockers in chronically treated patients undergoing conventional cardiac surgery. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Feasibility and Association of Neurohumoral Blocker Up-titration After Cardiac Resynchronization Therapy.

    PubMed

    Martens, Pieter; Verbrugge, Frederik H; Nijst, Petra; Bertrand, Philippe B; Dupont, Matthias; Tang, Wilson H; Mullens, Wilfried

    2017-08-01

    Cardiac resynchronization therapy (CRT) improves mortality and morbidity on top of optimal medical therapy in heart failure with reduced ejection fraction (HFrEF). This study aimed to elucidate the association between neurohumoral blocker up-titration after CRT implantation and clinical outcomes. Doses of angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and beta-blockers were retrospectively evaluated in 650 consecutive CRT patients implanted from October 2008 to August 2015 and followed in a tertiary multidisciplinary CRT clinic. All 650 CRT patients were on a maximal tolerable dose of ACE-I/ARB and beta-blocker at the time of CRT implantation. However, further up-titration was successful in 45.4% for ACE-I/ARB and in 56.8% for beta-blocker after CRT-implantation. During a mean follow-up of 37 ± 22 months, a total of 139 events occurred for the combined end point of heart failure admission and all-cause mortality. Successful, versus unsuccessful, up-titration was associated with adjusted hazard ratios of 0.537 (95% confidence interval 0.316-0.913; P = .022) for ACE-I/ARB and 0.633 (0.406-0.988; P = .044) for beta-blocker on the combined end point heart failure admission and all-cause mortality. Patients in the up-titration group exhibited a similar risk for death or heart failure admission as patients treated with the maximal dose (ACE-I/ARB: P = .133; beta-blockers: P = .709). After CRT, a majority of patients are capable of tolerating higher dosages of neurohumoral blockers. Up-titration of neurohumoral blockers after CRT implantation is associated with improved clinical outcomes, similarly to patients treated with the guideline-recommended target dose at the time of CRT implantation. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. [Dorzolamide: hypotensive efficacy in combination with beta-blockers. Long-term results].

    PubMed

    Domingo Gordo B; Urcelay Segura JL; Acero Peña A; Luezas Morcuende JJ; Arrevola Velasco L

    2000-12-01

    To know, in long term, the effects in IOP of dorzolamide as adjunctive treatment to beta-blockers. To compare the hypotensory potential added to the different beta-blockers (selective, non-selective, with I.S.A.). To compare its potential as hypotensive drug versus another drugs in association to beta-blockers- pilocarpine and dipivalilepinefrina. A descriptive-retrospective randomised study about 132 eyes with glaucoma, with 16 months of mean follow-up; divided into three groups: one of the patients treated with association to beta-blockers, and the two others patients treated with a combination of beta-blockers with pilocarpine or DPVE, in which they were substituted by dorzolamide. Student T was used for comparing the media. The average IOP reduction was 21.48 to 18.39 mmHg, with the addiction of dorzolamide to beta-blockers. Between the different beta-blockers, the non selective showed a higher hypotensive effect in association to dorzolamide (5.23 mmHg), more than selective (3.75 mmHg), but not significantly higher than those with I.S.A. (4.29 mmHg). In substitution of pilocarpine or DPVE, in its use associated to beta-blockers, dorzolamide showed a significantly higher efficacy, with an average IOP reduction of 4.16 mmHg by pilocarpine, and 4.33 by DPVE. Dorzolamide gets a higher hypotensive effect by adding it to patients in treatment with beta-blockers, principally with the non selective ones. In this way, it has shown a superior hypotensive effect than pilocarpine and DPVE.

  10. Incidence of tuberculosis among korean patients with ankylosing spondylitis who are taking tumor necrosis factor blockers.

    PubMed

    Kim, Eun-Mi; Uhm, Wan-Sik; Bae, Sang-Cheol; Yoo, Dae-Hyun; Kim, Tae-Hwan

    2011-10-01

    To assess the incidence and relative risk of new tuberculosis (TB) infections in Korean patients with ankylosing spondylitis (AS) and patients with AS who are undergoing treatment with tumor necrosis factor (TNF) blockers. New cases of TB were identified by reviewing the medical records of 919 patients with AS not treated with TNF blockers and those of 354 patients with AS treated with adalimumab (n = 66), infliximab (n = 78), or etanercept (n = 210) between 2002 and 2009. Reference data were obtained from the Korean National Tuberculosis Association. The mean incidence rate of TB was 69.8 per 100,000 person-years (PY) in the general population, 308 per 100,000 PY in the TNF blocker-naive AS cohort, and 561 per 100,000 PY in the TNF blocker-exposed AS cohort. The incidence rate of TB in the infliximab-treated AS cohort (540 per 100,000 PY) was higher than that in the adalimumab-treated AS cohort (490 per 100,000 PY). No cases of TB occurred in the etanercept-treated AS cohort. Comparing the relative risks of TB infections between the TNF blocker-exposed AS cohort and the TNF blocker-naive AS cohort, no statistically significant difference was identified (risk ratio 0.53; 95% CI 0.144-1.913). The risk of TB was higher in the TNF blocker-naive AS cohort than it was in the general population. However, the risk of TB was not increased in the TNF blocker-exposed AS cohort compared with the TNF blocker-naive AS cohort. Among patients with AS, etanercept is associated with a lower risk of TB compared with monoclonal antibodies.

  11. Underuse of β-blockers in heart failure and chronic obstructive pulmonary disease.

    PubMed

    Lipworth, Brian; Skinner, Derek; Devereux, Graham; Thomas, Victoria; Ling Zhi Jie, Joanna; Martin, Jessica; Carter, Victoria; Price, David B

    2016-12-01

    Although β-blockers are an established therapy in heart failure (HF) guidelines, including for patients with chronic obstructive pulmonary disease (COPD), there remain concerns regarding bronchoconstriction even with cardioselective β-blockers. We wished to assess the real-life use of β-blockers for patients with HF and comorbid COPD. We evaluated data from the Optimum Patient Care Research Database over a period of 1 year for co-prescribing of β-blockers with either an ACE inhibitor (ACEI) or angiotensin-2 receptor blocker (ARB) in patients with HF alone versus HF+COPD. Association with inhaler therapy was also evaluated. We identified 89 861 patients with COPD, 24 237 with HF and 10 853 with both conditions. In patients with HF+COPD, the mean age was 79 years; 60% were male, and 27% had prior myocardial infarction. Of patients with HF+COPD, 22% were taking a β-blocker in conjunction with either ACEI/ARB (n=2416) compared with 41% of patients with HF only (n=10 002) (adjusted OR 0.54, 95% CI 0.51 to 0.58, p<0.001). Among HF+COPD patients taking inhaled corticosteroid (ICS) with long-acting β-agonist (LABA) and long-acting muscarinic antagonist, 27% of patients were taking an ACEI/ARB with β-blockers (n=778) versus 46% taking an ACEI/ARB without β-blockers (n=1316). Corresponding figures for those patients taking ICS/LABA were 20% (n=583) versus 48% (n=1367), respectively. These data indicate a substantial unmet need for patients with COPD who should be prescribed β-blockers more often for concomitant HF. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  12. Clinical impact of selective and nonselective beta-blockers on survival in patients with ovarian cancer.

    PubMed

    Watkins, Jack L; Thaker, Premal H; Nick, Alpa M; Ramondetta, Lois M; Kumar, Sanjeev; Urbauer, Diana L; Matsuo, Koji; Squires, Kathryn C; Coleman, Robert L; Lutgendorf, Susan K; Ramirez, Pedro T; Sood, Anil K

    2015-10-01

    Preclinical evidence has suggested that sustained adrenergic activation can promote ovarian cancer growth and metastasis. The authors examined the impact of beta-adrenergic blockade on the clinical outcome of women with epithelial ovarian, primary peritoneal, or fallopian tube cancers (collectively, epithelial ovarian cancer [EOC]). A multicenter review of 1425 women with histopathologically confirmed EOC was performed. Comparisons were made between patients with documented beta-blocker use during chemotherapy and those without beta-blocker use. The median age of patients in the current study was 63 years (range, 21-93 years). The sample included 269 patients who received beta-blockers. Of those, 193 (71.7%) were receiving beta-1-adrenergic receptor selective agents, and the remaining patients were receiving nonselective beta antagonists. The primary indication for beta-blocker use was hypertension but also included arrhythmia and postmyocardial infarction management. For patients receiving any beta-blocker, the median overall survival (OS) was 47.8 months versus 42 months for nonusers (P =.04). The median OS based on beta-blocker receptor selectivity was 94.9 months for those receiving nonselective beta-blockers versus 38 months for those receiving beta-1-adrenergic receptor selective agents (P<.001). Hypertension was associated with decreased OS compared with no hypertension across all groups. However, even among patients with hypertension, a longer median OS was observed among users of a nonselective beta-blocker compared with nonusers (38.2 months vs 90 months; P<.001). Use of nonselective beta-blockers in patients with EOC was associated with longer OS. These findings may have implications for new therapeutic approaches. Cancer 2015;121:3435-43. © 2015 American Cancer Society. © 2015 American Cancer Society.

  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. Anti-Ro/SSA-associated corrected QT interval prolongation in adults: the role of antibody level and specificity.

    PubMed

    Lazzerini, Pietro Enea; Capecchi, Pier Leopoldo; Acampa, Maurizio; Morozzi, Gabriella; Bellisai, Francesca; Bacarelli, Maria Romana; Dragoni, Saverio; Fineschi, Irene; Simpatico, Antonella; Galeazzi, Mauro; Laghi-Pasini, Franco

    2011-10-01

    Recent evidence suggests that anti-Ro/SSA antibodies, strongly associated with the development of congenital heart block, may also be arrhythmogenic for the adult heart. In fact, anti-Ro/SSA-positive patients with connective tissue disease (CTD) frequently display corrected QT (QTc) prolongation associated with an increase in ventricular arrhythmias. However, QTc prolongation prevalence markedly differs throughout the studies (10-60%), but the reason why is not yet clear. The aim of this study was to evaluate whether anti-Ro/SSA-associated QTc prolongation in adult patients with CTD is related to antibody level and specificity. Forty-nine adult patients with CTD underwent a resting 12-lead electrocardiogram recording to measure QTc interval, and a venous withdrawal to determine anti-Ro/SSA antibody level and specificity (anti-Ro/SSA 52 kd and anti-Ro/SSA 60 kd) by immunoenzymatic methods and Western blotting. In our population, a direct correlation was demonstrated between anti-Ro/SSA 52-kd level and QTc duration (r = 0.38, P = 0.007), patients with a prolonged QTc had higher levels of anti-Ro/SSA 52 kd with respect to those with a normal QTc (P = 0.003), and patients with a moderate to high level (≥50 units/ml) of anti-Ro/SSA 52 kd showed a longer QTc interval (P = 0.008) and a higher QTc prolongation prevalence (P = 0.008) than those with a low positive/negative level (<50 units/ml). On the contrary, no association was found between QTc and anti-Ro/SSA 60-kd level. In anti-Ro/SSA-positive adult patients with CTD, the occurrence of QTc prolongation seems strictly dependent on the anti-Ro/SSA 52-kd level. This finding, possibly explaining the different QTc prolongation prevalence reported, strengthens the hypothesis that an extremely specific autoimmune cross-reaction is responsible for the anti-Ro/SSA-dependent interference on ventricular repolarization. Copyright © 2011 by the American College of Rheumatology.

  15. A deeper view of the CoRoT-9 planetary system. A small non-zero eccentricity for CoRoT-9b likely generated by planet-planet scattering

    NASA Astrophysics Data System (ADS)

    Bonomo, A. S.; Hébrard, G.; Raymond, S. N.; Bouchy, F.; Lecavelier des Etangs, A.; Bordé, P.; Aigrain, S.; Almenara, J.-M.; Alonso, R.; Cabrera, J.; Csizmadia, Sz.; Damiani, C.; Deeg, H. J.; Deleuil, M.; Díaz, R. F.; Erikson, A.; Fridlund, M.; Gandolfi, D.; Guenther, E.; Guillot, T.; Hatzes, A.; Izidoro, A.; Lovis, C.; Moutou, C.; Ollivier, M.; Pätzold, M.; Rauer, H.; Rouan, D.; Santerne, A.; Schneider, J.

    2017-07-01

    CoRoT-9b is one of the rare long-period (P = 95.3 days) transiting giant planets with a measured mass known to date. We present a new analysis of the CoRoT-9 system based on five years of radial-velocity (RV) monitoring with HARPS and three new space-based transits observed with CoRoT and Spitzer. Combining our new data with already published measurements we redetermine the CoRoT-9 system parameters and find good agreement with the published values. We uncover a higher significance for the small but non-zero eccentricity of CoRoT-9b () and find no evidence for additional planets in the system. We use simulations of planet-planet scattering to show that the eccentricity of CoRoT-9b may have been generated by an instability in which a 50 M⊕ planet was ejected from the system. This scattering would not have produced a spin-orbit misalignment, so we predict that the CoRoT-9b orbit should lie within a few degrees of the initial plane of the protoplanetary disk. As a consequence, any significant stellar obliquity would indicate that the disk was primordially tilted.

  16. [Use of neuromuscular blockers in the critical patient].

