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Sample records for atenolol

  1. Atenolol

    Science.gov (United States)

    ... other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart ... Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat ...

  2. Adsorption of Atenolol on Kaolinite

    Directory of Open Access Journals (Sweden)

    Yingmo Hu

    2015-01-01

    Full Text Available In this study the adsorption of atenolol (AT, a β-blocker, on kaolinite, a clay mineral of low surface charge, was investigated under varying initial AT concentration, equilibrium time, solution pH, ionic strength, and temperature conditions. The results showed that the amounts of AT uptake by kaolinite were close to its cation exchange capacity value and the AT adsorption was almost instantaneous, suggesting a surface adsorption. The adsorption was exothermic and the free energy of adsorption was small negative, indicating physical adsorption. The increase in ionic strength of the solution drastically reduced AT uptake on kaolinite. A significant reduction in AT uptake was found at solution pH below 5 or above 10. The FTIR results showed band shifting and disappearance for NH bending vibration and benzene ring skeletal vibration at 3360 and 1515 cm−1 and band splitting at 1412 and 1240 cm−1 attributed to C–N valence vibration coupled with NH bending vibrations and alkyl aryl ether linkage, suggesting the participation of NH, –O–, and benzene ring for AT adsorption on kaolinite.

  3. Behavioural parameters in hypertensives on atenolol therapy.

    Science.gov (United States)

    Chaswal, M; Singh, S; Shankar, N; Avasthi, R

    1999-06-01

    Behavioural responses which included psychological tests and cold pressor test as a stress test were studied in 20 mild to moderate hypertensives of both sexes, excluding smokers, alcoholics, secondary hypertensives and patients of chronic obstructive pulmonary diseases. Subjects were put on 2 weeks of placebo washout period followed by 6 weeks of treatment with atenolol. Following treatment with atenolol they showed no significant alteration in the scores of psychological tests which included Weschler adult intelligence scale for orientation, while showing significant depression in the rise of heart rate, systolic blood pressure and diastolic blood pressure following cold pressor test. On further analysis, the results showed that hypertensives on placebo had lower scores of memory and attention test as compared to normotensive controls. Besides this, hypertensives on placebo had higher rise of heart rate and systolic blood pressure as compared to normotensive controls after cold pressor test.

  4. Hepatotoxicity of atenolol therapy - A report of 2 cases

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    Somnath Mondal

    2013-01-01

    Full Text Available This case report highlights atenolol induced episodes of chronic and acute hepatotoxicities in 2 elderly hypertensive patients. The 1st patient manifested liver dysfunction after 8 months of 50 mg daily atenolol therapy and in the 2nd patient liver dysfunction was revealed within 3 weeks of 100 mg daily atenolol intake. There was no evidence of any other possible hereditary, traumatic, surgical, metabolic, infective, organic, or pathologic causes giving rise to these conditions. Possibilities of drug interactions were carefully ruled out and these episodes of hepatotoxicities were ‘probably’ drug (atenolol induced, as depicted by CIOMS/RUCAM scale. Withdrawal of the offending drug resulted in reversal of the diseased states. Routine liver function tests may be warranted in patients on atenolol therapy.

  5. Pharmacometabolomics reveals racial differences in response to atenolol treatment.

    Directory of Open Access Journals (Sweden)

    William R Wikoff

    Full Text Available Antihypertensive drugs are among the most commonly prescribed drugs for chronic disease worldwide. The response to antihypertensive drugs varies substantially between individuals and important factors such as race that contribute to this heterogeneity are poorly understood. In this study we use metabolomics, a global biochemical approach to investigate biochemical changes induced by the beta-adrenergic receptor blocker atenolol in Caucasians and African Americans. Plasma from individuals treated with atenolol was collected at baseline (untreated and after a 9 week treatment period and analyzed using a GC-TOF metabolomics platform. The metabolomic signature of atenolol exposure included saturated (palmitic, monounsaturated (oleic, palmitoleic and polyunsaturated (arachidonic, linoleic free fatty acids, which decreased in Caucasians after treatment but were not different in African Americans (p<0.0005, q<0.03. Similarly, the ketone body 3-hydroxybutyrate was significantly decreased in Caucasians by 33% (p<0.0001, q<0.0001 but was unchanged in African Americans. The contribution of genetic variation in genes that encode lipases to the racial differences in atenolol-induced changes in fatty acids was examined. SNP rs9652472 in LIPC was found to be associated with the change in oleic acid in Caucasians (p<0.0005 but not African Americans, whereas the PLA2G4C SNP rs7250148 associated with oleic acid change in African Americans (p<0.0001 but not Caucasians. Together, these data indicate that atenolol-induced changes in the metabolome are dependent on race and genotype. This study represents a first step of a pharmacometabolomic approach to phenotype patients with hypertension and gain mechanistic insights into racial variability in changes that occur with atenolol treatment, which may influence response to the drug.

  6. Nifedipine gastrointestinal therapeutic system versus atenolol in stable angina pectoris

    NARCIS (Netherlands)

    deVries, RJM; vandenHeuvel, AFM; Lok, DJA; Claessens, RJJ; Bernink, PJLM; Pasteuning, WH; Kingma, JH; Dunselman, PHJM

    1996-01-01

    The gastrointestinal therapeutic system formulation of nifedipine enables a once-daily dosing resulting in predictable, relatively constant plasma concentrations. To evaluate the efficacy and safety of this formulation and to compare this with the beta-blocker atenolol, we conducted a double-blind,

  7. A comparative study of atenolol, nifedipine and their combination in ...

    African Journals Online (AJOL)

    The antihypertensive effects, as assessed by clinical and ambulatory blood pressure measurement, of nifedipine slowrelease (SR), atenolol and the two In combination were evaluated In 28 known hypertenslv88 In a placebo-controlled, double-blind, randomlsed cross-over trial. Clinical blood pressure was significantly ...

  8. New alginic acid–atenolol microparticles for inhalatory drug targeting

    Energy Technology Data Exchange (ETDEWEB)

    Ceschan, Nazareth Eliana; Bucalá, Verónica [Planta Piloto de Ingeniería Química (PLAPIQUI), CONICET, Universidad Nacional del Sur (UNS), Camino La Carrindanga Km 7, 8000 Bahía Blanca (Argentina); Departamento de Ingeniería Química, UNS, Avenida Alem 1253, 8000 Bahía Blanca (Argentina); Ramírez-Rigo, María Verónica, E-mail: vrrigo@plapiqui.edu.ar [Planta Piloto de Ingeniería Química (PLAPIQUI), CONICET, Universidad Nacional del Sur (UNS), Camino La Carrindanga Km 7, 8000 Bahía Blanca (Argentina); Departamento de Biología, Bioquímica y Farmacia, UNS, San Juan 670, 8000 Bahía Blanca (Argentina)

    2014-08-01

    The inhalatory route allows drug delivery for local or systemic treatments in a noninvasively way. The current tendency of inhalable systems is oriented to dry powder inhalers due to their advantages in terms of stability and efficiency. In this work, microparticles of atenolol (AT, basic antihypertensive drug) and alginic acid (AA, acid biocompatible polyelectrolyte) were obtained by spray drying. Several formulations, varying the relative composition AT/AA and the total solid content of the atomized dispersions, were tested. The powders were characterized by: Fourier Transform Infrared Spectroscopy, Differential Scanning Calorimetry and Powder X-ray Diffraction, while also the following properties were measured: drug load efficiency, flow properties, particles size and density, moisture content, hygroscopicity and morphology. The ionic interaction between AA and AT was demonstrated, then the new chemical entity could improve the drug targeting to the respiratory membrane and increase its time residence due to the mucoadhesive properties of the AA polymeric chains. Powders exhibited high load efficiencies, low moisture contents, adequate mean aerodynamic diameters and high cumulative fraction of respirable particles (lower than 10 μm). - Highlights: • Novel particulate material to target atenolol to the respiratory membrane was developed. • Crumbled microparticles were obtained by spray drying of alginic–atenolol dispersions. • Ionic interaction between alginic acid and atenolol was demonstrated in the product. • Amorphous solids with low moisture content and high load efficiency were produced. • Relationships between the feed formulation and the product characteristics were found.

  9. Losartan versus atenolol-based antihypertensive treatment reduces cardiovascular events especially well in elderly patients

    DEFF Research Database (Denmark)

    Ruwald, Anne Christine H; Westergaard, Bo; Sehestedt, Thomas

    2012-01-01

    The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study has previously demonstrated a beneficial effect of losartan compared to atenolol-based antihypertensive treatment in patients with essential hypertension and left-ventricular hypertrophy (LVH). However, patient age often...... influences the choice of antihypertensive drugs. Therefore, we investigated the influence of age on the effects of losartan versus atenolol-based antihypertensive treatment....

  10. Mucous membrane pemphigoid in a patient with hypertension treated with atenolol: a case report.

    Science.gov (United States)

    Kanjanabuch, Patnarin; Arporniem, Samornroj; Thamrat, Suparat; Thumasombut, Pannipa

    2012-10-31

    Atenolol is commonly used by patients with hypertension, angina pectoris, or myocardial infarction. There have been reports of various adverse effects associated with the use of atenolol including bullous pemphigoid. To the best of our knowledge we present the first case report of atenolol-induced mucous membrane pemphigoid. A 42-year-old Thai man presented to our faculty after developing generalized fiery red gingiva and ulcerations on the buccal and labial mucosa after beginning atenolol treatment. Drug-induced mucous membrane pemphigoid was diagnosed from his clinical presentation and histopathologic and direct immunofluorescence examinations, combined with a history of beginning, and withdrawal, from atenolol therapy, with the lesions resolving after the cessation of atenolol therapy. To the best of our knowledge this is the first case of atenolol-induced oral mucous membrane pemphigoid reported in the literature. The observed lesions responded to withdrawal of the offending drug with complete remission. While drug-induced mucous membrane pemphigoid is an uncommon condition, dentists or other health care workers should include this condition in the differential diagnosis when a patient uses drugs suspected to be involved with drug-induced pemphigoid.

  11. Mucous membrane pemphigoid in a patient with hypertension treated with atenolol: a case report

    Science.gov (United States)

    2012-01-01

    Introduction Atenolol is commonly used by patients with hypertension, angina pectoris, or myocardial infarction. There have been reports of various adverse effects associated with the use of atenolol including bullous pemphigoid. To the best of our knowledge we present the first case report of atenolol-induced mucous membrane pemphigoid. Case presentation A 42-year-old Thai man presented to our faculty after developing generalized fiery red gingiva and ulcerations on the buccal and labial mucosa after beginning atenolol treatment. Drug-induced mucous membrane pemphigoid was diagnosed from his clinical presentation and histopathologic and direct immunofluorescence examinations, combined with a history of beginning, and withdrawal, from atenolol therapy, with the lesions resolving after the cessation of atenolol therapy. Conclusions To the best of our knowledge this is the first case of atenolol-induced oral mucous membrane pemphigoid reported in the literature. The observed lesions responded to withdrawal of the offending drug with complete remission. While drug-induced mucous membrane pemphigoid is an uncommon condition, dentists or other health care workers should include this condition in the differential diagnosis when a patient uses drugs suspected to be involved with drug-induced pemphigoid. PMID:23110919

  12. Effect in bronchial asthma of a new beta-adrenergic blocking drug atenolol (ICI 66, 082).

    Science.gov (United States)

    Boye, N P; Vale, J R

    1977-01-01

    The bronchial effect of intravenous atenolol (ICI 66.082) has been studied in a double-blind cross over trial in 10 patients with pronounced, labile bronchial asthama. A single i.v. dose of atenolol 3 mg. sufficient to cause a fall in heart rate and systolic blood pressure at rest, induced only a slight and clincially almost negligible impairment of ventilatory function. An ordinary therapeutic dose of salbutamol by inhalation far outweighed the bronchial effect of atenolol. The drug appears promising with regard to its cardio-selective properties.

  13. Synthesis and Spectroscopic Studies ofAtenolol Derivatives with Enhanced Lipophilicity as Potential Prodrugs

    OpenAIRE

    Tabba, Hani D.; Hassan, Mohamed A.; Hijawi, Ali S.; Voelter, Wolfgang

    2002-01-01

    Atenolol, a selective pi-adrenoceptor blocking agent is characterized by its low bioavailability. A number of atenolol prodrugs were synthesized to improve its lipid solubility and hence bioavailability. These compounds included an oxazolidine-2-thione derivative (II), a l,4-oxazine-2,3-dione derivative (III), and a series of oxazolidine derivatives (IVa-m). The structure of each compound was characterized by elemental analysis, infrared (IR), protonnuclear magnetic resonance ( H-NMR), and ma...

  14. Reduction of ventricular arrhythmias by early intravenous atenolol in suspected acute myocardial infarction.

    OpenAIRE

    Rossi, P R; Yusuf, S; Ramsdale, D.; Furze, L; Sleight, P

    1983-01-01

    The effect of intravenous atenolol on ventricular arrhythmias in acute myocardial infarction was assessed in 182 patients admitted within 12 hours of the onset of chest pain. Ninety-five patients were randomised to receive 5 mg intravenous atenolol followed immediately by 50 mg by mouth and 50 mg 12 hours later, then 100 mg daily for 10 days; 87 patients served as controls. The treated patients had significantly fewer ventricular extrasystoles; 58 control patients (67%) had R-on-T extrasystol...

  15. Atenolol versus propranolol for the treatment of infantile hemangiomas: a randomized controlled study.

    Science.gov (United States)

    Ábarzúa-Araya, Alvaro; Navarrete-Dechent, Cristián P; Heusser, Felipe; Retamal, Javiera; Zegpi-Trueba, María Soledad

    2014-06-01

    Infantile hemangiomas have a dramatic response to propranolol, a nonselective beta-blocker. However, this treatment is not risk-free and many patients are excluded because of respiratory comorbidities. Atenolol is a cardioselective beta-blocker that may have fewer adverse events. We sought to evaluate the effectiveness of atenolol against propranolol in a noninferiority trial. In all, 23 patients met the inclusion criteria and were randomized to receive either atenolol or propranolol. Thirteen patients were treated with atenolol and 10 with propranolol. Follow-up was made at baseline, 2 weeks, 4 weeks, and then monthly for 6 months. Patients treated with atenolol had a complete response of 53.8% and 60% with propranolol, respectively. These results were nonsignificant (P = .68). Relevant adverse events were not reported. The reduced number of patients could have influenced our results. Atenolol appears to be as effective as propranolol. We did not find significant differences between these results or any adverse events. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  16. Perioperative β-blockade: atenolol is associated with reduced mortality when compared to metoprolol.

    Science.gov (United States)

    Wallace, Arthur W; Au, Selwyn; Cason, Brian A

    2011-04-01

    The Atenolol study of 1996 provided evidence that perioperative β-blockade reduced postsurgical mortality. In 1998, the indications for perioperative β-blockade were codified as the Perioperative Cardiac Risk Reduction protocol and implemented at the San Francisco Veterans Affairs Medical Center. The current study tested the following hypothesis: Is there a difference in mortality rates between patients receiving perioperative atenolol and metoprolol? Epidemiologic analysis of the operations performed at the San Francisco Veterans Affairs Medical Center since 1996 was performed. High-risk inpatients with perioperative β-blockade were divided into two groups: patients who received perioperative atenolol only and those who received metoprolol only. Patients who switched between the two chronic oral β-blocker medications were excluded. IV administration of β-blockers was ignored. Propensity matching analysis was used to correct for population differences in risk factors. There were 38,779 operations performed from 1996 to 2008, with 24,739 inpatient procedures. Based on analysis of inpatient medication use, 3,787 patients received atenolol only (1,011) or metoprolol only (2,776). Thirty-day mortality (atenolol 1% vs. metoprolol 3%, P < 0.0008) and 1-yr mortality (atenolol 7% vs. metoprolol 13%, P < 0.0001) differed between the two β-blockers. Analysis based on inpatient and outpatient β-blocker use showed a similar pattern. Propensity matching that corrected for multiple cardiac risk factors found an odds ratio (OR) of 2.1 [95% CI 1.5-2.9], P < 0.0001 for increased 1-yr mortality with metoprolol for inpatient use. Perioperative β-blockade using atenolol is associated with reduced mortality compared with metoprolol.

  17. Differential effects of carvedilol and atenolol on plasma noradrenaline during exercise in humans

    Science.gov (United States)

    Herman, Rahmatina B; Jesudason, Peter J; Mustafa, Ali M; Husain, Ruby; Choy, Anna Maria J; Lang, Chim C

    2003-01-01

    Aims Evidence of long-term beneficial effects of β-blockers on mortality and morbidity in patients with heart failure has been demonstrated in recent randomized trials. However, not all β-blockers are identical. Carvedilol, a nonselective β- and α-adrenergic blocker, can potentially blunt the release of noradrenaline by blocking presynaptic β2-adrenergic receptors. To test this hypothesis, we have compared the effects of carvedilol and atenolol on plasma noradrenaline during exercise in healthy young volunteers. Methods This study investigated the differential effects of 2 weeks pretreatment with carvedilol 25 mg day−1 and atenolol 50 mg day−1 on plasma noradrenaline at rest and during exercise on a treadmill in a double-blind randomized crossover study, involving 12 healthy male volunteers (mean age 21.6 ± 0.3 years). Results Haemodynamic parameters at rest and during exercise were not significantly different in either carvedilol or atenolol pretreatment groups. However, carvedilol pretreatment significantly blunted the increase in plasma noradrenaline during exercise [393.8 ± 51.7 pg ml−1 (pretreatment) to 259.7 ± 21.2 pg ml−1 (post-treatment)], when compared with atenolol [340.4 ± 54.6 pg ml−1 (pretreatment) to 396.2 ± 32.0 pg ml−1 (post-treatment)]. The difference between carvedilol and atenolol (95% confidence interval) was −145.2, −351.0, P < 0.05. Conclusions We have demonstrated that carvedilol but not atenolol significantly blunted the increase in plasma noradrenaline during exercise. These findings may suggest a sympathoinhibitory effect of carvedilol that may enhance its ability to attenuate the cardiotoxicity associated with adrenergic stimulation in patients with heart failure. PMID:12580984

  18. In-vitro displacement interaction of atenolol and amlodipine on binding with bovine serum albumin when co-administered

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    Md. Ashraful Alam, Md. Abdul Awal, Mahbub Mostofa, Md. Kamrul Islam and Nusrat Subhan

    2007-06-01

    Full Text Available The binding of atenolol (selective β1-blocker and amlodipine (calcium channel blocker to bovine serum albumin (BSA was studied by equilibrium dialysis method in order to have an insight into the binding chemistry of these two to BSA. Free atenolol concentration was increased due to addition of amlodipine which reduced the binding of the compounds to BSA. However, the free fraction was increased to a level as it was expected from direct competitive displacement while the free atenolol concentration was increased according to increasing the amlodipine concentration when only the BSA was present. The result obtained when the binding site was blocked by sufficient amount of amlodipine was that the increment of free concentration of atenolol was prominent. When no amlodipine was added the free concentration of atenolol was only 28% whereas this release was 93 % to 98.01% when amlodipine was added with increasing concentration.

  19. Distinct effects of losartan and atenolol on vascular stiffness in Marfan syndrome.

    Science.gov (United States)

    Bhatt, Ami B; Buck, J Stewart; Zuflacht, Jonah P; Milian, Jessica; Kadivar, Samoneh; Gauvreau, Kimberlee; Singh, Michael N; Creager, Mark A

    2015-08-01

    We conducted a randomized, double-blind trial of losartan (100 mg QD) versus atenolol (50 mg QD) for 6 months in adults with Marfan syndrome. Carotid-femoral pulse wave velocity (PWV), central augmentation index (AIx), aortic diameter and left ventricular (LV) function were assessed with arterial tonometry and echocardiography. Thirty-four subjects (18 female; median age 35 years, IQR 27, 45) were randomized. Central systolic and diastolic blood pressure decreased comparably with atenolol and losartan (p = 0.64 and 0.31, respectively); heart rate decreased with atenolol (p = 0.02), but not with losartan. PWV decreased in patients treated with atenolol (-1.15 ± 1.68 m/s; p = 0.01), but not in those treated with losartan (-0.22 ± 0.59 m/s; p = 0.15; between-group difference p = 0.04). In contrast, AIx decreased in the losartan group (-9.6 ± 8.6%; p losartan reduces the AIx. By improving vascular stiffness via distinct mechanisms of action, there is physiologic value to considering the use of both medications in individuals with Marfan syndrome. © The Author(s) 2015.

  20. [Research on the effect of atenolol on lidocaine pharmacokinetics in rats].

    Science.gov (United States)

    Grădinaru, Irina; Ghiciuc, Cristina Mihaela; Nechifor, M; Dumitriu, G; Doloca, A

    2006-01-01

    The aim was to determine the influence of atenolol on lidocaine pharmacokinetics in rats for one hour interval of time (average of a dental intervention). The study was carried out on 2 groups of Wistar rats treated with saline solution (0.5 ml/kg), respectively with atenolol (1.5 mg/kg), administered orally 24 hours and 3 hours before intraperitoneal administration of lidocaine (1.5 mg/kg). Blood samples were collected before and 5, 10, 20, 30, 60 minutes after lidocaine administration. Lidocaine plasma concentrations were determined by HPLC. Some pharmacokinetic parameters of lidocaine were statistically significant higher (p < 0.05, ANOVA) for the rats treated with atenolol compared with control group: Cmax (196.97 +/- 2.15 ng/ml vs. 125.29 +/- 2.90 ng/ml), AUD (7734.07 +/- 129.06 ng/ ml x min vs. 4478.57 +/- 296.61 ng/ml x min), AUC1 after 5 minutes (314.23 +/- 6.59 ng/ml x min vs. 190.71 +/- 19.75 ng/ml x min). Tmax was 20 minutes, similar for both groups. local anesthesia with lidocaine might be enhanced in the presence of atenolol compared to controls.

  1. ADVERSE PRE- AND POSTNATAL EVENTS REPORTED TO FDA IN ASSOCIATION WITH MATERNAL ATENOLOL TREATMENT IN PREGNANCY

    Science.gov (United States)

    Atenolol is a beta-adrenoreceptor blocker used for treatment of hypertension in pregnancy. This study evaluates the reporting frequency of adverse pre- and postnatal outcomes in a series of 70 cases of maternal exposure during gestation, derived from 140 reports to FDA with Ateno...

  2. Ecotoxicity of ketoprofen, diclofenac, atenolol and their photolysis byproducts in zebrafish (Danio rerio)

    Energy Technology Data Exchange (ETDEWEB)

    Diniz, M.S., E-mail: mesd@fct.unl.pt [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Salgado, R., E-mail: r.salgado@campus.fct.unl.pt [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); ESTS-IPS, Escola Superior de Tecnologia de Setúbal do Instituto Politécnico de Setúbal, Rua Vale de Chaves, Campus do IPS, Estefanilha, 2910-761 Setúbal (Portugal); Pereira, V.J., E-mail: vanessap@itqb.unl.pt [Instituto de Biologia Experimental e Tecnológica (IBET), Av. da República (EAN), 2784-505 Oeiras (Portugal); Instituto de Tecnologia Química e Biológica (ITQB)—Universidade Nova de Lisboa (UNL), Estação Agronómica Nacional, Av. da República, 2780-157 Oeiras (Portugal); Carvalho, G., E-mail: gs.carvalho@fct.unl.pt [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Instituto de Biologia Experimental e Tecnológica (IBET), Av. da República (EAN), 2784-505 Oeiras (Portugal); Oehmen, A., E-mail: a.oehmen@fct.unl.pt [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Reis, M.A.M., E-mail: amr@fct.unl.pt [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Noronha, J.P., E-mail: jpnoronha@fct.unl.pt [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal)

    2015-02-01

    The occurrence of pharmaceutical compounds in wastewater treatment plants and surface waters has been detected worldwide, constituting a potential risk for aquatic ecosystems. Adult zebrafish, of both sexes, were exposed to three common pharmaceutical compounds (atenolol, ketoprofen and diclofenac) and their UV photolysis by-products over seven days. The results show that diclofenac was removed to concentrations < LOD after 5 min of UV irradiation. The oxidative stress response of zebrafish to pharmaceuticals and their photolysis by-products was evaluated through oxidative stress enzymes (glutathione-S-transferase, catalase, superoxide dismutase) and lipid peroxidation. Results suggest that the photolysis by-products of diclofenac were more toxic than those from the other compounds tested, showing an increase in GST and CAT levels, which are also supported by higher MDA levels. Overall, the toxicity of waters containing atenolol and ketoprofen was reduced after the parent compounds were transformed by photolysis, whereas the toxicity increased significantly from the by-products generated through diclofenac photolysis. Therefore, diclofenac photolysis would possibly necessitate higher irradiation time to ensure that the associated by-products are completely degraded to harmless form(s). - Highlights: • Toxicity evaluated for 3 common pharmaceuticals (atenolol, ketoprofen and diclofenac). • Toxicity assessed for the pharmaceuticals and UV photolysis by-products in zebrafish. • Diclofenac photolysis by-products are more toxic than the parent compound. • Ketoprofen and atenolol show stronger oxidative stress response than by-products. • UV photolysis should ensure full removal of diclofenac metabolites to avoid toxicity.

  3. Photodegradation kinetics and transformation products of ketoprofen, diclofenac and atenolol in pure water and treated wastewater

    Energy Technology Data Exchange (ETDEWEB)

    Salgado, R. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); ESTS-IPS, Escola Superior de Tecnologia de Setúbal do Instituto Politécnico de Setúbal, Rua Vale de Chaves, Campus do IPS, Estefanilha, 2910-761 Setúbal (Portugal); Pereira, V.J. [Instituto de Biologia Experimental e Tecnológica (IBET), Av. da República (EAN), 2784-505 Oeiras (Portugal); Instituto de Tecnologia Química e Biológica (ITQB) – Universidade Nova de Lisboa (UNL), Av. da República, Estação Agronómica Nacional, 2780-157 Oeiras, 5 Portugal (Portugal); Carvalho, G., E-mail: gs.carvalho@fct.unl.pt [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Instituto de Biologia Experimental e Tecnológica (IBET), Av. da República (EAN), 2784-505 Oeiras (Portugal); Soeiro, R. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Gaffney, V.; Almeida, C. [Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculdade de Farmácia da Universidade de Lisboa (FFUL), Av. Prof. Gama Pinto, 1600-049 Lisboa (Portugal); Cardoso, V. Vale; Ferreira, E.; Benoliel, M.J. [Empresa Portuguesa das Águas Livres, S.A., Direcção de Controlo de Qualidade da Água, Laboratório Central, Avenida de Berlim, 15, 1800-031 Lisboa (Portugal); and others

    2013-01-15

    Highlights: ► Direct UV photolysis of 3 pharmaceuticals in pure and waste water was investigated. ► Ketoprofen has higher photodegradion kinetics, followed by diclofenac and atenolol. ► MP/UV photodegradation products were identified for the 3 compounds. ► Photodegradation pathways were proposed to explain the obtained products. ► The persistent photoproducts were identified for each compound. -- Abstract: Pharmaceutical compounds such as ketoprofen, diclofenac and atenolol are frequently detected at relatively high concentrations in secondary effluents from wastewater treatment plants. Therefore, it is important to assess their transformation kinetics and intermediates in subsequent disinfection processes, such as direct ultraviolet (UV) irradiation. The photodegradation kinetics of these compounds using a medium pressure (MP) lamp was assessed in pure water, as well as in filtered and unfiltered treated wastewater. Ketoprofen had the highest time- and fluence-based rate constants in all experiments, whereas atenolol had the lowest values, which is consistent with the corresponding decadic molar absorption coefficient and quantum yield. The fluence-based rate constants of all compounds were evaluated in filtered and unfiltered wastewater matrices as well as in pure water. Furthermore, transformation products of ketoprofen, diclofenac and atenolol were identified and monitored throughout the irradiation experiments, and photodegradation pathways were proposed for each compound. This enabled the identification of persistent transformation products, which are potentially discharged from WWTP disinfection works employing UV photolysis.

  4. Atenolol induced HDL-C change in the pharmacogenomic evaluation of antihypertensive responses (PEAR study.

    Directory of Open Access Journals (Sweden)

    Caitrin W McDonough

    Full Text Available We sought to identify novel pharmacogenomic markers for HDL-C response to atenolol in participants with mild to moderate hypertension. We genotyped 768 hypertensive participants from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR study on the Illumina HumanCVD Beadchip. During PEAR, participants were randomized to receive atenolol or hydrochlorothiazide. Blood pressure and cholesterol levels were evaluated at baseline and after treatment. This study focused on participants treated with atenolol monotherapy. Association with atenolol induced HDL-C change was evaluated in 232 whites and 152 African Americans using linear regression. No SNPs achieved a Bonferroni corrected P-value. However, we identified 13 regions with consistent association across whites and African Americans. The most interesting of these regions were seven with prior associations with HDL-C, other metabolic traits, or functional implications in the lipid pathway: GALNT2, FTO, ABCB1, LRP5, STARD3NL, ESR1, and LIPC. Examples are rs2144300 in GALNT2 in whites (P=2.29x10(-4, β=-1.85 mg/dL and rs12595985 in FTO in African Americans (P=2.90x10(-4, β=4.52 mg/dL, both with consistent regional association (P<0.05 in the other race group. Additionally, baseline GALNT2 expression differed by rs2144300 genotype in whites (P=0.0279. In conclusion, we identified multiple gene regions associated with atenolol induced HDL-C change that were consistent across race groups, several with functional implications or prior associations with HDL-C.

  5. A molecular inclusion complex of atenolol with 2-hydroxypropyl-b-cyclodextrin; the production and characterization thereof

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    VESNA NIKOLIC

    2007-08-01

    Full Text Available The molecular inclusion complex of atenolol with 2-hydroxypropyl-b-cy­clodextrin was synthesized using the coprecipitation method. The complex obtained was characterized by FT-IR, 1H‑NMR, 13C-NMR spectroscopy, as well as by DSC and X-ray diffraction analysis. The DSC analysis confirmed the existence of the com­plex with the endothermic atenolol melting peak at about 155 ºC disappearing. The X-ray diffraction patterns of the complex and 2-hydroxypropyl-b-cyclodextrin were very similar, thus confirming the complete inclusion of the atenolol molecule within the cavity of the 2-hydroxypropyl-b-cyclodextrin. The peaks originating from ate­nolol were completely absent in the diffractogram of the complex. 1H-NMR and 13C-NMR spectra showed certain changes in the chemical shifts of protons and C atoms from atenolol and 2-hydroxypropyl-b-cyclodextrin, indicating that a complex had been formed and also which protons participated in the hydrogen bonds which formed the complex. The atenolol solubility in water was improved (254 mg com­plex cm-3, i.e., 37.5 mg atenolol cm-3, and in pH 3 HCl solution (251 mg com­plex cm-3, i.e., 37 mg atenolol cm-3 when compared to pure atenolol, and even when compared to the atenolol complex with b-cyclodextrin. The increased solubility en­sures greater bioavailability of the active component and, due to the low solubility, significantly corrects for the lack of the basic active substance and, simultaneously, increases its overall therapeutic effect, combined with reduced side effects.

  6. Long-term treatment with losartan versus atenolol improves insulin sensitivity in hypertension: ICARUS, a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, Michael H; Fossum, Eigil; Høieggen, Aud

    2005-01-01

    Hypertension and insulin resistance might be associated through peripheral vascular hypertrophy/rarefaction which compromises skeletal muscle blood flow and decreases glucose uptake, inducing insulin resistance. We hypothesized that treatment with losartan as compared to atenolol would improve...

  7. Long-term effect of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy

    DEFF Research Database (Denmark)

    Nielsen, F S; Rossing, P; Gall, M A

    1997-01-01

    The aim of our study was to evaluate whether inhibition of ACE (lisinopril 10-20 mg/day) can reduce the rate of decline in kidney function more than reducing blood pressure with conventional antihypertensive treatment (atenolol 50-100 mg/day), usually in combination with a diuretic. We performed...... a prospective, randomized, parallel study for 42 months, double blind for the first 12 months and single blind thereafter. Forty-three (21 lisinopril and 22 atenolol) hypertensive NIDDM patients with diabetic nephropathy were enrolled. Data from 36 patients (17 lisinopril and 19 atenolol, 60 +/- 7 years of age...... sustained decline (6 to 42 months) of 0.59 +/- 0.10 and 0.54 +/- 0.13 ml x min(-1) x month(-1) in the lisinopril and atenolol groups, respectively. No significant differences were observed in either initial or sustained decline in glomerular filtration rate between the two groups. Urinary albumin excretion...