    PubMed

    Sandiumenge, A; Anglés, R; Martínez-Melgar, J L; Torrado, H

    2008-02-01

    The use of neuromuscular blockers (NMB) is a frequent practice in Intensive Care Units. However most of the experience with the use of these agents come from the operating room used to deal with patients with different characteristics from those admitted in the ICU. Recent advances on neuromonitoring and the commercialization of newer agents make necessary the update in the management of NMB in the ICU. The NMB agent should be chosen attending to its pharmacokinetics and the physiopathology of the critically ill patient. Those NMB with organ-independent metabolism as well as those with rapid onset of action are the preferred ones for the use in the critically ill patient substituting older depolarizing agents and those whose metabolism is dependent on the liver and/or kidney, organs frequently impaired in the critically ill patients. Neuromuscular blocking in the critically ill patient should be done according to protocols and monitor its effects in order to avoid complications related to its prolonged use.

  17. Role of analgesics, sedatives, neuromuscular blockers, and delirium.

    PubMed

    Hall, Jesse B; Schweickert, William; Kress, John P

    2009-10-01

    A major focus on critical care medicine concerns the institution of life-support therapies, such as mechanical ventilation, during periods of organ failure to permit a window of opportunity to diagnose and treat underlying disorders so that patients may be returned to their prior functional status upon recovery. With the growing success of these intensive care unit-based therapies and longer-term follow-up of patients, severe weakness involving the peripheral nervous system and muscles has been identified in many recovering patients, often confounding the time course or magnitude of recovery. Mechanical ventilation is often accompanied by pharmacologic treatments including analgesics, sedatives, and neuromuscular blockers. These drugs and the encephalopathies accompanying some forms of critical illness result in a high prevalence of delirium in mechanically ventilated patients. These drug effects likely contribute to an impaired ability to assess the magnitude of intensive care unit-acquired weakness, to additional time spent immobilized and mechanically ventilated, and to additional weakness from the patient's relative immobility and bedridden state. This review surveys recent literature documenting these relationships and identifying approaches to minimize pharmacologic contributions to intensive care unit-acquired weakness.

  18. Beta blockers and the sensitivity of the thallium treadmill test

    SciTech Connect

    Martin, G.J.; Henkin, R.E.; Scanlon, P.J.

    1987-09-01

    The effect beta blockers (BB) may have on the sensitivity of the thallium treadmill test (Th-TMT) is controversial. The purpose of this study was to test the hypothesis that BB decrease the sensitivity of the Th-TMT. Two hundred three patients over a two-year period were identified who satisfied the following criteria. All had symptom-limited upright treadmill exercise tests with stress and redistribution thallium imaging, as well as coronary angiography within two months of the Th-TMT. Of 58 patients with CAD not on BB, 52 had an abnormal Th-TMT scan (sensitivity 90 percent). In comparison, the sensitivity of the Th-TMT scan in the 88 patients with CAD receiving BB was 76 percent (p less than 0.05). We conclude that BB may significantly decrease the sensitivity of the Th-TMT. Physicians should fully appreciate the higher false negative rate (24 vs 10 percent) for patients on BB and consider cautious withdrawal prior to diagnostic studies.

  19. Novel 'soft' beta-blockers as potential safe antiglaucoma agents.

    PubMed

    Bodor, N; elKoussi, A

    1988-04-01

    A series of novel "soft" beta-blockers was designed and synthesized based on the "inactive metabolite approach". Accordingly, the acidic metabolite of metoprolol was converted into various lipophilic esters. The new compounds were tested for their effect on the intraocular pressure (IOP) of rabbits using the ultra-short acting beta-adrenergic antagonist "Esmolol" as a reference compound. Most of the tested compounds displayed a higher and a more prolonged ocular hypotensive activity than the reference methyl ester. The adamantaneethyl ester 2 emerged as the best potential candidate for ophthalmic use as an antiglaucoma agent. This compound exhibited an effective and long lasting ocular hypotensive activity without local irritation to the eye. At the same time, it showed a very fast rate of hydrolysis in human blood (t1/2 = 7.0 minutes) to the inactive acid metabolite. This makes possible effective separation of the desired ocular activity from unwanted systemic beta-blocking action. Unilateral treatment with 2 produced reduction in the IOP only in the treated eye, consistent with the mechanism proposed.

  20. Angiotensin receptor blockers: are they related to lung cancer?

    PubMed Central

    Rao, Gowtham Adamane; Mann, Joshua R.; Shoaibi, Azza; Pai, Sachin G.; Bottai, Matteo; Sutton, Shawn Scott; Haddock, Kathlyn Sue; Bennett, Charles Lee; Hebert, James R.

    2013-01-01

    Introduction Angiotensin receptor blockers (ARBs) are commonly used antihypertensive medication with several other additional proven benefits. Recent controversy on association of lung cancer and other solid malignancy with the use of ARBs is concerning, although the follow-up studies have shown no such association. Methods We used data from the Department of Veterans Affairs electronic medical record system and registries to conduct a retrospective cohort study that compared first-time ARB users with nonusers in 1:15 ratio, after balancing for many baseline differences using inverse probability of treatment weights. We conducted time-to-event survival analyses on the weighted cohort. Results Of the 1 229 902 patients in the analytic cohort, 346 (0.44%) of the 78 075 treated individuals had a newly incident lung cancer and 6577 (0.57%) of 1 151 826 nontreated individuals were diagnosed with lung cancer. On double robust regression, the weighted hazard ratio was 0.74 (0.67–0.83, P<0.0001), suggesting a lung cancer reduction effect with ARB use. There was no difference in rates by ARB subtype. Conclusion In this large nationwide cohort of United States Veterans, we found no evidence to support any concern of increased risk of lung cancer among new users of ARBs compared with nonusers. Our findings were consistent with a protective effect of ARBs. PMID:23822929

  1. Golimumab, the newest TNF-α blocker, comes of age.

    PubMed

    Papagoras, Charalampos; Voulgari, Paraskevi V; Drosos, Alexandros A

    2015-01-01

    Golimumab, a fully human monoclonal antibody against tumour necrosis factor-α (TNF-α) is one of the newest biologics that has become available for the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Following the initial randomised double-blind placebo-controlled clinical trials, which demonstrated the efficacy and safety of the drug in the context of a limited patient sample and a relatively short time frame, golimumab has been the focus of continuous investigation through the extensions of the above-mentioned trials, new clinical trials and registries of biologic drug use in daily clinical practice. The review of this data and their inclusion in meta-analyses and indirect comparisons across TNF-α blockers suggest that golimumab possesses similar properties regarding efficacy and safety as the older monoclonal anti-TNF-α antibodies. The novelty of golimumab is perhaps its dosing regimen, i.e. subcutaneous self-administration once monthly, which allows for the least disturbance in the life of patients.

  2. 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.

  3. Emerging data on calcium-channel blockers: the COHORT study.

    PubMed

    Zanchetti, Alberto

    2003-02-01

    Multiple studies have demonstrated dihydropyridine calcium-channel blocker (CCB) therapy to be appropriate for the treatment of hypertension, as is reflected in treatment guidelines such as the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure in the United States and the 1999 World Health Organization-International Society of Hypertension report. As with any drug class, successful treatment with CCBs depends on good patient compliance, which often hinges on drug tolerability. The differing characteristics among the various generations of CCBs may contribute to some compounds demonstrating superior tolerability. To test this hypothesis, the COHORT trial (named for the large group of participants) was undertaken in 828 elderly hypertensive patients aged > or = 60 years. This trial investigated the possible differences in patient tolerability between the third-generation agent amlodipine and the latest-generation agents lercanidipine and lacidipine. The primary endpoint of the study was the percentage of patients reporting edema, the most common side effect associated with CCB therapy. The study results indicated that while all three treatments were similarly efficacious in lowering blood pressure, lercanidipine and lacidipine were much better tolerated than amlodipine whether they were used as single agents or as initial therapy combined with other antihypertensive drugs. These newest-generation dihydropyridine CCBs offer the potential to reduce side effects, improve patient compliance, and ultimately help patients reach target blood pressures as recommended by the aforementioned guidelines.

  4. 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.

  5. Treatment of C3 glomerulopathy with complement blockers.

    PubMed

    Vivarelli, Marina; Emma, Francesco

    2014-06-01

    C3 glomerulopathy (C3G) is a newly defined clinical entity comprising glomerular lesions with predominant C3 staining. Under this definition are now included membranoproliferative glomerulonephritis type II (dense deposit disease) and C3 glomerulonephritis. This group of glomerular diseases with a heterogeneous histological aspect shares a common pathogenesis, that is, a dysregulation of the alternative pathway of complement in the fluid phase leading to C3 deposition in the kidney. Recent advances have expanded our understanding of the underlying mechanisms, leading to the hypothesis that blocking the alternative complement pathway may be an effective treatment for C3Gs, as has been shown in other renal diseases driven by alternative pathway dysregulation, such as atypical hemolytic uremic syndrome. Results of 11 published cases of patients with different forms of C3G treated with eculizumab, an anti-C5 humanized monoclonal antibody, are encouraging. Given the complexity of disease pathogenesis in C3G, a patient-tailored approach including a comprehensive workup of complement abnormalities is necessary to evaluate the best treatment options. Clinical trials assessing effectiveness of different complement blockers on the background of the individual complement profile are needed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  6. 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).

  7. Antiarrhythmic action of beta-blockers: potential mechanisms.

    PubMed

    Dorian, Paul

    2005-06-01

    Sympathetic nervous system overactivity has been linked to ventricular tachyarrhythmias and sudden death. It has been hypothesized that the extent and nature of the arrhythmogenic effect of sympathetic stimulation depends on the underlying myocardial substrate, the mechanism of the arrhythmia, and the integrated effects of sympathetic stimulation in the particular individual circumstance. Multiple direct and indirect mechanisms of adrenergic action on the heart may benefit from the known antiarrhythmic actions of beta-blocker therapy and other interventions that decrease sympathetic tone. The antiarrhythmic mechanism of beta-blockade (and possibly alpha-blockade) will depend on the specific mechanism of the individual arrhythmia and will differ for those arrhythmias caused by tachycardia and ischemia, those caused by reentry and promoted by decreased conduction velocity and shortened refractoriness, and those caused by early or delayed afterdepolarizations, usually in the context of prolonged action potential duration. Antagonism of cardiac adrenergic activity by beta-blockade in particular is the best-established drug therapy to prevent ventricular arrhythmias.

  8. 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

  9. 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.

  10. Change in proteinuria after adding aldosterone blockers to ACE inhibitors or angiotensin receptor blockers in CKD: a systematic review.

    PubMed

    Bomback, Andrew S; Kshirsagar, Abhijit V; Amamoo, M Ahinee; Klemmer, Philip J

    2008-02-01

    The use of mineralocorticoid receptor blockers (MRBs) in patients with chronic kidney disease is growing, but data for efficacy in decreasing proteinuria are limited by a relative paucity of studies, many of which are small and uncontrolled. We performed a systematic review using the MEDLINE database (inception to November 1, 2006), abstracts from national meetings, and selected reference lists. Adult patients with chronic kidney disease and proteinuria. English-language studies investigating the use of MRBs added to long-term angiotensin-converting enzyme (ACE)-inhibitor and/or angiotensin receptor blocker (ARB) therapy in adult patients with proteinuric kidney disease. MRBs as additive therapy to conventional renin-angiotensin-aldosterone system blockade in patients with chronic kidney disease. Changes in proteinuria as the primary outcome; rates of hyperkalemia, changes in blood pressure, and changes in glomerular filtration rate as secondary outcomes. 15 studies met inclusion criteria for our review; 4 were parallel-group randomized controlled trials, 4 were crossover randomized controlled trials, 2 were pilot studies, and 5 were case series. When MRBs were added to ACE-inhibitor and/or ARB therapy, the reported proteinuria decreases from baseline ranged from 15% to 54%, with most estimates in the 30% to 40% range. Hyperkalemic events were significant in only 1 of 8 randomized controlled trials. MRB therapy was associated with statistically significant decreases in blood pressure and glomerular filtration rate in approximately 40% and 25% of included studies, respectively. Reported results were insufficient for meta-analysis, with only 2 studies reporting sufficient data to calculate SEs of their published estimates. We were unable to locate studies that showed no effect of MRB treatment over placebo, raising concern for publication bias. Although data suggest that adding MRBs to ACE-inhibitor and/or ARB therapy yields significant decreases in proteinuria

  11. Calcium channel blockers for inhibiting preterm labour and birth.

    PubMed

    Flenady, Vicki; Wojcieszek, Aleena M; Papatsonis, Dimitri N M; Stock, Owen M; Murray, Linda; Jardine, Luke A; Carbonne, Bruno

    2014-06-05

    Preterm birth is a major contributor to perinatal mortality and morbidity, affecting around 9% of births in high-income countries and an estimated 13% of births in low- and middle-income countries. Tocolytics are drugs used to suppress uterine contractions for women in preterm labour. The most widely used tocolytic are the betamimetics, however, these are associated with a high frequency of unpleasant and sometimes severe maternal side effects. Calcium channel blockers (CCBs) (such as nifedipine) may have similar tocolytic efficacy with less side effects than betamimetics. Oxytocin receptor antagonists (ORAs) (e.g. atosiban) also have a low side-effect profile. To assess the effects on maternal, fetal and neonatal outcomes of CCBs, administered as a tocolytic agent, to women in preterm labour. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (12 November 2013). All published and unpublished randomised trials in which CCBs were used for tocolysis for women in labour between 20 and 36 completed weeks' gestation. Two review authors independently assessed trial eligibility, undertook quality assessment and data extraction. Results are presented using risk ratio (RR) for categorical data and mean difference (MD) for data measured on a continuous scale with the 95% confidence interval (CI). The number needed to treat to benefit (NNTB) and the number needed to treat to harm (NNTH) were calculated for categorical outcomes that were statistically significantly different. This update includes 26 additional trials involving 2511 women, giving a total of 38 included trials (3550 women). Thirty-five trials used nifedipine as the CCB and three trials used nicardipine. Blinding of intervention and outcome assessment was undertaken in only one of the trials (a placebo controlled trial). However, objective outcomes defined according to timing of birth and perinatal mortality were considered to have low risk of detection bias.Two small trials comparing CCBs

  12. Data and calculus on isobolographic analysis to determine the antinociceptive interaction between calcium channel blocker and a TRPV1 blocker in acute pain model in mice.

    PubMed

    Silva, Juliana F; Palhares, Manuella R; Santos, Duana C; Silva-Junior, Cláudio A; Ferreira, Juliano; Gomez, Marcus V; Castro Junior, Célio J

    2017-10-01

    Determining antinociceptive interaction between Phα1β toxin (a voltage gated calcium channel blocker) and SB366791 (selective TRPV1 antagonist) may have both clinical and mechanistic implications for the pain management. This data in brief article is associated to the research paper "Synergistic antinociceptive effect of a calcium channel blocker and a TRPV1 blocker in an acute pain model in mice". This material supports the isobolographic analysis performed with the above drugs and shows: data of the dose response curves of the agents given as single drug or combination regimens. Mathematics and statistical processing of dose response curves, proportion of drugs dosage to be used in the combination, calculus of theoretical additive DE20 dose as well as experimentally obtained DE20 are provided. It is also presented details of statistical comparison between theoretical and experimentally obtained DE20.

  13. 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.

  14. Obstetric and perinatal outcome in anti-Ro/SSA-positive pregnant women: a prospective cohort study.

    PubMed

    Martínez-Sánchez, Nuria; Pérez-Pinto, Sergio; Robles-Marhuenda, Ángel; Arnalich-Fernández, Francisco; Martín Cameán, María; Hueso Zalvide, Edurne; Bartha, Jose Luis

    2017-04-01

    Anti-Ro/SS-A is one specific type of antinuclear antibodies. They are in the majority of cases associated with primary Sjögren syndrome (SS) but also in Systemic Lupus Erythematosus (SLE), rheumatoid arthritis (RA), and in healthy people. During pregnancy, they are mainly associated to congenital heart block (CHB) and neonatal lupus (NL). The aim of this study was to compare the rate of maternal and fetal complications between a series of anti-Ro/SS-A positive pregnant women prospectively followed. Forty-two anti-Ro/SSA antibodies positive pregnant women that were referred to our hospital between 2011 and 2015. Data about pregnancy follow-up and outcomes were prospectively recorded from electronic databases. Data included demographic characteristics of the patients and their diseases (type, treatments, profile of anti-Ro/SSA, and antiphospholipid antibodies), pregnancy complications (CHB, preeclampsia, preterm delivery), ultrasound examinations and conditions, and mode of delivery. Maternal age was 35.22 ± 3.42 years and most of them were either SLE (n = 16, 40%) or Sjögren syndrome (n = 15, 37.5%). The rest of them were asymptomatic carriers (n = 8; 20%), and there was only one case of rheumatoid arthritis (n = 1; 2.5%). The incidence of anti-Ro52 and anti-Ro60 positive was n = 13, 82.4% and n = 16, 100%, respectively. Anti-La/SSB antibodies were present in n = 17, 48,6% of the patients. Half of the patients were taking hydroxycloroquine (n = 18, 45%). Seven pregnancies were complicated by fetal anti-Ro-related cardiac disease (17.9%) including four cases (57.1%) of second-degree heart block, two cases of third degree heart block (28.6%) and one case (14.3%) of intense and diffuse hyperechogenicity in atrioventricular valves without heart block. Gestational age at diagnosis of these conditions was 23.2 ± 3.5 weeks. One of the 18 patients having hydroxychloroquine (5.6%) compared with the six of them in women not having this medication (6

  15. Pregnancy outcome in 100 women with autoimmune diseases and anti-Ro/SSA antibodies: a prospective controlled study.

    PubMed

    Brucato, A; Doria, A; Frassi, M; Castellino, G; Franceschini, F; Faden, D; Pisoni, M Pia; Solerte, L; Muscarà, M; Lojacono, A; Motta, M; Cavazzana, I; Ghirardello, A; Vescovi, F; Tombini, V; Cimaz, R; Gambari, P F; Meroni, P L; Canesi, B; Tincani, A

    2002-01-01

    Anti-Ro/SSA antibodies are associated with neonatal lupus but are also considered a possible cause for unexplained pregnancy loss and adverse pregnancy outcome. In a large multicentres cohort study we have prospectively followed 100 anti-Ro/SSA positive women (53 systemic lupus erythematosus (SLE)) during their 122 pregnancies and 107 anti-Ro/SSA negative women (58 SLE) (140 pregnancies). Anti-Ro/SSA antibodies were tested by immunoblot and counterimunoelectrophoresis. Mean gestational age at delivery (38 vs 37.9 weeks), prevalence of pregnancy loss (9.9 vs 18.6%), preterm birth (21.3 vs 13.9%), cesarean sections (49.2 vs 53.4%), premature rupture of membranes (4.9 vs 8.1%), preeclampsia (6.6 vs 8%), intrauterine growth retardation (0 vs 2.3%)and newborns small for gestational age (11.5 vs 5.8%) were similar in anti-Ro/SSA positive and negative SLE mothers; findings were similar in non-SLE women. Two cases of congenital heart block were observed out of 100 anti-Ro/SSA positive women. In conclusion, anti-Ro/SSA antibodies are responsible for congenital heart block but do not affect other pregnancy outcomes, both in SLE and in non-SLE women. The general outcome of these pregnancies is now very good, ifprospectively followed by multidisciplinary teams with ample experience in this field.

  16. 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.

  17. Ro52/SSA sensitizes cells to death receptor-induced apoptosis by down-regulating c-FLIP(L).

    PubMed

    Zhang, Jing; Fang, Lei; Zhu, Xuguo; Qiao, Yiting; Yu, Mei; Wang, Lu; Chen, Yuan; Yin, Wu; Hua, Zi-Chun

    2012-05-01

    Ro52/SSA is an autoantigen that presents in patients with SS (Sjögren's syndrome) and SLE (systemic lupus erythematosus). It increases cell death and redistributes itself to apoptotic blebs, but its pro-apoptotic function has not been completely identified. Overexpression of Ro52/SSA promoted cell apoptosis induced by DR (death receptor) in caspase-8-dependent manner. Ro52/SSA expression down-regulated c-FLIP(L) [cellular (Fas-associated death domain)-like interleukin 1β-converting enzyme-inhibitory protein long form] expression, and Ro52/SSA siRNAs (small interfering RNAs) increased c-FLIP(L) production, indicating that Ro52/SSA plays a role in c-FLIP(L) regulation. Ro52/SSA negatively regulated c-FLIP(L) transcriptional level probably by suppressing NF-κB (nuclear factor κB) signalling. The data suggest that Ro52/SSA is involved in DR-mediated apoptosis by regulating c-FLIP(L).

  18. Use of β-Blockers, Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Risk of Breast Cancer Recurrence: A Danish Nationwide Prospective Cohort Study

    PubMed Central

    Sørensen, Gitte Vrelits; Ganz, Patricia A.; Cole, Steven W.; Pedersen, Lars A.; Toft Sørensen, Henrik; Cronin-Fenton, Deirdre P.; Peter Garne, Jens; Christiansen, Peer M.; Lash, Timothy L.; Ahern, Thomas P.

    2013-01-01

    Purpose To estimate associations between use of β-blockers, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers (ARBs) and breast cancer recurrence in a large Danish cohort. Patients and Methods We enrolled 18,733 women diagnosed with nonmetastatic breast cancer between 1996 and 2003. Patient, treatment, and 10-year recurrence data were ascertained from the Danish Breast Cancer Cooperative Group registry. Prescription and medical histories were ascertained by linkage to the National Prescription Registry and Registry of Patients, respectively. β-Blocker exposure was defined in aggregate and according to solubility, receptor selectivity, and individual drugs. ACE inhibitor and ARB exposures were defined in aggregate. Recurrence associations were estimated with multivariable Cox regression models in which time-varying drug exposures were lagged by 1 year. Results Compared with never users, users of any β-blocker had a lower recurrence hazard in unadjusted models (unadjusted hazard ratio [HR] = 0.91; 95% CI, 0.81 to 1.0) and a slightly higher recurrence hazard in adjusted models (adjusted HR = 1.3; 95% CI, 1.1 to 1.5). Associations were similar for exposures defined by receptor selectivity and solubility. Although most individual β-blockers showed no association with recurrence, metoprolol and sotalol were associated with increased recurrence rates (adjusted metoprolol HR = 1.5, 95% CI, 1.2 to 1.8; adjusted sotalol HR = 2.0, 95% CI, 0.99 to 4.0). ACE inhibitors were associated with a slightly increased recurrence hazard, whereas ARBs were not associated with recurrence (adjusted ACE inhibitor HR = 1.2, 95% CI, 0.97 to 1.4; adjusted ARBs HR = 1.1, 95% CI, 0.85 to 1.3). Conclusion Our data do not support the hypothesis that β-blockers attenuate breast cancer recurrence risk. PMID:23650417

  19. 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

  20. 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.

  1. Limits to the presence of transiting circumbinary planets in CoRoT Data

    NASA Astrophysics Data System (ADS)

    Klagyivik, P.; Deeg, H. J.; Cabrera, J.; Csizmadia, Sz.; Almenara, J. M.

    2017-06-01

    Aims: During its flight phase, from 2007-2012, the CoRoT mission delivered light curves for over 2000 eclipsing binaries. Data from the Kepler mission have proven the existence of several transiting circumbinary planets. While light curves from CoRoT typically have lower precision and shorter coverage, the number of CoRoT targets is similar to that of Kepler and some of the known circumbinary planets could potentially be detected in CoRoT data as well. The aim of this work was to reanalyse the entire CoRoT Data set to search for the presence of circumbinary planets and to derive limits on the abundances of such planets. Methods: We developed a code that removes the signatures of eclipsing binaries from the light curves, and searches for quasi-periodic, transit-like features in the light curves after removal of binary eclipses and instrumental features. The code requires little information on sample systems and can also be used for other space missions, such as Kepler, K2, TESS, and PLATO. The code is broad in the requirements leading to detections, but was tuned to deliver an amount of detections that are manageable in a subsequent, mainly visual, assessment of their origin. Results: We identified three planet candidates in the CoRoT sample whose transits would have arisen from a single pass across the central binary; however, no candidates with transit events from multiple planetary orbits remained. We calculated the upper limits for the number of Jupiter, Saturn-, and Neptune-sized planets in co-planar orbits for different orbital period ranges. We found that there are much fewer giant planets in short periodic orbits around close binary systems than around single stars. Full Table 1 is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/602/A117

  2. 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

  3. Beta-blockers: recognising the assets in relation to coronary artery disease.

    PubMed

    Kendall, M J

    2000-01-01

    Beta-blockers have been shown to reduce the risk of coronary events and reduce the mortality of patients with hypertension and in those who have had a myocardial infarction. Furthermore, the evidence for long-term benefits in these two patient groups are much more convincing for beta-blockers than for other therapeutic agents used to treat these patient groups. In spite of this beta-blockers are underused because doctors believe that these drugs are contraindicated in many vulnerable patient groups. The data now available from the many trials and observational studies have shown that patients such as the elderly, those with some degree of heart failure, diabetics and those with chronic lung disease not only tolerate beta blockers but derive more benefit than more healthy patient groups.

  4. 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.

  5. 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. 

  6. 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

  7. New coupled-particle light-scattering assay for detection of Ro/SSA (52 and 60 kilodaltons) and La/SSB autoantibodies in connective tissue diseases.

    PubMed

    Bizzaro, N; Bonelli, F; Tonutti, E; Tozzoli, R; Villalta, D

    2001-09-01

    The diagnostic and analytical performance of the coupled-particle light-scattering assay in detecting anti-Ro/SSA autoantibodies (the 60-kDa [Ro60] and the 52-kDa [Ro52] antibodies) and anti-La/SSB autoantibodies was evaluated. The antigens were obtained by recombinant DNA procedures to include the most immunogenic epitopes for each protein by using a prokaryotic expression system. Serum samples from 151 patients with connective tissue diseases and 52 control subjects (including patients with viral infections, patients with Lyme disease, and healthy subjects) were studied. Sensitivities for detection of anti-Ro/SSA and anti-La/SSB were 88.2 and 95.2%, respectively; specificities were 97.6 and 98.1%, respectively. The intra-assay coefficient of variation (CV) ranged from 4.3 to 10.9% for anti-Ro/SSA and from 2.8 to 12.5% for anti-La/SSB; interassay CVs ranged from 6.5 to 13.2% and from 8.2 to 14.5%, respectively. Among the anti-Ro/SSA-positive samples, Ro60 was recognized by 66% of the test sera and Ro52 was recognized by 95% of the test sera. Thirty-four percent of the Ro/SSA-positive sera were reactive only with the Ro52 antigen, indicating that anti-Ro52 is the most common antibody specificity recognized by anti-Ro/SSA autoantibodies. No differences were found between the prevalences of anti-Ro60 and anti-Ro52 in relation to systemic lupus erythematosus or Sjögren's syndrome. The results of the present study indicate that this new immunoassay is an efficient diagnostic tool for the detection of anti-Ro/SSA and anti-La/SSB antibodies in patients with autoimmune disorders.