  8. Amlodipine-Valsartan Combination Decreases Central Systolic Blood Pressure More Effectively Than the Amlodipine-Atenolol Combination: The EXPLOR Study

    National Research Council Canada - National Science Library

    Boutouyrie, Pierre; Achouba, Assya; Trunet, Patrick; Laurent, Stéphane

    2010-01-01

    ...). The trial was designed to determine whether the advantages of angiotensin-receptor blockers over atenolol remained significant when both were combined with the calcium-channel blocker amlodipine...

  9. Design, Synthesis, and In Vitro Kinetics Study of Atenolol Prodrugs for the Use in Aqueous Formulations

    Directory of Open Access Journals (Sweden)

    Rafik Karaman

    2014-01-01

    Full Text Available Based on DFT, MP2, and the density functional from Truhlar group (hybrid GGA: MPW1k calculations for an acid-catalyzed hydrolysis of nine Kirby’s N-alkylmaleamic acids and two atenolol prodrugs were designed. The calculations demonstrated that the amide bond cleavage is due to intramolecular nucleophilic catalysis by the adjacent carboxylic acid group and the rate-limiting step is determined based on the nature of the amine leaving group. In addition, a linear correlation of the calculated and experimental rate values has drawn credible basis for designing atenolol prodrugs that are bitterless, are stable in neutral aqueous solutions, and have the potential to release the parent drug in a sustained release manner. For example, based on the calculated B3LYP/6-31 G (d,p rates, the predicted t1/2 (a time needed for 50% of the prodrug to be converted into drug values for atenolol prodrugs ProD 1-ProD 2 at pH 2 were 65.3 hours (6.3 hours as calculated by GGA: MPW1K and 11.8 minutes, respectively. In vitro kinetic study of atenolol prodrug ProD 1 demonstrated that the t1/2 was largely affected by the pH of the medium. The determined t1/2 values in 1N HCl, buffer pH 2, and buffer pH 5 were 2.53, 3.82, and 133 hours, respectively.

  10. Efficacy of losartan vs. atenolol for the prevention of aortic dilation in Marfan syndrome: a randomized clinical trial.

    Science.gov (United States)

    Forteza, Alberto; Evangelista, Arturo; Sánchez, Violeta; Teixidó-Turà, Gisela; Sanz, Paz; Gutiérrez, Laura; Gracia, Teresa; Centeno, Jorge; Rodríguez-Palomares, José; Rufilanchas, Juan Jose; Cortina, José; Ferreira-González, Ignacio; García-Dorado, David

    2016-03-21

    To determine the efficacy of losartan vs. atenolol in aortic dilation progression in Marfan syndrome (MFS) patients. A phase IIIb, randomized, parallel, double-blind study was conducted in 140 MFS patients, age range: 5-60 years, with maximum aortic diameter losartan (n = 70) or atenolol (n = 70). Doses were raised to a maximum of 1.4 mg/kg/day or 100 mg/day. The primary end-point was the change in aortic root and ascending aorta maximum diameter indexed by body surface area on magnetic resonance imaging after 36 months of treatment. No serious drug-related adverse effects were observed. Five patients presented aortic events during a follow-up (one in the losartan and four in the atenolol groups, P = 0.366). After 3 years of follow-up, aortic root diameter increased significantly in both groups: 1.1 mm (95% CI 0.6-1.6) in the losartan and 1.4 mm (95% CI 0.9-1.9) in the atenolol group, with aortic dilatation progression being similar in both groups: absolute difference between losartan and atenolol -0.3 mm (95% CI -1.1 to 0.4, P = 0.382) and indexed by BSA -0.5 mm/m2 (95% CI -1.2 to 0.1, P = 0.092). Similarly, no significant differences were found in indexed ascending aorta diameter changes between the losartan and atenolol groups: -0.3 mm/m2 (95% CI -0.8 to 0.3, P = 0.326). Among patients with MFS, the use of losartan compared with atenolol did not result in significant differences in the progression of aortic root and ascending aorta diameters over 3 years of follow-up. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  11. Atenolol attenuates autonomic dysfunction of rat jejunum submitted to cold ischemic preservation.

    Science.gov (United States)

    Taha, M O; Fraga, M M; Guimarães, F A; Jurkiewicz, A; Caricati-Neto, A

    2006-01-01

    In vitro studies have demonstrated that cold ischemic preservation (CIP) employed in small bowel transplantation produces loss of intestinal motility due to severe lesions of autonomic enteric nerves and that this autonomic dysfunction is attenuated by antioxidant agents. In this work, we investigated whether preservation with atenolol attenuated autonomic dysfunction of rat jejunum submitted to long-term CIP. Jejunal segments (2 cm) of Wistar rats (12 to 16 weeks old) were surgically isolated and preserved at 4 degrees C in Ringer's lactate solution without (-) or with (+) 1 mumol/L atenolol (AT). After preservation for 12 hours, AT+ and AT- preparations were mounted in parallel in isolated organ baths containing 10 mL Tyrode's solution at 37 degrees C for the study of neurogenic contractions evoked by electrical field stimulation (EFS; 10 to 30 Hz, 1-ms duration, 60 V) or by stimulation with nicotinic (nicotine, NIC) or muscarinic (carbachol, CCh) cholinoceptor agents as well as nicotine (hexamethonium, HEX) and muscarinic (atropine, ATR) antagonists. Contractions induced by EFS (30 Hz) were 46% higher in AT+ (0.38 +/- 0.02 g) than AT- (0.26 +/- 0.01 g), while contractions induced by NIC (1 mmol/L) were 84% higher in AT+ (0.46 +/- 0.03 g) than in AT- (0.25 +/- 0.02 g). In addition, contractions induced by CCh (1 mmol/L) were 34% higher in AT+ (0.87 +/- 0.06 g) than in AT- (0.65 +/- 0.08 g). EFS-, NIC-, and CCh-induced contractions were inhibited by pretreatment of jejunum with HEX or ATR (1 mumol/30 min), in AT+ and AT-. These results suggest that addition of atenolol in the preservation solution attenuated autonomic dysfunction of rat jejunum submitted to long-term CIP.

  12. PARTITION OF ATENOLOL AND PROPRANOLOL TABLETS AND ITS POSSIBLE IMPLICATION IN THEIR THERAPEUTIC EFFECT.

    Directory of Open Access Journals (Sweden)

    A. S. Inhã

    2016-07-01

    Full Text Available A medicament is defined as a pharmaceutical product that is obtained or prepared technologically. It should contain one or more active ingredients with other substances with prophylactic, curative, palliative or diagnostic purposes. The pharmaceutical dosage form of oral tablets is relevant given the advantages it presents. The drugs are produced in pre-established doses, doses that are patterns of each pharmaceutical company and may not meet the needs of all patients. There is still a need to reduce the cost or achieve lower dosages that are sometimes found not commercially available and therefore, frequently some patients are instructed to cut the tablets. ANVISA reports that the practice of tablets partition in half is harmful to the patient, especially if the tablet has some special kinds of releasing its contents, in a given period or location in the body, before dissolving completely or whether they have coatings. This work aims to analyze the partition of propranolol and atenolol tablets, and if the process of partition can influence in the uniformity of the drug between the halves obtained after splitting using the employment tablet cutters. These tablets Propranolol 40mg and Atenolol 50mg were chosen due to their common use to control blood pressure. The assay methodology of these active ingredients has been adapted from Brazilian Pharmacopoeia (1988 using spectrophotometry. The results showed that there was a variation in the dosage of atenolol tablets parties from 70-142% and for propranolol half tablets the variation was obtained around 90 and 112% of the half dosage. Propranolol data may have been better since these tablet shave a facilitator who is the divisor groove. The data indicate that the partition tablets should not be encouraged because it can lead to loss of efficacy in the treatment.

  13. Atenolol versus losartan in children and young adults with Marfan's syndrome.

    Science.gov (United States)

    Lacro, Ronald V; Dietz, Harry C; Sleeper, Lynn A; Yetman, Anji T; Bradley, Timothy J; Colan, Steven D; Pearson, Gail D; Selamet Tierney, E Seda; Levine, Jami C; Atz, Andrew M; Benson, D Woodrow; Braverman, Alan C; Chen, Shan; De Backer, Julie; Gelb, Bruce D; Grossfeld, Paul D; Klein, Gloria L; Lai, Wyman W; Liou, Aimee; Loeys, Bart L; Markham, Larry W; Olson, Aaron K; Paridon, Stephen M; Pemberton, Victoria L; Pierpont, Mary Ella; Pyeritz, Reed E; Radojewski, Elizabeth; Roman, Mary J; Sharkey, Angela M; Stylianou, Mario P; Wechsler, Stephanie Burns; Young, Luciana T; Mahony, Lynn

    2014-11-27

    Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers. We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events. From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [±SD] age, 11.5±6.5 years in the atenolol group and 11.0±6.2 years in the losartan group), who had an aortic-root z score greater than 3.0. The baseline-adjusted rate of change in the mean (±SE) aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139±0.013 and -0.107±0.013 standard-deviation units per year, respectively; P=0.08). Both slopes were significantly less than zero, indicating a decrease in the aortic-root diameter relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups. Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aortic-root dilatation between the two treatment groups over a 3-year period. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00429364.).

  14. INFLUENCE OF ENALAPRIL, DIGOXIN, ATENOLOL AND DILTIAZEM ON LIPID PEROXIDATION IN EXPERIMENTAL MODEL OF COMPLEX METABOLIC DISORDERS

    Directory of Open Access Journals (Sweden)

    A. A. Usanova

    2009-01-01

    Full Text Available Aim. To study influence of enalapril, digoxin, atenolol and diltiazem on lipid peroxidation and antioxidative protection in experimental disorders of glucose and lipid metabolism.Material and methods. White nonlinear mice were used for modeling of the complex metabolic disorders by alloxan and cholesterol infusion. Evaluation of acute drug toxicity and indicators of lipid peroxidation and antioxidant protection was performed. Superoxide dismutase and catalase activity, malondialdehyde concentration were evaluated.Results. Toxicity of digoxin, diltiazem, atenolol in complex metabolic disorders was increased, and toxicity of enalapril was unchanged. Enalapril had antioxidant effect. Atenolol had prooxidative effect in myocardium and kidneys, and diltiazem - in kidneys.Conclusion. Enalapril showed antioxidant effect and decreased concentration of secondary products of lipid peroxidation in renal tissue. It may be considered as the first line drug in complex metabolic disorders.

  15. INFLUENCE OF ENALAPRIL, DIGOXIN, ATENOLOL AND DILTIAZEM ON LIPID PEROXIDATION IN EXPERIMENTAL MODEL OF COMPLEX METABOLIC DISORDERS

    Directory of Open Access Journals (Sweden)

    A. A. Usanova

    2016-01-01

    Full Text Available Aim. To study influence of enalapril, digoxin, atenolol and diltiazem on lipid peroxidation and antioxidative protection in experimental disorders of glucose and lipid metabolism.Material and methods. White nonlinear mice were used for modeling of the complex metabolic disorders by alloxan and cholesterol infusion. Evaluation of acute drug toxicity and indicators of lipid peroxidation and antioxidant protection was performed. Superoxide dismutase and catalase activity, malondialdehyde concentration were evaluated.Results. Toxicity of digoxin, diltiazem, atenolol in complex metabolic disorders was increased, and toxicity of enalapril was unchanged. Enalapril had antioxidant effect. Atenolol had prooxidative effect in myocardium and kidneys, and diltiazem - in kidneys.Conclusion. Enalapril showed antioxidant effect and decreased concentration of secondary products of lipid peroxidation in renal tissue. It may be considered as the first line drug in complex metabolic disorders.

  16. Effects of nebivolol and atenolol on central aortic pressure in hypertensive patients: a multicenter, randomized, double-blind study.

    Science.gov (United States)

    Redón, Josep; Pascual-Izuel, Jose M; Rodilla, Enrique; Vicente, Antonio; Oliván, Josefina; Bonet, Josep; Torguet, Josep Pere; Calaforra, Oscar; Almirall, Jaume

    2014-06-01

    The main objective was to compare the mean change in augmentation index of hypertensive patients treated with nebivolol or atenolol. Multicenter, double-blind randomized study conducted in six Spanish centers. We enrolled outpatients between the ages of 40 and 65 years with mild or moderate essential hypertension (systolic blood pressure, SBP ≥ 140 mmHg to ≤ 179 mmHg and diastolic blood pressure, DBP ≥ 90 mmHg to ≤ 109 mmHg after a 2-week run-in placebo period). Patients received nebivolol 5 mg or atenolol 50 mg once daily. At week 3, atenolol could be titrated up to 100 mg qd for non-responders. Additionally, patients not achieving normal blood pressure after 6 weeks could be treated with 25 mg hydrochlorothiazide. Follow-up visits were at 3, 6 and 10 weeks. The final study population of 138 patients (58% men; median age 52.6 years, range 40-67 years) was randomized into two groups of 69 patients each. Baseline characteristics of the two groups were similar. At the screening visit, 69% presented with mild hypertension. Nebivolol modified the mean augmentation index to a lesser extent than atenolol after 10 weeks (mean difference 3.1%, 95% CI 0.55-5.69; p = 0.027). A higher proportion of patients in the atenolol group required a diuretic. Reductions in central aortic pressure and peripheral arterial pressure were similar for both treatment groups. The study confirms that nebivolol produces a less pronounced impact on augmentation index than atenolol.

  17. Massive Atenolol, Lisinopril, and Chlorthalidone Overdose Treated with Endoscopic Decontamination, Hemodialysis, Impella Percutaneous Left Ventricular Assist Device, and ECMO.

    Science.gov (United States)

    Heise, C William; Beutler, David; Bosak, Adam; Orme, Geoffrey; Loli, Akil; Graeme, Kimberlie

    2015-03-01

    Overdose of cardiovascular medications is increasingly associated with morbidity and mortality. We present a case of substantial atenolol, chlorthalidone, and lisinopril overdose treated by multiple modalities with an excellent outcome. Aggressive medical intervention did not provide sufficient hemodynamic stability in this patient with refractory cardiogenic and distributive shock. Impella® percutaneous left ventricular assist device and extracorporeal membrane oxygenation provided support while the effects of the overdose subsided. We present concentrations demonstrating removal of atenolol with continuous venovenous hemodiafiltration. This is the first report of esophagogastroduo denoscopy decontamination of this overdose with a large pill fragment burden.

  18. Studies on the inhibition of mild steel corrosion in hydrochloric acid solution by atenolol drug

    Directory of Open Access Journals (Sweden)

    G. Karthik

    2016-06-01

    Full Text Available The inhibition performance of atenolol on mild steel in 1 M hydrochloric acid solution was studied by weight loss and electrochemical methods. The results show the inhibition efficiency was found to increase with increasing the concentration of the inhibitor from 50 to 300 ppm. The maximum inhibition efficiency 93.8% was observed in the presence of 300 ppm inhibitor (in case of potentiodynamic polarization. The inhibition action of atenolol was explained in terms of adsorption on the mild steel surface. The adsorption process follows Langmuir isotherm via physical adsorption. Electrochemical Impedance spectroscopic technique (EIS exhibits one capacitive loop indicating that, the corrosion reaction is controlled by charge transfer process. Polarization measurements showed that the inhibitor is of a mixed type. The results obtained from the different methods are in good agreement. The surface morphologies of mild steel were examined by Fourier-transform infrared (FT-IR spectroscopy, scanning electron microscope (SEM. Further, the computational calculations are performed to find a relation between their electronic and structural properties.

  19. DIFFERENTIAL-EFFECTS OF ENALAPRIL AND ATENOLOL ON PROTEINURIA AND RENAL HEMODYNAMICS IN NONDIABETIC RENAL-DISEASE

    NARCIS (Netherlands)

    APPERLOO, AJ; DEZEEUW, D; SLUITER, HE; DEJONG, PE

    Objective - To compare the antihypertensive, renal haemodynamic and antiproteinuric effect of enalapril and atenolol in patients with proteinuria of non-diabetic origin. Design - Prospective, double blind, randomised 16 week study after a pretreatment period of at least three weeks. Setting -

  20. Long-term treatment with losartan versus atenolol improves insulin sensitivity in hypertension: ICARUS, a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, Michael H; Fossum, Eigil; Høieggen, Aud

    2005-01-01

    Hypertension and insulin resistance might be associated through peripheral vascular hypertrophy/rarefaction which compromises skeletal muscle blood flow and decreases glucose uptake, inducing insulin resistance. We hypothesized that treatment with losartan as compared to atenolol would improve...... insulin sensitivity through regression of peripheral vascular hypertrophy/rarefaction....

  1. Comparison of hypotensive and hypolipidemic effects of Catharanthus roseus leaves extract with atenolol on adrenaline induced hypertensive rats.

    Science.gov (United States)

    Ara, Naznin; Rashid, Mamunur; Amran, Md Shah

    2009-07-01

    The leaves extract of Catharanthus roseus was investigated for hypotensive and hypolipidemic effects in adrenaline-induced hypertensive rats (AIHR) and compared with those of Atenolol in a crossover design. The pharmacologically Active components responsible for hypotensive activities were isolated from plant using bioassay guided purification approach and the structure of the compounds was proposed by spectroscopic methods. Catharanthus roseus leaves extract and commercial drug Atenolol were administered through intraperitoneal (i.p) route for one week. Different biochemical parameters such as heart weight, blood glucose level, serum cholesterol level, serum triglyceride level, body weight and the relationships between them were measured. Catharanthus roseus leaves extract at a dose of 30 mg/155+/-15 gm of body weight was injected in rat at every morning during the treatment period. The dose of Atenolol was determined according to its pharmacokinetic parameters. Clinically effective plasma concentration as a hypotensive drug was obtained after the injection of 0.1 mg/155+/-15 gm of body weight of the drug. The Catharanthus roseus leaves extract made significant changes in each cardiovascular parameter after investigation. Catharanthus roseus leaves extract treated animals have shown the hypotensive effects. Hypotensive effects were also shown by Atenolol.

  2. Impact of feed counterion addition and cyclone type on aerodynamic behavior of alginic-atenolol microparticles produced by spray drying.

    Science.gov (United States)

    Ceschan, Nazareth Eliana; Bucalá, Verónica; Ramírez-Rigo, María Verónica; Smyth, Hugh David Charles

    2016-12-01

    The inhalatory route has emerged as an interesting non-invasive alternative for drug delivery. This allows both pulmonary (local) and systemic treatments (via alveolar absorption). Further advantages in terms of stability, dose and patient preference have often lead researchers to focus on dry powder inhaler delivery systems. Atenolol is an antihypertensive drug with low oral bioavailability and gastrointestinal side effects. Because atenolol possesses adequate permeation across human epithelial membranes, it has been proposed as a good candidate for inhalatory administration. In a previous work, atenolol was combined with alginic acid (AA) and microparticles were developed using spray-drying (SD) technology. Different AA/atenolol ratios, total feed solid content and operative variables were previously explored. In order to improve particle quality for inhalatory administration and the SD yield, in this work the AA acid groups not neutralized by atenolol were kept either free or neutralized to pH∼7 and two different SD cyclones were used. Particle morphology, flow properties, moisture uptake and in vitro aerosolization behavior at different pressure drops were studied. When the AA acid groups were neutralized, particle size decreased as a consequence of the lower feed viscosity. The SD yield and in vitro particle deposition significantly increased when a high performance cyclone was employed, and even when lactose carrier particles were not used. Although the in vitro particle deposition decreased when the storage relative humidity increased, the developed SD powders showed adequate characteristics to be administered by inhalatory route up to storage relative humidities of about 60%. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Titrimetric, spectrophotometric and kinetic methods for the assay of atenolol using bromate–bromide and methyl orange

    Directory of Open Access Journals (Sweden)

    KANAKAPURA BASAVAIAH

    2006-05-01

    Full Text Available Three new methods have been developed for the determination of atenolol in bulk drug and in tablet formulation. The methods are based on the oxidation–bromination reaction of the drug by bromine, generated in situ by the action of acid on a bromate–bromide mixture. In the titrimetric method, the drug is treated with a known excess of bromate–bromide mixture in hydrochloric acid medium, followed by the determination of the unreacted bromine iodometrically. The spectrophotometric method involves the addition of a measured excess of bromate–bromide reagent in hydrochloric acid medium to atenolol, and after ensuring the reaction had gone to completion, the unreacted bromine is treated with a fixed amount of methyl orange, and absorbance measured at 520 nm. The absorbance was found to increase linearly with increasing concentration of atenolol. The kinetic method depends on the existence of a linear relationship between the concentration of the drug and the time of the oxidation–bromination reaction, as indicated by the bleaching of methyl orange acid colour. The working conditions were optimized. The titrimetric method is based on a 1:1 reaction stoichiometry (atenolol:bromate and is applicable over the 3–20 mg range. The spectrophotometric method permits micro determination of the drug (0.5–4.0 mg ml-1with an apparentmolar absorptivity of 4.13x104 lmol-1 cm-1 and detection limit of 0.07 mg ml-1. The kinetic method is applicable in the concentration range 5–25 mg ml-1 with a detection limit of 3.72 mg ml-1. The proposed methods were successfully applied to the determination of atenolol in tablet preparations with mean recoveries of 97.63 to 101.78 %. The reliability of the assay was established by parallel determination by the reference method and by recovery studies using the standard addition technique.

  4. Photochemical degradation of atenolol, carbamazepine, meprobamate, phenytoin and primidone in wastewater effluents

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Mei Mei [Civil, Environmental and Architectural Engineering, 428 UCB, University of Colorado, Boulder, CO 80309 (United States); Southern Nevada Water Authority (SNWA), P.O. Box 99954, Las Vegas, NV 89193-9954 (United States); Trenholm, Rebecca [Southern Nevada Water Authority (SNWA), P.O. Box 99954, Las Vegas, NV 89193-9954 (United States); Rosario-Ortiz, Fernando L., E-mail: Fernando.rosario@colorado.edu [Civil, Environmental and Architectural Engineering, 428 UCB, University of Colorado, Boulder, CO 80309 (United States)

    2015-01-23

    Highlights: • The photochemical degradation of 5 compounds was evaluated in wastewater effluents. • Attenuation by sensitized photolysis was the most important degradation pathway. • Hydroxyl radical accounted for most of the degradation for aliphatic compounds. • Other transient oxidants could also significantly impact the degradation of the compounds. - Abstract: The photochemical degradation of five pharmaceuticals was examined in two secondary wastewater effluents. The compounds, which included atenolol, carbamazepine, meprobamate, phenytoin and primidone, were evaluated for both direct and sensitized photolysis. In the two wastewaters, direct photolysis did not lead to significant compound degradation; however, sensitized photolysis was an important removal pathway for the five pharmaceuticals. Upon solar irradiation, hydroxyl radical (HO·) was quantified using the hydroxylation of benzene and singlet oxygen ({sup 1}O{sub 2}) formation was monitored following the degradation of furfuryl alcohol. Degradation via sensitized photolysis was observed following five-day exposures for atenolol (69–91%), carbamazepine (67–98%), meprobamate (16–52%), phenytoin (44–85%), and primidone (34–88%). Varying removal is likely a result of the differences in reactivity with transient oxidants. Averaged steady state HO· concentrations ranged from 1.2 to 4.0 × 10{sup −16} M, whereas the concentrations of {sup 1}O{sub 2} were 6.0–7.6 × 10{sup −14} M. Partial removal due to presence of HO· indicates it was not the major sink for most compounds examined. Other transient oxidants, such as {sup 1}O{sub 2} and triplet state effluent organic matter, are likely to play important roles in fates of these compounds.

  5. Photoreactivity of hydroxylated multi-walled carbon nanotubes and its effects on the photodegradation of atenolol in water.

    Science.gov (United States)

    Zhang, Ya; Zhou, Lei; Zeng, Chao; Wang, Qi; Wang, Zunyao; Gao, Shixiang; Ji, Yuefei; Yang, Xi

    2013-11-01

    In spite of the increasing concerns about the fate of pharmaceuticals and personal care products (PPCPs) and the nanomaterial pollution in aquatic ecosystem, the effects of carbon nanotubes on the photochemical transformation of PPCPs are less considered. In this study, the photochemical production of reactive oxygen species (ROS) were examined in colloidal dispersions of hydroxylated multi-walled carbon nanotubes (MWNT-OH) under simulated solar irradiation using a Xenon lamp. Two kinds of ROS, (1)O2 and OH, were confirmed by their molecular probes, furfuryl alcohol (FFA) and p-chlorobenzoic acid (PCBA). The steady-state concentrations of (1)O2 and OH were calculated as 1.30×10(-14) M and 5.02×10(-16) M, respectively. The effects of MWNT-OH on photodegradation of atenolol (ATL) were investigated in the presence of natural water components, i.e., dissolved organic matters (DOMs), nitrate (NO3(-)) and ferric ions (Fe(3+)). Photoproducts of atenolol were identified by solid phase extraction-liquid chromatography-mass spectrometry (SPE-LC-MS) analysis techniques. Three potential photochemical pathways of atenolol, including the hydroxylation on aromatic ring, the loss of amide group and the cleavage of ether oxygen bond as well as di-polymerization of reaction intermediates were tentatively proposed. Using the radical quenching method, reaction with OH was determined as the major photolysis pathway of atenolol in irradiated MWNT-OH suspensions. These findings of the production of ROS and their effects on the photodegradation of organic contaminants provided useful information for assessing environmental risk of MWNT-OH. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Hypertension on Target with TENORMIN (HOTT) Study-Evaluation of the Effectiveness and Safety of Atenolol in Indian Population

    OpenAIRE

    Qayum Mukaddam; Manoj M Naik; Abhijit Trailokya

    2014-01-01

    Background: Atenolol is a widely used anti-hypertensive drug worldwide. Despite well-studied from other population, due to the paucity of data from Indians, this study was conducted. Materials and Methods: This was a prospective cohort study conducted in 566 tertiary care hospitals in India. Adult male or female naïve patients with Stage I 1 or Stage II 2 (Seventh Report of the Joint National Committee) essential hypertension or patients uncontrolled on current monotherapy or other combinatio...

  7. The role of dissolved organic matters in the aquatic photodegradation of atenolol

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Chao; Ji, Yuefei; Zhou, Lei; Zhang, Ya [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210046 (China); Yang, Xi, E-mail: yangxi@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210046 (China)

    2012-11-15

    Highlights: Black-Right-Pointing-Pointer The main reactive species in the photosensitization between atenolol and DOMs is {center_dot}OH. Black-Right-Pointing-Pointer Dissolved organic matter (DOM) can quench {center_dot}OH and screen light. Black-Right-Pointing-Pointer High yield of {center_dot}OH was observed with iron ions and DOM coexisting under irradiation. Black-Right-Pointing-Pointer SRFA can promote addition of {center_dot}OH on aromatic ring. - Abstract: Atenolol (ATL) is a photostable and hydrolysis resistant beta-blocker and has been frequently detected in natural water. In this study, mechanism on aquatic photodegradation of ATL was investigated with an emphasis on the role of dissolved organic matters (DOMs) as well as other natural water compositions (nitrate, bicarbonate and ferric ions). Significant acceleration of photodegradtion of ATL was observed in the presence of each DOMs added, namely Suwannee River Fulvic Acid (SRFA), Suwannee River Humic Acid (SRHA), Nordic Lake Fulvic Acid (NOFA) and Nordic Lake Humic Acid (NOHA). Hydroxyl radical ({center_dot}OH) was determined as the main reactive species in this process, instead of singlet oxygen or excited triplet of DOM. Addition of these four DOMs all inhibited photodegradation of ATL in nitrate solutions through reducing nitrated-derived {center_dot}OH and screening photons absorbed by nitrate. No loss of ATL was detected in bicarbonate solution with or without DOMs. Bicarbonate exhibited a scavenger of {center_dot}OH derived from DOMs. However, in the presence of iron species, photodegradation of ATL was significantly enhanced by the addition of each DOM, due to the high yield of {center_dot}OH in the photoprocess of Fe(III)-DOM complex. The photoproducts distribution of ATL demonstrated that SRFA promote the hydroxylation on aromatic ring in the presence of nitrate and reduce the ketone moiety to alcohol in the system of ferric ions. Our findings indicate that DOMs should be considered in

  8. Formulation and evaluation of mouth disintegrating tablets of atenolol and atorvastatin.

    Science.gov (United States)

    Sarfraz, R M; Khan, H U; Mahmood, A; Ahmad, M; Maheen, S; Sher, M

    2015-01-01

    In this study, mouth-disintegrating tablets of atenolol and atorvastatin combination were formulated using superdisintegrants to impart fast disintegration. Fifteen formulations were prepared based on different concentrations of two superdisintegrants, croscarmellose sodium and Kyron-T134. Three different techniques such as direct compression, effervescent and sublimation were used to study the effect of manufacturing processes, nature and concentration of superdisintegrants on various features of these tablets. Five formulations were made using each method. Precompression studies like bulk density, tapped density, angle of repose, Carr's compressibility index, Hausner's ratio and compatibility studies such as Fourier transform infrared spectroscopy and differential scanning calorimetry were performed. Various features such as hardness, thickness, diameter, weight variation, friability, disintegration time, dissolution studies, wetting time, wetting volume, water absorption ratio, modified disintegration, uniformity of contents and stability were evaluated. Finally results were statistically analyzed by the application of one way ANOVA test. Formulation F13 containing Kyron-T134 (6%) and croscarmellose sodium (2%) was found to be the best among all fifteen formulations prepared in all aspects evaluated. Sublimation method is found to be the best among three methods of preparation used.

  9. Formulation and Evaluation of Mouth Disintegrating Tablets of Atenolol and Atorvastatin

    Science.gov (United States)

    Sarfraz, R. M.; Khan, H. U.; Mahmood, A.; Ahmad, M.; Maheen, S.; Sher, M.

    2015-01-01

    In this study, mouth-disintegrating tablets of atenolol and atorvastatin combination were formulated using superdisintegrants to impart fast disintegration. Fifteen formulations were prepared based on different concentrations of two superdisintegrants, croscarmellose sodium and Kyron-T134. Three different techniques such as direct compression, effervescent and sublimation were used to study the effect of manufacturing processes, nature and concentration of superdisintegrants on various features of these tablets. Five formulations were made using each method. Precompression studies like bulk density, tapped density, angle of repose, Carr's compressibility index, Hausner's ratio and compatibility studies such as Fourier transform infrared spectroscopy and differential scanning calorimetry were performed. Various features such as hardness, thickness, diameter, weight variation, friability, disintegration time, dissolution studies, wetting time, wetting volume, water absorption ratio, modified disintegration, uniformity of contents and stability were evaluated. Finally results were statistically analyzed by the application of one way ANOVA test. Formulation F13 containing Kyron-T134 (6%) and croscarmellose sodium (2%) was found to be the best among all fifteen formulations prepared in all aspects evaluated. Sublimation method is found to be the best among three methods of preparation used. PMID:25767322

  10. H2Ti3O7 Nanotubes Decorated with Silver Nanoparticles for Photocatalytic Degradation of Atenolol

    Directory of Open Access Journals (Sweden)

    Mariana Hinojosa-Reyes

    2017-01-01

    Full Text Available The photocatalytic degradation/adsorption process of the β-blocker atenolol (ATL under UV irradiation is described using two types of silver decorated catalysts: silver/titania and silver/titanates. The silver ions were reduced on the surface of TiO2-P25-Degussa using gallic acid. Silver/titanates were prepared by a microwave-assisted hydrothermal method using the silver/titania as the starting material to obtain the hydrogen titanate (H2Ti3O7 structure with tubular morphology. These materials were characterized by X-ray diffraction, UV-Vis spectroscopy, N2 physisorption, temperature programmed reduction, TEM, and FTIR spectroscopy. During the photocatalytic process, the ATL molecules were completely converted to amino-diol byproducts. It is the first time that these materials have been applied during the photocatalytic process in the degradation of pharmaceuticals products. The success of the silver nanoparticles (2 nm consists of the homogeneous distribution over the surface of titanate nanotubes inhibiting the hole/electron recombination promoting the oxidation process. The Ag@H2Ti3O7 with a concentration of silver as 1.0% shows the highest adsorption/degradation of ATL than the Ag@TiO2 and the P25-Degussa. The great performance in the reuse test consists in the strong attachment of the silver nanoparticles on the titanium surface that inhibits the silver lixiviation during the photocatalytic tests.