  8. New Coupled-Particle Light-Scattering Assay for Detection of Ro/SSA (52 and 60 Kilodaltons) and La/SSB Autoantibodies in Connective Tissue Diseases

    PubMed Central

    Bizzaro, Nicola; Bonelli, Fabrizio; Tonutti, Elio; Tozzoli, Renato; Villalta, Danilo

    2001-01-01

    The diagnostic and analytical performance of the coupled-particle light-scattering assay in detecting anti-Ro/SSA autoantibodies (the 60-kDa [Ro60] and the 52-kDa [Ro52] antibodies) and anti-La/SSB autoantibodies was evaluated. The antigens were obtained by recombinant DNA procedures to include the most immunogenic epitopes for each protein by using a prokaryotic expression system. Serum samples from 151 patients with connective tissue diseases and 52 control subjects (including patients with viral infections, patients with Lyme disease, and healthy subjects) were studied. Sensitivities for detection of anti-Ro/SSA and anti-La/SSB were 88.2 and 95.2%, respectively; specificities were 97.6 and 98.1%, respectively. The intra-assay coefficient of variation (CV) ranged from 4.3 to 10.9% for anti-Ro/SSA and from 2.8 to 12.5% for anti-La/SSB; interassay CVs ranged from 6.5 to 13.2% and from 8.2 to 14.5%, respectively. Among the anti-Ro/SSA-positive samples, Ro60 was recognized by 66% of the test sera and Ro52 was recognized by 95% of the test sera. Thirty-four percent of the Ro/SSA-positive sera were reactive only with the Ro52 antigen, indicating that anti-Ro52 is the most common antibody specificity recognized by anti-Ro/SSA autoantibodies. No differences were found between the prevalences of anti-Ro60 and anti-Ro52 in relation to systemic lupus erythematosus or Sjögren's syndrome. The results of the present study indicate that this new immunoassay is an efficient diagnostic tool for the detection of anti-Ro/SSA and anti-La/SSB antibodies in patients with autoimmune disorders. PMID:11527804

  9. Umbilical Cord Blood Levels of Maternal Antibodies Reactive with p200 and Full Length Ro52 in the Assessment of Risk for Cardiac Manifestations of Neonatal Lupus

    PubMed Central

    Reed, Joanne H.; Clancy, Robert M.; Lee, Kristen H.; Saxena, Amit; Izmirly, Peter M.; Buyon, Jill P.

    2012-01-01

    Objective Maternal anti-Ro autoantibodies associate with cardiac manifestations of neonatal lupus (cardiac NL), yet only 2% of women with this reactivity have an affected child. Identification of a more specific marker would channel intense monitoring to fetuses at greater risk. This study aims to determine whether autoantibodies against Ro52 amino acids 200–239 (p200) confer added risk over autoantibodies to full length Ro52, Ro60 or La. Methods/Results Anti-Ro-exposed pregnancies resulting in cardiac NL or no cardiac manifestations were identified from the Research Registry for Neonatal Lupus and PR Interval and Dexamethasone Evaluation. Umbilical cord (n=123) and maternal (n=115) samples were evaluated by ELISA. The frequencies of p200, Ro52, Ro60 and La autoantibodies were not significantly different between affected and unaffected children. However, neonatal anti-Ro52 and Ro60 titers were highest in cardiac NL and their unaffected siblings compared to unaffected neonates without a cardiac NL sibling. Although both maternal anti-Ro52 and p200 autoantibodies were less than 50% specific for cardiac NL, anti-p200 was the least likely of the Ro autoantibodies to be false positive in mothers who have never had an affected child. Titers of anti-Ro52 and p200 did not differ during a cardiac NL or unaffected pregnancy from the same mother. Conclusion Maternal reactivity to p200 does not confer an added risk to fetal conduction defects over full length Ro52 or Ro60 autoantibodies. Mothers who may never be at risk for having an affected child have lower anti-Ro60 titers and may require less stringent echocardiographic monitoring compared to women with high titer autoantibodies. PMID:22511615

  10. 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.

  11. 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

  12. 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.

  13. Age-Related Differences in Bitter Taste and Efficacy of Bitter Blockers

    PubMed Central

    Mennella, Julie A.; Reed, Danielle R.; Roberts, Kristi M.; Mathew, Phoebe S.; Mansfield, Corrine J.

    2014-01-01

    Background Bitter taste is the primary culprit for rejection of pediatric liquid medications. We probed the underlying biology of bitter sensing and the efficacy of two known bitter blockers in children and adults. Methods A racially diverse group of 154 children (3-10 years old) and their mothers (N = 118) evaluated the effectiveness of two bitter blockers, sodium gluconate (NaG) and monosodium glutamate (MSG), for five food-grade bitter compounds (quinine, denatonium benzoate, caffeine, propylthiouracil (PROP), urea) using a forced-choice method of paired comparisons. The trial was registered at clinicaltrials.gov (NCT01407939). Results The blockers reduced bitterness in 7 of 10 bitter-blocker combinations for adults but only 3 of 10 for children, suggesting that efficacy depends on age and is also specific to each bitter-blocker combination. Only the bitterness of urea was reduced by both blockers in both age groups, whereas the bitterness of PROP was not reduced by either blocker in either age group regardless of TAS2R38 genotype. Children liked the salty taste of the blocker NaG more than did adults, but both groups liked the savory taste of MSG equally. Conclusions and Relevance Bitter blocking was less effective in children, and the efficacy of blocking was both age and compound specific. This knowledge will pave the way for evidence-based strategies to help develop better-tasting medicines and highlights the conclusion that adult panelists and genotyping alone may not always be appropriate in evaluating the taste of a drug geared for children. PMID:25050705

  14. A novel hypothesis for the binding mode of HERG channel blockers

    SciTech Connect

    Choe, Han . E-mail: hchoe@amc.seoul.kr; Nah, Kwang Hoon; Lee, Soo Nam; Lee, Han Sam; Lee, Hui Sun; Jo, Su Hyun; Leem, Chae Hun; Jang, Yeon Jin

    2006-05-26

    We present a new docking model for HERG channel blockade. Our new model suggests three key interactions such that (1) a protonated nitrogen of the channel blocker forms a hydrogen bond with the carbonyl oxygen of HERG residue T623; (2) an aromatic moiety of the channel blocker makes a {pi}-{pi} interaction with the aromatic ring of HERG residue Y652; and (3) a hydrophobic group of the channel blocker forms a hydrophobic interaction with the benzene ring of HERG residue F656. The previous model assumes two interactions such that (1) a protonated nitrogen of the channel blocker forms a cation-{pi} interaction with the aromatic ring of HERG residue Y652; and (2) a hydrophobic group of the channel blocker forms a hydrophobic interaction with the benzene ring of HERG residue F656. To test these models, we classified 69 known HERG channel blockers into eight binding types based on their plausible binding modes, and further categorized them into two groups based on the number of interactions our model would predict with the HERG channel (two or three). We then compared the pIC{sub 5} value distributions between these two groups. If the old hypothesis is correct, the distributions should not differ between the two groups (i.e., both groups show only two binding interactions). If our novel hypothesis is correct, the distributions should differ between Groups 1 and 2. Consistent with our hypothesis, the two groups differed with regard to pIC{sub 5}, and the group having more predicted interactions with the HERG channel had a higher mean pIC{sub 5} value. Although additional work will be required to further validate our hypothesis, this improved understanding of the HERG channel blocker binding mode may help promote the development of in silico predictions methods for identifying potential HERG channel blockers.

  15. Angiotensin II receptor antagonists (AT1-blockers, ARBs, sartans): similarities and differences

    PubMed Central

    van Zwieten, P.A.

    2006-01-01

    A survey is presented of the registered non-peptidergic angiotensin II receptor antagonists (AT1 blockers, ARBs, sartans) and their general properties and similarities. Accordingly, their receptor profile, pharmacokinetic and therapeutic applications are discussed. In addition, attention is paid to the individual characteristics of the AT1 blockers now available. A few components of this category offer additional potentially beneficial properties, owing to their pharmacological or metabolic characteristics. Such additional properties are critically discussed for eprosartan, losartan, telmisartan and valsartan. PMID:25696573

  16. Topical beta-blockers are not associated with an increased risk of treatment for depression.

    PubMed

    Kaiserman, Igor; Kaiserman, Nadia; Elhayany, Asher; Vinker, Shlomo

    2006-07-01

    To investigate the effect of topical beta-blockers on the prevalence of depression among glaucoma patients. Retrospective observational population-based cohort study. We reviewed the electronic medical records of all the members in a district of the largest health maintenance organization in Israel (Central District of Clalit Health Services) who were older than 20 years (317,469 members). We documented all antiglaucoma prescriptions (n = 274,023) and all antidepressant prescriptions (n = 16,948) filled by glaucoma patients in the district between January 1, 2001 and December 31, 2003. We included only those patients who filled at least 6 consecutive antiglaucoma prescriptions at least once every 2 months (n = 6597; 5846 [88.6%] were treated with topical beta-blockers). Depressed patients were defined as patients that filled at least four prescriptions for antidepressants during the study period (n= 810, 12.3% of all glaucoma patients). Relationship of topical beta-blocker use and prevalence of depression among glaucoma patients. No significant demographic differences were noted between glaucoma patients treated and not treated with topical beta-blockers. Of those treated and not treated with beta-blockers, 12.2% (12.7% after age-adjustment) and 12.7%, respectively, were also receiving drug therapy for depression (P = 0.7, chi-square test). With stratification by age, treatment with topical beta-blockers did not influence the prevalence of depression in any age group. Logistic regression analysis revealed a significant effect of age, place of birth, and gender on the prevalence of depression, but the prevalence of use of topical beta-blockers had no significant effect. Use of topical beta-blockers by glaucoma patients does not appear to increase the risk of depression in this population.

  17. [Oral versus intravenous beta-blockers for computed tomography coronary angiography? A randomized controlled trial].

    PubMed

    Tardáguila de la Fuente, G; Delgado Sánchez-Gracián, C; Aguilar Arjona, J A; Prada González, R; Fernández Pérez, G; Tardáguila Montero, F

    2011-01-01

    To determine whether the time employed in the radiological management of outpatients undergoing computed tomography (CT) coronary angiography varies in function of whether oral or intravenous beta-blockers are administered. This was a prospective, analytical, randomized controlled trial. A total of 40 patients with heart rates greater than 65 beats per minute were randomly assigned to one of two groups. Patients in group 1 were administered oral beta-blockers and patients in group 2 were administered intravenous beta-blockers. We measured the overall time from entry to the radiology department to exit from the CT examination room. We also measured heart rate, blood pressure, and the number of conclusive studies. The median (interquartile range) overall time was 120 (100-150) minutes in the 19 patients who received oral beta-blockers compared to 35 (27.5-67.5) minutes in the 21 patients who received intravenous beta-blockers (p<0.001). The median time that patients were in the CT examination room was 10 (6-15) minutes in Group 1 and 10 (9-20) minutes in Group 2 (p = 0.57). The decrease in mean arterial pressure was 10 mmHg after the administration of intravenous beta-blockers compared to 3.3 mmHg after the administration of oral beta-blockers (p = 0.01). No significant differences were found in the diagnostic quality of the examinations. The time employed in the radiological management of patients undergoing CT coronary angiography is significantly lower when beta-blockers are administered intravenously. There was no difference in the time patients were in the CT examination room or in the diagnostic quality of the examinations. Copyright © 2010 SERAM. Published by Elsevier Espana. All rights reserved.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. Evaluation of Mutagenicity of Mebudipine, a New Calcium Channel Blocker

    PubMed Central

    Gholami, Saeid; Soleimani, Fatemeh; Hoseini Shirazi, Farshad; Touhidpour, Maryam; Mahmoudian, Massoud

    2010-01-01

    Mebudipine is a new dihydropyridine calcium channel blocker, synthesized in our laboratory, for treatment of hypertension. It has shown a better efficacy than other drugs in this group. For assessing the risks of this drug, certain safety tests in the preclinical stage have been performed. In this study mutagenic effect of mebudipine was evaluated using Ames assay that could assess the mutagenicity of drugs and their metabolites using liver enzymes (S-9 mix). This procedure is approved as a predictive test, with a high predictive value. Salmonella TA102 (Ames assay) was used with and without S-9 in this study. For preparing S-9 mix, rat liver enzymes induced by phenobarbital were separated in KCl 0.154 M (0.154 M), as the solvent. Mebudipine was dissolved in polyethylenglycol 400. Mutagenicity test was performed in 6 doses from 39 μg to 1250 μg per every plate, in the presence and absence of the S-9 mix. The positive control sodium azide was dissolved in a dose of 5 μg/plate dissolved in polyethylenglycol 400 and negative control was polyethylenglycol 400 with no added agent. The colony counts of all doses in plates with S-9 were between 200-400 and in plates without S9 was between100-300. The colony counts in both states (with and without S-9) of all doses were in the range suggested by Ames assay for the safe drugs and were different from the positive control groups and equal to the negative controls. Mebudipine and its metabolites were not found to be mutagen on Salmonella TA102, based on Ames assay. PMID:24363706

  3. Evaluation of mutagenicity of mebudipine, a new calcium channel blocker.

    PubMed

    Gholami, Saeid; Soleimani, Fatemeh; Hoseini Shirazi, Farshad; Touhidpour, Maryam; Mahmoudian, Massoud

    2010-01-01

    Mebudipine is a new dihydropyridine calcium channel blocker, synthesized in our laboratory, for treatment of hypertension. It has shown a better efficacy than other drugs in this group. For assessing the risks of this drug, certain safety tests in the preclinical stage have been performed. In this study mutagenic effect of mebudipine was evaluated using Ames assay that could assess the mutagenicity of drugs and their metabolites using liver enzymes (S-9 mix). This procedure is approved as a predictive test, with a high predictive value. Salmonella TA102 (Ames assay) was used with and without S-9 in this study. For preparing S-9 mix, rat liver enzymes induced by phenobarbital were separated in KCl 0.154 M (0.154 M), as the solvent. Mebudipine was dissolved in polyethylenglycol 400. Mutagenicity test was performed in 6 doses from 39 μg to 1250 μg per every plate, in the presence and absence of the S-9 mix. The positive control sodium azide was dissolved in a dose of 5 μg/plate dissolved in polyethylenglycol 400 and negative control was polyethylenglycol 400 with no added agent. The colony counts of all doses in plates with S-9 were between 200-400 and in plates without S9 was between100-300. The colony counts in both states (with and without S-9) of all doses were in the range suggested by Ames assay for the safe drugs and were different from the positive control groups and equal to the negative controls. Mebudipine and its metabolites were not found to be mutagen on Salmonella TA102, based on Ames assay.

  4. Analysis of published economic evaluations of angiotensin receptor blockers.

    PubMed

    Theodoratou, Dorina; Maniadakis, Nikos; Fragoulakis, Vasilis; Stamouli, Eugenia

    2009-01-01

    In this study we reviewed the published literature on the economic evaluation of the use of angiotensin receptor blockers (ARBs) for the treatment of hypertension, either primary or due to diabetes. An extensive literature review was undertaken. The HEED (Health Economic Evaluations Database) of the Office for Health Economics and the NHS-EED (NHS Economic Evaluation Database) databases were searched. Keywords used were "losartan", "irbesartan", "valsartan", "candesartan", "olmesartan", "telmisartan", "eprosartan", "primary hypertension" and "diabetes". The study included all articles retrieved from 2001 onwards. Exclusion criteria included economic evaluations of ARBs for other indications (e.g. heart failure, myocardial infarction, etc.), an underage population, as well as prevalence studies of hypertension for a disease-specific population. Of the 63 studies retrieved in the literature search, 35 were included in the review. The majority of the studies were of irbesartan (16) or losartan (8). In each study, the model used country-specific data to project and evaluate the clinical and cost outcomes of the treatment arms. The most common method undertaken was cost-consequence analysis (52.94%) followed by cost-effectiveness analysis (32.35%). In most cases, costs and benefits results were not synthesised. Results failed to show a clear advantage in favour of specific therapy, as the outcomes suffered from heterogeneity, referred to specific circumstances and were rather difficult to compare. For different treatment comparators, all the analyses demonstrated an improved life expectancy and a cost-saving choice. The robustness of results was tested with a series of sensitivity analyses, which showed a statistically significant result in each case. The evidence from this review suggests that the available ARBs represent a cost-saving and cost-effective treatment compared with other conventional treatment options for patients with hypertension and associated

  5. Prostate effect in dogs with the aldosterone receptor blocker eplerenone.

    PubMed

    Levin, Stuart; McMahon, Ellen; John-Baptiste, Annette; Bell, Rosonald R

    2013-02-01

    Eplerenone (Inspra) is an aldosterone receptor antagonist approved for the treatment of hypertension and heart failure after a myocardial infarction. In vitro receptor binding and transactivation studies showed eplerenone had high selectivity for the mineralocorticoid receptor over other steroid receptors (glucocorticoid, androgen, and progesterone). The most sensitive off-target effect of orally administered eplerenone preclinically was prostate atrophy in dogs. Dose-related prostate atrophy was observed at eplerenone dosages ≥15 mg/kg/day for 13 weeks or longer. The no observed adverse effect level (NOAEL) for the prostate effect in dogs was 5 mg/kg/day. The maximal effect was seen by 13 weeks and the atrophy was reversible even after 1 year of daily treatment. An additional study demonstrated dogs with eplerenone-induced prostate atrophy (confirmed by intrarectal ultrasound) had slightly decreased semen volume but no compound-related effects on libido, semen protein content, sperm motility, daily sperm production, or epididymal sperm transit time. Four possible mechanisms for prostate effect were investigated: (1) inhibition of testosterone synthesis and secretion; (2) inhibition of 5α-reductase, the enzyme within the prostate that converts testosterone into the more active growth factor dihydrotestosterone (DHT); (3) competitive antagonism of the androgen receptor; and (4) inhibition of 5α-reductase or competitive antagonism of the androgen receptor by aldosterone, which increased in dogs treated with eplerenone. Data from these studies supported blockade of androgen receptors at suprapharmacological concentrations of eplerenone. Another mineralocorticoid blocker, spironolactone, had greater antiandrogenic activity than eplerenone both in vivo and in vitro, and it has well known clinically significant antiandrogenic effects in humans, whereas eplerenone does not.

  6. Aminoalkynyldithianes. A new class of calcium channel blockers.

    PubMed

    Adams, T C; Dupont, A C; Carter, J P; Kachur, J F; Guzewska, M E; Rzeszotarski, W J; Farmer, S G; Noronha-Blob, L; Kaiser, C

    1991-05-01

    Several dithiane derivatives, prepared as intermediates for compounds structurally related to the therapeutically useful antimuscarinic agent oxybutynin, were effective inhibitors of calcium ion induced contraction of guinea pig ileal strips and of KCl-induced calcium entry into neuronal cells. Although the first member of this series, 2-[5-(diethylamino)-3-pentynyl]-1,3-dithiane (2a), was only marginally effective, its condensation product with diphenyl ketone, i.e. 2-[5-(diethylamino)-3-pentynyl]-2-(a,a-diphenyl-a- hydroxymethyl)-1,3-dithiane (3a), demonstrated weak, but significant, calcium channel antagonist activity. As part of a structure-activity relationship (SAR) study, various structural analogues of 2a and 3a were prepared and examined for calcium antagonist properties. In addition to these structural types, ring bridged (tricyclic) congeners of 3, i.e. 4, related bicyclic compounds 5, dehydroxylated derivatives 6, some homologous 2-[[[(N,N-disubstituted-amino)methyl]2- phenyl-1,3-dithianes (7), and a series of 2-[6-[N,N-disubstituted-amino)methyl]-1-hydroxy-1-phenyl- 4-hexynyl]-1,3-dithianes (8) were prepared and studied for calcium channel blocking activity. In general, greatest potency was noted in the tricyclic series 4; however, a definitive SAR could not be established. A structural similarity between several potent calcium antagonists having the structures 7c, 8b, and 8d and the well-known calcium channel blockers verapamil and tiapamil suggests these compounds may act at the same site. Compounds in the other classes (2-6) failed to show clearly defined SAR and their potency differed markedly in two tests for calcium channel antagonist activity. These results may indicate that the dithiane derivatives 2-6 produce their effects in a manner differing from that of the calcium channel antagonists diltiazem, verapamil, and nitrendepine.

  7. Angiotensin receptor blocker telmisartan suppresses renal gluconeogenesis during starvation

    PubMed Central

    Tojo, Akihiro; Hatakeyama, Saaya; Kinugasa, Satoshi; Nangaku, Masaomi

    2015-01-01

    The kidney plays an important role in gluconeogenesis during starvation. To clarify the anti-diabetic action of angiotensin receptor blockers, we examined the effects of telmisartan on the sodium-glucose co-transporters (SGLT) and the pathways of renal gluconeogenesis in streptozotocin-induced diabetes mellitus (DM) rats. At 4 weeks, the DM rats treated with/without telmisartan for 2 weeks and normal control rats were used for the study after a 24-hour fast. SGLT2 expressed on the brush border membrane of the proximal convoluted tubules increased in the DM rats, but decreased in the rats treated with telmisartan. The expression of restriction enzymes of gluconeogenesis, glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase increased in the proximal tubules in the DM rats, whereas these enzymes decreased in the kidneys of the rats treated with telmisartan. The elevated cytoplasmic glucose-6-phosphate and glucose levels in the kidney of DM rats significantly decreased in those treated with telmisartan, whereas those levels in the liver did not show significant change. Meanwhile, the high plasma glucose levels in the DM rats during the intravenous insulin tolerance tests were ameliorated by telmisartan. The increased fasting plasma glucose levels after 24 hours of starvation in the DM rats thus returned to the control levels by telmisartan treatment. In conclusion, the increased renal SGLT2 expression, elevated renal gluconeogenesis enzymes and extent of insulin-resistance in the DM rats were ameliorated by telmisartan therapy, thus resulting in decreased plasma glucose levels after 24 hours of fasting. PMID:25709483

  8. 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

  9. 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

  10. 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

  11. Current and future status of beta-blockers in the treatment of hypertension.

    PubMed

    Chrysant, Steven G; Chrysant, George S; Dimas, Billy

    2008-06-01

    Beta-adrenergic receptor blockers (beta-blockers) are effective and safe antihypertensive drugs, and have been recommended as first-line therapy for hypertension by all Joint National Committees (JNCs) for the prevention, detection, evaluation, and treatment of high blood pressure (BP) from the first to the last (JNC-7) in 2003. However, recently questions have been raised by several investigators regarding the antihypertensive effectiveness and safety of these drugs. The Medline literature on this subject was searched and pertinent studies were retrieved. Other pertinent references from existing publications were retrieved and analyzed up to 2007. Additionally, a historical perspective on the discovery of beta-blockers and their mechanism of action is given. Most of the reviewed short-term and long-term clinical trials demonstrate an effective and safe antihypertensive pattern for the beta-blockers. The weaknesses identified include the adverse effect of older beta-blockers on glucose control and stroke protection, especially in older persons. These adverse effects are attributed to their mechanism of action and BP effectiveness. On the basis of the evidence presented, beta-blockers are effective and safe antihypertensive drugs and should still be recommended as first-line therapy in most uncomplicated hypertensive patients, either alone or in combination with other drugs. There are reservations regarding their administration to diabetic and older hypertensive patients. However, when compelling indications for their use exist, they should not be withheld.

  12. 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

  13. Histamine-2 receptor blockers alter the fecal microbiota in premature infants.

    PubMed

    Gupta, Raegan W; Tran, Lynn; Norori, Johana; Ferris, Michael J; Eren, A Murat; Taylor, Christopher M; Dowd, Scot E; Penn, Duna

    2013-04-01

    Bacterial colonization is considered a major risk factor for necrotizing enterocolitis (NEC). The objective of the present study was to test the hypothesis that histamine-2 receptor (H2-) blockers alter colonic bacterial colonization by analyzing and comparing the fecal microbiota in premature infants with and without H2-blocker therapy using sensitive molecular biological techniques. Seventy-six premature infants ≤1500 g or <34 weeks gestation were enrolled in this case-controlled, cross-sectional study. Stool samples were collected from 25 infants receiving H2-blockers and 51 babies who had never received them. Following DNA extraction and PCR amplification of 16S rRNA, 454 pyrosequencing was undertaken and the resulting sequences were subjected to comparison with published sequence libraries. Proteobacteria and Firmicutes were the major phyla contributing to fecal microbial communities. Microbial diversity was lower, relative abundance of Proteobacteria (primarily of the family Enterobacteriaceae) was increased, whereas that of Firmicutes was decreased in the stools of infants receiving H2-blockers compared with those who had never received them. Although not designed to look specifically at the effect of H2-blockers on the incidence of NEC, our study suggests that their use lowers fecal microbial diversity and shifts the microfloral pattern toward Proteobacteria. These alterations in fecal microbiota may predispose the vulnerable immature gut to necrotizing enterocolitis and suggest prudence in the use of H2-blockers in the premature infant.

  14. 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

  15. 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

  16. 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

  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. 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.

  19. 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.

  20. 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.

  1. 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).

  2. [Oral treatment of severe psoriasis with a new aromatic retinoid (Ro 10-9359) (author's transl)].

    PubMed

    Guilhou, J J; Malbos, S; Meynadier, J

    1978-10-01

    The aromatic retinoic acid derivative Ro 10-9359 was administered orally to 25 severe psoriatic patients (14 with generalized plaques, 7 erythrodermic, 4 pustular). The initial dose was 25 mg/20 kg body weight daily for 4 weeks; afterwards the same posology was given every other day during several months (Max : 18 months). Excellent results were obtained in 16 patients (64 p. 100) particularly in severe erythrodermic and pustular psoriasis. However, under follow-up therapy relapses sometimes occurred leading to temporary resumption of initial posology. The most important side effects are cheilitis, palmoplantar scaling with thinning of the skin, hyperhidrosis and diffuse hair loss. A slight increase of transaminases and of alkaline phosphatases was found in a few patients. The Ro 10-9359 compound is a very useful new therapy of severe psoriasis.

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

    PubMed

    Szalay, Viktor

    2015-08-14

    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.

  4. ASTRO APEx(®) and RO-ILS™ are applicable to medical malpractice in radiation oncology.

    PubMed

    Zaorsky, Nicholas G; Ricco, Anthony G; Churilla, Thomas M; Horwitz, Eric M; Den, Robert B

    2016-11-01

    To analyze malpractice trials in radiation oncology and assess how ASTRO APEx(®) and RO-ILS™ apply to such cases. The Westlaw database was reviewed using PICOS/PRISMA methods. Fisher's exact and Mann-Whitney U tests were used to find factors associated with outcomes. Of 34 cases identified, external beam was used in 26 (77%). The most common factors behind malpractice were excessive toxicity (80%) and lack of informed consent (66%). ASTRO APEx pillars and ROI-LS had applicability to all but one case. Factors favoring the defendant included statute of limitations (odds ratio: 8.1; 95% CI: 1.3-50); those favoring the plaintiff included patient death (odds ratio: 0.7; 95% CI: 0.54-0.94). APEx and RO-ILS are applicable to malpractice trials in radiation oncology.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. THE FUTURE OF THE SUN: AN EVOLVED SOLAR TWIN REVEALED BY CoRoT

    SciTech Connect

    Do Nascimento, J.-D. Jr.; Da Costa, J. S.; Castro, M.; Takeda, Y.; Melendez, J.