  11. COMPARISON OF NEBIVOLOL AND ATENOLOL ON BLOOD PRESSURE, BLOOD SUGAR AND LIPID PROFILE IN PATIENTS WITH ESSENTIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    Anand Dev

    2016-08-01

    Full Text Available BACKGROUND Beta-blocker is considered to be a very effective antihypertensive drug to control hypertension. But National Institute for Health and Clinical Excellence (NICE recommended that it should no longer be used as first-line drug as the treatment of uncomplicated hypertension. This recommendation was based on the various studies showing increased risk of new onset Diabetes Mellitus and derangement of lipid metabolism with the use of beta-blocker. These studies were mainly based on Atenolol with or without diuretics. We are in need of a beta-blocker that has effective antihypertensive properties without altering the metabolic profile like blood sugar level and lipid metabolism. Nebivolol, a b1-selective blocker, has got more or less the similar properties. It increases insulin sensitivity in patients with insulin resistance due to its vasodilator properties. Also, antioxidant properties of nebivolol, and increase in nitric oxide properties by reducing its oxidative inactivation may be responsible for beneficial lipid and carbohydrate metabolic profile. MATERIALS AND METHOD A prospective study was conducted between December 2011 to August 2013 on 60 patients at medicine outpatient department (OPD of Katihar Medical College, Katihar, after getting approval from the Institutional Ethics Committee. The patients meeting the inclusion criteria were explained in detail about the nature of the trial, its purpose, procedures, and followup. They were provided with detailed trial information sheet. Written informed consent was obtained from those who volunteered to participate in the trial. RESULTS In our study, the mean difference of systolic blood pressure from baseline and at 24 weeks was 40.20±1.74 in the Atenolol group and 43.80±1.405 in the Nebivolol group. Similarly, in Atenolol group, diastolic blood pressure is decreased by 17±1.3 and 19.4±1.223 in Nebivolol group. In our study, the mean difference of blood sugar level from baseline and

  12. Implication of different initial beta blockers on treatment persistence: atenolol vs new-generation beta blocker, a population-based study.

    Science.gov (United States)

    Choi, Yun Jung; Ah, Young-Mi; Kong, Jisun; Choi, Kyung Hee; Kim, Baegeum; Han, Nayoung; Yu, Yun Mi; Oh, Jung Mi; Shin, Wan Gyoon; Lee, Hae-Young; Lee, Ju-Yeun

    2016-08-01

    Potential heterogeneity within the same class of drug in terms of persistence may lead to different clinical implications. Given that the increased risks of mortality and cardiovascular events are due, in part, to the lack of persistent use of antihypertensive medications, the objective of this study was to evaluate 1-year persistence of new-generation beta blockers compared to atenolol in antihypertensive treatment-naïve patients. A total of 9978 patients aged 18 years or older with hypertension newly diagnosed in 2012, without hypertension-related complication and initiated treatment with beta blocker monotherapy during 2012 were included in the analysis. Rate and duration of treatment and drug persistence were compared between atenolol and new-generation beta blockers. Hazards of discontinuation in nonatenolol compared to atenolol were evaluated using a multivariate Cox proportional model. The rate of treatment persistence was higher in the nonatenolol group (57.35% vs 53.40%, PNew-generation beta blockers demonstrated a lower risk of treatment discontinuation (HR: 0.91, 95% CI: 0.86-0.96) compared to atenolol; a notable improvement was observed with carvedilol and nebivolol (HR: 0.74, 95% CI: 0.69-0.80 and HR: 0.79, 95% CI: 0.70-0.89, respectively), whereas betaxolol showed a substantially greater hazard for discontinuation compared to atenolol. This study demonstrated a meaningful improvement in treatment persistence with new-generation beta blockers compared to atenolol, with betaxolol as exception. © 2016 John Wiley & Sons Ltd.

  13. The effect of atenolol on NT-proBNP and troponin in asymptomatic cats with severe left ventricular hypertrophy because of hypertrophic cardiomyopathy: a pilot study.

    Science.gov (United States)

    Jung, S W; Kittleson, M D

    2011-01-01

    Atenolol often is used empirically in cats with hypertrophic cardiomyopathy (HCM) before the onset of heart failure, although evidence of efficacy is lacking. Cardiac biomarkers play a critical role in the early detection of subclinical cardiac disease, in the prediction of long-term prognosis, and in monitoring the response to therapy in humans. Circulating concentrations of the biomarkers N-terminal pro-B type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) will decrease after chronic administration of atenolol PO to cats with severe HCM but no signs of heart failure. Six Maine Coon or Maine Coon cross cats with severe HCM. Cats were treated with atenolol (12.5 mg PO q12 h) for 30 days. No cat had left ventricular dynamic outflow tract obstruction caused by systolic anterior motion of the mitral valve. The concentrations of NT-proBNP and cTnI were assayed before and on the last day of drug administration. There was no statistically significant change in NT-proBNP (median before, 394 pmol/L; range, 71-1,500 pmol/L; median after, 439 pmol/L; range, 24-1,500 pmol/L; P = .63) or in cTnI (median before, 0.24 ng/mL; range, 0.10-0.97 ng/mL; median after, 0.28 ng/mL; range, 0.09-1.0 ng/mL; P = .69) after administration of atenolol. Atenolol administration did not decrease NT-proBNP or cTnI concentrations in cats with severe left ventricular hypertrophy caused by hypertrophic cardiomyopathy. These results suggest that atenolol did not decrease myocardial ischemia and myocyte death in these cats. A larger clinical trial is warranted to verify these findings. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  14. Interaction of PEGylated anti-hypertensive drugs, amlodipine, atenolol and lisinopril with lipid bilayer membrane: A molecular dynamics simulation study.

    Science.gov (United States)

    Yousefpour, Abbas; Modarress, Hamid; Goharpey, Fatemeh; Amjad-Iranagh, Sepideh

    2015-08-01

    The interaction of PEGylated anti-hypertensive drugs, amlodipine, atenolol and lisinopril with lipid bilayer membrane dimyristoylphosphatidylcholine (DMPC) has been studied in nine different simulation systems consisting of 128 lipid molecules and appropriate number of water molecules by molecular dynamics method and by utilizing GROMACS software. The influences of PEGylation on the mentioned drugs and the differences in application of two types of spacer molecules on the performance of drugs and DMPC membrane have been evaluated and mass density of the components in the simulation box, mean square displacement (MSD), electrostatic potential, hydrogen bonding, radial distribution function (RDF), area per lipid, order parameter, and angle distribution of the component molecules including drug, DMPC and PEG has been investigated. Furthermore, umbrella sampling analysis indicated that, PEGylation of the drugs made amlodipine to behave more hydrophilic, whereas in case of lisinopril and atenolol, PEGylation made these drugs to behave more hydrophobic. In almost all of the simulated systems, PEGylation increased the diffusion coefficient of the drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Investigation of Biowaivers for Immediate Release Formulations Containing BCS III Drugs, Acyclovir, Atenolol, and Ciprofloxacin Hydrochloride, Using Dissolution Testing.

    Science.gov (United States)

    Reddy, Nallagundla H S; Patnala, Srinivas; Kanfer, Isadore

    2017-02-01

    The dissolution of several products containing Biopharmaceutical Classification System (BCS) class III drugs, acyclovir, atenolol, and ciprofloxacin hydrochloride, listed in the WHO essential drug list (EDL), was tested and compared with their respective comparator pharmaceutical products (CPPs) marketed in South Africa and India. US Pharmacopeia (USP) buffers of pH 1.2, 4.5, and 6.8 were used as dissolution media and tested using USP apparatus 2 at 75 rpm and 900 ml. Nine acyclovir products were tested, and only three dissolved very rapidly in all media; i.e., they showed a release of >85% in 15 min. Eight atenolol products tested were all very rapidly dissolving in all three pH media. Ten ciprofloxacin hydrochloride products were tested, and the results showed that only five products met the WHO biowaiver criteria. This study indicates that not all marketed products containing the same BCS III active pharmaceutical ingredient (API) in similar strength and dosage form are necessarily in vitro equivalent as per the WHO biowaiver criteria. Furthermore, selection and availability of an innovator product as CPP are important considerations that can affect the outcomes of such studies.

  16. A Localized Surface Plasmon Resonance Sensing Method for Simultaneous Determination of Atenolol and Amiloride in Pharmaceutical Dosage Forms and Urine Samples

    Directory of Open Access Journals (Sweden)

    Marwa R. El-Zahry

    2018-01-01

    Full Text Available This contribution describes a simple, fast, and sensitive application of localized surface plasmon resonance effect of silver nanoparticles for simultaneous determination of antihypertensive drugs’ mixture atenolol and amiloride in both pharmaceutical dosage forms and in biological samples (urine. Silver nanoparticles were prepared by chemical reduction of silver nitrate using hydroxylamine HCL in an alkaline medium. Application of silver-hydroxylamine nanoparticles (SH NPs provides many advantages including reproducibility, sensitivity, and cost effective way of analyte determination. Amiloride has four amino groups which act as attachment points on the surface of silver nanoparticles resulting in a synergistic effect on the absorption intensity of atenolol, leading to increase the sensitivity of the determination of both compounds. This method shows excellent advantages comparing with the previously reported methods, including accuracy, precision, and selectivity. The linear range of atenolol is 1 × 10−5–1 × 10−4 mol·L−1 and of amiloride is 1 × 10−6–1 × 10−5 mol·L−1. The limit of detection (LOD values of atenolol and amiloride are 0.89 × 10−5 and 0.42 × 10−6 mol·L−1, respectively.

  17. Characteristics of children and young adults with Marfan syndrome and aortic root dilation in a randomized trial comparing atenolol and losartan therapy

    NARCIS (Netherlands)

    Lacro, R.V.; Guey, L.T.; Dietz, H.C.; Pearson, G.D.; Yetman, A.T.; Gelb, B.D.; Loeys, B.L.; Benson, D.W.; Bradley, T.J.; Backer, J. de; Forbus, G.A.; Klein, G.L.; Lai, W.W.; Levine, J.C.; Lewin, M.B.; Markham, L.W.; Paridon, S.M.; Pierpont, M.E.; Radojewski, E.; Selamet Tierney, E.S.; Sharkey, A.M.; Wechsler, S.B.; Mahony, L.

    2013-01-01

    BACKGROUND: The Pediatric Heart Network designed a clinical trial to compare aortic root growth and other short-term cardiovascular outcomes in children and young adults with Marfan syndrome randomized to receive atenolol or losartan. We report here the characteristics of the screened population and

  18. Lifelong treatment with atenolol decreases membrane fatty acid unsaturation and oxidative stress in heart and skeletal muscle mitochondria and improves immunity and behavior, without changing mice longevity

    Science.gov (United States)

    Gómez, Alexia; Sánchez-Roman, Ines; Gomez, Jose; Cruces, Julia; Mate, Ianire; Lopez-Torres, Mónica; Naudi, Alba; Portero-Otin, Manuel; Pamplona, Reinald; De la Fuente, Monica; Barja, Gustavo

    2014-01-01

    The membrane fatty acid unsaturation hypothesis of aging and longevity is experimentally tested for the first time in mammals. Lifelong treatment of mice with the β1-blocker atenolol increased the amount of the extracellular-signal-regulated kinase signaling protein and successfully decreased one of the two traits appropriately correlating with animal longevity, the membrane fatty acid unsaturation degree of cardiac and skeletal muscle mitochondria, changing their lipid profile toward that present in much more longer-lived mammals. This was mainly due to decreases in 22:6n-3 and increases in 18:1n-9 fatty acids. The atenolol treatment also lowered visceral adiposity (by 24%), decreased mitochondrial protein oxidative, glycoxidative, and lipoxidative damage in both organs, and lowered oxidative damage in heart mitochondrial DNA. Atenolol also improved various immune (chemotaxis and natural killer activities) and behavioral functions (equilibrium, motor coordination, and muscular vigor). It also totally or partially prevented the aging-related detrimental changes observed in mitochondrial membrane unsaturation, protein oxidative modifications, and immune and behavioral functions, without changing longevity. The controls reached 3.93 years of age, a substantially higher maximum longevity than the best previously described for this strain (3.0 years). Side effects of the drug could have masked a likely lowering of the endogenous aging rate induced by the decrease in membrane fatty acid unsaturation. We conclude that it is atenolol that failed to increase longevity, and likely not the decrease in membrane unsaturation induced by the drug. PMID:24612513

  19. COMPARISON OF THE SAFETY AND EFFICACY OF BISOPROLOL VERSUS ATENOLOL IN STABLE EXERCISE-INDUCED ANGINA-PECTORIS - A MULTICENTER INTERNATIONAL RANDOMIZED STUDY OF ANGINA-PECTORIS (MIRSA)

    NARCIS (Netherlands)

    DEMUINCK, ED; BUCHNERMOELL, D; VANDEVEN, LLM; LIE, KI

    Bisoprolol 10 mg and atenolol 100 mg once daily were compared regarding efficacy and safety in stable effort angina in a 12-week, multicenter, double-blind, randomized, parallel-group study. Efficacy was evaluated with angina pectoris diaries and bicycle exercise tests. Spontaneously mentioned

  20. The effect on heart rate of combining single-dose fingolimod with steady-state atenolol or diltiazem in healthy subjects.

    Science.gov (United States)

    Kovarik, John M; Lu, Michael; Riviere, Gilles-Jacques; Barbet, Irene; Maton, Steve; Goldwater, D Ronald; Schmouder, Robert L

    2008-05-01

    The sphingosine-1-phosphate receptor modulator fingolimod (FTY720) is known to elicit a negative chronotropic effect at treatment initiation that attenuates over time with continued dosing. The authors determined the effect of combining a single dose of fingolimod with steady-state atenolol or diltiazem on heart rate and mean arterial pressure. In a partially randomized, single-blind, placebo-controlled, three-period, crossover study, 25 healthy subjects received (1) a single oral 5-mg dose of fingolimod, (2) either 50 mg atenolol or 240 mg diltiazem once daily for 5 days, and (3) the antihypertensive for 5 days and a single dose of fingolimod on day 5. Telemetry and pharmacokinetic data were collected. The daytime mean heart rate nadir was 15% lower when fingolimod was combined with atenolol (42 +/- 7 bpm) compared with fingolimod alone (51 +/- 9 bpm) yielding a combination/monotherapy ratio of 0.85 (90%CI, 0.79-0.92). The daytime mean heart rate nadir from fingolimod alone (55 +/- 5 bpm) was not altered when combined with diltiazem (56 +/- 8 bpm) yielding a ratio of 0.99 (0.94-1.05). There was no clinically relevant change in mean arterial pressure when fingolimod was administered with atenolol or diltiazem compared with administration of the drugs alone in normotensive subjects. The pharmacokinetics of the drugs were not altered during coadministration. Adding fingolimod to a beta-blocker such as atenolol resulted in a moderately lower mean heart rate nadir compared with fingolimod alone. However, subjects who had a stronger negative chronotropic response to fingolimod alone (nadir < 50 bpm) had minimal or no further reduction in heart rate with the drug combination. Adding fingolimod to a calcium channel blocker such as diltiazem did not further lower the heart rate compared to fingolimod alone.

  1. Avaliação do teor de Atenolol em comprimidos divididos com faca caseira e aparelho cortador Evaluación de la proporción de Atenolol en comprimidos divididos con cuchillo casero y con cortador Evaluation of the content of Atenolol tablets divided with a knife and homemade machine cutter

    Directory of Open Access Journals (Sweden)

    Mariangela Tirico Auricchio

    2011-01-01

    Full Text Available OBJETIVO: Avaliar se o teor de Atenolol em fragmentos de comprimidos nas dosagens de 100 mg, 50 mg e 25 mg partidos em duas e quatro partes com auxílio de faca caseira e de aparelho cortador de comprimidos é diferente em função do modo como a divisão é realizada. MÉTODOS: Os comprimidos íntegros foram divididos com faca caseira e com aparelho cortador de comprimidos, e os teores de Atenolol foram determinados em todos os fragmentos. RESULTADOS: Não houve diferença significativa entre os teores obtidos, após divisão dos comprimidos com faca caseira ou com aparelho cortador, apesar da divisão levar a acentuada dispersão dos teores entre os fragmentos, na divisão em metade, a dispersão dos resultados deu-se entre 7,8% e 12,1%, e quando divididos em quatro partes, foi entre 9,2% e 21,1%, indicando a possibilidade de comprometer a eficácia do tratamento dos pacientes independente de como a divisão foi feita. CONCLUSÃO: Os resultados indicaram a ocorrência de dispersão maior do que a estabelecida para garantir uniformidade da dose recebida a cada administração do medicamento independente da forma de realizar a divisão, seja por meio de faca caseira ou com aparelho cortador de comprimidos.OBJETIVO: Evaluar si la proporción de Atenolol en fragmentos de comprimidos en las dosis de 100 mg, 50 mg y 25 mg partidos en dos y cuatro partes con la ayuda de un cuchillo casero y de un cortador de comprimidos es diferente en función al modo cómo se realiza la división. MÉTODOS: Los comprimidos enteros fueron divididos con un cuchillo casero y con un cortador de comprimidos, siendo determinadas las proporciones de Atenolol en todos los fragmentos. RESULTADOS: No hubo diferencia significativa entre las proporciones obtenidas, después de la división de los comprimidos tanto con cuchillo casero como con el cortador. A pesar de que la división lleve una acentuada dispersión de las proporciones entre los fragmentos, en la división por

  2. Disposição cinética do atenolol em pacientes coronarianos submetidos a revascularização do miocárdio Kinetic disposition of atenolol in coronary patients submitted to the CABG surgery

    Directory of Open Access Journals (Sweden)

    Fátima da Silva Leite

    2006-06-01

    Full Text Available A isquemia miocárdica é um importante fator de risco para a mortalidade e eventos cardiovasculares no perioperatório de cirurgias cardíacas e não-cardíacas, sendo que a administração profilática de beta-bloqueadores nesse período, reduz estes riscos. Sabe-se que alterações fisiológicas ocorridas durante a cirurgia de revascularização do miocárdio (RM com circulação extracorpórea (CEC podem afetar as concentrações plasmáticas e a cinética de muitos fármacos. Neste estudo, investigou-se a farmacocinética do atenolol em pacientes com angina instável e sem prejuízo renal, submetidos à revascularização com CEC e em terapia crônica com atenolol peroral. O estudo farmacocinético exigiu coleta de amostras sangüíneas seriadas após as doses pré- e pós-operatória. Comparado ao pré-operatório, registrou-se redução não significativa no volume de distribuição e na depuração plasmática após a cirurgia, permanecendo inalterada a meia-vida biológica (p>0,05. Uma correlação linear negativa entre meia-vida e depuração pode ser estabelecida nos dois períodos do estudo (r: -0,77, p= 0,06 no pré-operatório e r: -0,89, p= 0,06 no pós-operatório, enquanto que se estimou correlação linear direta entre volume de distribuição e meia-vida biológica apenas no pré-cirúrgico (r: 0,54, p= 0,03 no pré-operatório e r: 0,09, p= 0,03 no pós-operatório. Conclui-se que a cirurgia de revascularização auxilia no restabelecimento da extensão da distribuição do atenolol.Myocardium ischemia is an important factor of risk for mortality and cardiovascular events in the perioperative period of cardiac and non cardiac surgeries. However, the prophylactic administration of beta-blocker agents could reduce these risks. Physiologic changes, occurred during the coronary artery bypass graft (CABG surgery with cardiopulmonary bypass (CPB, could alter plasma concentration and pharmacokinetics of many drugs. This study

  3. Hypertension on Target with TENORMIN (HOTT Study-Evaluation of the Effectiveness and Safety of Atenolol in Indian Population

    Directory of Open Access Journals (Sweden)

    Qayum Mukaddam

    2014-01-01

    Full Text Available Background: Atenolol is a widely used anti-hypertensive drug worldwide. Despite well-studied from other population, due to the paucity of data from Indians, this study was conducted. Materials and Methods: This was a prospective cohort study conducted in 566 tertiary care hospitals in India. Adult male or female naïve patients with Stage I 1 or Stage II 2 (Seventh Report of the Joint National Committee essential hypertension or patients uncontrolled on current monotherapy or other combination therapy. Demographic details, blood pressure and heart rate readings (weeks 2, 8, and 12 and drug-related details of the study participants were collected and analyzed. Results: A total of 2657 participants were evaluated. The mean (standard deviation [SD] baseline systolic and diastolic blood pressure of the study participants were 161.73 (15.13 and 99.21 (11.37, respectively. Mean (SD of the baseline heart rate was 84.39 (10.17 beats/min. Statistically significant reductions (P < 0.05 were noted in both the blood pressures and heart rate at all the follow-up visits in comparison to baseline. Of the total 632 patients with Stage I hypertension, 153 (24.21% achieved a reduction in blood pressure <120/80 mmHg, while 245 (38.77% had their blood pressure between 121 and 140 mmHg systolic and/or 81-90 mmHg diastolic at 12 weeks of therapy. Global assessment of the efficacy and tolerability were found to be at least satisfactory in the majority of the study participants. Conclusion: To conclude, atenolol as an anti-hypertensive agent seems to be promising both in terms of effectiveness and safety profile in the Indian population.

  4. Effects of Atenolol on Growth Performance, Mortality Due to Ascites, Antioxidant Status and Some Blood Parameters in Broilers under Induced Ascites

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    mokhtar fathi

    2016-11-01

    Full Text Available Introduction Broiler chickens are intensively selected for productive traits. The management of these highly productive animals must be optimal to allow their full genetic potential to be expressed. If this is not done, inefficient production and several metabolic diseases such as ascites become apparent. Investigations in mammals indicated that the b- adrenoreceptor characteristics are differentially regulated by chronic hypoxia and play an important role in the cardiovascular system. The density of b-adrenergic receptors was higher in cardiac cells of ascites sensitive birds compared with ascites-resistant ones. Moreover, the characteristics of b-adreno receptors are different in cardiac cells of birds with right ventricular hypertrophy and heart failure compared with healthy birds. Treatment with the selective b1-adrenoceptor blocker, atenolol, abolished right ventricular hypertrophy in response to hypoxia compared with normoxic condition in rats. Materials and Methods This study investigated the comparative effects of different levels of atenolol Growth performance, Mortality due to ascites, antioxidant status and blood parameters in broilers under induced ascites. Six hundred one-day-old male broilers (Ross 308 in a completely randomized experimental design with four treatments (Positive control, negative control, and two levels of 30 and 60 ppm atenolol with five replicates of thirty birds were applied. Birds in positive control were reared in natural temperature without atenolol, the other bird groups were reared in cold temperature with 0, 30 and 60 ppm atenolol. The average daily feed intake (ADFI, average daily weight gain (ADWG and feed conversion ratio (FCR for each group of birds were calculated and mortality was daily weighed, recorded and used to correct the FCR. Observations were made daily to record the incidence of ascites and mortality. Diagnosis of ascites generally depends on observation of the following symptoms: (1 right

  5. Desarrollo y validacion de un metodo rapido por cromatografia liquida de alta resolucion con inyeccion directa de la muestra para la determinacion de atenolol, propranolol y carvedilol en plasma humano

    National Research Council Canada - National Science Library

    del Rosario Brunetto, Maria; Clavijo, Sabrina; Delgado, Yelitza; Orozco, Wendy; Ayala, Carlos; Gallignani, Maximo; Calderon-Gonzalez, Laura

    2011-01-01

    En el presente trabajo se desarrollo un metodo automatizado y robusto para la determinacion simultanea de atenolol, propranolol y carvedilol en muestras de plasma humano por cromatografia liquida de alta resolucion (CLAR...

  6. Factors screening to statistical experimental design of racemic atenolol kinetic resolution via transesterification reaction in organic solvent using free Pseudomonas fluorescens lipase.

    Science.gov (United States)

    Agustian, Joni; Kamaruddin, Azlina Harun; Aboul-Enein, Hassan Y

    2017-07-01

    As the (R)-enantiomer of racemic atenolol has no β-blocking activity and no lack of side effects, switching from the racemate to the (S)-atenolol is more favorable. Transesterification of racemic atenolol using free enzymes investigated as a resource to resolve the racemate via this method is limited. Screenings of enzyme, medium, and acetyl donor were conducted first to give Pseudomonas fluorescens lipase, tetrahydrofuran, and vinyl acetate. A statistical design of the experiment was then developed using Central Composite Design on some operational factors, which resulted in the conversions of 11.70-61.91% and substrate enantiomeric excess (ee) of 7.31-100%. The quadratic models are acceptable with R 2 of 95.13% (conversion) and 89.63% (ee). The predicted values match the observed values reasonably well. Temperature, agitation speed, and substrate molar ratio factor have low effects on conversion and ee, but enzyme loading affects the responses highly. The interaction of temperature-agitation speed and temperature-substrate molar ratio show significant effects on conversion, while temperature-agitation speed, temperature-substrate molar ratio, and agitation speed-substrate molar ratio affect ee highly. Optimum conditions for the use of Pseudomonas fluorescens lipase, tetrahydrofuran, and vinyl acetate were found at 45°C, 175 rpm, 2000 U, and 1:3.6 substrate molar ratio. © 2017 Wiley Periodicals, Inc.

  7. Application of bromate-bromide mixture as a green brominating agent for the spectrophotometric determination of atenolol in pharmaceuticals

    Directory of Open Access Journals (Sweden)

    Prashanth Nagaraj Kudige

    2012-01-01

    Full Text Available Two highly sensitive spectrophotometric methods are proposed for the quantification of atenolol (ATN in pure drug as well as in pharmaceutical formulations. The methods are based on the bromination reaction of ATN with a known excess of bromate-bromide mixture in acid medium followed by the determination of unreacted bromine. The residual bromine is determined by its reaction with excess iodide and the liberated iodine (I3□ is either measured at 360 nm (method A or reacted with starch followed by the measurement of the starch-iodine chromogen at 570 nm (method B. Under the optimum conditions, ATN could be assayed in the concentration ranges of 0.5-9.0 and 0.3-6.0μg mL-1 for method A and method B, respectively, with corresponding molar absorptivity values of 2.36×104 and 2.89×104 L/mol.cm. Sandell’s sensitivity values are found to be 0.0113 and 0.0092 μg/cm2 for method A and method B, respectively. The proposed methods were successfully applied to the analysis of different commercial brands of pharmaceutical formulations and the results obtained by the proposed methods were in good agreement with those obtained using the reference method. The reliability of the methods was further ascertained by recovery studies using standard- addition method.

  8. Sensitive Spectrophotometric Determination of Atenolol in Pharmaceutical Formulations Using Bromate-Bromide Mixture as an Eco-Friendly Brominating Agent

    Directory of Open Access Journals (Sweden)

    Kudige N. Prashanth

    2012-01-01

    Full Text Available Three simple and sensitive spectrophotometric methods are proposed for the determination of atenolol (ATN in bulk drug and tablets. The methods are based on the bromination of ATN by the bromine generated in situ by the action of the acid on the bromate–bromide mixture followed by the determination of unreacted bromine by reacting with a fixed amount of either meta-cresol purple (MCP and measuring the absorbance at 540 nm (method A and 445 nm (method B or erioglaucine (EGC and measuring the absorbance at 630 nm (method C. Beer's law is valid within the concentration ranges of 1.0–20.0, 2.0–40.0 and 1.0–8.0 μg/mL for method A, method B and method C, respectively. The calculated molar absorptivities were found to be 1.20×104, 4.51×103 and 3.46×104  L/mol⋅cm for method A, method B and method C, respectively. Sandell’s sensitivity values, correlation coefficients, limits of detection and quantification are also reported. Recovery results were statistically compared with those of a reference method by applying Student’s t- and F-test. The novelty of the present study is the measurement of two different colors using MCP, that is, red-pink color of MCP in acid medium at 540 nm and yellowish-orange color of brominated MCP at 445 nm.

  9. Long-term treatment of clonidine, atenolol, amlodipine and dihydrochlorothiazide, but not enalapril, impairs the sexual function in male spontaneously hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Li-Li Lin

    Full Text Available This study was designed to investigate the impact of representative antihypertensive drugs of 5 classes on the sexual function in male spontaneously hypertensive rats (SHR at doses that achieved similar blood pressure (BP reduction. The experiment was performed in 6 groups of male SHR. The dose are 20 μg/kg/day for clonidine, 3 mg/kg/day for enalapril, 20 mg/kg/day for atenolol, 2 mg/kg/day for amlodipine, and 10 mg/kg/day for dihydrochlorothiazide. SHR were treated for 3 months, and then the penile erection and sexual behavior were detected. After BP recording, SHR were killed to evaluate the organ-damage, weight of accessory sex organs and levels of follicle-stimulating hormone (FSH, luteinizing hormone (LH and testosterone in serum. Five drugs had the similar efficacy on BP reduction. All drugs except of enalapril, significantly prolonged the mount latency, and decreased the mount frequency (P<0.05. Clonidine also reduced the conception rate (45% vs. 80% in control group, P<0.05. Amlodipine and dihydrochlorothiazide significantly increased the testosterone level (0.79±0.30, 0.80±0.34 vs. 0.49±0.20 in control group, unit: ng/dl, P<0.05. Enalapril, atenolol and amlodipine also significantly decreased the BP variability (systolic, 8.2±2.5, 7.6±1.8, 8.9±2.0 vs. 12.2±3.8 in control group, unit: mm Hg. All these drugs significantly decreased the organ-damage (P<0.05. In conclusion, long-term treatment with 5 common antihypertensive drugs possessed obvious organ protection in SHR. Clonidine, atenolol, amlodipine and dihydrochlorothiazide, but not enalapril, impair sexual function.

  10. A randomized, double blind pilot study to assess the effects of losartan vs. atenolol on the biophysical properties of the aorta in patients with Marfan and Loeys-Dietz syndromes.

    Science.gov (United States)

    Sandor, George G S; Alghamdi, Mohammed H; Raffin, Leslie A; Potts, Mary T; Williams, Lindsey D; Potts, James E; Kiess, Marla; van Breemen, Casey

    2015-01-20

    Patients with Marfan (MFS) and Loeys-Dietz (LDS) syndromes have been shown to have abnormal aortic biophysical properties. The purpose of this study was to compare the effects of 12-months of therapy with atenolol or losartan on vascular function in young patients with MFS and LDS. Seventeen patients with MFS or LDS were recruited and randomized to treatment with atenolol, 25-50mg, or losartan, 25mg daily. Prior to treatment and following therapy, echocardiography for left ventricular size, function and aortic root size was performed. Pulse wave velocity (PWV), input (Zi, ZiF) and characteristic (Zc, ZcF) impedances, arterial stiffness (Ep and β-index), total arterial compliance (TAC), mean (Wm) and total (Wt) hydraulic power, efficiency, power cost per unit of forward flow (Wt/CI) and brachial artery flow-mediated dilation (FMD) were measured. The atenolol group consisted of 9 females (17.6years) and the losartan group 7 males and 1 female (17.0years). Their height, weight, BSA, BMI, systolic and diastolic blood pressures were similar. Baseline to 12-month changes for atenolol and losartan were PWV (20% vs -14%), Zi (-2% vs -27%), Zc (-20% vs -27%), Ep (1%, vs -13%), β-index (10% vs 14%), FMD (11% vs 20%), TAC (3% vs 42%), Wm (-24% vs 15%), Wt (-24% vs 17%), and Wt/CI (3% vs 21%). There was a trend for losartan to decrease PWV and stiffness indexes while atenolol decreased power and power/unit flow. This pilot study suggests that atenolol and losartan may have different mechanisms of action on vascular function. A larger clinical trial is needed to confirm these effects.Clinical trials registration NCT00593710 (ClinicalTrials.gov). Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Effects of losartan compared with atenolol on lipids in patients with hypertension and left ventricular hypertrophy: the Losartan Intervention For Endpoint reduction in hypertension study

    DEFF Research Database (Denmark)

    Olsen, Michael Hecht; Wachtell, Kristian; Beevers, Gareth

    2009-01-01

    infarction, or stroke. We measured total and high-density lipoprotein cholesterol at baseline and annually during 4.8 years of losartan-based compared with atenolol-based treatment in 8611 patients with hypertension and left ventricular hypertrophy. RESULTS: Patients randomized to losartan-based or atenolol......-based treatment had similar baseline total (6.04 +/- 1.12 vs. 6.05 +/- 1.13 mmol/l, NS) and high-density lipoprotein (HDL) cholesterol (1.50 +/- 0.44 vs. 1.49 +/- 0.44 mmol/l, NS). Total cholesterol decreased significantly but equally (-0.37 +/- 1.05 vs. -0.34 +/- 1.09 mmol/l, NS), whereas HDL cholesterol......OBJECTIVE: Beta-blockers and angiotensin II receptor blockers have different effects on lipids. METHODS: We examined lipid levels in the Losartan Intervention For Endpoint reduction in hypertension study and their impact on the primary composite endpoint of cardiovascular death, myocardial...