    2013-07-10

    The question of whether the Sun is peculiar within the class of solar-type stars has been the subject of active investigation over the past three decades. Although several solar twins have been found with stellar parameters similar to those of the Sun (albeit in a range of Li abundances and with somewhat different compositions), their rotation periods are unknown, except for 18 Sco, which is younger than the Sun and with a rotation period shorter than solar. It is difficult to obtain rotation periods for stars of solar age from ground-based observations, as a low-activity level implies a shallow rotational modulation of their light curves. CoRoT has provided space-based long time series from which the rotation periods of solar twins as old as the Sun could be estimated. Based on high-signal-to-noise, high-resolution spectroscopic observations gathered at the Subaru Telescope, we show that the star CoRoT ID 102684698 is a somewhat evolved solar twin with a low Li abundance. Its rotation period is 29 {+-} 5 days, compatible with its age (6.7 Gyr) and low lithium content, A{sub Li} {approx}< 0.85 dex. Interestingly, our CoRoT solar twin seems to have enhanced abundances of the refractory elements with respect to the Sun, a typical characteristic of most nearby twins. With a magnitude V {approx_equal} 14.1, ID 102684698 is the first solar twin revealed by CoRoT, the farthest field solar twin so far known, and the only solar twin older than the Sun for which a rotation period has been determined.

  15. The acoustic cut-off frequency of roAp stars

    NASA Astrophysics Data System (ADS)

    Audard, N.; Kupka, F.; Morel, P.; Provost, J.; Weiss, W. W.

    1998-07-01

    Some of the rapidly oscillating (roAp) stars, have frequencies which are larger than the acoustic cut-off frequency determined from published stellar models which usually assume a grey atmosphere. As the cut-off frequency depends on the T(tau ) relation, we have computed models and adiabatic frequencies for pulsating Ap stars with more realistic atmospheres which include a frequency dependent treatment of radiative transfer, take blanketing effects into account, and which have a better treatment of the radiative pressure. In addition, we are using opacity distribution functions specific to the atmospheric composition. With these improvements over the classical stellar models the theoretical acoustic cut-off frequency for roAp stars are increased by about 200 mu Hz, which brings them close to the observations. We restrict the comparison of our computations with observations to those two `pathological' roAp stars for which more reliable astrophysical parameters are available, HD 24712 and alpha Cir, and comment briefly on a third one, HD 134214. For alpha Cir we find models which have indeed a cut-off frequency beyond the largest observed frequency and which are well within the Teff - L/L_⊙ error box. For HD 24712 only models which are hotter by about 100 K and less luminous by nearly 10% than what is actually the most probable value derived by spectroscopy would have an acoustic cut-off frequency large enough. HD 134214 fits our models best, however, the error box for Teff - L/L_⊙ is the largest of all three stars. One may thus speculate that the old controversy about a mismatch between observed largest frequencies and theoretical cut-off frequencies of roAp star models is resolved. Based on hipparcos data.

  16. 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).

  17. The experiences of pregnancy in women with SSA/Ro52 autoantibodies.

    PubMed

    Tingström, Joanna; Barimani, Mia; Sonesson, Sven-Erik; Wahren-Herlenius, Marie; Henriksson, Elisabet Welin

    2010-12-01

     Congenital heart block may develop in the foetus during pregnancy in SSA/Ro52 autoantibody-positive women. The aim of this study was to investigate how women with SSA/Ro52 autoantibodies experience their pregnancy in terms of the risk of developing foetal heart block, and in undergoing serial ultrasound Doppler echocardiography to detect early signs of congenital heart block.  Data were collected through individual semi-structured interviews with SSA/Ro52-positive women post-pregnancy (n = 14). The interviews were audio-taped, transcribed verbatim and analysed according to qualitative content analysis.  Three categories emerged from the responses: information, emotional response and support. The information received prior to and during early pregnancy was focused on the need for attending a specialized antenatal clinic, and information on the risk for congenital heart block was scarce or missing. During gestational weeks 18-24, when the ultrasound/Doppler examinations were performed, all women described increased stress. However, the interaction with the caregivers made the women feel more safe and secure. Several women also said that they did not emotionally acknowledge the pregnancy until after gestational week 24. None had been offered psychological support.  There is a need for structured information and organized programmes for the surveillance of women who are SSA/Ro52 positive during their pregnancy. Further, offering psychological support to the women and their families to manage the stress and to facilitate the early attachment to the child should be considered. Copyright © 2010 John Wiley & Sons, Ltd.

  18. 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⊙.

  19. 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.

  20. Foam-Mat Freeze-Drying of Bifidobacterium longum RO175: Viability and Refrigerated Storage Stability.

    PubMed

    Izquierdo-López, Danilo; Goulet, Jacques; Ratti, Cristina

    2017-01-01

    Foaming as a pretreatment was used prior to freeze-drying of Bifidobacterium longum RO175 to investigate the potential acceleration of the drying rate and increase in microorganism viability after the process. A study on storage of foamed and nonfoamed freeze-dried products at 4 °C completed this study. B. longum RO175 in foamed medium could be freeze-dried in 1/7 to 1/4 of the time required for nonfoamed suspensions. In addition, foamed suspensions presented higher viability immediately after freeze-drying (13.6% compared to 12.81 % or 11.46%, depending on the cryoprotective media). Refrigerated storage led to a reduction in B. longum RO175 viability for all tested protective agents (foamed and nonfoamed). No correlation between glass transition temperature and stability of probiotic powders was observed during storage. In addition, lower viability after 56 d of storage was observed for foamed materials, probably due to foam porous structure and higher hygroscopicity, and oxygen presence and moisture pickup during storage. © 2016 Institute of Food Technologists®.

  1. Quantum scattering calculations for ro-vibrational de-excitation of CO by hydrogen atoms

    NASA Astrophysics Data System (ADS)

    Song, Lei; Balakrishnan, N.; van der Avoird, Ad; Karman, Tijs; Groenenboom, Gerrit C.

    2015-05-01

    We present quantum-mechanical scattering calculations for ro-vibrational relaxation of carbon monoxide (CO) in collision with hydrogen atoms. Collisional cross sections of CO ro-vibrational transitions from v = 1, j = 0 - 30 to v' = 0, j' are calculated using the close coupling method for collision energies between 0.1 and 15 000 cm-1 based on the three-dimensional potential energy surface of Song et al. [J. Phys. Chem. A 117, 7571 (2013)]. Cross sections of transitions from v = 1, j ≥ 3 to v' = 0, j' are reported for the first time at this level of theory. Also calculations by the more approximate coupled states and infinite order sudden (IOS) methods are performed in order to test the applicability of these methods to H-CO ro-vibrational inelastic scattering. Vibrational de-excitation rate coefficients of CO (v = 1) are presented for the temperature range from 100 K to 3000 K and are compared with the available experimental and theoretical data. All of these results and additional rate coefficients reported in a forthcoming paper are important for including the effects of H-CO collisions in astrophysical models.

  2. [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.

  3. 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.

  4. Influence of surface properties of RO membrane on membrane fouling for treating textile secondary effluent.

    PubMed

    Yin, Zhonglong; Yang, Cheng; Long, Chao; Li, Aimin

    2017-07-01

    Reverse osmosis (RO) is a promising technology for treating and reusing textile secondary effluent (SE). To better understand the effect of membrane surface properties on membrane fouling, the performances of three commercial polyamide thin-film composite RO membranes (BW30-4040, CPA2-4040, and RE-4040-FEN) with different roughness and hydrophilicity were investigated for treating textile SE. The RO membranes were characterized by ATR-FTIR, SEM, AFM, and contact angle, respectively. The results showed that the flux increased with an increase in the surface hydrophilicity of membrane. CPA2-4040 had the highest hydrophilic surface and thus the largest initial flux. There was a strong correlation between the membrane fouling and the surface roughness; the fouling increased with an increase in the surface roughness. The roughest surface of CPA2-4040 led to the most significantly flux decline. However, the fouling reversibility was not related directly to surface roughness. BW30-4040 with the secondary roughness and the most hydrophobic surface had the highest fouling reversibility. This was mainly due to the primary hydrophilicity of textile SE in nature. Fluorescence excitation-emission matrix (EEM) showed that hydrophilic neutral protein-like matters and soluble microbial products (SMP) were the main foulants, thus stronger affinity with hydrophilic surface of membrane. Graphical abstract ᅟ.

  5. 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.

  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. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. 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.

  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. RoCoMAR: Robots' Controllable Mobility Aided Routing and Relay Architecture for Mobile Sensor Networks

    PubMed Central

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

    2013-01-01

    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. PMID:23881134

  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. Pregnancy Outcomes in Patients with Autoimmune Diseases and Anti-Ro/SSA Antibodies

    PubMed Central

    Cimaz, Rolando; Caporali, Roberto; Ramoni, Véronique; Buyon, Jill

    2013-01-01

    Anti-Ro/SSA antibodies are associated with neonatal lupus (congenital heart block (CHB), neonatal transient skin rash, hematological and hepatic abnormalities), but do not negatively affects other gestational outcomes, and the general outcome of these pregnancies is now good, when followed by experienced multidisciplinary teams. The prevalence of CHB, defined as an atrioventricular block diagnosed in utero, at birth, or within the neonatal period (0–27 days after birth), in the offspring of an anti-Ro/SSA-positive women is 1–2%, of neonatal lupus rash around 10–20%, while laboratory abnormalities in asymptomatic babies can be detected in up to 27% of cases. The risk of recurrence of CHB is ten times higher. Most of the mothers are asymptomatic at delivery and are identified only by the birth of an affected child. Half of these asymptomatic women develop symptoms of a rheumatic disease, most commonly arthralgias and xerophtalmia, but few develop lupus nephritis. A standard therapy for CHB is still matter of investigation, although fluorinated corticosteroids have been reported to be effective for associated cardiomyopathy. Serial echocardiograms and obstetric sonograms, performed at least every 1–2 weeks starting from the 16th week of gestational age, are recommended in anti-Ro/SSA-positive pregnant women to detect early fetal abnormalities that might be a target of preventive therapy. PMID:20012231

  12. A full-duplex WDM-RoF system based on tunable optical frequency comb generator

    NASA Astrophysics Data System (ADS)

    Zhang, Chan; Ning, TiGang; Li, Jing; Pei, Li; Li, Chao; Ma, Shaoshuo

    2015-06-01

    A prototype of full-duplex wavelength-division-multiplexing-based radio-over-fiber (WDM-RoF) system using a single continuous wave (CW) laser at central station (CS) is proposed and investigated. In the proposal, the tunable optical frequency comb (OFC) generator is performed by cascading an electro-absorption modulator (EAM), a phase modulator (PM) and a Mach-Zehnder intensity modulator (IM). Then the proposed OFC is used as the source of WDM-RoF network. The base station (BS) is simplified by using central carrier along with downlink multi-frequency millimeter-wave signals (MMWs). In the scheme, we obtain 21 comb lines within 0.2 dB power deviation with an interval about 10 GHz. Then we apply it to a bidirectional 1:7 WDM-RoF cellular network. For the downlink, three MMWs with frequencies of 40 GHz, 60 GHz and 80 GHz are obtained. For the uplink, 7 WDM channels carrying upstream signal are converted simultaneously. Both down and uplink delivery over 20 km transmission with less than 1 dB power penalty, which shows high spectral-efficiency and good performance over long-distance delivery.

  13. Isoprene NO3 Oxidation Products from the RO2 + HO2 Pathway.

    PubMed

    Schwantes, Rebecca H; Teng, Alexander P; Nguyen, Tran B; Coggon, Matthew M; Crounse, John D; St Clair, Jason M; Zhang, Xuan; Schilling, Katherine A; Seinfeld, John H; Wennberg, Paul O

    2015-10-08

    We describe the products of the reaction of the hydroperoxy radical (HO(2)) with the alkylperoxy radical formed following addition of the nitrate radical (NO(3)) and O(2) to isoprene. NO(3) adds preferentially to the C(1) position of isoprene (>6 times more favorably than addition to C(4)), followed by the addition of O(2) to produce a suite of nitrooxy alkylperoxy radicals (RO(2)). At an RO(2) lifetime of ∼30 s, δ-nitrooxy and β-nitrooxy alkylperoxy radicals are present in similar amounts. Gas-phase product yields from the RO(2) + HO(2) pathway are identified as 0.75-0.78 isoprene nitrooxy hydroperoxide (INP), 0.22 methyl vinyl ketone (MVK) + formaldehyde (CH(2)O) + hydroxyl radical (OH) + nitrogen dioxide (NO(2)), and 0-0.03 methacrolein (MACR) + CH(2)O + OH + NO(2). We further examined the photochemistry of INP and identified propanone nitrate (PROPNN) and isoprene nitrooxy hydroxyepoxide (INHE) as the main products. INHE undergoes similar heterogeneous chemistry as isoprene dihydroxy epoxide (IEPOX), likely contributing to atmospheric secondary organic aerosol formation.

  14. Quantum scattering calculations for ro-vibrational de-excitation of CO by hydrogen atoms

    SciTech Connect

    Song, Lei; Avoird, Ad van der; Karman, Tijs; Groenenboom, Gerrit C.; Balakrishnan, N.

    2015-05-28

    We present quantum-mechanical scattering calculations for ro-vibrational relaxation of carbon monoxide (CO) in collision with hydrogen atoms. Collisional cross sections of CO ro-vibrational transitions from v = 1, j = 0 − 30 to v′ = 0, j′ are calculated using the close coupling method for collision energies between 0.1 and 15 000 cm{sup −1} based on the three-dimensional potential energy surface of Song et al. [J. Phys. Chem. A 117, 7571 (2013)]. Cross sections of transitions from v = 1, j ≥ 3 to v′ = 0, j′ are reported for the first time at this level of theory. Also calculations by the more approximate coupled states and infinite order sudden (IOS) methods are performed in order to test the applicability of these methods to H–CO ro-vibrational inelastic scattering. Vibrational de-excitation rate coefficients of CO (v = 1) are presented for the temperature range from 100 K to 3000 K and are compared with the available experimental and theoretical data. All of these results and additional rate coefficients reported in a forthcoming paper are important for including the effects of H–CO collisions in astrophysical models.

  15. [Anti- SSA/Ro and Anti-SSB/ La Antibodies in Patients with Yusho].

    PubMed

    Tsuji, Hiroshi

    2015-05-01

    To investigate chronic immune effects of polychlorinated biphenyl (PCB) and polychlorinated dibenzofuran (PCDF), anti-SSA/Ro and anti-SSB/La antibodies were studied in serum of 213 patients with Yusho and 63 control subjects in 2013. Anti-SSA/Ro antibodies were found in 4.2% (9/213) of patients with Yusho and 1.6% (1/63) of control subjects. The prevalence rates of anti-SSA/Ro antibodies in Yusho patients were not associated with blood PCB concentration or blood 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) concentration. Anti-SSB/La antibodies were found in 1.4% (3/213) of patients of Yusho, but none of controls. Furthermore, high concentrations of PCB and 2,3,4,7,8-PeCDF were present in Yusho patients with anti-SSB/La antibodies. We conclude that anti-SSB/La antibody is present in patients with Yusho, and it may be associated with PCB and 2,3,4,7,8-PeCDF in the blood.

  16. 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.

  17. 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

  18. The relationship between anti-Ro (SS-A) antibody-positive Sjögren's syndrome and anti-Ro (SS-A) antibody-positive lupus erythematosus.

    PubMed

    Provost, T T; Talal, N; Harley, J B; Reichlin, M; Alexander, E

    1988-01-01

    Ten Ro(SS-A) antibody-positive patients with Sjögren's syndrome and lupus erythematosus are described. These patients have a disease process characterized by the frequent appearance of annular polycyclic lupus lesions of subacute cutaneous lupus erythematosus (SCLE), as well as neurologic and pulmonary disease. The Ro(SS-A) antibody-positive patients may have Sjögren's syndrome for many years and then suddenly develop lupus erythematosus, and vice versa. These studies demonstrate that the patient with Ro(SS-A) antibody may exhibit a dynamic clinical disease expression over time and that there is a closer pathologic relationship between Sjögren's syndrome and SCLE in these patients with Ro(SS-A)-antibody than has previously been appreciated. Furthermore, Ro(SS-A)-positive patients with Sjögren's syndrome and lupus erythematosus appear to have a much more guarded prognosis than those Ro(SS-A)-positive lupus patients described under the classifications of antinuclear antibody-negative lupus erythematosus and SCLE.

  19. A comparison of propranolol and compound RO3-4787 in the treatment of arterial hypertension in man.

    PubMed

    George, C F; Lewis, P J; Steiner, J A; Dollery, C T

    1975-06-01

    1. The effects of propranolol and RO3-4787, a new beta-adrenoceptor antagonist with a partial agonist activity, have been studied in a blind, cross-over comparison with placebo. 2. In ten patients who completed the study, the two drugs produced a similar reduction in blood pressure; the reduction in heart rate with propranolol was significantly (P less than 0.001) greater than that produced by RO3-4787. 3. Plasma renin activity averaged 4.13 +/- 1.37 ng h-1 ml-1 on placebo, fell to 3.64 +/- 1.47 ng h-1 ml-1 on propranolol and to 2.50 +/- 1.39 ng h-1 ml-1 on RO3-4787. 4. No correlation was demonstrable between the log plasma concentration of either propranolol or RO3-4787 and change in blood pressure.

  20. β Adrenergic blockers lower renin in patients treated with ACE inhibitors and diuretics

    PubMed Central

    Holmer, S; Hense, H; Danser, A; Mayer, B; Riegger, G; Schunkert, H

    1998-01-01

    Objective—To examine the effect of concomitant intake of β blockers with angiotensin converting enzyme (ACE) inhibitors, diuretics, or both on plasma renin concentrations in a population based sample (MONICA survey, Augsburg, Germany).
Subject and methods—728 individuals were studied, of whom 171 were treated using monotherapy (ACE inhibitor (n = 21), diuretic (n = 10), or β blocker (n = 72)), or combination treatment (ACE inhibitor + diuretic (n = 32), ACE inhibitor + β blocker (n = 7), diuretic + β blocker (n = 22), ACE inhibitor + diuretic + β blocker (n = 7)). The remaining 557 individuals were untreated. Indications for treatment were hypertension (75%), coronary artery disease with (12%) or without (3%) hypertension, or unknown (10%).
Results—Mean (SEM) renin concentrations in individuals treated with an ACE inhibitor (41 (8) mU/l), a diuretic (41 (10) mU/l), or the combination of an ACE inhibitor and a diuretic (54 (10) mU/l) were raised compared with untreated individuals (17 (1) mU/l; p < 0.05 each). Monotherapy with a β blocker, however, decreased mean renin concentrations (12 (1) mU/l; p < 0.01 v untreated). Renin concentrations in individuals taking a β blocker with either an ACE inhibitor (21 (8) mU/l), or a diuretic (22 (4) mU/l), or with both an ACE inhibitor and a diuretic (21 (7) mU/L), were significantly lower compared with renin concentrations in groups not receiving β blocker treatment (p < 0.05 each).
Conclusion—These data suggest that the upregulation of renin by treatment with ACE inhibitors, diuretics, or both can be largely prevented by concomitant β blocker treatment.

 Keywords: adrenergic β receptor blocker;  angiotensin converting enzyme inhibitor;  renin;  hypertension PMID:9764058

  1. Effect of beta-blockers on exacerbation rate and lung function in chronic obstructive pulmonary disease (COPD).

    PubMed

    Duffy, Sean; Marron, Robert; Voelker, Helen; Albert, Richard; Connett, John; Bailey, William; Casaburi, Richard; Cooper, J Allen; Curtis, Jeffrey L; Dransfield, Mark; Han, MeiLan K; Make, Barry; Marchetti, Nathaniel; Martinez, Fernando; Lazarus, Stephen; Niewoehner, Dennis; Scanlon, Paul D; Sciurba, Frank; Scharf, Steven; Reed, Robert M; Washko, George; Woodruff, Prescott; McEvoy, Charlene; Aaron, Shawn; Sin, Don; Criner, Gerard J

    2017-06-19

    Beta-blockers are commonly prescribed for patients with cardiovascular disease. Providers have been wary of treating chronic obstructive pulmonary disease (COPD) patients with beta-blockers due to concern for bronchospasm, but retrospective studies have shown that cardio-selective beta-blockers are safe in COPD and possibly beneficial. However, these benefits may reflect symptom improvements due to the cardiac effects of the medication. The purpose of this study is to evaluate associations between beta-blocker use and both exacerbation rates and longitudinal measures of lung function in two well-characterized COPD cohorts. We retrospectively analyzed 1219 participants with over 180 days of follow up from the STATCOPE trial, which excluded most cardiac comorbidities, and from the placebo arm of the MACRO trial. Primary endpoints were exacerbation rates per person-year and change in spirometry over time in association with beta blocker use. Overall 13.9% (170/1219) of participants reported taking beta-blockers at enrollment. We found no statistically significant differences in exacerbation rates with respect to beta-blocker use regardless of the prevalence of cardiac comorbidities. In the MACRO cohort, patients taking beta-blockers had an exacerbation rate of 1.72/person-year versus a rate of 1.71/person-year in patients not taking beta-blockers. In the STATCOPE cohort, patients taking beta-blockers had an exacerbation rate of 1.14/person-year. Patients without beta-blockers had an exacerbation rate of 1.34/person-year. We found no detrimental effect of beta blockers with respect to change in lung function over time. We found no evidence that beta-blocker use was unsafe or associated with worse pulmonary outcomes in study participants with moderate to severe COPD.

  2. Resting pulse rates in a glaucoma clinic: the effect of topical and systemic beta-blocker usage.

    PubMed

    Tattersall, C; Vernon, S; Singh, R

    2006-02-01

    Beta-blockers have, for 25 years, been a commonly used agent in the treatment of raised intraocular pressure (IOP). Beta-blockers can also reduce the pulse rate. With no available literature examining a cohort of patients, this study aims to investigate the resting pulse rates in patients attending a specialist glaucoma clinic in order to identify if routine review of ophthalmic medication use is indicated. The resting pulse rates of patients attending a glaucoma clinic were measured using pulseoximetry, with a medical and drug history established for each patient. In all, 205 patients were included in the study. A total of 101 (49%) of patients were using beta-blockers in some form. The mean pulse rate for patients not using beta-blockers (104 patients) was 76 beats per minute (bpm), for topical use only (68 patients) it was 70.3 bpm, for oral use (18 patients) it was 64.7 bpm, and 58 bpm for patients using both topical and oral beta-blockers (15 patients). Groups using beta-blockers (oral, topical, oral and topical) were considered in relation to patients not using beta-blockers. All groups using beta-blockers showed a significant association with causing a bradycardia of less than 60 bpm. Patients with a pulse rate of less than 50 bpm were significantly more likely to be using topical and oral beta-blockers than oral beta-blockers alone (P=0.01). Topical beta-blockers should be used with caution, even in the presence of established systemic beta-blocker use. Routine pulse rate monitoring and review of ophthalmic medication are indicated in patients using beta-blocker therapy.

  3. Cellular mechanism of the conduction abnormalities induced by serum from anti-Ro/SSA-positive patients in rabbit hearts.

    PubMed Central

    Garcia, S; Nascimento, J H; Bonfa, E; Levy, R; Oliveira, S F; Tavares, A V; de Carvalho, A C

    1994-01-01

    In this study, IgG fractions from sera of SLE patients with anti-Ro/SSA or anti-Ro/SSA and anti-La/SSB activity were tested in Langendorff preparations of adult rabbit hearts, aiming to reproduce the cardiac manifestations observed in neonatal lupus in an experimental model. The hearts were perfused with normal Tyrode's solution for 30 min, followed by perfusion with Tyrode's containing 0.3 mg/ml of anti-Ro/SSA- (or anti-Ro/La-) positive IgG (nine sera), anti-ribonucleoprotein (RNP)-positive IgG (five sera), or IgG fractions from normal donors (five sera). In one third of the experiments done with anti-Ro/La-positive IgG, heart block was observed. With the remaining fractions, a decrease in heart rate of 17.1% was observed, but normal sinus rhythm was maintained. The IgG fractions with anti-RNP activity (five experiments) and from normal sera (six experiments) reduced heart rates by 12.9 and 3.3%, respectively, but heart block was not observed. To further characterize the cellular mechanisms involved in the conduction disturbances observed in the whole rabbit hearts, we conducted experiments with ventricular myocytes isolated from young rabbit hearts, studied by whole cell patch-clamp technique. In these experiments, the slow inward currents were analyzed during the superfusion of the cell with normal Tyrode's solution and 5 min after superfusion with Tyrode's solution containing 0.3 mg/ml of anti-Ro/SSA- (or anti-Ro/La-) positive IgG (five sera), anti-RNP-positive IgG (three sera), or IgG from normal donors (four sera). Resting and action potential amplitudes were not affected by any of the sera used. The anti-Ro/SSA IgG fraction induced a mean reduction in the peak slow inward current of 31.6%. IgG fractions with anti-RNP activity reduced slow inward current by 4.4%, whereas IgG fractions from normal donors increased this current by 3.3%. IgG-free fractions from sera of patients with anti-Ro/SSA activity did not alter the peak slow inward current. These results

  4. Enzymatic cleaning of biofouled thin-film composite reverse osmosis (RO) membrane operated in a biofilm membrane reactor.

    PubMed

    Khan, Mohiuddin; Danielsen, Steffen; Johansen, Katja; Lorenz, Lindsey; Nelson, Sara; Camper, Anne

    2014-02-01

    Application of environmentally friendly enzymes to remove thin-film composite (TFC) reverse osmosis (RO) membrane biofoulants without changing the physico-chemical properties of the RO surface is a challenging and new concept. Eight enzymes from Novozyme A/S were tested using a commercially available biofouling-resistant TFC polyamide RO membrane (BW30, FilmTech Corporation, Dow Chemical Co.) without filtration in a rotating disk reactor system operated for 58 days. At the end of the operation, the accumulated biofoulants on the TFC RO surfaces were treated with the three best enzymes, Subtilisin protease and lipase; dextranase; and polygalacturonase (PG) based enzymes, at neutral pH (~7) and doses of 50, 100, and 150 ppm. Contact times were 18 and 36 h. Live/dead staining, epifluorescence microscopy measurements, and 5 μm thick cryo-sections of enzyme and physically treated biofouled membranes revealed that Subtilisin protease- and lipase-based enzymes at 100 ppm and 18 h contact time were optimal for removing most of the cells and proteins from the RO surface. Culturable cells inside the biofilm declined by more than five logs even at the lower dose (50 ppm) and shorter incubation period (18 h). Subtilisin protease- and lipase-based enzyme cleaning at 100 ppm and for 18 h contact time restored the hydrophobicity of the TFC RO surface to its virgin condition while physical cleaning alone resulted in a 50° increase in hydrophobicity. Moreover, at this optimum working condition, the Subtilisin protease- and lipase-based enzyme treatment of biofouled RO surface also restored the surface roughness measured with atomic force microscopy and the mass percentage of the chemical compositions on the TFC surface estimated with X-ray photoelectron spectroscopy to its virgin condition. This novel study will encourage the further development and application of enzymes to remove biofoulants on the RO surface without changing its surface properties.