  12. Comparative evaluation of atenolol and clonidine premedication on cardiovascular response to nasal speculum insertion during trans-sphenoid surgery for resection of pituitary adenoma: A prospective, randomised, double-blind, controlled study

    Directory of Open Access Journals (Sweden)

    Devendra Gupta

    2011-01-01

    Full Text Available Severe cardiovascular responses in the form of tachycardia and hypertension following nasal speculum insertion occur during sublabial rhinoseptal trans-sphenoid approach for resection of small pituitary tumours. We compare the effects of preoperative administration of clonidine (α-2 agonist and atenolol (α-blocker over haemodynamic response, caused by speculum insertion during trans-sphenoid pituitary resection. We enrolled 66 patients in age range 18-65 years, of ASA I-II, and of either sex undergoing elective sublabial rhinoseptal trans-sphenoidal hypophysectomy. Group I (control received placebo, group II (clonidine received tablet clonidine 5 μg/kg, and group III (atenolol received tablet atenolol 0.5 mg/kg. The heart rate increased on speculum insertion and 5 and 10 minutes following speculum insertion as compared to the pre-speculum values in the control group, while no change in the heart rate was observed in other groups (P<0.05. There was a rise in the mean arterial pressure during and 5, 10, and 15 minutes after nasal speculum insertion in the control group, whereas it was not seen in other groups (P<0.05. We therefore suggest that oral clonidine and oral atenolol (given 2 hours prior to surgery is an equally effective and safe method of attenuating haemodynamic response caused by nasal speculum insertion during trans-sphenoid pituitary resection.

  13. An economic assessment of losartan-based versus atenolol-based therapy in patients with hypertension and left-ventricular hypertrophy : Results from the Losartan Intervention For Endpoint reduction (LIFE) study adapted to The Netherlands

    NARCIS (Netherlands)

    Boersma, Cornelis; Carides, George W.; Atthobari, Jarir; Voors, Adriaan A.; Postma, Maarten J.

    Background: The Losartan Intervention For Endpoint reduction (LIFE) study was a randomized, doubleblind trial that compared the effects of losartan-based treatment with those of atenolol-based treatment on cardiovascular disease (CVD)-related morbidity and mortality in 9193 patients with

  14. Efeitos da associação da estimulação atrial dinâmica em duplo sítio atrial com atenolol na prevenção da fibrilação atrial recorrente Effects of the association of dual-site dynamic atrial overdrive and atenolol in preventing recurrent atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Antonio da Silva Menezes Júnior

    2007-01-01

    Full Text Available OBJETIVO: Avaliar os efeitos da estimulação atrial otimizada (EAO (estimulação duplo-sítio atrial, freqüência acima da intrínseca e algoritmo funcional específico e uso de atenolol, na prevenção da fibrilação atrial (FA recorrente. Desfecho primário: quantificar a taxa de episódios de FA. Desfechos secundários: qualidade de vida, avaliação de sintomas específicos cardiovasculares, taxa de internações hospitalares, taxa de cardioversões elétricas e farmacológicas e eventos cardíacos adversos. MÉTODOS: Vinte e sete pacientes com FA paroxística recorrente e doença do nó sinusal foram submetidos ao implante de marcapasso duplo-sítio atrial e ventricular e iniciaram com atenolol 100 mg/dia, a seguir foram randomizados em dois grupos, grupo I (3 meses iniciais com EAO e algoritmo especifico ligado e mais 3 com o mesmo desligado e grupo II (seqüência inversa do grupo I. O modo de estimulação foi DDDR e após 3 meses, foram submetidos à avaliação clínica e eletrônica do sistema de estimulação - mudança automática de modo (AMS, Holter de 24 horas, ecocardiograma e questionário SF-36. Em seguida, foram cruzados e após 6 meses, nova avaliação. RESULTADOS: Pacientes com EAO, quando comparados ao grupo com algoritmo desligado, apresentaram menores taxas de: FA/semana (pOBJECTIVE: Evaluate the effects of optimized atrial stimulation - OAS (dual-site atrial pacing, heart rate above the intrinsic rate, and specific functional algorithm, and the use of atenolol in preventing recurrent atrial fibrillation (AF. Primary endpoint: to quantify the rate of AF episodes. Secondary endpoints: assessment of quality of life, specific cardiovascular symptoms, rate of hospital admissions, rate of electrical and pharmacological cardioversions, and adverse cardiac events. METHODS: Twenty-five patients with recurrent episodes of paroxysmal AF and sinus node disease had dual-site atrial and ventricular pacemakers implanted, and were

  15. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled

    DEFF Research Database (Denmark)

    Dahlöf, Björn; Sever, Peter S; Poulter, Neil R

    2005-01-01

    The apparent shortfall in prevention of coronary heart disease (CHD) noted in early hypertension trials has been attributed to disadvantages of the diuretics and beta blockers used. For a given reduction in blood pressure, some suggested that newer agents would confer advantages over diuretics an...... and beta blockers. Our aim, therefore, was to compare the effect on non-fatal myocardial infarction and fatal CHD of combinations of atenolol with a thiazide versus amlodipine with perindopril....

  16. Polypill for the treatment of cardiovascular diseases part 2. LC-MS/TOF characterization of interaction/degradation products of atenolol/lisinopril and aspirin, and mechanisms of formation thereof.

    Science.gov (United States)

    Kumar, Vijay; Malik, Satish; Singh, Saranjit

    2008-11-04

    A polypill for cardiovascular diseases (CVD) is under development. It is proposed to contain a combination of antithrombotic agent (aspirin), low-dose blood pressure lowering agents, i.e., angiotensin-converting enzyme inhibitor (lisinopril), one among a beta-blocker (atenolol) or diuretic (hydrochlorothiazide), and a statin (simvastatin/atorvastatin/pravatsatin, etc.). Due to the presence of multiple drugs in the same formulation, there is a strong likelihood of interaction among the drugs and/or their products. In a previous study, we observed formation of a number of interaction/degradation products from atenolol and lisinopril in the presence of aspirin. Accordingly, the purpose of this study was to characterize the resolved products using high resolution mass spectrometric and fragmentation analyses using a LC-MS/TOF system. Initially, studies were carried out on the drugs (atenolol, lisinopril and aspirin) to establish their complete fragmentation pattern. These studies were then extended to degraded samples to postulate the structures of interaction/degradation products. The characterized structures were justified through mechanistic explanations.

  17. Degradation of atenolol via heterogeneous activation of persulfate by using BiOCl@Fe3O4catalyst under simulated solar light irradiation.

    Science.gov (United States)

    Shi, Yahong; Chen, Hongche; Wu, Yanlin; Dong, Wenbo

    2018-01-01

    Efficient oxidative degradation of pharmaceutical pollutants in aquatic environments is of great importance. This study used magnetic BiOCl@Fe 3 O 4 catalyst to activate persulfate (PS) under simulated solar light irradiation. This degradation system was evaluated using atenolol (ATL) as target pollutant. Four reactive species were identified in the sunlight/BiOCl@Fe 3 O 4 /PS system. The decreasing order of the contribution of each reactive species on ATL degradation was as follows: h +  ≈ HO ·  > O 2 ·-  > SO 4 ·- . pH significantly influenced ATL degradation, and an acidic condition favored the reaction. High degradation efficiencies were obtained at pH 2.3-5.5. ATL degradation rate increased with increased catalyst and PS contents. Moreover, ATL mineralization was higher in the sunlight/BiOCl@Fe 3 O 4 /PS system than in the sunlight/BiOCl@Fe 3 O 4 or sunlight/PS system. Nine possible intermediate products were identified through LC-MS analysis, and a degradation pathway for ATL was proposed. The BiOCl@Fe 3 O 4 nanomagnetic composite catalyst was synthesized in this work. This catalyst was easily separated and recovered from a treated solution by using a magnet, and it demonstrated a high catalytic activity. Increased amount of the BiOCl@Fe 3 O 4 catalyst obviously accelerated the efficiency of ATL degradation, and the reusability of the catalyst allowed the addition of a large dosage of BiOCl@Fe 3 O 4 to improve the degradation efficiency.

  18. Potential Use of Polyvinyl Acetate-Polyvinylpyrrolidone Mixture for the Development of Atenolol Sustained Release Matrix Tablets: Optimization of Formulation through in Vitro-in Vivo Assessment Study.

    Science.gov (United States)

    Owayez, Ali Saeed; Abd El-Ghany, Galal Mahmoud; Abu Hashim, Irhan Ibrahim

    2017-01-01

    The objective of this study was to develop sustained release matrix tablets of atenolol (AT) using different concentrations of polyvinyl acetate-polyvinylpyrrolidone mixture (KSR) (20, 30, or 40%) with various types of fillers such as spray dried lactose (SP.D.L), avicel pH 101 (AV), and emcompress (EMS). The physical characteristics of the prepared tablets were evaluated. Characterization of the optimized formulation was performed using Fourier transform (FT)-IR spectroscopy and differential scanning calorimetry (DSC). Moreover, the in vitro release profiles of AT formulations were investigated in different pH dissolution media. Drug release kinetics and mechanisms were also determined. The results revealed that there was no potential incompatibility of the drug with the polymer. The release profiles of AT were affected by the concentration of KSR, fillers used, and pH of the dissolution media. The drug release kinetic from most of the formulations obeyed Higuchi diffusion model. The selected formulae were investigated for their stability by storage at 30 and 40°C with atmospheric humidity and 75% relative humidity (RH), respectively. The results demonstrated that no change in the physicochemical properties of the tablets stored at 30°C/atmospheric RH in comparison with some changes at 40°C/75% RH. Finally, the in vivo study provided an evidence that the optimized AT tablet containing 40% KSR and SP.D.L exhibited prominent higher oral bioavailability and more efficient sustained-release effect than the drug alone or the commercial tablet product. It is noteworthy that KSR could be considered as a promising useful release retardant for the production of AT sustained release matrix tablets.

  19. Quetiapine for the prevention of migraine refractory to the combination of atenolol + nortriptyline + flunarizine: an open pilot study Quetiapina para a prevenção da migrânea refratária à combinação de atenolol + nortriptilina + flunarizina: estudo piloto aberto

    Directory of Open Access Journals (Sweden)

    Abouch V Krymchantowski

    2008-01-01

    Full Text Available BACKGROUND: Migraine is a prevalent neurological disorder. Although prevention is the mainstream treatment, some patients are refractory to standard therapies. AIM: To evaluate the use of quetiapine (QTP in the preventive treatment of refractory migraine, defined as previous unresponsiveness to the combination atenolol + nortriptyline + flunarizine. METHOD: Thirty-four consecutive patients (30 women and 4 men with migraine (ICHD-II and headache attacks on less than 15 days per month not overusing symptomatic medications were studied. The main inclusion criterion was the lack of response (50% headache reduction. The mean frequency of migraine days decreased from 10.2 to 6.2 and the average consumption of rescue medications decreased from 2.3 to 1.2 days/week. Adverse events were reported by 9 (31% patients. CONCLUSION: Although limited by the open design, this study provides a pilot data to support the use of quetiapine in preventive treatment of refractory migraine.INTRODUÇÃO: A migrânea é uma doença neurológica prevalente. Embora a prevenção seja o esteio principal do tratamento, alguns pacientes são refratários aos tratamentos tradicionais. OBJETIVO: Avaliar o uso da quetiapina (QTP no tratamento preventivo da migrânea refratária definida como ausência de resposta ao uso prévio da combinação de atenolol com nortriptilina e flunarizina. MÉTODO: Trinta e quatro pacientes consecutivos (30 mulheres e 4 homens com migrânea (CIC-II e crises de cefaléia em menos de 15 dias/mês sem uso excessivo de sintomáticos foram estudados. O critério de inclusão principal foi a não obtenção na redução da frequência de cefaléia >50% após 10 semanas de uso da combinação de atenolol (60 mg/dia + nortriptilina (25 mg/dia + flunarizina (3 mg/dia. Os pacientes iniciaram a QTP como tratamento único na dose de 25 mg à noite e aumentaram-na até 75 mg. Após 10 semanas de uso, a frequência da cefaléia, o consumo de sintomáticos e os

  20. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial

    DEFF Research Database (Denmark)

    Dahlöf, Björn; Sever, Peter S; Poulter, Neil R

    2005-01-01

    The apparent shortfall in prevention of coronary heart disease (CHD) noted in early hypertension trials has been attributed to disadvantages of the diuretics and beta blockers used. For a given reduction in blood pressure, some suggested that newer agents would confer advantages over diuretics...... and beta blockers. Our aim, therefore, was to compare the effect on non-fatal myocardial infarction and fatal CHD of combinations of atenolol with a thiazide versus amlodipine with perindopril....

  1. catalysed oxidation of atenolol by alkaline permanganate

    Indian Academy of Sciences (India)

    Unknown

    as antihypertensive drug.13 It is also used for anti- angina treatment to relieve symptoms, improve toler- ance and as an anti-arrhythmic to regulate heartbeat and present infections. It is also used in management of alcohol ... The application of Beer's law to permanganate at 526 nm is verified, giving ε = 2083 ± 50 dm3 ...

  2. A comparative study of atenolol, nifedipine and their combination in ...

    African Journals Online (AJOL)

    1991-01-05

    Jan 5, 1991 ... related target organ damage by average day-time blood pressure. Clin Exp. Hypertens [A] 1985; 7: 267-278. 22. Mann S, Millar-Craig MW, Raftery EB. Superiority of 24 hour measurement of blood pressure over clinic values in determining prognosis in hypertension. Clin Erp Hypertens [A] 1985; 7: 279-282.

  3. A comparative study of atenolol, nifedipine and their combination in ...

    African Journals Online (AJOL)

    1991-01-05

    Jan 5, 1991 ... were analysed by a chi-square test using Yates's correction where appropriate. Results are quoted as mean ± standard error. All results are rounded off to the .... and Cardiovascular Disease. New York: Raven Press, 1984: 339-346. 7. Murphy MB, Scriven AJ, Dollery cr. Efficacy of nifedipine as a step-3.

  4. Contrasting hemodynamic mechanisms of losartan- vs. atenolol-based antihypertensive treatment

    DEFF Research Database (Denmark)

    Greve, Anders M; Olsen, Michael H; Bella, Jonathan N

    2012-01-01

    Pharmaceutical differences in central hemodynamics might influence cardiac response to antihypertensive treatment despite similar lowering of brachial blood pressure (BP).......Pharmaceutical differences in central hemodynamics might influence cardiac response to antihypertensive treatment despite similar lowering of brachial blood pressure (BP)....

  5. Value of the addition of Amlodipine to atenolol in patients with angina pectoris despite adequate beta blockade

    NARCIS (Netherlands)

    Dunselman, PHJM; Bouwens, LHM; Herweijer, AH; Bernink, PJLM

    1998-01-01

    Anginal patients who remain symptomatic despite optimally dosed beta blockade may also be given dihydropyridine calcium antagonists. This treatment regimen was examined in a double-blind parallel, randomized, controlled study in 147 patients with angina and positive bicycle exercise tests despite

  6. Different effects of calcium antagonist and beta-blocker therapy on left-ventricular diastolic function in ischemic heart disease. A direct comparison of the impact of mibefradil and atenolol

    DEFF Research Database (Denmark)

    Hassager, C; Thygesen, K; Grande, P

    2001-01-01

    OBJECTIVE: To compare the effect of a calcium antagonist and a beta-blocker on left-ventricular diastolic function in patients with ischemic heart disease. METHODS: 138 patients with chronic stable angina pectoris were randomized in a multicenter, double-blind trial to treatment with either...

  7. EVALUATION OF IMPORTANCE OF CENTRAL EFFECTS OF ATENOLOL AND METOPROLOL MEASURED BY HEART-RATE-VARIABILITY DURING MENTAL PERFORMANCE-TASKS, PHYSICAL EXERCISE, AND DAILY-LIFE IN STABLE POSTINFARCT PATIENTS

    NARCIS (Netherlands)

    TUININGA, YS; CRIJNS, HJGM; BROUWER, J; VANDENBERG, MP; MANINTVELD, AJ; MULDER, G; LIE, KI

    1995-01-01

    Background Physical exercise and mental work cause alterations in cardiac autonomic control. beta-Blockers protect the heart against stress, and this effect may be in part centrally mediated. In this context, the lipophilicity of the drug would be clinically relevant. Methods and Results Thirty

  8. Different effects of calcium antagonist and beta-blocker therapy on left-ventricular diastolic function in ischemic heart disease. A direct comparison of the impact of mibefradil and atenolol

    DEFF Research Database (Denmark)

    Hassager, C; Thygesen, K; Grande, P

    2001-01-01

    OBJECTIVE: To compare the effect of a calcium antagonist and a beta-blocker on left-ventricular diastolic function in patients with ischemic heart disease. METHODS: 138 patients with chronic stable angina pectoris were randomized in a multicenter, double-blind trial to treatment with either......-ventricular diastolic function in patients with chronic stable angina. However, they affect different parameters and thus apparently act through different mechanisms....

  9. Does calcium channel blockade and beta-adrenergic blockade affect platelet function and fibrinolysis to a varying degree?

    DEFF Research Database (Denmark)

    Fornitz, Gitte Gleerup; Mehlsen, J; Winther, K

    1995-01-01

    The effects of isradipine and atenolol on platelet function and fibrinolytic activity were studied in 10 male patients with mild untreated hypertension. After a 2-week placebo run-in period, the volunteers were randomized to either isradipine 2.5 mg twice daily or atenolol 100 mg daily for a 6...... as the fast-acting inhibitor against tissue plasminogen activator usually termed PAI-1. During atenolol and isradipine therapy, blood pressure (BP) was equally reduced (p Heart rate (HR) decreased during atenolol treatment but was not changed by isradipine. Platelet activity in vivo estimated as B...

  10. Does calcium channel blockade and beta-adrenergic blockade affect platelet function and fibrinolysis to a varying degree?

    DEFF Research Database (Denmark)

    Fornitz, Gitte Gleerup; Mehlsen, J; Winther, K

    1995-01-01

    tended to improve fibrinolysis, as shown by a decrease in PAI, 1 h after exercise. Reducing BP with isradipine or atenolol results in a similar decrease in platelet activity and PAI-level, tested at rest and 1 h after rest, respectively. During exercise, platelet activity increased during atenolol...

  11. THE ROLE OF S-AMLODIPINE IN ARTERIAL HYPERTENSION THERAPY WITH COMBINATION OF CALCIUM CHANNEL BLOCKERS AND BETA-BLOCKERS

    Directory of Open Access Journals (Sweden)

    M. A. Maksimova

    2013-01-01

    Full Text Available Aim. To study efficacy and safety of calcium channel blocker, S-amlodipine, in combination with β-blocker, atenolol, in patients with arterial hypertension (HT 1-2 degree com- pared to fixed combination of racemic amlodipine and atenolol.Material and methods. Patients (n=31, 7 men and 24 women with HT 1–2 degree were included into the study. The patients were randomized into two groups by the com- binations sequence. Treatment with each combination lasted 4 weeks. Office blood pressure (BP was assessed at baseline and at the end of the treatment periods, possible side effects were registered.Results. All patients completed the study. Both combination of S-amlodipine+atenolol and fixed combination of racemic amlodipine+atenolol reduced systolic (in average, -15.9 and -12.7 mm Hg, respectively and diastolic (in average, -7.3 and -5.3 mmHg, respectively BP significantly. Heart rate also decreased during therapy (in average, -3 and -4 bt/min, respectively. The differences between combinations BP and heart rate effects were not significant. 8 and 16 adverse events were registered during S-amlodipine+atenolol and racemic amlodipine+atenolol therapies, respectively Conclusion. Combination of S-amlodipine+atenolol, as well as combination of racemic amlodipine+atenolol are effective in the treatment of patients with HT 1-2 degree, however combination with S-amlodipine has less number of adverse events.

  12. Aspirin and Extended-Release Dipyridamole

    Science.gov (United States)

    ... anticoagulants ('blood thinners') such as warfarin (Coumadin) and heparin; beta-blockers such as acebutolol (Sectral), atenolol (Tenormin), ... such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant ...

  13. Effect of ACE insertion/deletion and 12 other polymorphisms on clinical outcomes and response to treatment in the life study

    DEFF Research Database (Denmark)

    2010-01-01

    OBJECTIVE: This pharmacogenetics substudy from the Losartan Intervention for Endpoint reduction in Hypertension study in patients with hypertension and left ventricular hypertrophy (LVH) treated with the angiotensin receptor blocker losartan versus the beta-blocker atenolol for 4.8 years tested....... These polymorphisms were chosen because they could affect blood pressure control or the pharmacological action of losartan or atenolol. METHODS: We genotyped 3503 patients, 1774 on losartan and 1729 on atenolol. RESULTS: ACE and the 12 other genotypes did not affect the reduction in systolic blood pressure, diastolic...... blood pressure, pulse pressure, mean arterial pressure, or heart rate, or treatment differences between losartan and atenolol on these endpoints, as assessed by general linear models. Also, ACE and the 12 other genotypes did not affect risk of the primary composite endpoint or its components stroke...

  14. Can Beta Blockers Cause Weight Gain?

    Science.gov (United States)

    Beta blockers: Do they cause weight gain? Can beta blockers cause weight gain? Answers from Sheldon G. Sheps, ... can occur as a side effect of some beta blockers, especially the older ones, such as atenolol (Tenormin) ...

  15. Pilocarpine

    Science.gov (United States)

    ... by radiotherapy in people with head and neck cancer and to treat dry mouth in people with ... Mytelase); antihistamines; atropine (Motofen, in Lomotil, in Lonox); beta blockers such as atenolol (Tenormin), labetalol (Normodyne), metoprolol (Lopressor, ...

  16. Aldesleukin

    Science.gov (United States)

    ... Be sure to mention any of the following: beta blockers such as atenolol (Tenormin), labetalol (Normodyne), metoprolol (Lopressor, Toprol XL), nadolol (Corgard), and propranolol (Inderal); certain cancer chemotherapy medications such as asparaginase (Elspar), cisplatin (Platinol), ...

  17. Terbinafine

    Science.gov (United States)

    ... class of medications called antifungals. It works by stopping the growth of fungi. ... Be sure to mention any of the following: amiodarone (Cordarone, Nexterone, Pacerone); beta blockers such as atenolol ( ...

  18. Temporal variations and trends in loads of commonly used pharmaceuticals to large wastewater treatment plants in Sweden, a case study (Ryaverket)

    DEFF Research Database (Denmark)

    Paxeus, Nicklas; Bester, Kai; El-taliawy, Haitham

    Loads of individual commonly used analgesics (ibuprofen, diclofenac), antibiotics (sulfamethoxazole, trimethoprim), β-blockers (atenolol, metoprolol, sotalol, propranolol) and neuroleptics (carbamazepine, citalopram) to a large scale operating WWTP in Sweden (Ryaverket) were studied by monitoring...

  19. Genetic Algorithm Optimized Neural Networks Ensemble as ...

    African Journals Online (AJOL)

    NJD

    Genetic Algorithm Optimized Neural Networks Ensemble as. Calibration Model for Simultaneous Spectrophotometric. Estimation of Atenolol and Losartan Potassium in Tablets. Dondeti Satyanarayana*, Kamarajan Kannan and Rajappan Manavalan. Department of Pharmacy, Annamalai University, Annamalainagar, Tamil ...

  20. Beneficial effect of isradipine on the development of left ventricular hypertrophy in mild hypertension

    DEFF Research Database (Denmark)

    Mehlsen, J; Fornitz, Gitte Gleerup; Haedersdal, C

    1993-01-01

    The objective of this study was to analyze the long-term hemodynamic effects of the calcium antagonist isradipine in mild hypertension compared with those of the beta 1-selective adrenoceptor antagonist atenolol, focusing in particular on the development of cardiac hypertrophy. Ten male patients...... with isradipine (254 +/- 55 g). The results indicate that antihypertensive treatment with isradipine as monotherapy may prevent the development of left ventricular hypertrophy whereas treatment with atenolol as monotherapy does not appear to offer this possibility....

  1. [The effect of antihypertensive drugs on the anaesthetic effect of lidocaine in hypertensive patients who need dental treatment].

    Science.gov (United States)

    Grădinaru, Irina; Grădinaru, Marilena; Ghiciuc, Cristina Mihaela; Nechifor, M; Tatarciuc, Monica; Dimitriu, G; Doloca, A

    2005-01-01

    The study evaluated the influence of atenolol/nifedipine on the local anaesthesia with lidocaine in 64 patients with essential arterial hypertension following dietetic regimen and divided in: control group (21 patients), atenolol-treated group (21 patients with atenolol therapy) and nifedipine-treated group (22 patients with nifedipine therapy). Atenolol/nifedipine was administrated three hours before anaesthesia (1.5 mg lidocaine/kg body weight) applied on Spix Spina. The atenolol/nifedipine influence on the anaesthetic intensity was evaluated both by the patient and dentist using scales for the appreciation of pain intensity (Visual Analogue Scale, Numerical Rating Scale) at 0 minutes (before anaesthesia), 5, 10, 20, 30, 60 minutes (moments for the determination of lidocaine plasmatic concentrations). There were no statistically significant differences between the values appreciated by the patient and dentist. Our data demonstrated a significant decrease of pain intensity in patients treated with atenolol/nifedipine. Very good inverse correlation was found between lidocaine concentrations and pain intensity.

  2. Left Ventricular Wall Stress-Mass-Heart Rate Product and Cardiovascular Events in Treated Hypertensive Patients

    DEFF Research Database (Denmark)

    Devereux, Richard B; Bang, Casper N; Roman, Mary J

    2015-01-01

    randomized treatment, the triple product was reduced more by atenolol, with prevalences of elevated triple product of 39% versus 51% on losartan (both P≤0.001). In Cox regression analyses adjusting for age, smoking, diabetes mellitus, and prior stroke, MI, and heart failure, 1 SD lower triple product......In the Losartan Intervention for End Point Reduction in Hypertension (LIFE) study, 4.8 years' losartan- versus atenolol-based antihypertensive treatment reduced left ventricular hypertrophy and cardiovascular end points, including cardiovascular death and stroke. However, there was no difference...... in myocardial infarction (MI), possibly related to greater reduction in myocardial oxygen demand by atenolol-based treatment. Myocardial oxygen demand was assessed indirectly by the left ventricular mass×wall stress×heart rate (triple product) in 905 LIFE participants. The triple product was included as time...

  3. Effect of ACE insertion/deletion and 12 other polymorphisms on clinical outcomes and response to treatment in the life study

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Kontula, Kimmo; Benn, Marianne

    2010-01-01

    OBJECTIVE: This pharmacogenetics substudy from the Losartan Intervention for Endpoint reduction in Hypertension study in patients with hypertension and left ventricular hypertrophy (LVH) treated with the angiotensin receptor blocker losartan versus the beta-blocker atenolol for 4.8 years tested...... whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and 12 other previously well-characterized polymorphisms of hypertension susceptibility genes affected blood pressure reduction, heart rate reduction, cardiovascular events, and/or response to treatment....... These polymorphisms were chosen because they could affect blood pressure control or the pharmacological action of losartan or atenolol. METHODS: We genotyped 3503 patients, 1774 on losartan and 1729 on atenolol. RESULTS: ACE and the 12 other genotypes did not affect the reduction in systolic blood pressure, diastolic...

  4. The Anglo-Scandinavian Cardiac Outcomes Trial: blood pressure-lowering limb: effects in patients with type II diabetes

    DEFF Research Database (Denmark)

    Ostergren, Jan; Poulter, Neil R; Sever, Peter S

    2008-01-01

    . METHODS: Patients had either untreated hypertension or treated hypertension. For those with type II diabetes mellitus, inclusion criteria required at least two additional risk factors. Patients were randomized to amlodipine with addition of perindopril as required (amlodipine-based) or atenolol...... with addition of thiazide as required (atenolol-based). Therapy was titrated to achieve a target blood pressure of less than 130/80 mmHg. RESULTS: The trial was terminated early due to significant benefits on mortality and stroke associated with the amlodipine-based regimen. In patients with diabetes mellitus......, the amlodipine-based treatment reduced the incidence of the composite endpoint--total cardiovascular events and procedures--compared with the atenolol-based regimen (hazard ratio 0.86, confidence interval 0.76-0.98, P=0.026). Fatal and nonfatal strokes were reduced by 25% (P=0.017), peripheral arterial disease...

  5. beta-Adrenoreceptor antagonists reduce cancer cell proliferation, invasion, and migration.

    Science.gov (United States)

    Işeri, Ozlem Darcansoy; Sahin, Feride Iffet; Terzi, Yunus Kasım; Yurtcu, Erkan; Erdem, S Remzi; Sarialioglu, Faik

    2014-11-01

    Propranolol, atenolol, and ICI118,551 are non-selective β-adrenergic receptor (AR), β1-AR, and β2-AR antagonists, respectively. We investigated the efficacy of propranolol, atenolol, and ICI118,551 on proliferation, migration, and invasion of non-stimulated breast (MCF7), colon (HT-29), and hepatocellular (HepG2) cancer cells. β-AR expression profiling of cells was performed by real time PCR. Cell proliferation was determined by MTT. Boyden chamber and scratch assays were performed to evaluate invasion and migration. All cell lines expressed β-ARs. ICI118,551 was the most cytotoxic, whereas atenolol was the least effective β-AR antagonist for 24, 48, and 72 h. Cell invasion was inhibited by ICI118,551 (45, 46, and 50% for MCF7, HT29, and HepG2, respectively) and propranolol (72, 65, and 90% for MCF7, HT29, and HepG2, respectively). Propranolol, atenolol, and ICI118,551 reduced migration of MCF7, HT-29, and HepG2 cells to varying extents depending on the application concentration and duration. Propranolol and atenolol reduced migration of MCF7 and HT-29 in a concentration-dependent manner, whereas migration of these cells decreased after 48 and 72 h of ICI118,551 applications. Beta2-AR antagonist seemed to be the most cytotoxic β-blocker on non-stimulated cancer cells. Propranolol and ICI118,551 were more effective than atenolol in inhibiting invasion and migration of non-stimulated MCF7 and HT-29 cells; ICI118,551 being the most potent. Concordantly, β2-selective blockage seemed to be more effective for non-stimulated cells. Effect of the selective β-AR antagonists showed variation depending on the concentration, incubation time, and histological origin of cells.

  6. The effect of beta-blockers on ventilatory function in chronic bronchitis.

    Science.gov (United States)

    Ranchod, A; Keeton, G R; Benatar, S R

    1982-03-20

    The effect of propranolol and atenolol on air-flow obstruction in patients with chronic bronchitis was evaluated by means of a double-blind, placebo-controlled cross-over trial. Fifteen patients with chronic bronchitis and mild air-flow obstruction, in whom there was no clinical suggestion of asthma, were studied. Two patients developed symptomatic increases in air-flow obstruction on propranolol and were withdrawn from the study. A symptomatically insignificant but statistically significant increase in air-flow obstruction was observed during treatment with both propranolol and atenolol.

  7. Lisinopril improves endothelial dysfunction in hypertensive NIDDM subjects with diabetic nephropathy

    DEFF Research Database (Denmark)

    Nielsen, F S; Rossing, P; Gall, M A

    1997-01-01

    in these patients. Therefore the aim of our study was to evaluate whether inhibition of angiotensin-converting enzyme (with lisinopril 10-20 mg day-1) could ameliorate endothelial dysfunction more than reducing blood pressure with conventional antihypertensive treatment (atenolol 50-100 mg day-1), usually...... escape rate of albumin (TERalb; i.e. initial disappearance of intravenously injected 125I-labelled human serum albumin); serum concentrations of von Willebrand factor (vWF), using ELISA, and urinary albumin excretion rate (UAE). Data are presented for 32 patients (16 lisinopril and 16 atenolol; age 60...