  5. The Roles of Tidal Evolution and Evaporative Mass Loss in the Origin of CoRoT-7 b

    NASA Technical Reports Server (NTRS)

    Jackson, Brian; Miller, Neil; Barnes, Rory; Raymond, Sean N.; Fortney, Jonathan J.; Greenberg, Richard

    2010-01-01

    CoRoT-7 b is the first confirmed rocky exoplanet, but, with an orbital semimajor axis of 0.0172 au, its origins may be unlike any rocky planet in our Solar System. In this study, we consider the roles of tidal evolution and evaporative mass loss in CoRoT-7 b's history, which together have modified the planet's mass and orbit. If CoRoT-7 b has always been a rocky body, evaporation may have driven off almost half its original mass, but the mass loss may depend sensitively on the extent of tidal decay of its orbit. As tides caused CoRoT-7 b's orbit to decay, they brought the planet closer to its host star, thereby enhancing the mass loss rate. Such a large mass loss also suggests the possibility that CoRoT-7 b began as a gas giant planet and had its original atmosphere completely evaporated. In this case, we find that CoRoT-7 b's original mass probably did not exceed 200 Earth masses (about two-third of a Jupiter mass). Tides raised on the host star by the planet may have significantly reduced the orbital semimajor axis, perhaps causing the planet to migrate through mean-motion resonances with the other planet in the system, CoRoT-7 c. The coupling between tidal evolution and mass loss may be important not only for CoRoT-7 b but also for other close-in exoplanets, and future studies of mass loss and orbital evolution may provide insight into the origin and fate of close-in planets, both rocky and gaseous.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

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

    PubMed

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

    1996-03-01

    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.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. β-Blocker-Associated Risks in Patients With Uncomplicated Hypertension Undergoing Noncardiac Surgery.

    PubMed

    Jørgensen, Mads E; Hlatky, Mark A; Køber, Lars; Sanders, Robert D; Torp-Pedersen, Christian; Gislason, Gunnar H; Jensen, Per Føge; Andersson, Charlotte

    2015-12-01

    Perioperative β-blocker strategies are important to reduce risks of adverse events. Effectiveness and safety may differ according to patients' baseline risk. To determine the risk of major adverse cardiovascular events (MACEs) associated with long-term β-blocker therapy in patients with uncomplicated hypertension undergoing noncardiac surgery. Association study based on in-hospital records and out-of-hospital pharmacotherapy use using a Danish nationwide cohort of patients with uncomplicated hypertension treated with at least 2 antihypertensive drugs (β-blockers, thiazides, calcium antagonists, or renin-angiotensin system [RAS] inhibitors) undergoing noncardiac surgery between 2005 and 2011. Various antihypertensive treatment regimens, chosen as part of usual care. Thirty-day risk of MACEs (cardiovascular death, nonfatal ischemic stroke, nonfatal myocardial infarction) and all-cause mortality, assessed using multivariable logistic regression models and adjusted numbers needed to harm (NNH). The baseline characteristics of the 14,644 patients who received β-blockers (65% female, mean [SD] age, 66.1 [12.0] years) were similar to those of the 40,676 patients who received other antihypertensive drugs (57% female, mean [SD] age, 65.9 [11.8] years). Thirty-day MACEs occurred in 1.3% of patients treated with β-blockers compared with 0.8% of patients not treated with β-blockers (P < .001). β-Blocker use was associated with increased risks of MACEs in 2-drug combinations with RAS inhibitors (odds ratio [OR], 2.16 [95% CI, 1.54-3.04]), calcium antagonists (OR, 2.17 [95% CI, 1.48-3.17]), and thiazides (OR, 1.56 [95% CI, 1.10-2.22]), compared with the reference combination of RAS inhibitors and thiazides. Results were similar for all-cause mortality. Risk of MACEs associated with β-blocker use seemed especially pronounced for patients at least 70 years old (number needed to harm [NNH], 140 [95% CI, 86-364]), for men (NNH, 142 [95% CI, 93-195]), and for patients

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

    PubMed

    Puymirat, Etienne; 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

    2016-09-20

     To assess the association between early and prolonged β blocker treatment and mortality after acute myocardial infarction.  Multicentre prospective cohort study.  Nationwide French registry of Acute ST- and non-ST-elevation Myocardial Infarction (FAST-MI) (at 223 centres) at the end of 2005.  2679 consecutive patients with acute myocardial infarction and without heart failure or left ventricular dysfunction.  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.  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.  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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  18. 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

  19. Low titer, isolated anti Ro/SSA 60 kd antibodies is correlated with positive pregnancy outcomes in women at risk of congenital heart block.

    PubMed

    Tonello, Marta; Hoxha, Ariela; Mattia, Elena; Zambon, Alessandra; Visentin, Silvia; Cerutti, Alessia; Ghirardello, Anna; Milanesi, Ornella; Ruffatti, Amelia

    2017-05-01

    Congenital heart block (CHB) is an autoantibody mediated disorder presumably caused by placental transmission of maternal autoantibodies to Ro/SSA 52 kd, p200, Ro/SSA 60 kd, La/SSB ribonucleoproteins. This study investigated the clinical significance of isolated anti-Ro/SSA 52 kd, anti-p200, anti-Ro/SSA 60 kd, and anti-La/SSB antibodies in positive pregnant patients. One hundred sixty-three pregnant women positive to anti-Ro/SSA 52 kd and/or anti-Ro/SSA 60 kd and/or anti-La/SSB antibodies were prospectively enrolled in the study. Anti-Ro52, anti-Ro60, anti-p200, and anti-La antibodies were assayed using home-made ELISA assays. Isolated antibody positivity was found in 25 women (15.3%), while multiple antibody positivity in 138 (84.7%). Twenty-four developed CHB, and the 139 had a favorable pregnancy outcome. The prevalence of isolated anti-Ro/SSA 60 kd antibodies was significantly higher (p < 0.046) as the prevalence of lower mean antibody titers (p < 0.0001) in the later group. Confirmation of these results by large-scale studies could lead clinicians to recommend less stringent fetal echocardiography monitoring in women with isolated anti-Ro/SSA 60 kd antibodies.

  20. Outcomes in adolescents with postural orthostatic tachycardia syndrome treated with midodrine and beta-blockers.

    PubMed

    Lai, Cindy C; Fischer, Philip R; Brands, Chad K; Fisher, Jennifer L; Porter, Co-Burn J; Driscoll, Sherilyn W; Graner, Kevin K

    2009-02-01

    Postural orthostatic tachycardia syndrome (POTS) is associated with debilitating fatigue, dizziness, and discomfort in previously healthy adolescents. The effects of medical therapy have not been well studied in this patient population. This study assessed the relative efficacy and impact of drug therapy on the functioning and quality of life in adolescents with POTS. A retrospective, single center, chart review analysis with a follow-up written survey was conducted on a group of 121 adolescents who had undergone autonomic reflex screening at the Mayo Clinic from 2002 to 2005 as part of an evaluation for possible POTS. Of 121 surveys sent, 47 adolescents returned a completed survey. In this cohort of patients, the two most commonly prescribed drug therapies were midodrine (n = 13) and beta-blockers (n = 14). Patients in the midodrine group were comparable to patients in the beta-blocker group in gender, age, pretreatment postural heart rate changes, and months from initial evaluation to survey completion. More patients treated with a beta-blocker reported improvement after visiting Mayo Clinic (100% vs 62%, P = 0.016) and more attributed their progress to medication (63.6% vs 36.4%, P = 0.011) than did those treated with midodrine. Treatment with both midodrine and beta-blockers was associated with overall improvement in POTS patients' general health; however, adolescents taking beta-blockers were more likely than those taking midodrine to credit the role of medications in their improvement.

  1. 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

  2. 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.

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

    PubMed

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

    2016-02-01

    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. 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. Mice with Pompe disease were treated with propranolol (a β-blocker) or clenbuterol in combination with ERT, or with ERT alone. 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. Propranolol, a commonly prescribed β-blocker, reduced weight, 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. 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.

  5. 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.

  6. Elevated IL-1β levels in anti-Ro/SSA connective tissue diseases patients with prolonged corrected QTc interval.

    PubMed

    Pisoni, Cecilia N; Reina, Silvia; Arakaki, Diego; Eimon, Alicia; Carrizo, Carolina; Borda, Enri

    2015-01-01

    Patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) have increased IL-1β levels. IL-1β and other pro-inflammatory cytokines have a modulating activity on cardiac ion channels and have been associated with increased arrhythmic risk in rheumatoid arthritis patients. Likewise, adult patients with connective tissue diseases (CTDs) may have prolonged QTc intervals associated with the presence of anti-Ro/SSA antibodies. Our objective was to evaluate the presence of serum IL-1β in subjects with CTDs, in relation to the presence of anti-Ro/SSA antibodies and QTc interval duration. 12-lead electrocardiograms (ECG) were performed and blood was withdrawn, measuring electrolytes, IL-1β anti-Ro/SSA antibodies by ELISA in 73 patients with CTDs. 55 patients were anti-Ro/SSA positive and 18 were anti-Ro/SSA negative. Patients with anti-Ro/SSA positive antibodies had a significantly greater median IL-1β serum level: 7.29 (range: 0.17-17.3 pg/ml) compared to patients with anti-Ro/SSA negative antibodies whose median was: 1.67 (range 0.55-4.12 pg/ml) p<0.001. The mean QTc interval values obtained in both groups were not significantly different (417.7±23.1 vs. 414.7±21.2, p=0.63). The QTc interval was prolonged in 11 (20%) patients, who were all anti-Ro/SSA positive versus 0 (0 %) in anti-Ro/SSA negative patients p=0.05. Median IL-1β levels were: 8.7 (range: 2.69-15.1 pg/ml) in patients with prolonged QTc interval versus median: 5.0 (range: 0.17-17.3 pg/ml) in those with normal QTc interval values (<440ms) p=0.006. IL-1β is elevated in patients with CTDs that have both anti-Ro/SSA antibodies and prolonged QTc intervals.

  7. Stellar Ro

    NASA Astrophysics Data System (ADS)

    Featherstone, Nicholas

    2017-05-01

    Our understanding of the interior dynamics that give rise to a stellar dynamo draws heavily from investigations of similar dynamics in the solar context. Unfortunately, an outstanding gap persists in solar dynamo theory. Convection, an indispensable component of the dynamo, occurs in the midst of rotation, and yet we know little about how the influence of that rotation manifests across the broad range of convective scales present in the Sun. We are nevertheless well aware that the interaction of rotation and convection profoundly impacts many aspects of the dynamo, including the meridional circulation, the differential rotation, and the helicity of turbulent EMF. The rotational constraint felt by solar convection ultimately hinges on the characteristic amplitude of deep convective flow speeds, and such flows are difficult to measure helioseismically. Those measurements of deep convective power which do exist disagree by orders of magnitude, and until this disagreement is resolved, we are left with the results of models and those less ambiguous measurements derived from surface observations of solar convection. I will present numerical results from a series of nonrotating and rotating convection simulations conducted in full 3-D spherical geometry. This presentation will focus on how convective spectra differ between the rotating and non-rotating models and how that behavior changes as simulations are pushed toward more turbulent and/or more rotationally-constrained regimes. I will discuss how the surface signature of rotationally-constrained interior convection might naturally lead to observable signatures in the surface convective pattern, such as supergranulation and a dearth of giant cells.

  8. 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). Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Spontaneous rupture of atrioventricular valve tensor apparatus as late manifestation of anti-Ro/SSA antibody-mediated cardiac disease.

    PubMed

    Cuneo, Bettina F; Fruitman, Deborah; Benson, D Woodrow; Ngan, Bo-Yee; Liske, Michael R; Wahren-Herlineus, Marie; Ho, S Yen; Jaeggi, Edgar

    2011-03-01

    Atrioventricular (AV) block and endocardial fibroelastosis associated with dilated cardiomyopathy are the most common clinical manifestations of anti-Ro/SSA-mediated fetal cardiac disease. Valvar dysfunction has not been a prominent feature of this disease; however, recent anecdotal cases have suggested an association between rupture of the AV valve tensor apparatus and maternal anti-Ro/SSA antibodies. In the present study, we have described the clinical and laboratory findings and reviewed the published data for infants of anti-Ro/SSA-positive pregnancies with AV valve insufficiency due to chordal rupture from the papillary muscles. The histopathologic features of the papillary muscle and ventricular free wall and septum biopsy specimens were examined and compared to the sections of AV leaflets from 6 autopsied fetuses with anti-Ro/SSA-mediated complete AV block without chordal disruption. Specific epitopes to the p200 region of Ro52, and Ro60 antibodies were evaluated in cases with chordal rupture. Severe AV valve insufficiency was detected prenatally (as early as 34 weeks of gestation) or postnatally (as late as 182 days) after areas of patchy echogenicity were noted in the papillary muscle at 19 to 22 weeks of gestation. Postnatally, urgent valve surgery was performed in 5 of 6 patients;