  8. Endoscopic Treatment of a Gastric Dieulafoy's Lesion

    African Journals Online (AJOL)

    She denied any prior history of vomiting blood, early satiety, or change in stool color prior to the first episode. She also denied any previous use of alcohol or report of liver disease. Her medications were atenolol, nifedipine, losartan, metformin, and mixtard insulin. She denied using aspirin, clopidogrel, or any non- steroidal ...

  9. Case reports

    African Journals Online (AJOL)

    with a 1-day history of severe ischaemic-type chest pain occurring at rest and associated autonomic symptoms of nausea, vomiting and excessive sweating. This pain was preceded by a 1-month history of intermittent chest pain. She had a background ... heparin, aspirin, simvastatin, atenolol, Lugol's iodine, carbimazole and ...

  10. Case reports

    African Journals Online (AJOL)

    history of progressive generalised muscle weakness. Her main complaints were limb weakness, blurred ... had no family history of any neuromuscular disease. On neurological examination she had bilateral ptosis .... heparin, aspirin, simvastatin, atenolol, Lugol's iodine, carbimazole and cholestyramine. The pain resolved ...

  11. Omkostningseffektivitet ved hypertensionsbehandling med Losartan i Danmark

    DEFF Research Database (Denmark)

    Keiding, Hans; Hildebrandt, Per; Burke, Thomas

    2006-01-01

    Formålet med denne analyse var set såvel fra samfundets som fra det danske sundhedsvæsens perspektiv at evaluere omkostningseffektiviteten af losartan sammenlignet med atenolol ved behandling af hypertension, baseret på Losartan Intervention For Endpoint (LIFE)-undersøgelsens data Udgivelsesdato...

  12. Author Details

    African Journals Online (AJOL)

    Manavalan, R. Vol 59 (2006) - Articles Genetic Algorithm Optimized Neural Networks Ensemble as Calibration Model for Simultaneous Spectrophotometric Estimation of Atenolol and Losartan Potassium in Tablets Abstract PDF. ISSN: 0379-4350. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for ...

  13. Selective regulation of beta 1- and beta 2-adrenoceptors in the human heart by chronic beta-adrenoceptor antagonist treatment

    NARCIS (Netherlands)

    Michel, M. C.; Pingsmann, A.; Beckeringh, J. J.; Zerkowski, H. R.; Doetsch, N.; Brodde, O. E.

    1988-01-01

    1. In 44 patients undergoing coronary artery bypass grafting, the effect of chronic administration of the beta-adrenoceptor antagonists sotalol, propranolol, pindolol, metoprolol and atenolol on beta-adrenoceptor density in right atria (containing 70% beta 1- and 30% beta 2-adrenoceptors) and in

  14. Case report

    African Journals Online (AJOL)

    ebutamanya

    2015-01-22

    Jan 22, 2015 ... the severity of the right ventricular outflow tract tachycardia remains a key question. Indeed several hospitalizations were required with a relative resistance to antiarrhythmic drugs (atenolol alone, acebutolol). The causes of ventricular tachycardia during pregnancy are multiple [1,4-7] including peripartum.

  15. contribution of growth hormone-releasing hormone and ...

    African Journals Online (AJOL)

    Side-effects. On occasion bolus IV doses of GHRH caused flushing and warmth of the face, transient tachycardia and a slight lowering of blood pressure. The administration of bromocriptine and atenolol in combination caused dizziness after the test in 2 elderly subjects, presumably due to hypotension. 0 adverse effects ...

  16. Genetic Algorithm Optimized Neural Networks Ensemble as ...

    African Journals Online (AJOL)

    Improvements in neural network calibration models by a novel approach using neural network ensemble (NNE) for the simultaneous spectrophotometric multicomponent analysis are suggested, with a study on the estimation of the components of an antihypertensive combination, namely, atenolol and losartan potassium.

  17. Beta-adrenergic receptor subtypes differentially affect apoptosis in adult rat ventricular myocytes

    National Research Council Canada - National Science Library

    Zaugg, M; Xu, W; Lucchinetti, E; Shafiq, S A; Jamali, N Z; Siddiqui, M A

    2000-01-01

    .... METHODS AND RESULTS-Myocytes were first exposed to norepinephrine (NE) alone (10 mcmol/L) or NE+atenolol (AT) (10 mcmol/L) for 12 hours. AT, a beta(1)-selective AR antagonist, abolished the NE-induced increase in nick end-labeling...

  18. Aromatic Amines Exert Contrasting Effects on the Anticoagulant Effect of Acetaldehyde upon APTT

    Directory of Open Access Journals (Sweden)

    La'Teese Hall

    2014-01-01

    Full Text Available The pharmacological effects of amphetamine, procaine, procainamide, DOPA, isoproterenol, and atenolol upon activated partial thromboplastin time in the absence and presence of acetaldehyde have been investigated. In the absence of acetaldehyde, amphetamine and isoproterenol exhibit a procoagulant effect upon activated partial thromboplastin time, whereas atenolol and procaine display anticoagulant effects upon activated partial thromboplastin time. DOPA and procainamide do not alter activated partial thromboplastin time. Premixtures of procaine with acetaldehyde produce an additive anticoagulant effect on activated partial thromboplastin time, suggesting independent action of these compounds upon clotting factors. Premixtures of amphetamine with acetaldehyde, as well as atenolol with acetaldehyde, generate a detoxication of the anticoagulant effect of acetaldehyde upon activated partial thromboplastin time. A similar statistically significant decrease in activated partial thromboplastin time is seen when procainamide is premixed with acetaldehyde for 20 minutes at room temperature. Premixtures of DOPA and isoproterenol with acetaldehyde do not affect an alteration in activated partial thromboplastin time relative to acetaldehyde alone. Hence, a selective interaction of atenolol, procaine, and amphetamine with acetaldehyde to produce detoxication of the acetaldehyde is suggested, undoubtedly due to the presence of amino, hydroxyl, or amide groups in these drugs.

  19. Case reports

    African Journals Online (AJOL)

    She was assessed as having thyrotoxicosis with non-ST-segment elevation myocardial infarction (NSTEMI) and was treated with an infusion of unfractionated heparin, aspirin, simvastatin, atenolol, Lugol's iodine, carbimazole and cholestyramine. The pain resolved on this treatment. Several hours later the pain recurred and ...

  20. Markers of collagen synthesis is related to blood pressure and vascular hypertrophy: a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, M H; Christensen, M K; Wachtell, K

    2005-01-01

    with a losartan- or an atenolol-based regimen. Furthermore, we measured intima-media thickness of the common carotid arteries (IMT), minimal forearm vascular resistance (MFVR) by plethysmography and ambulatory 24-h BP in around half of the patients. At baseline, PICP/ICTP was positively related to IMT (r=0.24, P...

  1. AUTHOR INDEX

    Indian Academy of Sciences (India)

    Unknown

    Mugesh G see Roy G. 287. Mukherjee J. Fixation of CO2 in air: Synthesis and crystal structure of a µ3-CO3-bridged tricopper(II) compound. 111. Mukherjee R see Mukherjee J. 111. Mukherjee T see Patel K. 53, 311. Mulla R M. Kinetic, mechanistic and spectral investigation of ru- thenium (III)-catalysed oxidation of atenolol ...

  2. Effects of Nebivolol on Endothelial Gene Expression during Oxidative Stress in Human Umbilical Vein Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Ulisse Garbin

    2008-01-01

    Full Text Available The endothelium plays a key role in the development of atherogenesis and its inflammatory and proliferative status influences the progression of atherosclerosis. The aim of this study is to compare the effects of two beta blockers such as nebivolol and atenolol on gene expression in human umbilical vein endothelial cells (HUVECs following an oxidant stimulus. HUVECs were incubated with nebivolol or atenolol (10 micromol/L for 24 hours and oxidative stress was induced by the addition of oxidized (ox-LDL. Ox-LDL upregulated adhesion molecules (ICAM-1, ICAM-2, ICAM-3, E-selectin, and P-selectin; proteins linked to inflammation (IL-6 and TNFalpha, thrombotic state (tissue factor, PAI-1 and uPA, hypertension such as endothelin-1 (ET-1, and vascular remodeling such as metalloproteinases (MMP-2, MMP-9 and protease inhibitor (TIMP-1. The exposure of HUVECs to nebivolol, but not to atenolol, reduced these genes upregulated by oxidative stress both in terms of protein and RNA expression. The known antioxidant properties of the third generation beta blocker nebivolol seem to account to the observed differences seen when compared to atenolol and support the specific potential protective role of this beta blocker on the expression of a number of genes involved in the initiation and progression of atherosclerosis.

  3. Effects of beta-adrenergic blockers with different ancillary properties on lipid peroxidation in hyperthyroid rat cardiac muscle.

    Science.gov (United States)

    Asayama, K; Dobashi, K; Hayashibe, H; Kato, K

    1989-10-01

    To determine whether beta-blockade protects rat heart against thyroxine (T4)-induced accelelation of lipid peroxidation, in vivo effects of 3 beta-blockers with different ancillary properties on the mitochondrial oxidative enzyme, antioxidant enzymes and lipid peroxide were investigated. The rats were rendered hyperthyroid by adding T4 to their drinking water for 3 weeks and were treated simultaneously with either carteolol (a blocker with partial agonist activity; 30 mg/kg/day), atenolol (50 mg/kg/day) or arotinolol (a blocker with weak alpha-blocking action; 50 mg/kg/day). The T4-induced tachycardia was alleviated completely by either atenolol or arotinolol, but only partially by carteolol. Cytochrome c oxidase activity in the heart muscle was increased by T4 with a parallel increase in manganese (mitochondrial) superoxide dismutase. Atenolol, but neither carteolol nor arotinolol, suppressed this increase. Similarly, the T4-induced acceleration of lipid peroxidation was suppressed by atenolol alone. Glutathione peroxidase was markedly decreased, and both copper zinc (cytosolic) superoxide dismutase and catalase were also decreased or tended to be decreased by T4. The levels of these 3 enzymes were only minimally affected by the beta-blocker treatments. These results suggest that beta-blockade suppresses mitochondrial hypermetabolism and protects heart muscle against oxidative stress in hyperthyroidism, and that the ancillary properties of beta-blockers such as partial agonist activity and alpha-blocking action negate the protection.

  4. Beneficial effect of isradipine on the development of left ventricular hypertrophy in mild hypertension

    DEFF Research Database (Denmark)

    Mehlsen, J; Fornitz, Gitte Gleerup; Haedersdal, C

    1993-01-01

    The objective of this study was to analyze the long-term hemodynamic effects of the calcium antagonist isradipine in mild hypertension compared with those of the beta 1-selective adrenoceptor antagonist atenolol, focusing in particular on the development of cardiac hypertrophy. Ten male patients ...

  5. Long-term efficacy and safety of sustained-release diltiazem in the ...

    African Journals Online (AJOL)

    A.C.P., F.A.C.C.. Accepted 30 Mar 1990. Reprint requests [0: Dr D. P. Myburgh, Dept of Cardiology, Institute for Aviation Medicine,. Private Bag lG, Verwoerdbwg, 0140 RSA. diltiazem (Tilazem; Parke-Davis) was compared with that of atenolol.' The study was extended in order to evaluate the long-term efficacy and safety of ...

  6. Drug-Drug Multicomponent Solid Forms: Cocrystal, Coamorphous and Eutectic of Three Poorly Soluble Antihypertensive Drugs Using Mechanochemical Approach.

    Science.gov (United States)

    Haneef, Jamshed; Chadha, Renu

    2017-08-01

    The present study deals with the application of mechanochemical approach for the preparation of drug-drug multicomponent solid forms of three poorly soluble antihypertensive drugs (telmisartan, irbesartan and hydrochlorothiazide) using atenolol as a coformer. The resultant solid forms comprise of cocrystal (telmisartan-atenolol), coamorphous (irbesartan-atenolol) and eutectic (hydrochlorothiazide-atenolol). The study emphasizes that solid-state transformation of drug molecules into new forms is a result of the change in structural patterns, diminishing of dimers and creating new facile hydrogen bonding network based on structural resemblance. The propensity for heteromeric or homomeric interaction between two different drugs resulted into diverse solid forms (cocrystal/coamorphous/eutectics) and become one of the interesting aspects of this research work. Evaluation of these solid forms revealed an increase in solubility and dissolution leading to better antihypertensive activity in deoxycorticosterone acetate (DOCA) salt-induced animal model. Thus, development of these drug-drug multicomponent solid forms is a promising and viable approach to addressing the issue of poor solubility and could be of considerable interest in dual drug therapy for the treatment of hypertension.

  7. De nieuwste studie naar bloeddrukverlaging door amlodipine: begin van de aftocht van beta-blokkers

    NARCIS (Netherlands)

    van den Meiracker, A. H.; van Montfrans, G. A.

    2006-01-01

    In the 'Anglo-Scandinavian cardiac outcomes trial-blood pressure lowering arm' (ASCOT-BPLA), a regimen ofamlodipine and perindopril was compared with a classic regimen of atenolol and bendroflumethiazide in over 19,000 hypertensive subjects. Most likely related to a lower systolic blood pressure, a

  8. Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA)

    DEFF Research Database (Denmark)

    Poulter, Neil R; Wedel, Hans; Dahlöf, Björn

    2005-01-01

    Results of the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) show significantly lower rates of coronary and stroke events in individuals allocated an amlodipine-based combination drug regimen than in those allocated an atenolol-based combination drug regimen (HR...

  9. CHAPTER 1

    African Journals Online (AJOL)

    Dr Olaleye

    medication use, analyze computerized administration data sets and evaluate ... for easy sorting and further analysis was done with the aid of SPSS .... Figure 3. Occurrence of antihypertensives as Monotherapy. Table 4. Types of antihypertensive drug encountered. Antihypertensive Drugs n. %. Amlodipine. 7. 14. Atenolol. 4.

  10. Development and evaluation of degradable hydroxyapatite/sodium ...

    Indian Academy of Sciences (India)

    ... with grain sizes less than 100 μ m. The HSC composite tablets exhibited a dense structure, excellent compressive strength and excellent in-vitro release behaviour of atenolol. The results indicated that HAp powders and their composite tablets can be promised as economic raw materials and carriers for low-dose drugs.

  11. Kinetic, mechanistic and spectral investigation of ruthenium (III ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 117; Issue 1. Kinetic, mechanistic and spectral investigation of ruthenium (III)-catalysed oxidation of atenolol by alkaline permanganate (stopped-flow technique). Rahamatalla M Mulla Gurubasavaraj C Hiremath Sharanappa T Nandibewoor. Full Papers Volume 117 ...

  12. Are lipophilic beta-blockers preferable for peri-operative ...

    African Journals Online (AJOL)

    As a result, the role of the physicochemical properties of beta-blockers can only be determined in the simpler setting of myocardial infarction. Therefore, we conducted a restricted systematic review to evaluate the effect of initiating atenolol and metoprolol on the prevention of ventricular fibrillation following acute myocardial ...

  13. Are lipophilic beta-blockers preferable for peri-operative ...

    African Journals Online (AJOL)

    Adele

    management of hypertension and post myocardial infarction.4-6. Are lipophilic beta-blockers preferable for peri-operative cardioprotection? Implications from a limited systematic review of the efficacy of atenolol and metoprolol in preventing in-hospital ventricular fibrillation following acute myocardial infarction.

  14. Browse Title Index

    African Journals Online (AJOL)

    Items 151 - 200 of 444 ... O Mazimba, IB Masesane, RRT Majinda, A Muzila. Vol 59 (2006), Genetic Algorithm Optimized Neural Networks Ensemble as Calibration Model for Simultaneous Spectrophotometric Estimation of Atenolol and Losartan Potassium in Tablets, Abstract PDF. D Satyanarayana, K Kannan, R Manavalan.

  15. [Efficacy and safety of different beta-blockers in patients with isolated systolic hypertension associated with diabetes mellitus and obstructive pulmonary diseases].

    Science.gov (United States)

    Kukes, V G; Ostroumova, O D; Mamaev, V I; Batutina, A M; Abakumov, Iu E; Zykova, A A

    2003-01-01

    To compare efficacy and safety of atenolol, methoprolol and bisoprolol, as the most usable beta-blockers, in patients with isolated systolic arterial hypertension (ISAH) and concomitant diabetes mellitus (DM) and/or chronic obstructive pulmonary disease (COPD). Forty tow patients with ISAH and coronary heart disease, 30 patients with these diseases associated with DM and 32 patients with associated COPD were randomized into three groups. Group 1 received atenolol in a dose 25 mg twice a day, group 2--metoprolol tartrate in a dose 25-50 mg twice a day, group 3--bisoprolol in a single dose 5-10 mg/day. All the patients were examined before the treatment and in 8 weeks. Arterial pressure was assessed at 24-h monitoring (ABPM-04 unit, Mediteck, Hungary) and quality of life (QL) was estimated by DISS Disability Scale. In addition, blood glucose was measured in patients with concomitant DM, external respiration function (ERF) was studied before and after the treatment in patients with concomitant COPD. In all ISAH patients there was a significant fall of systolic arterial pressure and heart rate. 2 hours after intake of atenolol and methoprolol blood glucose lowered significantly in diabetics as well as peak volume expiration velocity in patients with COPD. In the bisoprolol group ERF and blood glucose in DM and COPD patients remained unchanged. Atenolol deteriorated QL by the "job" and "social life" scales, methoprolol--by the scale "job" while bisoprolol improved the above parameters. The results of bisoprolol treatment are better than those of methoprolol and atenolol treatment of hypertensive patients with concomitant DM and COPD.

  16. Nebivolol in the management of essential hypertension: a review.

    Science.gov (United States)

    McNeely, W; Goa, K L

    1999-04-01

    Nebivolol is a lipophilic beta1-blocker. It is devoid of intrinsic sympathomimetic or membrane stabilising activity but appears to have nitric oxide-mediated vasodilatory effects. Nebivolol is administered as a racemic mixture of equal proportions of d- and l-enantiomers. The drug does not significantly influence glucose or plasma lipid metabolism and appears to have a protective effect on left ventricular function. At the recommended dosage (5 mg once daily) nebivolol reduces resting diastolic blood pressure as effectively as standard therapeutic dosages of atenolol, metoprolol, lisinopril and nifedipine, as shown in comparative trials. Nebivolol reduced blood pressure significantly more than enalapril 10 mg daily in the short but not the long term, although the enalapril dose may not have been optimal. Nebivolol has an additive effect in combination with hydrochlorothiazide. Standing blood pressure and/or mean 24-hour ambulatory blood pressure is significantly and similarly reduced with nebivolol, atenolol or nifedipine. Nebivolol tended to prevent increases in early morning blood pressure better than nifedipine. Overall response rates to nebivolol therapy (a decrease in sitting/supine diastolic blood pressure to or = 10 mm Hg fall in diastolic blood pressure) ranged from 58 to 81% after 4 to 52 weeks' treatment. In comparative studies, response rates were greater in nebivolol than in enalapril or metoprolol recipients, but not significantly different from those in atenolol or nifedipine recipients. Nebivolol 5 mg once daily is well tolerated in patients with hypertension. Adverse events are infrequent, transient and mild to moderate. Those reported most often include headache, fatigue, paraesthesias and dizziness. Several studies reported no signs of orthostatic hypotension with nebivolol. Comparative trials revealed no significant differences between the frequency and severity of adverse events in patients receiving nebivolol, atenolol, enalapril or placebo

  17. Immediate haemodynamic effects of a novel partial agonist, beta 1-adrenoceptor blocking drug ICI 141,292 after intravenous administration to healthy young volunteers and patients with ischaemic heart disease

    DEFF Research Database (Denmark)

    Bonde, J; Svendsen, T L; Lyngborg, K

    1987-01-01

    decreased approximately 8% following all three doses of ICI 141,292 and 14.9% after atenolol 5 mg. No changes in blood pressure were observed under resting conditions after any of the drugs. In six patients with ischaemic heart disease the intrinsic sympathomimetic activity following intravenous...... were administered intravenously. The attenuation in exercise induced tachycardia varied between 16.0 and 21.2% (P less than 0.01). A significant reduction in blood pressure could be demonstrated following all three doses of ICI 141,292 and atenolol during exercise. At rest in the sitting position HR....... No significant changes were observed in mean arterial blood pressure, stroke volume or total peripheral resistance whereas an increase in supine resting mean pulmonary arterial pressure of 3.4 mm Hg (P less than 0.05) could be demonstrated. ICI 141,292 seems to be a potent (at least five times as potent...

  18. Immediate haemodynamic effects of a novel partial agonist, beta 1-adrenoceptor blocking drug ICI 141,292 after intravenous administration to healthy young volunteers and patients with ischaemic heart disease

    DEFF Research Database (Denmark)

    Bonde, J; Svendsen, T L; Lyngborg, K

    1987-01-01

    ICI 141,292 is a new beta 1-adrenoceptor blocking drug. The beta 1-adrenoceptor antagonistic effect of ICI 141,292 was examined in a double-blind, randomised crossover study in eight healthy young volunteers and compared with atenolol. Three doses of ICI 141,292 (1, 2 and 4 mg) and atenolol 5 mg....... No significant changes were observed in mean arterial blood pressure, stroke volume or total peripheral resistance whereas an increase in supine resting mean pulmonary arterial pressure of 3.4 mm Hg (P less than 0.05) could be demonstrated. ICI 141,292 seems to be a potent (at least five times as potent...

  19. An assessment of the partial agonist activity of Ro 31-1118, flusoxolol and pindolol in man.

    OpenAIRE

    McCaffrey, P. M.; Riddell, J G; Shanks, R G

    1987-01-01

    1. The effects of single oral doses of three beta-adrenoceptor partial agonists (Ro 31-1118, flusoxolol and pindolol), two beta-adrenoceptor antagonists (propranolol and atenolol), two beta-adrenoceptor agonists (salbutamol and prenalterol) and placebo on sleeping heart rate, quality of sleep, supine heart rate, exercise heart rate, blood pressure, forearm blood flow and finger tremor were studied in eight healthy male volunteers. 2. Sleeping heart rate was increased by Ro 31-1118, flusoxolol...

  20. Beta-blocker subtype and risks of perioperative adverse events following non-cardiac surgery: a nationwide cohort study.

    Science.gov (United States)

    Jørgensen, Mads E; Sanders, Robert D; Køber, Lars; Mehta, Kala; Torp-Pedersen, Christian; Hlatky, Mark A; Pallisgaard, Jannik L; Shaw, Richard E; Gislason, Gunnar H; Jensen, Per F; Andersson, Charlotte

    2017-08-14

    Beta-blockers vary in pharmacodynamics and pharmacokinetic properties. It is unknown whether specific types are associated with increased perioperative risks. We evaluated perioperative risks associated with beta-blocker subtypes, overall and in patient subgroups. We performed a Danish Nationwide cohort study, 2005-2011, of patients treated chronically with beta blocker (atenolol, bisoprolol, carvedilol, metoprolol, propranolol, or other) prior to non-cardiac surgery. Risks of 30-day all-cause mortality (ACM) and 30-day major adverse cardiovascular events (MACE) were estimated using adjusted logistic regression models and odds ratios with 95% confidence intervals. We identified 61 660 patients, most frequently treated with metoprolol (67% of patients, mean age 69 years, 49% males), atenolol (10% of patients, mean age 68 years, 36% males), or carvedilol (9% of patients, mean age 68 years, 60% males). The crude incidences of ACM and MACE were 4.1 and 3.5% in patients with metoprolol, 3.0 and 2.3% with atenolol, and 4.8 and 4.6% with carvedilol. In adjusted models, risks were not significantly different with atenolol (ACM; 1.10 [0.92-1.32], MACE; 1.08 [0.90-1.31]) or carvedilol (ACM; 0.99 [0.85-1.16], MACE; 1.07 [0.92-1.25]), compared with metoprolol. Risks of ACM were significantly lower in prior myocardial infarction patients treated with carvedilol (0.62 [0.43-0.87]) and no different in patients with uncomplicated hypertension (1.41 [0.83-2.40]). Risks did not differ in analyses stratified by age, surgery priority, duration of anaesthesia or surgery risk (all P for interaction >0.05). Risks of ACM and MACE did not systematically differ by beta-blocker subtype. Findings may guide clinical practice and future trials.

  1. The left atrium, atrial fibrillation, and the risk of stroke in hypertensive patients with left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Wachtell, K.; Devereux, R.B.; Lyle, P.A.

    2008-01-01

    was superior to atenolol-based treatment for reducing new-onset AF and complications, especially stroke, associated with new-onset or pre-existing AF. Potential mechanisms of AF prevention by angiotensin receptor blockade supported by LIFE results include greater reduction in left atrial size and LV...... hypertrophy. Differential effects of antihypertensive treatment on the left atrium and left ventricle may help prevent AF and reduce risk of stroke associated with hypertensive heart disease Udgivelsesdato: 2008/12...

  2. Effects of preoperative β-blocker on blood loss and blood transfusion during spinal surgeries with sodium nitroprusside-controlled hypotension

    Directory of Open Access Journals (Sweden)

    Yasser Mohamed Amr

    2012-01-01

    Full Text Available Background: The present study sought to determine whether premedication with oral β-blocker before hypotensive anesthesia with sodium nitroprusside could improve the quality of surgical field, decrease the blood loss, and decrease the need for homologous blood transfusion and duration of surgery. Methods: Eighty patients scheduled for spinal fixation surgery were included in a prospective, randomized, double-blinded study. Patients were classified into two groups: Group I received oral atenolol 50 mg twice one day before surgery; and Group II received placebo tablets identical in appearance to atenolol tablets for the same period and interval. All patients in both the groups received intraoperative sodium nitroprusside (SNP as a hypotensive agent. Hemodynamic variables, amount of sodium nitroprusside used, quality of surgical field, and the amount of homologous blood transfusion and blood loss were compared between groups. Results: Heart rate and amount of SNP used were significantly less (P<0.0001 in the atenolol group, but no significant difference was found in intraoperative mean arterial blood pressure (MABP between the two groups. The time of surgeries was significantly shorter in Group I than in Group II (185±15.21 vs 225±12.61 min, P<0.0001. The quality of surgical field was better in Group I than in Group II in all times of measurements, P<0.0001. The amount of blood loss and the amount of packed red blood cells transfused were significantly less in Group I than in Group II, P<0.0001. No clinically significant complications were observed in either group. Conclusion: Premedication with oral atenolol 50 mg twice/day for one day before hypotensive anesthesia with SNP during spinal surgeries seems to be clinically safe and effective to reduce heart rate, amount of SNP used, amount of blood loss, and amount of blood transfused with better quality of surgical field.

  3. Exercise haemodynamics and maximal exercise capacity during beta-adrenoceptor blockade in normotensive and hypertensive subjects.

    OpenAIRE

    Baak, M.A.; Koene, F M; Verstappen, F T

    1988-01-01

    1. The effects of atenolol administration on maximal exercise capacity and exercise haemodynamics have been compared in eight normotensive and eight mildly hypertensive subjects, matched for sex, age, body weight, and maximal oxygen uptake, and familiar with maximal exercise testing. 2. Supine and exercise blood pressure, and exercise total peripheral resistance were significantly higher, and exercise cardiac output was significantly lower in the hypertensive than in the normotensive subjects...

  4. Factors Influencing Medication Adherence in Hypertensive Women Ages 35 to 50 Years

    Science.gov (United States)

    1991-06-11

    the study (sodium intake, use of alcohol , tobacco, and caffeine, family history, age at menarche, and use of contraceptives). Unique to the nuns’ life...therapies, alcohol abuse, and excessive salt intake (Mueller & Laragh, 1990). Pathology of high blood pressure. High blood pressure, because of its...Hydrochlorothiazide Atenolol Verapamil *HCL Dyazide (Tenormin) (Calan SR*) Furosemide Propranolol HCL Diltiazem HCL (Lasix) (Inderal) (Cardizem) Ni fed ipine ACE

  5. Photodegradation of selected β-blockers in aqueous fulvic acid solutions: kinetics, mechanism, and product analysis.

    Science.gov (United States)

    Chen, Yong; Li, Hong; Wang, Zongping; Li, Huijie; Tao, Tao; Zuo, Yuegang

    2012-06-01

    The photodegradation of the widely used β-blockers atenolol and metoprolol were investigated in the presence of fulvic acid (FA) under simulated sunlight. Both atenolol and metoprolol undergo indirect photodegradation in the FA solutions. The triplet excited state of FA ((3)FA(∗)) was verified to be main reactive species responsible for the photosensitized degradation of β-blockers. An electron transfer mechanism for the interaction between β-blockers and (3)FA(∗) was proposed on the basis of a series of experiments. Magnetic property of metal ions exhibited significant impact on photosensitized degradation. Diamagnetic metal ions such as Mg(2+), Ca(2+), Zn(2+), and Al(3+) negligibly affected the degradation. In contrast, paramagnetic metal ions including Mn(2+), Cu(2+), Fe(3+), and Cr(3+) markedly inhibited the reactions in the order of Cr(3+) < Fe(3+) < Cu(2+) < Mn(2+). The inhibition was related to the complexation ability with FA. By LC-ESI-MS/MS analysis, deisopropyl-atenolol (metoprolol) was identified as the main photosensitized product. The degradation pathways of β-blockers involving electron transfer processes were proposed. This finding strongly suggests that (3)FA(∗) was important reactive species for the degradation of β-blockers in natural waters. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Single nucleotide polymorphisms in the apolipoprotein B and low density lipoprotein receptor genes affect response to antihypertensive treatment

    Directory of Open Access Journals (Sweden)

    Kahan Thomas

    2004-09-01

    Full Text Available Abstract Background Dyslipidemia has been associated with hypertension. The present study explored if polymorphisms in genes encoding proteins in lipid metabolism could be used as predictors for the individual response to antihypertensive treatment. Methods Ten single nucleotide polymorphisms (SNP in genes related to lipid metabolism were analysed by a microarray based minisequencing system in DNA samples from ninety-seven hypertensive subjects randomised to treatment with either 150 mg of the angiotensin II type 1 receptor blocker irbesartan or 50 mg of the β1-adrenergic receptor blocker atenolol for twelve weeks. Results The reduction in blood pressure was similar in both treatment groups. The SNP C711T in the apolipoprotein B gene was associated with the blood pressure response to irbesartan with an average reduction of 19 mmHg in the individuals carrying the C-allele, but not to atenolol. The C16730T polymorphism in the low density lipoprotein receptor gene predicted the change in systolic blood pressure in the atenolol group with an average reduction of 14 mmHg in the individuals carrying the C-allele. Conclusions Polymorphisms in genes encoding proteins in the lipid metabolism are associated with the response to antihypertensive treatment in a drug specific pattern. These results highlight the potential use of pharmacogenetics as a guide for individualised antihypertensive treatment, and also the role of lipids in blood pressure control.

  7. Differential effects of 3 beta blockers on lipid peroxidation in hyperthyroid muscle.

    Science.gov (United States)

    Asayama, K; Hayashibe, H; Dobashi, K; Kato, K

    1990-08-01

    To determine whether beta blockade protects against the acceleration of lipid peroxidation in hyperthyroid rat soleus (slow-oxidative) muscle, in vivo chronic (3 weeks) effects of 3 beta blockers with different ancillary properties on mitochondrial oxidative enzymes, antioxidant enzymes, and thiobarbituric acid-reactive substances were investigated. The rats were rendered hyperthyroid by the administration of thyroxine and treated simultaneously with either carteolol (a nonselective blocker with partial agonist activity; 30 mg/kg/day), atenolol (a beta 1-selective blocker; 50 mg/kg/day), or arotinolol (a nonselective blocker with weak alpha-blocking action; 50 mg/kg/day) over a 3 week period. Hyperthyroidism induced tachycardia, an increase in the mitochondrial oxidative enzymes, manganese (mitochondrial) superoxide dismutase and thiobarbituric acid-reactive substances, and a decrease in the other antioxidant enzymes. The tachycardia was alleviated completely by either atenolol or arotinolol, but partially by carteolol. Arotinolol, but neither carteolol nor atenolol, inhibited the increase in oxidative enzymes and thiobarbituric acid-reactive substances. The levels of antioxidant enzymes were minimally affected by the beta-blocker treatment. Beta 2-, and possibly alpha- as well, but not beta 1-, blockade suppressed mitochondrial hypermetabolism and protected against peroxidative injury in the hyperthyroid soleus muscle. Partial agonist activity was not beneficial.

  8. Transport of beta-blockers and calcium antagonists by diffusion in cat myocardium

    DEFF Research Database (Denmark)

    Haunsø, S; Sejrsen, P; Svendsen, J H

    1991-01-01

    . In anesthetized cats the hearts were excised. Apparent diffusion coefficients in cat myocardium at 37 degrees C (D'37) for 14C-verapamil (protein bound), 3H-metoprolol (lipophilic), 3H-atenolol (hydrophilic), and 3H-propranolol (lipophilic and protein bound) were determined by means of a "true transient diffusion......" method and compared with the free diffusion coefficients in water (D37). D'37 of 14C-verapamil, 3H-metoprolol, 3H-atenolol, and 3H-propranolol (in cm2 s-1 10(5)) were (mean +/- SEM) 0.025 +/- 0.002, 0.055 +/- 0.003, 0.041 +/- 0.007, and 0.025 +/- 0.002, respectively. The mean diffusive progression...... of the concentration profile of 3H-metoprolol and 3H-atenolol into the tissue during 20 min was calculated to be 0.36 and 0.31 mm, respectively. The protein binding of 14C-verapamil and 3H-propranolol caused a significant fall in the progression to 0.24 mm for both drugs. These results indicate that, by diffusion...

  9. Occurrence and fate of the angiotensin II receptor antagonist transformation product valsartan acid in the water cycle--a comparative study with selected β-blockers and the persistent anthropogenic wastewater indicators carbamazepine and acesulfame.

    Science.gov (United States)

    Nödler, Karsten; Hillebrand, Olav; Idzik, Krzysztof; Strathmann, Martin; Schiperski, Ferry; Zirlewagen, Johannes; Licha, Tobias

    2013-11-01

    The substantial transformation of the angiotensin II receptor antagonist valsartan to the transformation product 2'-(2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-carboxylic acid (referred to as valsartan acid) during the activated sludge process was demonstrated in the literature and confirmed in the here presented study. However, there was a severe lack of knowledge regarding the occurrence and fate of this compound in surface water and its behavior during drinking water treatment. In this work a comparative study on the occurrence and persistency of valsartan acid, three frequently used β-blockers (metoprolol, atenolol, and sotalol), atenolol acid (one significant transformation product of atenolol and metoprolol), and the two widely distributed persistent anthropogenic wastewater indicators carbamazepine and acesulfame in raw sewage, treated wastewater, surface water, groundwater, and tap water is presented. Median concentrations of valsartan acid in the analyzed matrices were 101, 1,310, 69, waters valsartan acid was found just as relevant as the analyzed β-blockers and the anticonvulsant carbamazepine. Regarding its persistency in surface waters it was comparable to carbamazepine and acesulfame. Furthermore, removal of valsartan acid during bank filtration was poor, which demonstrated the relevance of this compound for drinking water suppliers. Regarding drinking water treatment (Muelheim Process) the compound was resistant to ozonation but effectively eliminated (≥90%) by subsequent activated carbon filtration. However, without applying activated carbon filtration the compound may enter the drinking water distribution system as it was demonstrated for Berlin tap water. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Effect of redox conditions on pharmaceutical loss during biological wastewater treatment using sequencing batch reactors

    Energy Technology Data Exchange (ETDEWEB)

    Stadler, Lauren B., E-mail: lstadler@umich.edu [Department of Civil and Environmental Engineering, University of Michigan, 1351 Beal Avenue, EWRE, Ann Arbor, MI 48109 (United States); Su, Lijuan, E-mail: lijuansu@buffalo.edu [Department of Chemistry, University at Buffalo, State University of New York, Buffalo, NY 14260 (United States); Moline, Christopher J., E-mail: christopher.moline@hdrinc.com [Department of Civil and Environmental Engineering, University of Michigan, 1351 Beal Avenue, EWRE, Ann Arbor, MI 48109 (United States); Ernstoff, Alexi S., E-mail: alexer@dtu.dk [Department of Civil and Environmental Engineering, University of Michigan, 1351 Beal Avenue, EWRE, Ann Arbor, MI 48109 (United States); Aga, Diana S., E-mail: dianaaga@buffalo.edu [Department of Chemistry, University at Buffalo, State University of New York, Buffalo, NY 14260 (United States); Love, Nancy G., E-mail: nglove@umich.edu [Department of Civil and Environmental Engineering, University of Michigan, 1351 Beal Avenue, EWRE, Ann Arbor, MI 48109 (United States)

    2015-01-23

    Highlights: • Pharmaceutical fate was studied in SBRs operated at different redox conditions. • Stable carbon oxidation and nitrification occurred under microaerobic conditions. • Losses of atenolol and trimethoprim were highest under fully aerobic conditions. • Loss of sulfamethoxazole was highest under microaerobic conditions. • Deconjugation occurred during treatment to form sulfamethoxazole and desvenlafaxine. - Abstract: We lack a clear understanding of how wastewater treatment plant (WWTP) process parameters, such as redox environment, impact pharmaceutical fate. WWTPs increasingly install more advanced aeration control systems to save energy and achieve better nutrient removal performance. The impact of redox condition, and specifically the use of microaerobic (low dissolved oxygen) treatment, is poorly understood. In this study, the fate of a mixture of pharmaceuticals and several of their transformation products present in the primary effluent of a local WWTP was assessed in sequencing batch reactors operated under different redox conditions: fully aerobic, anoxic/aerobic, and microaerobic (DO concentration ≈0.3 mg/L). Among the pharmaceuticals that were tracked during this study (atenolol, trimethoprim, sulfamethoxazole, desvenlafaxine, venlafaxine, and phenytoin), overall loss varied between them and between redox environments. Losses of atenolol and trimethoprim were highest in the aerobic reactor; sulfamethoxazole loss was highest in the microaerobic reactors; and phenytoin was recalcitrant in all reactors. Transformation products of sulfamethoxazole and desvenlafaxine resulted in the reformation of their parent compounds during treatment. The results suggest that transformation products must be accounted for when assessing removal efficiencies and that redox environment influences the degree of pharmaceutical loss.

  11. The role of sympathetic and vagal cardiac control on complexity of heart rate dynamics.

    Science.gov (United States)

    Silva, Luiz Eduardo Virgilio; Silva, Carlos Alberto Aguiar; Salgado, Helio Cesar; Fazan, Rubens

    2017-03-01

    Analysis of heart rate variability (HRV) by nonlinear approaches has been gaining interest due to their ability to extract additional information from heart rate (HR) dynamics that are not detectable by traditional approaches. Nevertheless, the physiological interpretation of nonlinear approaches remains unclear. Therefore, we propose long-term (60 min) protocols involving selective blockade of cardiac autonomic receptors to investigate the contribution of sympathetic and parasympathetic function upon nonlinear dynamics of HRV. Conscious male Wistar rats had their electrocardiogram (ECG) recorded under three distinct conditions: basal, selective (atenolol or atropine), or combined (atenolol plus atropine) pharmacological blockade of autonomic muscarinic or β1-adrenergic receptors. Time series of RR interval were assessed by multiscale entropy (MSE) and detrended fluctuation analysis (DFA). Entropy over short (1 to 5, MSE1-5) and long (6 to 30, MSE6-30) time scales was computed, as well as DFA scaling exponents at short (αshort, 5 ≤ n ≤ 15), mid (αmid, 30 ≤ n ≤ 200), and long (αlong, 200 ≤ n ≤ 1,700) window sizes. The results show that MSE1-5 is reduced under atropine blockade and MSE6-30 is reduced under atropine, atenolol, or combined blockade. In addition, while atropine expressed its maximal effect at scale six, the effect of atenolol on MSE increased with scale. For DFA, αshort decreased during atenolol blockade, while the αmid increased under atropine blockade. Double blockade decreased αshort and increased αlong Results with surrogate data show that the dynamics during combined blockade is not random. In summary, sympathetic and vagal control differently affect entropy (MSE) and fractal properties (DFA) of HRV. These findings are important to guide future studies.NEW & NOTEWORTHY Although multiscale entropy (MSE) and detrended fluctuation analysis (DFA) are recognizably useful prognostic/diagnostic methods, their physiological

  12. Tratamento farmacológico da hiperalgesia experimentalmente induzida pelo núcleo pulposo Pharmacologic treatment of hyperalgesia experimentally induced by nucleus pulposus

    Directory of Open Access Journals (Sweden)

    André Luiz de Souza Grava

    2010-01-01

    Full Text Available OBJETIVO: Avaliar o efeito de drogas anti-inflamatórias (dexametasona, indometacina, atenolol, indometacina e atenolol e analgésica (morfina sobre a hiperalgesia experimentalmente induzida pelo núcleo pulposo em contato com o gânglio da raiz dorsal de L5. MÉTODOS: Trinta ratos Wistar machos com peso de 220 a 250g foram utilizados no estudo. A indução da hiperalgesia foi realizada por meio do contato de fragmento de núcleo pulposo retirado da região sacrococcígea e colocado sobre o gânglio da raiz dorsal de L5. Os 30 animais foram divididos em grupos experimentais de acordo com a droga utilizada. As drogas foram administradas durante duas semanas a partir da realização do procedimento cirúrgico para a indução da hiperalgesia. A hiperalgesia mecânica e térmica foram avaliadas por meio do teste da pressão constante da pata, von Frey eletrônico e Hargraves por um período de sete semanas. RESULTADOS: A maior redução da hiperalgesia foi observada no grupo de animais tratados pela morfina, seguido pela dexametasona, indometacina e atenolol. A redução da hiperalgesia foi observada após a interrupção da administração das drogas, com exceção do grupo de animais tratados com morfina, nos quais ocorreu aumento da hiperalgesia após a interrupção do tratamento. CONCLUSÕES: A hiperalgesia induzida pelo contato do núcleo pulposo com o gânglio da raiz dorsal pode ser reduzida com a administração de anti-inflamatórios e analgésicos, tendo sido observado a maior redução da hiperalgesia com a administração da morfina e dexametasona.OBJECTIVE: To evaluate the effect of antiinflammatory (dexamethasone, indomethacin, atenolol, indomethacin and atenolol and analgesic drugs (morphine on hyperalgesia experimentally induced by nucleus pulposus (NP contact with the L5- dorsal root ganglion (DRG. METHODS: Thirty male Wistar rats with weights ranging from 220 to 250 g were used in the study. The hyperalgesia was induced by

  13. An analysis of the dissipation of pharmaceuticals under thirteen different soil conditions.

    Science.gov (United States)

    Kodešová, Radka; Kočárek, Martin; Klement, Aleš; Golovko, Oksana; Koba, Olga; Fér, Miroslav; Nikodem, Antonín; Vondráčková, Lenka; Jakšík, Ondřej; Grabic, Roman

    2016-02-15

    The presence of human and veterinary pharmaceuticals in the environment is recognized as a potential threat. Pharmaceuticals have the potential to contaminate soils and consequently surface and groundwater. Knowledge of contaminant behavior (e.g., sorption onto soil particles and degradation) is essential when assessing contaminant migration in the soil and groundwater environment. We evaluated the dissipation half-lives of 7 pharmaceuticals in 13 soils. The data were evaluated relative to the soil properties and the Freundlich sorption coefficients reported in our previous study. Of the tested pharmaceuticals, carbamazepine had the greatest persistence (which was mostly stable), followed by clarithromycin, trimethoprim, metoprolol, clindamycin, sulfamethoxazole and atenolol. Pharmaceutical persistence in soils was mostly dependent on the soil-type conditions. In general, lower average dissipation half-lives and variability (i.e., trimethoprim, sulfamethoxazole, clindamycin, metoprolol and atenolol) were found in soils of better quality (well-developed structure, high nutrition content etc.), and thus, probably better microbial conditions (i.e., Chernozems), than in lower quality soil (Cambisols). The impact of the compound sorption affinity onto soil particles on their dissipation rate was mostly negligible. Although there was a positive correlation between compound dissipation half-life and Freundlich sorption coefficient for clindamycin (R=0.604, psoil-type conditions. Based on the calculated dissipation and sorption data, carbamazepine would be expected to have the greatest potential to migrate in the soil water environment, followed by sulfamethoxazole, trimethoprim and metoprolol. The transport of clindamycin, clarithromycin and atenolol through the vadose zone seems less probable. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. The possible role of medial prefrontal cortex beta-1-adrenoceptors in morphine-induced amnesia.

    Science.gov (United States)

    Torkaman-Boutorabi, Anahita; Hashemi-Hezaveh, Seyed-Milad; Sheidadoust, Hadi; Zarrindast, Mohammad-Reza

    2014-01-01

    The prelimbic region of the medial prefrontal cortex (mPFC) in the brain is crucial for memory. Norepinephrine elicits an important influence on mPFC functions. The stimulation of β-adrenoceptors (β-ARs) may play a critical role in the consolidation of long-term memory. The present study examines the possible role of β₁-ARs located in the mPFC on morphine-induced amnesia in rats. The animals were bilaterally implanted with chronic cannulas in the mPFC, trained in a step-through-type passive avoidance task and tested 24 h after training to measure step-through latency. Our present results indicated that posttraining intraperitoneal administration of morphine (2.5, 5 and 7.5 mg/kg) dose-dependently reduced the step-through latency. Different doses of xamoterol (0.01, 0.1 and 1 µg/rat) have shown no significant change in the step-through latency, but posttraining intra-mPFC microinjection of atenolol (0.2 and 0.4 µg/rat) had an amnesic effect. Moreover, atenolol-caused amnesia was reversed by an ineffective dose of xamoterol (0.1 µg/rat). On the other hand, coadministration of an ineffective dose of atenolol (0.1 µg/rat) with an ineffective dose of morphine (2.5 mg/kg) induced an amnesic effect. Meanwhile, xamoterol had no effect on morphine-induced amnesia. These results suggest that β₁-ARs of the prelimbic region in the mPFC may play an important role in morphine-induced amnesia. © 2014 S. Karger AG, Basel.

  15. Use of carvedilol in hypertension: an update

    Directory of Open Access Journals (Sweden)

    Leonetti G

    2012-05-01

    Full Text Available Gastone Leonetti,1 Colin G Egan21Istituto Auxologico Italiano, Ospedale San Luca, Milan, Italy; 2Primula Multimedia SRL, Pisa, ItalyAbstract: β-blockers are effective antihypertensive agents and, together with diuretics, have been the cornerstone of pioneering studies showing their benefits on cardiovascular morbidity and mortality as a consequence of blood pressure reduction in patients with hypertension. However, evidence from recent meta-analyses have demonstrated no benefit afforded by atenolol compared with placebo in risk of mortality, myocardial infarction, or stroke, and a higher risk of mortality and stroke with atenolol/propranolol compared with other antihypertensive drug classes. Thus, the effect of these agents on cardiovascular morbidity and mortality in hypertensive patients, especially their use in uncomplicated hypertension, has remained largely controversial. However, it is recognized that the clinical studies used in these meta-analyses were mainly based on the older second-generation β-blockers, such as atenolol and metoprolol. Actually, considerable heterogeneity in, eg, pharmacokinetic, pharmacological, and physicochemical properties exists across the different classes of β-blockers, particularly between the second-generation and newer third-generation agents. Carvedilol is a vasodilating noncardioselective third-generation β-blocker, without the negative hemodynamic and metabolic effects of traditional β-blockers, which can be used as a cardioprotective agent. Compared with conventional β-blockers, carvedilol maintains cardiac output, has a reduced prolonged effect on heart rate, and reduces blood pressure by decreasing vascular resistance. Studies have also shown that carvedilol exhibits favorable effects on metabolic parameters, eg, glycemic control, insulin sensitivity, and lipid metabolism, suggesting that it could be considered in the treatment of patients with metabolic syndrome or diabetes. The present report

  16. Role of primary substrate composition and concentration on attenuation of trace organic chemicals in managed aquifer recharge systems.

    Science.gov (United States)

    Alidina, Mazahirali; Li, Dong; Ouf, Mohamed; Drewes, Jörg E

    2014-11-01

    This study was undertaken to investigate the role of primary substrate composition and concentration on the attenuation of biodegradable emerging trace organic chemicals (TOrCs) in simulated managed aquifer recharge (MAR) systems. Four sets of soil columns were established in the laboratory, each receiving synthetic feed solutions comprising different ratios and concentrations of peptone-yeast and humic acid as the primary substrate to investigate the effect on removal of six TOrCs (atenolol, caffeine, diclofenac, gemfibrozil, primidone, and trimethoprim). Based on abiotic control experiments, adsorption was not identified as a significant attenuation mechanism for primidone, gemfibrozil and diclofenac. Caffeine, atenolol and trimethoprim displayed initial adsorptive losses, however, adsorption coefficients derived from batch tests confirmed that adsorption was limited and in the long-term experiment, biodegradation was the dominant attenuation process. Within a travel time of 16 h, caffeine - an easily degradable compound exhibited removal exceeding 75% regardless of composition or concentration of the primary substrate. Primidone - a poorly degradable compound, showed no removal in any column regardless of the nature of the primary substrate. The composition and concentration of the primary substrate, however, had an effect on attenuation of moderately degradable TOrCs, such as atenolol, gemfibrozil and diclofenac, with the primary substrate composition seeming to have a larger impact on TOrC attenuation than its concentration. When the primary substrate consisted mainly of refractory substrate (humic acid), higher removal of the moderately degradable TOrCs was observed. The microbial communities in the columns receiving more refractory carbon, were noted to be more diverse and hence likely able to express a wider range of enzymes, which were more suitable for TOrC transformation. The effect of the primary substrate on microbial community composition, diversity

  17. Cardiovascular action of a cardioselective Ca(2+)channel blocker AH-1058 in conscious dogs assessed by telemetry.

    Science.gov (United States)

    Takahara, A; Dohmoto, H; Yoshimoto, R; Sugiyama, A; Hashimoto, K

    2001-02-09

    AH-1058, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-[(E)-3-(3-methoxy-2-nitro)phenyl-2-propenyl]piperidine hydrochloride, is a novel Ca(2+)channel blocker exerting cardioselective action in isolated or anesthetized canine heart preparations. To clarify the cardiac and hemodynamic action of AH-1058 in conscious dogs, we assessed the effects of the drug on the hemodynamic parameters continuously recorded by telemetry in conscious unrestrained beagle dogs, and its cardiovascular effects were compared with those of verapamil, disopyramide and atenolol. Oral administration of AH-1058 (0.15, 0.3 and 0.6 mg/kg) reduced the systolic blood pressure and maximal upstroke velocity of the left ventricular pressure (LVdP/dt(max)), increased heart rate and prolonged the QA interval in a dose-dependent manner whereas the drug did not affect diastolic blood pressure. Verapamil at 10 mg/kg reduced systolic and diastolic blood pressure with little effect on heart rate, LVdP/dt(max) and QA interval. Disopyramide at 20 mg/kg increased systolic and diastolic blood pressure, decreased LVdP/dt(max) and prolonged the QA interval with little changes in heart rate. Atenolol at 10 mg/kg decreased LVdP/dt(max) and prolonged the QA interval with little changes in systolic blood pressure, diastolic blood pressure and heart rate. The time course of the cardiohemodynamic action of AH-1058 was longer than those of the other drugs. These results suggest that AH-1058 is a long-acting cardiodepressive drug, and its hemodynamic profile is obviously different from that of disopyramide and atenolol. This unique cardiovascular profile may be beneficial for the treatment of certain pathological processes in which selective inhibition of the ventricular Ca(2+)channels would be the target of drug therapy.

  18. Influence of arotinolol hydrochloride on heart rate spectrum in hypertensive subjects.

    Science.gov (United States)

    Harasawa, Y; Imaizumi, T; Ando, S; Masaki, H; Harada, S; Momohara, M; Takeshita, A

    1994-05-01

    Influence of arotinolol hydrochloride and atenolol on the balance between the sympathetic and parasympathetic nervous systems was evaluated in 8 hypertensive subjects by spectral analysis of heart rate (HR) and systemic blood pressure (BP). Before and after administration of either arotinolol (n = 7) or atenolol (n = 7) for 2 weeks, BP was continuously and non-invasively monitored by a finger-cuff manometry (Finapres). A time series of instantaneous HR was constructed from the BP signal. A time series of mean BP was also constructed. Spectral analysis was performed by the use of an autoregressive algorithm on these time series (approximately 180 sec). Each spectrum was subdivided into low-(0.05-0.15 Hz, LF) and high-frequency (0.15-0.4 Hz, HF) components, and each component was divided by the sum of the two for normalization. As a measure of the balance between the sympathetic and parasympathetic nervous systems, the ratio of LF to HF (LF/HF) was evaluated. Arotinolol increased fractional HF in the HR spectrum from 0.45 +/- 0.12 to 0.73 +/- 0.08 (p < 0.01) and decreased fractional LF from 0.55 +/- 0.12 to 0.27 +/- 0.08 (p < 0.01); consequently, it decreased LF/HF from 1.4 +/- 0.5 to 0.4 +/- 0.2 (p < 0.01). Atenolol had similar effects on these parameters. Neither of these beta-adrenergic blockades produced a discernible decrease in LF/HF in the BP spectrum. In conclusion, these beta-adrenergic blockades decreased LF/HF in the HR spectrum in hypertensive subjects, which suggests that they improved the balance between the sympathetic and parasympathetic nervous systems.

  19. Beta blockers and breast cancer mortality: a population- based study.

    Science.gov (United States)

    Barron, Thomas I; Connolly, Roisin M; Sharp, Linda; Bennett, Kathleen; Visvanathan, Kala

    2011-07-01

    Preclinical studies have demonstrated that antagonism of β₂-adrenergic signaling inhibits several pathways necessary for breast tumor progression and metastasis. A series of population-based observational studies were conducted to examine associations between beta blocker use and breast tumor characteristics at diagnosis or breast cancer-specific mortality. Linked national cancer registry and prescription dispensing data were used to identify women with a diagnosis of stage I to IV invasive breast cancer between January 1, 2001, and December 31, 2006. Women taking propranolol (β₁/β₂ antagonist; n = 70) or atenolol (β₁ antagonist; n = 525), in the year before breast cancer diagnosis were matched (1:2) to women not taking a beta blocker (n = 4,738). Associations between use of propranolol or atenolol and risk of local tumor invasion at diagnosis (T4 tumor), nodal or metastatic involvement at diagnosis (N2/N3/M1 tumor), and time to breast cancer-specific mortality were assessed. Propranolol users were significantly less likely to present with a T4 (odds ratio [OR], 0.24, 95% CI, 0.07 to 0.85) or N2/N3/M1 (OR, 0.20; 95% CI, 0.04 to 0.88) tumor compared with matched nonusers. The cumulative probability of breast cancer-specific mortality was significantly lower for propranolol users compared with matched nonusers (hazard ratio, 0.19; 95% CI, 0.06 to 0.60). There was no difference in T4 or N2/N3/M1 tumor incidence or breast cancer-specific mortality between atenolol users and matched nonusers. The results provide evidence in humans to support preclinical observations suggesting that inhibiting the β₂-adrenergic signaling pathway can reduce breast cancer progression and mortality.

  20. Exposure of the Main Italian River Basin to Pharmaceuticals

    Directory of Open Access Journals (Sweden)

    Federico Ferrari

    2011-01-01

    Full Text Available This study give a preliminary survey of pharmaceutical contamination and accumulation in surface waters and sediments along the river Po basin (74,000 km2, the largest in Italy, a strategic region for the Italian economy: it collects sewage from a vast industrialized area of Italy (Autorità di Baciono del fiume Po, 2006, 2009. 10 pharmaceuticals (atenolol, propanolol, metoprolol, nimesulide, furosemide, carbamazepine, ranitidine, metronidazole, paracetamol, and atorvastatin from several therapeutic classes were searched in 54 sampling points along the river Po from the source to the delta, and at the mouth of its major effluents. In water samples were found pharmaceuticals in the range of 0.38–0.001 μg/L, except for furosemide (max conc. 0.605 μg/L, paracetamol (max conc. 3.59 μg/L, metoprolol (never detected and for atenolol (not analysed. In sediment samples, only paracetamol was not detected, while the others were generally found in the range of 0.4–0.02 μg/kg ww with high concentrations for atenolol (max conc. 284 μg/kg ww and furosemide (max conc. 98.4 μg/kg ww. The findings confirm also STPs as point sources of contamination. Despite of the much evidence for the adverse effects of pharmaceuticals in the aquatic environment, the observed low levels cannot be considered to pose a serious risk to human health; further studies are necessary for a comprehensive risk assessment.

  1. CLINICAL AND ECONOMICAL ASSESSMENTS OF METOPROLOL TARTRATE/SUCCINATE USAGE IN PATIENTS WITH ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    M. V. Soura

    2008-01-01

    Full Text Available Clinical and clinicoeconomical studies review is presented as well as results of author’s comparative cost analysis on metoprolol tartrate (Betaloc and metoprolol succinate (Betaloc ZOK usage in patients with ischemic heart disease. Efficacy of metoprolol therapy is proven in randomized clinical studies in patients with angina and myocardial infarction (MI. In angina patients metoprolol prevents cardiac attacks, MI, reduces nitroglycerine consumption, increases exercise tolerability, prolongs the exercise time before ST segment depression (succinate better than tartrate, decrease of angina intensity. In MI patients metoprolol therapy reduces mortality, sudden death, recurring MI and the rate of early post MI angina attacks. Nowadays metoprolol is the only β-blocker having indication on secondary MI prevention. Besides for the present metoprolol succinate is the only β-blocker with proven direct antisclerosis effect. According to Swedish clinicoeconomical study in patients after MI secondary prevention with metoprolol therapy saves the costs in comparison with placebo. American clinicoeconomical model of metoprolol and atenolol usage in all patients with MI could result in significant reduction in mortality and recurring MI rate, prolong the life and improve its quality, save financial resources. The cost of monthly treatment of angina patient with metoprolol tartrate (Betaloc and metoprolol succinate (Betaloc ZOK is 135 and 354 rubles, respectively. The price range of comparative β-blockers in ascending order is the following: atenolol (Atenolol Nicomed → metoprolol tartrate (Betaloc → metoprolol succinate (Betaloc ZOK → bisoprolol (Concor → nebivolol (Nebilet. In conclusion, metoprolol therapy is the one of mostly economically reasonable approach.

  2. Role of primary substrate composition and concentration on attenuation of trace organic chemicals in managed aquifer recharge systems

    KAUST Repository

    Alidina, Mazahirali

    2014-11-01

    This study was undertaken to investigate the role of primary substrate composition and concentration on the attenuation of biodegradable emerging trace organic chemicals (TOrCs) in simulated managed aquifer recharge (MAR) systems. Four sets of soil columns were established in the laboratory, each receiving synthetic feed solutions comprising different ratios and concentrations of peptone-yeast and humic acid as the primary substrate to investigate the effect on removal of six TOrCs (atenolol, caffeine, diclofenac, gemfibrozil, primidone, and trimethoprim). Based on abiotic control experiments, adsorption was not identified as a significant attenuation mechanism for primidone, gemfibrozil and diclofenac. Caffeine, atenolol and trimethoprim displayed initial adsorptive losses, however, adsorption coefficients derived from batch tests confirmed that adsorption was limited and in the long-term experiment, biodegradation was the dominant attenuation process. Within a travel time of 16h, caffeine - an easily degradable compound exhibited removal exceeding 75% regardless of composition or concentration of the primary substrate. Primidone - a poorly degradable compound, showed no removal in any column regardless of the nature of the primary substrate. The composition and concentration of the primary substrate, however, had an effect on attenuation of moderately degradable TOrCs, such as atenolol, gemfibrozil and diclofenac, with the primary substrate composition seeming to have a larger impact on TOrC attenuation than its concentration. When the primary substrate consisted mainly of refractory substrate (humic acid), higher removal of the moderately degradable TOrCs was observed. The microbial communities in the columns receiving more refractory carbon, were noted to be more diverse and hence likely able to express a wider range of enzymes, which were more suitable for TOrC transformation. The effect of the primary substrate on microbial community composition, diversity

  3. Different drug classes have variable effects on blood pressure depending on the time of day.

    Science.gov (United States)

    Morgan, Trefor O; Anderson, Adrianne

    2003-01-01

    Blood pressure (BP) is controlled by a variety of systems, the activities of which vary throughout the day. As drugs are developed that selectively block these systems, the fall in BP may not be consistent over 24 h. A total of 24 patients (aged >65 years) with systolic BP (SBP; >150 mm Hg) that had not been treated entered a substudy of a larger study performed in 74 patients. In a double blind, crossover study with a balanced design, they received placebo, atenolol 50 mg, perindopril 8 mg, felodipine 10 mg, or hydrochlorothiazide 50 mg. The study periods were 2 months. Ambulatory BP monitoring was performed at the end of each period, and was divided into awake periods (9:00 AM to 10:00 PM), sleep periods (12:00 AM to 6:00 AM), and morning periods (6:00 AM to 9:00 AM). Medication was taken at 9:00 AM. The four drug classes lowered 24-h mean SBP (P morning SBP, and the falls with the other three drugs were significant and were greater than the fall with atenolol. The fall in sleep BP with perindopril was greater than with the other drug classes. The awake-sleep difference in SBP increased with perindopril, stayed the same with felodipine and hydrochlorothiazide, and was reduced by atenolol. In this study, the response to the different drug classes differed. The response to drugs that work relatively nonspecifically (diuretics, calcium blockers) was relatively consistent over 24 h. The response to beta blockers and to angiotensin converting enzyme inhibitors reflected the activity of control systems. This finding supports the concept of multiple drug therapy that may need to be tailored to the time of day.

  4. Modification of mesoporous silica surface applied as drug delivery system; Modificacao de silica mesoporosa aplicada como sistema de liberacao de droga

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, G.F.; Sousa, A.; Sousa, E.M.B., E-mail: graciellefandrade@yahoo.com.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2010-07-01

    A mesoporous silica with ordered cubic structure, SBA16, was chemically modified with different alcoxisilanos using solvents with different solubility parameters (methanol and toluene), to evaluate its effectiveness as a matrix for the controlled delivery of atenolol. The structural characteristics of the material were evaluated by small angle XRD, N{sub 2} adsorption and scanning electron microscopy. The degree of functionalization of the matrix was evaluated using techniques of FTIR, thermal analysis and elemental analysis CHN. It was found that the type of solvent influences the degree of functionalization and this significantly affects the release process. (author)

  5. Prognostic importance of hemoglobin in hypertensive patients with electrocardiographic left ventricular hypertrophy: the Losartan Intervention For End point reduction in hypertension (LIFE) study

    DEFF Research Database (Denmark)

    Olsen, Michael Hecht; Wachtell, Kristian; Beevers, Gareth

    2008-01-01

    baseline hemoglobin measurements were randomized to losartan- or atenolol-based treatment and followed for 4.8 years for end points of all-cause mortality and composite of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. RESULTS: U-shaped relations were observed between deciles...... of baseline hemoglobin and all-cause mortality and the composite end point. In univariate Cox models, baseline hemoglobin in the lowest gender-specific decile (women/men: end point (HR 1......) and the composite end point (HR 1.36, 95% CI 1.08-1.71, P

  6. Imidazo[1,2-a]pyridin-3-amines as potential HIV-1 non-nucleoside reverse transcriptase inhibitors

    CSIR Research Space (South Africa)

    Bode, ML

    2011-06-01

    Full Text Available in this study. HN N N NH CN CN TMC-278 Figure 5. PAMPA permeabilities and AlogP values for HIV RT inhibitors. Compounds were incubated in PAMPA plates for 5 h at 37 ?C at a starting concentration of 100 ?M in the donor wells. Atenolol, pindolol... INOVA instrument. Samples were referenced against chloroform at 77.00 ppm for 13C and against tetramethylsilane at 0.00 ppm for 1H. Spin multiplicities are given as s (singlet), br s (broad singlet), d (doublet), dd (doublet of doublets), t (triplet...

  7. Hypertension--er det lige meget, hvordan vi saenker blodtrykket?

    DEFF Research Database (Denmark)

    Mehlsen, Jesper

    2008-01-01

    ASCOT compared the effect of atenolol combined with a thiazide versus amlodipine with perindopril in hypertensive patients. It also studied the effect of atorvastatin in those with normal cholesterol. ASCOT concluded that reductions in cardiovascular events with atorvastatin were significant......, and that amlodipine-based treatment prevented more cardiovascular events. The latter seemed to be due to better control of central blood pressure. Both statin and amlodipine-based treatments were cost-effective. According to the ASCOT study, it does matter how blood pressure is lowered....

  8. Hypertension--er det lige meget, hvordan vi saenker blodtrykket?

    DEFF Research Database (Denmark)

    Mehlsen, Jesper

    2008-01-01

    , and that amlodipine-based treatment prevented more cardiovascular events. The latter seemed to be due to better control of central blood pressure. Both statin and amlodipine-based treatments were cost-effective. According to the ASCOT study, it does matter how blood pressure is lowered.......ASCOT compared the effect of atenolol combined with a thiazide versus amlodipine with perindopril in hypertensive patients. It also studied the effect of atorvastatin in those with normal cholesterol. ASCOT concluded that reductions in cardiovascular events with atorvastatin were significant...

  9. Adsorption of pharmaceutical compounds and an endocrine disruptor from aqueous solutions by carbon materials.

    Science.gov (United States)

    Sotelo, José L; Rodríguez, Araceli R; Mateos, María M; Hernández, Sergio D; Torrellas, Silvia A; Rodríguez, Juan G

    2012-01-01

    Adsorption has been used to study the removal of atenolol, caffeine, diclofenac and isoproturon, pharmaceutical compounds as emerging contaminants and an endocrine disruptor from ultrapure water and a municipal wastewater treatment plant effluent with three carbonaceous materials: activated carbon, multiwalled carbon nanotubes and carbon nanofibers. The adsorption capacities were studied in the temperature range of 25-65°C and pH range from 3 to 9. Several model isotherms were used to model the adsorption equilibrium data. Also, the competitive adsorption was evaluated.

  10. Evaluation of microwave oven heating for prediction of drug-excipient compatibilities and accelerated stability studies

    DEFF Research Database (Denmark)

    Schou-Pedersen, Anne Marie V; Østergaard, Jesper; Cornett, Claus

    2015-01-01

    a design of experiments (DoE) approach in order to be able to rank excipients regarding reactivity: Study A: cetirizine with PEG 400, sorbitol, glycerol and propylene glycol. Study B: 6-aminocaproic acid with citrate, acetate, tartrate and gluconate. Study C: atenolol with citric, tartaric, malic, glutaric......, and sorbic acid. The model formulations were representative for oral solutions (co-solvents), parenteral solutions (buffer species) and solid dosage forms (organic acids applicable for solubility enhancement). The DoE studies showed overall that the same impurities were generated by microwave oven heating...

  11. Perianesthetic refractory anaphylactic shock with cefuroxime in a patient with history of penicillin allergy on multiple antihypertensive medications

    Directory of Open Access Journals (Sweden)

    Deb Sanjay Nag

    Full Text Available Abstract We report a case of perianesthetic refractory anaphylactic shock with cefuroxime in a patient with history of penicillin allergy on regular therapy with atenolol, losartan, prazosin and nicardipine. Severe anaphylactic shock was only transiently responsive to 10 mL of (1:10,000 epinephrine and needed norepinephrine and dopamine infusion. Supportive therapy with vasopressors and inotropes along with mechanical ventilation for the next 24 hours resulted in complete recovery. She was successfully operated upon 2 weeks later with the same anesthetic drugs but intravenous ciprofloxacin as the alternative antibiotic for perioperative prophylaxis.

  12. Beta-adrenergic blocking drugs and renal function

    Energy Technology Data Exchange (ETDEWEB)

    Walters, L.; Dormehl, I. (Nuclear Development Corp. of South Africa (Pty.) Ltd., Pelindaba, Pretoria. Inst. of Life Sciences); Goosen, D.J.; Avenant, J.C.; Du Plessis, M.; Jacobs, N.; Schoeman, H.S.

    1983-10-01

    A baboon model was used to investigate the effects of atenolol, nadolol, sotalol and labetalol on renal function. The glomerular filtration rate (GFR) and renal blood flow (RBF) were measured, using radionuclides and a gamma camera, before and after 1 week's oral administration of these drugs. All the drugs caused an increase in the GFR, but this reached statistical significance only in the cases of sotalol (P smaller than 0,025) and labetalol (0,05 smaller than P smaller than 0,10). The RBF was not significantly changed, although it decreased in all cases.

  13. Ultrasound-assisted extraction method for the simultaneous determination of emerging contaminants in freshwater sediments.

    Science.gov (United States)

    de Sousa, Diana Nara Ribeiro; Grosseli, Guilherme Martins; Mozeto, Antonio Aparecido; Carneiro, Renato Lajarim; Fadini, Pedro Sergio

    2015-10-01

    Sediments are the fate of several emerging organic contaminants, such as pharmaceuticals, personal care products and hormones, and therefore an important subject in environmental monitoring studies. In the present work, a simple and sensitive method was developed, validated and applied for the simultaneous extraction of atenolol, caffeine, carbamazepine, diclofenac, ibuprofen, naproxen, propranolol, triclosan, estrone, 17-β-estradiol and 17-α-ethinylestradiol using ultrasound-assisted extraction from freshwater sediment samples followed by solid-phase extraction clean-up and liquid chromatography with tandem mass spectrometry detection. The solvent type and extraction pH were evaluated to obtain the highest recoveries of the compounds. The best method shows absolute recoveries between 54.0 and 94.4% at 50 ng/g concentration. The method exhibits good precision with relative standard deviation ranging from 1.0-16%. The detection and quantification limits ranged from 0.006-0.067 and 0.016-0.336 ng/g, respectively. The developed method was successfully applied to freshwater sediment samples collected from different sites in Jundiaí River basin of São Paulo State, Brazil. The compounds atenolol, caffeine, propranolol and triclosan were detected in all the sampling sites with concentrations of 13.8, 41.0, 28.5 and 176 ng/g, respectively. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Involvement of alpha- and beta-adrenoceptors in the automaticity of the isolated guinea pig pulmonary vein myocardium.

    Science.gov (United States)

    Irie, Masahiko; Tsuneoka, Yayoi; Shimobayashi, Mariko; Hasegawa, Nao; Tanaka, Yusuke; Mochizuki, Soh; Ichige, Sho; Hamaguchi, Shogo; Namekata, Iyuki; Tanaka, Hikaru

    2017-04-01

    We examined the involvement of adrenoceptors in the automaticity of the pulmonary vein myocardium, which probably plays a crucial role in the generation of atrial fibrillation. The automatic activity of the myocardium in guinea pig pulmonary vein tissue preparations were monitored by contractile force or membrane potential measurement. In quiescent preparations, application of noradrenaline induced an automatic activity. The firing frequency was reduced by prazosin or atenolol. Methoxamine induced an automatic activity of low frequency, which was accelerated by further application of isoproterenol. In preparations driven at a constant frequency, noradrenaline, in the presence of atenolol, caused a depolarizing shift of the resting membrane potential and an increase in the slope of the diastolic depolarization. In contrast, in the presence of prazosin, noradrenaline had no effect on the slope, but caused acceleration of the late repolarization and a hyperpolarizing shift of the maximum diastolic potential. At clinically relevant concentrations, carvedilol significantly inhibited the noradrenaline-induced activity but bisoprolol did not. It was concluded that α1- and β1-adrenoceptor stimulation enhance automaticity through different mechanisms in the guinea pig pulmonary vein myocardium. Dual blockade of these adrenoceptors appears to be effective for suppressing noradrenaline-induced pulmonary vein automaticity and probably atrial fibrillation. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  15. Anti-hypertensive drugs have different effects on ventricular hypertrophy regression

    Directory of Open Access Journals (Sweden)

    Celso Ferreira Filho

    2010-01-01

    Full Text Available OBJECTIVES: There is a direct relationship between the regression of left ventricular hypertrophy (LVH and a decreased risk of mortality. This investigation aimed to describe the effects of anti-hypertensive drugs on cardiac hypertrophy through a meta-analysis of the literature. METHODS: The Medline (via PubMed, Lilacs and Scielo databases were searched using the subject keywords cardiac hypertrophy, antihypertensive and mortality. We aimed to analyze the effect of anti-hypertensive drugs on ventricle hypertrophy. RESULTS: The main drugs we described were enalapril, verapamil, nifedipine, indapamina, losartan, angiotensin-converting enzyme inhibitors and atenolol. These drugs are usually used in follow up programs, however, the studies we investigated used different protocols. Enalapril (angiotensin-converting enzyme inhibitor and verapamil (Ca++ channel blocker caused hypertrophy to regress in LVH rats. The effects of enalapril and nifedipine (Ca++ channel blocker were similar. Indapamina (diuretic had a stronger effect than enalapril, and losartan (angiotensin II receptor type 1 (AT1 receptor antagonist produced better results than atenolol (selective β1 receptor antagonist with respect to LVH regression. CONCLUSION: The anti-hypertensive drugs induced various degrees of hypertrophic regression.

  16. [Preliminary data on combined assessment of tolerance to exercise, left ventricular contractile function in ischemic heart disease patients taking bradycardic agents].

    Science.gov (United States)

    Safonova, E V; Zharova, E A; Samoĭlenko, L E; Sergienko, V B

    2003-01-01

    To study effects of bradicardia induced by atenolol, diltiazem and ivabradin on exercise tolerance, myocardial perfusion and left ventricular contractile function in patients with stable angina pectoris. The trial included 7 male patients aged 57 +/- 2.6 years with coronary heart disease, stable angina of functional class II free of cardiac failure and severe arterial hypertension, with a positive and reproducible VEM test after therapy discontinuation. For 10 consecutive days with 5-day intervals, all the patients received atenolol, diltiazem, ivabradin in doses lowering heart rate at rest by 20% from the initial level. Before the treatment all the patients were studied with VEM test, perfusion synchronized single-photon emission computerized tomoscintigraphy of the myocardium (PSSPECT) at rest and exercise. On day 10 of each drug intake PSSPECT and VEM test were performed if the expected heart rate was achieved. Each of the studied drugs resulted in a 22-24% reduction in the heart rate at rest accompanied by a significant rise in exercise tolerance, improvement of performance and myocardial perfusion. There were no significant changes in left ventricular contractility. A 20% reduction in resting heart rate due to monotherapy with drugs having a bradicardic effect leads to positive changes in exercise tolerance and myocardial perfusion.

  17. Mesoporous silica/apatite nanocomposite: special synthesis route to control local drug delivery.

    Science.gov (United States)

    Sousa, A; Souza, K C; Sousa, E M B

    2008-05-01

    Synthetic hydroxyapatite is widely used in medicine and dentistry due its notable biocompatibility and bioactivity properties. The hydroxyapatite incorporation into silica has demonstrated excellent bioactivity or biodegradability, according to the content of calcium ions. Procedures to obtain ordered mesoporous silicates rely on the micelle-forming properties of a surfactant, whose chemical composition, size and concentration control the structural dimensions of the final material. This paper reports the synthesis of two types mesoporous materials: pure MCM-41 and a nanocomposite of apatite and mesoporous silica, MCM-41-HA. The samples were charged with atenolol as a model drug and in vitro release essays were carried out. The bioactivity behavior was investigated as a function of soaking time in simulated body fluid. The materials were characterized by X-ray diffraction, N2 adsorption, FTIR spectroscopy, scanning electron microscopy, dispersive energies spectroscopy, and transmission electron microscopy. The influence of the release rate of atenolol molecules from pure MCM-41 mesoporous and containing hydroxyapatite was demonstrated, since it results in a very slowly drug delivery from the nanocomposite system.

  18. Biodegradation of pharmaceuticals and endocrine disruptors with oxygen, nitrate, manganese (IV), iron (III) and sulfate as electron acceptors

    Science.gov (United States)

    Schmidt, Natalie; Page, Declan; Tiehm, Andreas

    2017-08-01

    Biodegradation of pharmaceuticals and endocrine disrupting compounds was examined in long term batch experiments for a period of two and a half years to obtain more insight into the effects of redox conditions. A mix including lipid lowering agents (e.g. clofibric acid, gemfibrozil), analgesics (e.g. diclofenac, naproxen), beta blockers (e.g. atenolol, propranolol), X-ray contrast media (e.g. diatrizoic acid, iomeprol) as well as the antiepileptic carbamazepine and endocrine disruptors (e.g. bisphenol A, 17α-ethinylestradiol) was analyzed in batch tests in the presence of oxygen, nitrate, manganese (IV), iron (III), and sulfate. Out of the 23 selected substances, 14 showed a degradation of > 50% of their initial concentrations under aerobic conditions. The beta blockers propranolol and atenolol and the analgesics pentoxifylline and naproxen showed a removal of > 50% under anaerobic conditions. In particular naproxen proved to be degradable with oxygen and under most anaerobic conditions, i.e. with manganese (IV), iron (III), or sulfate. The natural estrogens estriol, estrone and 17β-estradiol showed complete biodegradation under aerobic and nitrate-reducing conditions, with a temporary increase of estrone during transformation of estriol and 17β-estradiol. Transformation of 17β-estradiol under Fe(III)-reducing conditions resulted in an increase of estriol as well. Concentrations of clofibric acid, carbamazepine, iopamidol and diatrizoic acid, known for their recalcitrance in the environment, remained unchanged.

  19. Anti-Hypertensive Drugs Have Different Effects on Ventricular Hypertrophy Regression

    Science.gov (United States)

    Filho, Celso Ferreira; de Abreu, Luiz Carlos; Valenti, Vitor E.; Ferreira, Marcelo; Meneghini, Adriano; Silveira, José Alexandre; Pérez Riera, Andrés R.; Colombari, Eduardo; Murad, Neif; Santos-Silva, Paulo Roberto; da Silva, Lovian José Henrique Pereira; Vanderlei, Luiz Carlos Marques; Carvalho, Tatiana D.; Ferreira, Celso

    2010-01-01

    OBJECTIVES: There is a direct relationship between the regression of left ventricular hypertrophy (LVH) and a decreased risk of mortality. This investigation aimed to describe the effects of anti-hypertensive drugs on cardiac hypertrophy through a meta-analysis of the literature. METHODS: The Medline (via PubMed), Lilacs and Scielo databases were searched using the subject keywords cardiac hypertrophy, antihypertensive and mortality. We aimed to analyze the effect of anti-hypertensive drugs on ventricle hypertrophy. RESULTS: The main drugs we described were enalapril, verapamil, nifedipine, indapamina, losartan, angiotensin-converting enzyme inhibitors and atenolol. These drugs are usually used in follow up programs, however, the studies we investigated used different protocols. Enalapril (angiotensin-converting enzyme inhibitor) and verapamil (Ca++ channel blocker) caused hypertrophy to regress in LVH rats. The effects of enalapril and nifedipine (Ca++ channel blocker) were similar. Indapamina (diuretic) had a stronger effect than enalapril, and losartan (angiotensin II receptor type 1 (AT1) receptor antagonist) produced better results than atenolol (selective β1 receptor antagonist) with respect to LVH regression. CONCLUSION: The anti-hypertensive drugs induced various degrees of hypertrophic regression. PMID:20668631

  20. Carvedilol stimulates nitric oxide synthesis in rat cardiac myocytes.

    Science.gov (United States)

    Kurosaki, K; Ikeda, U; Maeda, Y; Shimada, K

    2000-02-01

    The purpose of this study was to investigate the effects of the beta-adrenergic blocker carvedilol on nitric oxide (NO) synthesis in cardiac myocytes. We measured the accumulation of nitrite, a stable oxidation product of NO, and the expression of inducible NO synthase (iNOS) protein in cultured neonatal rat cardiac myocytes. Incubation of the cultures with interleukin 1 beta (IL-1 beta; 10 ng/ml) caused a marked increase in nitrite production. Although carvedilol alone showed no effect on nitrite accumulation, it significantly enhanced IL-1 beta-induced nitrite production by cardiac myocytes. The effect of carvedilol was completely abolished in the presence of aminoguanidine or actinomycin D. The nitrite production enhanced by carvedilol was accompanied by increased iNOS protein expression. Unlike carvedilol, other beta-blockers, namely propranolol, atenolol and arotinolol, did not enhance IL-1 beta-induced nitrite production. Addition of isoproterenol significantly increased nitrite production by IL-1 beta-stimulated cardiac myocytes. Atenolol suppressed this isoproterenol-induced nitrite accumulation, while carvedilol further increased the nitrite accumulation. These findings indicate that carvedilol increases NO synthesis in IL-1 beta-stimulated rat cardiac myocytes by a beta-adrenoceptor-independent mechanism. Copyright 2000 Academic Press.

  1. Spectrofluorometric determination of some beta-blockers in tablets and human plasma using 9,10-dimethoxyanthracene-2-sodium sulfonate.

    Science.gov (United States)

    Abdine, H; Sultan, M A; Hefnawy, M M; Belal, F

    2005-04-01

    A simple and sensitive spectrofluorometric method was developed for the quantitative determination of some beta-blockers, namely arotinolol, atenolol and labetalol as hydrochloride salts. The method is based on the reaction of these drugs as n-electron donors with the fluorogenic reagent 9,10-dimethoxy-2-anthracene sulfonate (DMAS) as pi-acceptor in acidic medium. The obtained ion-pairs were extracted into chloroform and measured spectrofluorometrically at 452 nm after excitation at 385 nm. The fluorescence intensity-concentration plots are rectilinear over the ranges of 0.5-5 microg x ml(1), 1.0-11.0 microg x ml(1) and 0.6-6.4 microg x ml(1) for labetalol, atenolol and arotinolol, respectively. The different parameters affecting the reaction pathway were thoroughly studied and optimized. No interference was observed from the common pharmaceutical excipients. The proposed method was successfully applied to the analysis of tablets and the results were statistically compared with those obtained by reference methods. The method was further extended to the in vitro determination of the drugs in spiked human plasma, the % recoveries (n = 3) ranged from 96.98 +/- 1.55 to 98.28 +/- 2.19. A proposal of the reaction pathway was postulated.

  2. Prevention of atherosclerosis by specific AT1-receptor blockade with candesartan cilexetil

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    Vasilios Papademetriou

    2001-03-01

    Full Text Available Several studies indicate that blockade of the renin-angiotensin-aldosterone system (RAAS can prevent atherosclerosis and vascular events, but the precise mechanisms involved are still unclear. In this study, we investigated the effect of the AT 1-receptor blocker, candesartan, in the prevention of atherosclerosis in Watanabe heritable hyperlipidaemic (WHHL rabbits and also the effect of AT1-receptor blockade in the uptake of oxidised LDL by macrophage cell cultures. In the first set of experiments, 12 WHHL rabbits were randomly assigned to three groups: placebo, atenolol 5 mg/kg daily or candesartan 2 mg/kg daily for six months. Compared with controls and atenolol-treated rabbits, candesartan treatment resulted in a significant 50—60% reduction of atherosclerotic plaque formation and a 66% reduction in cholesterol accumulation in the thoracic aorta.Studies in macrophage cultures indicated that candesartan prevented uptake of oxidised LDL-(oxLDL-cholesterol by cultured macrophages. Candesartan inhibited the uptake of oxLDL in a dose-dependent manner, reaching a maximum inhibition of 70% at concentrations of 5.6 µg/ml. Further studies in other animal models and well-designed trials in humans are warranted to further explore the role of AT1-receptor blockade in the prevention of atherosclerosis.

  3. Factors affecting drug adsorption on beta zeolites.

    Science.gov (United States)

    Pasti, Luisa; Sarti, Elena; Cavazzini, Alberto; Marchetti, Nicola; Dondi, Francesco; Martucci, Annalisa

    2013-05-01

    The adsorption behaviour of three commonly used drugs, namely ketoprofen, hydrochlorothiazide and atenolol, from diluted aqueous solutions on beta zeolites with different SiO2/Al2O3 ratio (i.e. 25, 38 and 360) was investigated by changing the ionic strength and the pH, before and after thermal treatment of the adsorbents. The selective adsorption of drugs was confirmed by thermogravimetry and X-ray diffraction. The adsorption capacity of beta zeolites was strongly dependent on both the solution pH and the alumina content of the adsorbent. Such a remarkable difference was interpreted as a function of the interactions between drug molecules and zeolite surface functional groups. Atenolol was readily adsorbed on the less hydrophobic zeolite, under pH conditions in which electrostatic interactions were predominant. On the other hand, ketoprofen adsorption was mainly driven by hydrophobic interactions. For undissociated molecules the adsorption capability increased with the increase of hydrophobicity. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Cutaneous reactions due to antihypertensive drugs

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    Upadhayai J

    2006-01-01

    Full Text Available Out of a total of 1147 patients on antihypertensive drugs, 23 (2.04% developed adverse cutaneous drug reactions (ACDR. The commonest antihypertensive drug group causing ACDR was beta-blockers of which atenolol was the commonest culprit. The second most common group was calcium channel blockers with amlodipine as the commonest offender. The most common patterns of ACDR observed included urticaria followed by lichenoid drug eruption (LDE. We noted 2 new patterns of reactions; (i one patient developed brownish blue pigmentation of nails while on atenolol for 3 years, which resolved in 4 months after withdrawal and (ii another patient on amlodipine for 8 years developed Schamberg′s like purpuric pigmentation, which resolved on withdrawal of drug within 3 months. These findings have not been reported in the literature earlier. This study is presented for paucity of Indian data on ACDR due to antihypertensive drugs, and remarkable advancement in area of cardiovascular and antihypertensive pharmacology and a large number of population taking antihypertensive drugs.

  5. Effects of soil moisture depletion on vegetable crop uptake of pharmaceuticals and personal care products (PPCPs).

    Science.gov (United States)

    Santiago, Sergio; Roll, Deborah M; Ray, Chittaranjan; Williams, Clinton; Moravcik, Philip; Knopf, Allan

    2016-10-01

    Agricultural crops have a long history of being irrigated with recycled wastewater (RW). However, its use on vegetable crops has been of concern due to the potential prevalence of microcontaminants, such as pharmaceuticals and personal care products (PPCPs) in the latter, which represents a possible health hazard to consumers. We investigated the uptake of three PPCPs (atenolol, diclofenac, and ofloxacin), at three different concentrations in irrigation water (0.5, 5, and 25 μg L -1 ) in relation to three varying volumetric soil moisture depletion levels of 14 % (-4.26 kPa), 10 % (-8.66 kPa), and 7 % (-18.37 kPa) by various vegetable crop species. Experiments were conducted in a split-split block completely randomized design. PPCPs were extracted using a developed method of accelerated solvent extraction and solid phase extraction and analyzed via liquid chromatography mass spectrometry (LCMS). Results indicate that all treated crops were capable of PPCP uptake at nanogram per gram concentrations independent of the applied soil moisture depletion levels and PPCP concentrations. Ofloxacin was the chemical with the highest uptake amounts, followed by atenolol and then diclofenac. Although the results were not statistically significant, higher concentrations of PPCPs were detected in plants maintained under higher soil moisture levels of 14 % (-4.26 kPa).

  6. Cardioprotection, attenuated systemic inflammation, and survival benefit of beta1-adrenoceptor blockade in severe sepsis in rats.

    Science.gov (United States)

    Ackland, Gareth L; Yao, Song T; Rudiger, Alain; Dyson, Alex; Stidwill, Ray; Poputnikov, Dmitry; Singer, Mervyn; Gourine, Alexander V

    2010-02-01

    To explore the hypothesis that beta-1 adrenoreceptor blockade may be protective through the attenuation of sympathetic hyperactivity and catecholaminergic inflammatory effects on cardiac and hepatic function. Prospective, randomized, controlled study. Animal laboratory in a university medical center. Male adult Wistar rats. Peripheral beta1-adrenoceptor blockade through daily intraperitoneal injection (metoprolol, 100 mg x kg(-1); atenolol, 6 mg x kg(-1)) or central nervous system beta1-adrenoceptor blockade (intracerebroventricular metoprolol, 25 microg) to achieve approximately 20% heart rate reduction in rats for 2 days before or after the induction of lethal endotoxemia, cecal ligation and puncture, or fecal peritonitis. Peripheral beta1-adrenoceptor blockade established for 2 days before lethal endotoxemia markedly improved survival in both metoprolol-treated (n = 16; log rank test, p = .002) and atenolol-treated (n = 15; p = .03) rats. Overall mortality in cecal ligation and puncture was similar between metoprolol (40%; n = 10) and saline (50%; n = 10) pretreatment (p = .56), but the median time to death was increased by 33 hrs in metoprolol-treated rats (p = .03). Metoprolol pretreatment reduced hepatic expression of proinflammatory cytokines and lowered plasma interleukin-6 (both p inflammatory and cardioprotective effects, with mortality reduction if commenced before a septic insult. Its role in sepsis should be explored further.

  7. Postmeningitis headache: case report Cefaléia pós-meningite: relato de caso

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    André Palma da Cunha Matta

    2007-06-01

    Full Text Available We report a case of a 18-year-old female patient that developed a migraine-like headache following an acute meningococcal meningitis. She had no previous history of recurrent headaches. The pain was intense, pulsatile and throbbing, typically unilateral, without aura. Its frequency increased during the following weeks and a prophylactic treatment with amitriptyline and atenolol was initiated. There was remission of the attacks.Relatamos o caso de uma paciente de 18 anos, previamente hígida, sem história pregressa de cefaléia, que apresentou um quadro agudo caracterizado por febre, cefaléia holocraniana, sonolência, vômitos e sinais de irritação meníngea. Teve investigação laboratorial compatível com meningite meningocócica. Recebeu o tratamento adequado, evoluindo com regressão do quadro infeccioso. Desenvolveu, entretanto, episódios recorrentes de cefaléia pulsátil, sem aura, unilateral, de forte intensidade e acompanhada por náusea e fotofobia. A freqüência dos episódios aumentou progressivamente até que se instituiu tratamento profilático com atenolol e amitriptilina, havendo remissão da dor.

  8. Corrigendum to “Sorption/desorption of non-hydrophobic and ionisable pharmaceutical and personal care products from reclaimed water onto/from a natural sediment” Sci Total Environ 472 (2014) 273–281

    Energy Technology Data Exchange (ETDEWEB)

    Martínez-Hernández, Virtudes, E-mail: virtudes.martinez@imdea.org [IMDEA Agua, Madrid Institute for Advanced Studies in Water, Parque Científico Tecnológico de la Universidad de Alcalá, 28805 Alcalá de Henares, Madrid (Spain); Meffe, Raffaella; Herrera, Sonia [IMDEA Agua, Madrid Institute for Advanced Studies in Water, Parque Científico Tecnológico de la Universidad de Alcalá, 28805 Alcalá de Henares, Madrid (Spain); Arranz, Elena [University of Alcalá, Geography and Geology Department, 28871 Alcalá de Henares, Madrid (Spain); Bustamante, Irene de [IMDEA Agua, Madrid Institute for Advanced Studies in Water, Parque Científico Tecnológico de la Universidad de Alcalá, 28805 Alcalá de Henares, Madrid (Spain); University of Alcalá, Geography and Geology Department, 28871 Alcalá de Henares, Madrid (Spain)

    2015-02-01

    In the present work, the sorption of pharmaceutical and personal care products (PPCPs) (acetaminophen, atenolol, carbamazepine, caffeine, naproxen and sulphamethoxazole) onto the natural organic matter (NOM) and the inorganic surfaces of a natural sandy loam sediment was quantified separately. The quantification was based on the PPCP charge, their degree of ionisation, their octanol-water partitioning coefficient (K{sub OW}) and the sediment organic carbon fraction (ƒ{sub OC}). PPCP desorption from the sediment was examined under conditions of infiltrating water containing a high concentration of inorganic ions (mimicking infiltrating reclaimed water), and a low concentration (and smaller diversity) of inorganic ions (mimicking rainwater infiltration). Batch tests were performed using a sediment/water ratio of 1:4 and a PPCP initial concentration ranging from 1 to 100 μg L{sup −1}. The results showed the type and degree of PPCP ionisation to strongly influence the sorption of these compounds onto the sediment. The sorption of cationic species onto the sediment was higher than that of anionic species and mostly reversible; the sorption of neutral species was negligible with the exception of caffeine. The anionic species sorbed less onto the sediment, but also desorbed less easily. Most of the compounds showed a sorption that was highly influenced by interaction with mineral surfaces. The presence of inorganic ions had no impact on the desorption of the PPCPs from the sediment. According to the calculated percentages of removal, the mobility followed the order: carbamazepine > acetaminophen > naproxen > atenolol > sulphamethoxazole > caffeine.

  9. Glycemia in newborns of hypertensive mothers according to maternal treatment Glicemia no recém-nascido de mãe hipertensa de acordo com a terapêutica materna

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    Silvana Darcie

    2004-01-01

    Full Text Available PURPOSE: To evaluate the evolution of glycemic levels in newborns of hypertensive mothers according to maternal treatment. METHODS: Prospective randomized study, including 93 newborns of mothers treated with isradipine (n = 39, atenolol (n = 40, or low sodium diet (control group - n=14. Glycemia was determined at birth (mother and newborn by the oxidase glucose method and in the 1st, 3rd, 6th, 12th, and 24th hours after birth (newborn by a test strip method. The evolution of glycemia was analyzed in each group (Friedman test. The groups were compared regarding glycemia (Kruskall-Wallis test, and linear regression models were constructed for the analyses (independent variable = maternal glycemia; dependent variables = umbilical cord, 3rd, and 6th hour glycemia. RESULTS: There were no statistically significant differences among the mean blood glucose levels of the 3 groups in any of the assessments. There was a correlation between maternal and umbilical cord blood glucose in the isradipine (r = 0.61; P OBJETIVO: Avaliar o comportamento da glicemia em recém-nascidos (RN de mães hipertensas conforme o tratamento materno. MÉTODOS: Estudo prospectivo, randomizado, incluindo 93 RN de mães tratadas com isradipina(n=39, atenolol (n=40 ou dieta - controle (n=14. Determinou-se a glicemia ao nascimento (mãe e RN, pela glicose oxidase e na 1ª., 3ª., 6ª., 12ª. e 24ª. horas (RN, por fita reagente. A evolução da glicemia, em cada grupo, foi analisada (Teste de Friedman. Os grupos foram comparados, quanto às glicemias, em cada momento (Teste de Kruskall-Wallis e foram ajustados modelos de regressão linear para as glicemias (variável independente = glicemia materna; variáveis dependentes = glicemias de cordão, 3ª. e 6ª. horas. RESULTADOS: Não houve diferença estatisticamente significante entre as glicemias médias dos 3 grupos, em qualquer uma das coletas. Houve correlação entre as glicemias materna e de cordão umbilical nos grupos

  10. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial.

    Science.gov (United States)

    Pepine, Carl J; Handberg, Eileen M; Cooper-DeHoff, Rhonda M; Marks, Ronald G; Kowey, Peter; Messerli, Franz H; Mancia, Giuseppe; Cangiano, José L; Garcia-Barreto, David; Keltai, Matyas; Erdine, Serap; Bristol, Heather A; Kolb, H Robert; Bakris, George L; Cohen, Jerome D; Parmley, William W

    2003-12-03

    Despite evidence of efficacy of antihypertensive agents in treating hypertensive patients, safety and efficacy of antihypertensive agents for coronary artery disease (CAD) have been discerned only from subgroup analyses in large trials. To compare mortality and morbidity outcomes in patients with hypertension and CAD treated with a calcium antagonist strategy (CAS) or a non-calcium antagonist strategy (NCAS). Randomized, open label, blinded end point study of 22 576 hypertensive CAD patients aged 50 years or older, which was conducted September 1997 to February 2003 at 862 sites in 14 countries. Patients were randomly assigned to either CAS (verapamil sustained release) or NCAS (atenolol). Strategies specified dose and additional drug regimens. Trandolapril and/or hydrochlorothiazide was administered to achieve blood pressure goals according to guidelines from the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) of less than 140 mm Hg (systolic) and less than 90 mm Hg (diastolic); and less than 130 mm Hg (systolic) and less than 85 mm Hg (diastolic) if diabetes or renal impairment was present. Trandolapril was also recommended for patients with heart failure, diabetes, or renal impairment. Primary: first occurrence of death (all cause), nonfatal myocardial infarction, or nonfatal stroke; other: cardiovascular death, angina, adverse experiences, hospitalizations, and blood pressure control at 24 months. At 24 months, in the CAS group, 6391 patients (81.5%) were taking verapamil sustained release; 4934 (62.9%) were taking trandolapril; and 3430 (43.7%) were taking hydrochlorothiazide. In the NCAS group, 6083 patients (77.5%) were taking atenolol; 4733 (60.3%) were taking hydrochlorothiazide; and 4113 (52.4%) were taking trandolapril. After a follow-up of 61 835 patient-years (mean, 2.7 years per patient), 2269 patients had a primary outcome event with no statistically significant

  11. Are we misunderstanding beta-blockers.

    Science.gov (United States)

    Cruickshank, J M

    2007-08-09

    In myocardial ischaemia and heart failure, beta-blockers with intrinsic sympathomimetic activity (ISA) e.g. pindolol, xamoterol, bucindolol, nebivolol, have performed poorly in reducing morbidity and mortality. In both indications beta-1 blockade is the vital active ingredient. Beta-1 blockade (bisoprolol) is now an alternative first-line choice to Ace-inhibition in the treatment of heart failure. The therapeutic role of beta-blockers in hypertension is less well understood, particularly since the new recommendations in the UK from the NICE committee stating that: 1. beta-blockers are no longer preferred as a routine initial therapy, 2. the combination with diuretics is discouraged due to the risk of induced diabetes, and 3. in younger patients first-choice initial therapy should be an ACE-inhibitor. Recent data from the Framingham Heart Study and other epidemiological studies have indicated that the development of diastolic hypertension in younger subjects is closely linked to weight-increase and an increase in peripheral resistance; such subjects have a high adrenergic drive and cardiac output. In contrast, elderly systolic hypertension mostly arises de novo via poor vascular compliance. Thus in younger, probably overweight, hypertensives (including diabetics) first-line beta-blockade has performed well in preventing myocardial infarction (a fact hidden by meta-analyses that do not take age into account). Conversely, in elderly hypertensives first-line beta-blockade (atenolol) has performed poorly in reducing cardiovascular risk (due to partial beta-2 blockade atenolol evokes metabolic disturbance and does not improve vascular compliance, or effectively lower central aortic pressure or reverse left ventricular hypertrophy). Thus beta-blockers like atenolol are ill-equipped for first-line therapy in elderly hypertension. Some beta-blockers, e.g. bisoprolol (up to 10 mg/day is highly beta-1 selective) and nebivolol (beta-2/3 intrinsic sympathomimetic activity), do

  12. COMPARATIVE STUDY OF COMBINED DRUGS OF ENALAPRIL MALEATE AND HYDROCHLOROTHIAZIDE: «RENIPRIL HT» AND «CO-RENITEC» IN PATIENTS WITH MILD TO MODERATE ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    S. Y. Martsevich

    2015-12-01

    Full Text Available Aim. Tto study efficiency and safety of new combined drug of enalapril maleate and hydrochlorothiazide “Renipril HT: in patients with mild to moderate arterial hypertension (AH in comparison with the original combined drug with the same substances – “Co-renitec”, possibility of reaching target blood pressure (BP level with separate treatment with each drug, and in combination with atenolol if necessary.Material and methods. 30 patients (11 men and 19 women with mild to moderate AH took part in randomized, open, cross over study. 10-14 days before the study started, previous antihypertensive treatment had been canceled for all the patients. Each patient by turns was treated during 6 weeks with Renipril HT (RH and Co-renitec (CR. Efficiency of antihypertensive therapy was assessed at visits to physician every 2 weeks within the whole period of study. Within first 2 weeks patients were treated with RH 10/12,5 mg daily or CR 10/6,25 mg daily. Within next 2 weeks doses of drugs were doubled if target BP level (<140/90 mmHg was not reached. If therapy with doubled doses of combined drugs was inefficient, atenolol 25 mg daily was added for the last 2 weeks of treatment with each drug. After 6-week treatment with the first randomized drug, antihypertensive therapy was canceled for 7-14 days depending on addition of atenolol to the therapy.Results. After 6-week treatment with RH average level of systolic BP reduced by 21,8 mmHg compared to the initial level, after 6-week treatment with CR – by 23,8 mmHg. Average level of diastolic BP reduced by 10,8 and 13,5 mmHg respectively (differences between drugs in BP decrease are not significant. By the end of 6-week treatment with RH target BP level was reached in 74% of patients, with CR - in 64% of patients. Bigger number of side-effects was registered in treatment with RH (p=0,03, but most part of them were not severe and didn’t demand therapy correction.Conclusion. New combined drug of enalapril

  13. COMPARATIVE STUDY OF COMBINED DRUGS OF ENALAPRIL MALEATE AND HYDROCHLOROTHIAZIDE: «RENIPRIL HT» AND «CO-RENITEC» IN PATIENTS WITH MILD TO MODERATE ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    S. Y. Martsevich

    2005-01-01

    Full Text Available Aim. Tto study efficiency and safety of new combined drug of enalapril maleate and hydrochlorothiazide “Renipril HT: in patients with mild to moderate arterial hypertension (AH in comparison with the original combined drug with the same substances – “Co-renitec”, possibility of reaching target blood pressure (BP level with separate treatment with each drug, and in combination with atenolol if necessary.Material and methods. 30 patients (11 men and 19 women with mild to moderate AH took part in randomized, open, cross over study. 10-14 days before the study started, previous antihypertensive treatment had been canceled for all the patients. Each patient by turns was treated during 6 weeks with Renipril HT (RH and Co-renitec (CR. Efficiency of antihypertensive therapy was assessed at visits to physician every 2 weeks within the whole period of study. Within first 2 weeks patients were treated with RH 10/12,5 mg daily or CR 10/6,25 mg daily. Within next 2 weeks doses of drugs were doubled if target BP level (<140/90 mmHg was not reached. If therapy with doubled doses of combined drugs was inefficient, atenolol 25 mg daily was added for the last 2 weeks of treatment with each drug. After 6-week treatment with the first randomized drug, antihypertensive therapy was canceled for 7-14 days depending on addition of atenolol to the therapy.Results. After 6-week treatment with RH average level of systolic BP reduced by 21,8 mmHg compared to the initial level, after 6-week treatment with CR – by 23,8 mmHg. Average level of diastolic BP reduced by 10,8 and 13,5 mmHg respectively (differences between drugs in BP decrease are not significant. By the end of 6-week treatment with RH target BP level was reached in 74% of patients, with CR - in 64% of patients. Bigger number of side-effects was registered in treatment with RH (p=0,03, but most part of them were not severe and didn’t demand therapy correction.Conclusion. New combined drug of enalapril

  14. Effect of basic and acidic additives on the separation of some basic drug enantiomers on polysaccharide-based chiral columns with acetonitrile as mobile phase.

    Science.gov (United States)

    Gogaladze, Khatuna; Chankvetadze, Lali; Tsintsadze, Maia; Farkas, Tivadar; Chankvetadze, Bezhan

    2015-03-01

    The separation of enantiomers of 16 basic drugs was studied using polysaccharide-based chiral selectors and acetonitrile as mobile phase with emphasis on the role of basic and acidic additives on the separation and elution order of enantiomers. Out of the studied chiral selectors, amylose phenylcarbamate-based ones more often showed a chiral recognition ability compared to cellulose phenylcarbamate derivatives. An interesting effect was observed with formic acid as additive on enantiomer resolution and enantiomer elution order for some basic drugs. Thus, for instance, the enantioseparation of several β-blockers (atenolol, sotalol, toliprolol) improved not only by the addition of a more conventional basic additive to the mobile phase, but also by the addition of an acidic additive. Moreover, an opposite elution order of enantiomers was observed depending on the nature of the additive (basic or acidic) in the mobile phase. © 2015 Wiley Periodicals, Inc.

  15. [Establishment of MDCK-pHaMDR cell model and standard operation procedure for assessing blood-brain barrier permeability of chemical components of traditional Chinese medicine].

    Science.gov (United States)

    Yang, Yan-Fang; Wu, Ni; Yang, Xiu-Wei

    2016-07-01

    To establish MDCK-pHaMDR cell model and standard operation procedure for assessing the blood-brain barrier permeability of chemical components of traditional Chinese medicine. MDCK-pHaMDR cell model was evaluated by determining the morphology features, transepithelial electrical resistance, bidirectional transport and intracellular accumulation of Rhodamine 123 and the apparent permeability of positive control drugs caffeine and atenolol. The MDCK-pHaMDR cell model had satisfactory integrity and tightness, and stable expression of P-gp. In addition, the transport results of the positive control drugs were consistent with the reported values in literature. All the parameters tested of the MDCK-pHaMDR cell model were consistent with the requirements, so the model can be used to study the blood-brain barrier permeability of chemical components of traditional Chinese medicine. Copyright© by the Chinese Pharmaceutical Association.

  16. Mesoporous Silica SBA-16 Functionalized with Alkoxysilane Groups: Preparation, Characterization, and Release Profile Study

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    Gracielle Ferreira Andrade

    2012-01-01

    Full Text Available A mesoporous material sphere based on silica, SBA-16, was chemically modified with alkoxysilane using two different solvents: methanol and toluene. The influence of the chemical modification of the matrix on the release rate of a model drug was also studied. The structural characteristics of the materials were evaluated by small-angle X-ray diffraction, N2 adsorption, and transmission electron microscopy. The functionalization of the matrix was evaluated using thermal analysis, FTIR spectroscopy, 13C and 29Si solid-state nuclear magnetic resonance, and elemental analysis, CHN. The results show that alkoxysilane groups have been chemically bonded to silicon atoms on the surface of cubic Im3m mesoporous silica. The influence of the release rate of atenolol molecules from chemically modified mesoporous SBA-16 could be identified, since significant differences could be observed among the release patterns of the different materials.

  17. Beta-blocker subtype and risks of perioperative adverse events following non-cardiac surgery

    DEFF Research Database (Denmark)

    Jørgensen, Mads E.; Sanders, Robert D.; Køber, Lars

    2017-01-01

    Aims: Beta-blockers vary in pharmacodynamics and pharmacokinetic properties. It is unknown whether specific types are associated with increased perioperative risks. We evaluated perioperative risks associated with beta-blocker subtypes, overall and in patient subgroups. Methods and results: We...... performed a Danish Nationwide cohort study, 2005-2011, of patients treated chronically with beta blocker (atenolol, bisoprolol, carvedilol, metoprolol, propranolol, or other) prior to non-cardiac surgery. Risks of 30-day all-cause mortality (ACM) and 30-day major adverse cardiovascular events (MACE) were...... in analyses stratified by age, surgery priority, duration of anaesthesia or surgery risk (all P for interaction >0.05). Conclusion: Risks of ACM and MACE did not systematically differ by beta-blocker subtype. Findings may guide clinical practice and future trials....

  18. Effect of beta-adrenoceptor blockers on human ether-a-go-go-related gene (HERG) potassium channels

    DEFF Research Database (Denmark)

    Dupuis, Delphine S; Klaerke, Dan A; Olesen, Søren-Peter

    2005-01-01

    Patients with congenital long QT syndrome may develop arrhythmias under conditions of increased sympathetic tone. We have addressed whether some of the beta-adrenoceptor blockers commonly used to prevent the development of these arrhythmias could per se block the cardiac HERG (Human Ether....... These data showed that HERG blockade by beta-adrenoceptor blockers occurred only at high micromolar concentrations, which are significantly above the recently established safe margin of 100 (Redfern et al., 2003).......-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride) blocked the HERG channel with similar affinity, whereas the beta1-receptor antagonists metoprolol and atenolol showed weak effects. Further, the four compounds blocked HERG channels expressed in a mammalian HEK293 cell line...

  19. The role of graphene oxide and graphene oxide-based nanomaterials in the removal of pharmaceuticals from aqueous media: a review.

    Science.gov (United States)

    Khan, Ayub; Wang, Jian; Li, Jun; Wang, Xiangxue; Chen, Zhongshan; Alsaedi, Ahmed; Hayat, Tasawar; Chen, Yuantao; Wang, Xiangke

    2017-03-01

    In this review paper, the ill effects of pharmaceuticals (PhAs) on the environment and their adsorption on graphene oxide (GO) and graphene oxide-based (GO-based) nanomaterials have been summarised and discussed. The adsorption of prominent PhAs discussed herein includes beta-blockers (atenolol and propranolol), antibiotics (tetracycline, ciprofloxacin and sulfamethoxazole), pharmaceutically active compounds (carbamazepine) and analgesics such as diclofenac. The adsorption of PhAs strictly depends upon the experimental conditions such as pH, adsorbent and adsorbate concentrations, temperature, ionic strength, etc. To understand the adsorption mechanism and feasibility of the adsorption process, the adsorption isotherms, thermodynamics and kinetic studies were also considered. Except for some cases, GO and its derivatives show excellent adsorption capacities for PhAs, which is crucial for their applications in the environmental pollution cleanup.

  20. Impact of carbon dosing on micro-pollutants removal in MBBR post-denitrification systems

    DEFF Research Database (Denmark)

    Escola, Monica; Torresi, Elena; Gy Plósz, Benedek

    operation and indigenous micro-pollutants concentrations, different dosages of methanol and ethanol were used to manipulate the carbon-to-nitrate ratio in the two systems. This test revealed that atenolol, citalopram and trimethoprim were efficiently removed, with removal percentages from 56 to 98%, 17......Dosing of carbon as methanol or ethanol is a common practice in post-denitrification steps during wastewater treatment by MBBR technology. The impact of the carbon dosage on micro-pollutants removal, in terms of type (methanol or ethanol) and concentration was investigated. First, with continuous...... to 53% and 30 to 100 % respectively. However, type or concentration of carbon did not lead to different micro-pollutant removal rates. Second, an anoxic-batch test with the same wastewater but containing spiked micro-pollutants (2 ng/mL) was conducted. The batch test showed that acetyl...

  1. Impact of carbon-dosing on micro-pollutants removal in MBBR post-denitrification systems

    DEFF Research Database (Denmark)

    Escola Casas, Monica; Torresi, Elena; Plósz, Benedek G.

    and indigenous micro-pollutants concentrations, different methanol and ethanol dosages were used to manipulate the carbon-to-nitrate ratio in two MBBRs. Atenolol, citalopram and trimethoprim were efficiently removed in both reactors. However, type or concentration of carbon did not correlate to micro-pollutant......Dosing of methanol or ethanol is a common practice in post-denitrification steps during wastewater treatment by MBBR technology. The carbon-dosage impact on micro- pollutants removal, in terms of type (methanol or ethanol) and concentration was investigated. First, with continuous operation...... the removal of such compounds. In contrast, for moderately degraded micro-pollutants, the biofilm developed under methanol dosing presented the highest removal rate constants. This might mean that the primary metabolism of methanol improved the metabolism of these micro-pollutants. In general...

  2. Pulmonary artery dissection following balloon valvuloplasty in a dog with pulmonic stenosis.

    Science.gov (United States)

    Grint, K A; Kellihan, H B

    2017-04-01

    A 3-month-old, 9.9 kg, male pit bull cross was referred for evaluation of collapse. A left basilar systolic heart murmur graded V/VI and a grade IV/VI right basilar systolic heart murmur were ausculted. Echocardiography showed severe pulmonic stenosis characterized by annular hypoplasia, leaflet thickening, and leaflet fusion. After 1 month of atenolol therapy, a pulmonic valve balloon valvuloplasty procedure was performed, and the intra-operative right ventricular pressure was reduced by 43%. Echocardiography, performed the following day, showed apparent rupture of a pulmonary valve leaflet and a membranous structure within the pulmonary artery consistent with a dissecting membrane. Short-term follow-up has shown no apparent progression of the pulmonary artery dissection and the patient remains free of clinical signs. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Effects of beta-adrenergic blockers on drug-induced tremors.

    Science.gov (United States)

    Iwata, S; Nomoto, M; Fukuda, T

    1993-03-01

    We studied the effect of various kinds of beta-adrenergic blockers on oxotremorine-, harmaline- and thyrotropin-releasing hormone (TRH)-induced tremors in mice. To investigate what property of beta-blockers plays the main role in suppressing tremor, we employed five beta-blockers (propranolol, atenolol, butoxamine, pindolol, and arotinolol). All drugs suppressed oxotremorine-induced tremors but none reduced harmaline-induced tremors. Even though TRH-induced tremors were decreased significantly only by propranolol and high doses of arotinolol, all drugs had a tendency to reduce the tremor. We concluded that neuropharmacological mechanisms underlying to harmaline-induced tremors were different from those of TRH- and oxotremorine-induced tremors and that features of beta-blockers (beta 1- or beta 2-selectivity, intrinsic sympathomimetic activity, and membrane stabilizing activity) did not primarily contribute to the suppression of tremors.

  4. Nicardipine may impair glucose metabolism in hypertensive diabetic patients.

    Science.gov (United States)

    Sasaki, H; Naka, K; Kishi, Y; Ohoshi, T; Hagihara, T; Matsuo, H; Sowa, R; Matsumoto, G; Sanke, T; Nanjo, K

    1994-11-01

    The respective effects of 6 month's administration of beta-blockers (atenolol, metoprolol, carteolol and arotinolol), calcium-channel blockers (nicardipine, diltiazem) and angiotensin converting enzyme inhibitor (enalapril) on hemoglobin A1c (HbA1c) levels were evaluated in hypertensive patients with non-insulin-dependent diabetes mellitus (NIDDM), using a retrospective method. NIDDM patients with stable HbA1c and body weight were selected for this study. The following results were obtained. (1) The administration of nicardipine or beta-blockers significantly elevated HbA1c levels. (2) The administration of diltiazem or enalapril did not have any influence on HbA1c levels. These findings suggest that not only beta-blocker but nicardipine (dihydropyridine type calcium-channel blocker) may cause deterioration in glucose metabolism in NIDDM patients.

  5. Effect of beta-adrenergic receptor antagonists on nicotine-induced tail-tremor in rats.

    Science.gov (United States)

    Suemaru, K; Gomita, Y; Furuno, K; Araki, Y

    1993-09-01

    The effects of various beta-adrenergic receptor antagonists on nicotine-induced tail-tremor were investigated in rats. Atenolol (5 and 10 mg/kg, IP), arotinolol (5 and 10 mg/kg, IP), and carteolol (5 and 10 mg/kg, IP), hydrophilic beta-adrenergic receptor antagonists, did not affect the tail-tremor induced by nicotine given at a dose of 0.5 mg/kg SC. However, propranolol (5-20 mg/kg, IP) and pindolol (5-20 mg/kg, IP), nonselective and lipophilic beta-adrenergic receptor antagonists, did suppress the tail-tremor dose dependently. In contrast, metoprolol (5-20 mg/kg, IP), lipophilic and beta 1-selective adrenergic receptor antagonists, did not show such an effect. These results suggest that nicotine-induced tail-tremors may be mediated through central beta 2-adrenergic receptors as an appearance and developmental mechanism.

  6. [Effect of arotinolol on the incomplete tetanic contractions of the cat soleus muscle--relation to its anti-tremorgenic action].

    Science.gov (United States)

    Hara, Y; Sugimoto, S; Ono, H

    1993-08-01

    The effect of arotinolol on the incomplete tetanic contractions of the cat soleus muscle was studied. Isoproterenol and epinephrine injected intravenously decreased the tension and degree of fusion of incomplete tetanic contractions of the soleus muscle in anesthetized cats. Intravenous arotinolol (> 3 micrograms/kg), propranolol (> 30 micrograms/kg) and pindolol (> 3 micrograms/kg) blocked the effects of isoproterenol and epinephrine, but atenolol (-300 micrograms/kg), prazosin (0.1-10 micrograms/kg) and phentolamine (10, 30 micrograms/kg) did not block them. These results indicate that the receptors involved can be classified as of the beta 2-type. It is proposed that arotinolol may inhibit beta 2-adrenoceptors in the extrafusal muscle fibers of slow muscle, and thereby reduces the amplitude of tremor by changing the incomplete tetanic contractions of the muscle to the complete ones.

  7. HEART FAILURE, DIABETES, BETA-BLOCKERS AND RISK OF HYPOGLYCEMIA

    Directory of Open Access Journals (Sweden)

    A. A. Aleksandrov

    2008-01-01

    Full Text Available Aim. To evaluate an influence of carvedilol on risk of hypoglycemia in patients with diabetes type 2 (D2 and chronic heart failure (CHF treated with angiotensin converting enzyme (ACE inhibitors.Material and methods. 13 patients (10 men, 3 women; aged 59,8±6,7 y.o. with D2 and CHF caused by ischemic heart disease were included in the study. Before inclusion all patients were treated with ACE inhibitors and various beta-blockers (atenolol, metoprolol, bisoprolol. These beta-blockers were changed for carvedilol. Heart ultrasonography, blood pressure control, glycemia monitoring, HbA1c level determination were performed before, during and after carvedilol therapy.Results. Carvedilol reduces frequency and duration of hypoglycaemia episodes. There were not episodes of severe hypoglycaemia during carvedilol therapy.Conclusion. Carvedilol reduces risk of hypoglycemia when it is used in combination with ACE inhiditors in diabetic patients with CHF.

  8. Improvement in Hemodynamics After Methylene Blue Administration in Drug-Induced Vasodilatory Shock: A Case Report.

    Science.gov (United States)

    Laes, JoAn R; Williams, David M; Cole, Jon B

    2015-12-01

    The purpose of this study is to describe a case where methylene blue improved hemodynamics in a poisoned patient. This is a single case report where a poisoned patient developed vasodilatory shock following ingestion of atenolol, amlodipine, and valsartan. Shock persisted after multiple therapies including vasopressors, high-dose insulin, hemodialysis, and 20% intravenous fat emulsion. Methylene blue (2 mg/kg IV over 30 min) was administered in the ICU with temporal improvement as measured by pulmonary artery catheter hemodynamic data pre- and post-methylene blue administration. Within 1 h of methylene blue administration, systemic vascular resistance improved (240 dyn s/cm5 increased to 1204 dyn s/cm5), and vasopressor requirements decreased with maintenance of mean arterial pressure 60 mmHg. Methylene blue may improve hemodynamics in drug-induced vasodilatory shock and should be considered in critically ill patients poisoned with vasodilatory medications refractory to standard therapies.

  9. Impact of left ventricular geometry on prognosis in hypertensive patients with left ventricular hypertrophy (the LIFE study)

    DEFF Research Database (Denmark)

    Gerdts, E.; Cramariuc, D.; Simone, G. de

    2008-01-01

    AIMS: Less is known about the relation between in-treatment left ventricular (LV) geometry and risk of cardiovascular events. We assessed LV geometric patterns on baseline and annual echocardiograms as time-varying predictors of the primary composite endpoint (cardiovascular death, stroke......, and myocardial infarction) in 937 hypertensive patients with LV hypertrophy during 4.8 years losartan- or atenolol-based treatment in the Losartan Intervention for Endpoint reduction in hypertension (LIFE) echocardiography substudy. METHODS AND RESULTS: LV geometry was determined from LV mass/body surface area...... including LV geometric patterns as time-varying variables and adjusting for treatment, Framingham risk score, race, and time-varying systolic blood pressure, the patterns independently predicted higher risk of primary composite endpoints [HR 2.99 (1.16-7.71) for concentric remodelling, HR 1.79 (1...

  10. NEBIVOLOL: A THIRD GENERATION BETA BLOCKER AS ANTIHYPERTENSION AGENT

    Directory of Open Access Journals (Sweden)

    Ni Putu Wirantari

    2013-07-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE Hypertension is a silent killer because it causes complications in vital organs unwitting patients. Beta blockers are generally a choice of safe and effective drugs for initial treatment of hypertension. However, the current hypertension treatment guidelines said beta blockers were not suitable use as first-line therapy because of complications caused. On the use of atenolol found an increased incidence of cardiovascular death of 24%, 14% and cardiac complications 23% cerebrovascular complications. Nebivolol is a third-generation beta-blocker that is highly selective for ?1-adrenergic receptors and has the ability as a direct vasodilator was able to stimulate the activity of endothelial L-arginin/nitric oxide synthase, is expected nebivolol can reduce blood pressure so can achieve blood pressure that expected.

  11. Análise de fármacos em águas por SPE-UPLC-ESI-MS/MS

    Directory of Open Access Journals (Sweden)

    Vanessa de Jesus Gaffney

    2014-01-01

    Full Text Available A method was developed for the analysis of 31 pharmaceutical compounds in Lisbon's drinking water system, using solid-phase extraction (SPE and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS. The method was validated through estimation of the linearity range, method detection and quantification limits, matrix effects, precision and accuracy. The method detection and quantification limit ranges were 0.009-10 and 0.03-33 ng/L, respectively. Analytes were quantified in water samples collected from the EPAL (Empresa Portuguesa das Águas Livres S.A. supply system. Carbamazepine, atenolol, sulfadiazine, sulfamethazine, sulfapyridine, sulfamethoxazole, acetaminophen, caffeine and erythromycin were quantified in the analysed samples.

  12. TR146 cells grown on filters as a model of human buccal epithelium

    DEFF Research Database (Denmark)

    Nielsen, H M; Rassing, M R; Nielsen, Hanne Mørck

    2000-01-01

    The objective of the present study was to evaluate the TR146 cell culture model as an in vitro model of human buccal epithelium. For this purpose, the permeability of water, mannitol and testosterone across the TR146 cell culture model was compared to the permeability across human, monkey...... (logD(oct; 7.4)) and capacity factor (k') and to their polar water accessible surface area (PWASA). For water, mannitol, testosterone and some of the beta-adrenoceptor antagonists, the permeability enhancement across the TR146 cell culture model in the presence of sodium glycocholate (GC......) was determined. The mannitol and testosterone permeability across the TR146 cell culture model could be related to the permeability across porcine and human buccal mucosa. The permeability of the beta-adrenoceptor antagonists across the TR146 cell culture model varied between 2.2 x 10(-6) cm/s (atenolol) and 165...

  13. March 2014 pulmonary case of the month: the cure may be worse than the disease

    Directory of Open Access Journals (Sweden)

    Penupolu S

    2014-03-01

    Full Text Available No abstract available. Article truncated at 150 words. History of Present Illness: A 51 year old woman was seen with a chief complaint of gradually increasing shortness of breath. She was at baseline five months prior to presentation but noticed dyspnea on minimal exertion initially at a higher altitude, gradually progressing to dyspnea at rest. She was tried on 2 courses of antibiotics with no significant improvement. In addition to the dyspnea, she has some non productive cough but no fevers. PMH, SH, FH: She had a renal transplant in 1997 for IgA disease and has a history of type II diabetes and hypertension. She is a life long nonsmoker and has only occasional alcohol use. She is employed as a utility designer and has no exposure to any dusts, fumes or exotic animals. Family history is noncontributory. Medications: Atenolol, Lasix, Prednisone 2 mg q daily, Rosuvastatin, Sirolimus 2 mg po q daily ...

  14. Impact of diabetes on treatment-induced changes in left ventricular structure and function in hypertensive patients with left ventricular hypertrophy. The LIFE study

    DEFF Research Database (Denmark)

    Gerdts, E; Okin, P M; Omvik, P

    2009-01-01

    BACKGROUND AND AIM: Diabetes is associated with left ventricular hypertrophy (LVH) and impaired systolic function in hypertensive patients, but less is known about its impact on LVH regression and functional improvement during antihypertensive treatment. METHODS AND RESULTS: We performed annual...... echocardiography in 730 non-diabetic and 93 diabetic patients (aged 55-80 years) with hypertension and electrocardiographic LVH during 4.8-year losartan- or atenolol-based treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Baseline mean blood pressure (BP) and LV mass did...... shortening (both phypertensive patients with LVH, diabetes is associated with more residual LVH and less improvement in systolic LV function by echocardiography over 4.8 years of antihypertensive treatment....

  15. Two-chiral component microemulsion EKC - chiral surfactant and chiral oil. Part 2: diethyl tartrate.

    Science.gov (United States)

    Kahle, Kimberly A; Foley, Joe P

    2007-08-01

    In this second study on dual-chirality microemulsions containing a chiral surfactant and a chiral oil, a less hydrophobic and lower interfacial tension chiral oil, diethyl tartrate, is employed (Part 1, Foley, J. P. et al.., Electrophoresis, DOI: 10.1002/elps.200600551). Six stereochemical combinations of dodecoxycarbonylvaline (DDCV: R, S, or racemic, 2.00% w/v), racemic 2-hexanol (1.65% v/v), and diethyl tartrate (D, L, or racemic, 0.88% v/v) were examined as pseudostationary phases (PSPs) for the enantioseparation of six chiral pharmaceutical compounds: pseudoephedrine, ephedrine, N-methyl ephedrine, metoprolol, synephrine, and atenolol. Average efficiencies increased with the addition of a chiral oil to R-DDCV PSP formulations. Modest improvements in resolution and enantioselectivity (alpha(enant)) were achieved with two-chiral-component systems over the one-chiral-component microemulsion. Slight enantioselective synergies were confirmed using a thermodynamic model. Results obtained in this study are compared to those obtained in Part 1 as well as those obtained with chiral MEEKC using an achiral, low-interfacial-tension oil (ethyl acetate). Dual-chirality microemulsions with the more hydrophobic oil dibutyl tartrate yielded, relative to diethyl tartrate, higher efficiencies (100,000-134,000 vs. 80,800-94,300), but lower resolution (1.64-1.91 vs. 2.08-2.21) due to lower enantioselectivities (1.060-1.067 vs. 1.078-1.081). Atenolol enantiomers could not be separated with the dibutyl tartrate-based microemulsions but were partially resolved using diethyl tartrate microemulsions. A comparable single-chirality microemulsion based on the achiral oil ethyl acetate yielded, relative to diethyl tartrate, lower efficiency (78 300 vs. 91 600), higher resolution (1.99 vs. 1.83), and similar enantioselectivities.

  16. Autoantibodies with beta-adrenergic activity from chronic chagasic patients induce cardiac arrhythmias and early afterdepolarization in a drug-induced LQT2 rabbit hearts.

    Science.gov (United States)

    Jiménez, Marco Antonio Vidal; Nascimento, José H M; Monnerat, Gustavo; Maciel, Leonardo; Paiva, Claudia N; Pedrosa, Roberto Coury; Campos de Carvalho, Antonio C; Medei, Emiliano

    2017-08-01

    Cardiac arrhythmias are one of the main causes of death in ChCP and other dilated cardiomyopathies. Previous studies demonstrated that ventricular arrhythmias are associated with the presence of autoantibodies with beta-adrenergic activity, Ab-β. The aim of this study was to investigate whether Ab-β, present in chronic chagasic patients (ChCP), induce cardiac arrhythmias in the pharmacological type-2 long QT syndrome model (LQTS-2). The LQTS2 was established by perfusion of Tyrode saline solution with a potassium channel blocker E-4031 (5μM) in isolated rabbit hearts or in rabbit cardiac strips, in order to record ECG or action potential, respectively. Autoantibodies from ChCP activating (Ab-β) or not (Ab-NR) cardiac beta 1-adrenergic receptors were used. Ab-β, but not Ab-NR, were able to significantly shorten QT, QTc and increase Tpeak-Tend interval in the LQTS-2. A positive correlation between higher QTc and Tpeak-Tend was found after Ab-β perfusion in the same model. In addition, in the LQTS-2 model, in almost 75% (11/15) of the hearts perfused with Ab-β, ventricular and atrio-ventricular electrical disturbances were observed. Atenolol abolished all Ab-β-induced arrhythmias. Ab-β, when perfused in a cellular LQTS-2, drastically reduced the action potential duration and evoked early afterdepolarization (EAD's), while Ab-NR did not modulate the AP properties in the LQTS-2. The results indicate that Ab-β were able to induce cardiac arrhythmias and EAD's. This phenomenon can explain, at least in part, the cellular mechanism of Ab-β-induced arrhythmias. Furthermore, atenolol is effective for the treatment of Ab-β-induced arrhythmias. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  17. Multitracer experiment to evaluate the attenuation of selected organic micropollutants in a karst aquifer.

    Science.gov (United States)

    Hillebrand, Olav; Nödler, Karsten; Sauter, Martin; Licha, Tobias

    2015-02-15

    The increasing pressure on drinking water resources necessitates an efficient management of potential and actual drinking water resources. Karst aquifers play a key role in the supply of the world's population with drinking water. Around one quarter of all drinking water is produced from these types of aquifers. Unfortunately due to the aquifer characteristics with extremely high hydraulic conductivities and short residence times, these systems are vulnerable to contamination. For successful management, a fundamental understanding of mass transport and attenuation processes with respect to potential contaminants is vital. In this study, a multitracer experiment was performed in a karst aquifer in SW-Germany for determining the attenuation capacity of a karst environment by assessing the environmental fate of selected relevant micropollutants. Uranine, acesulfame and carbamazepine were injected into a sinkhole as reference tracers together with the reactive compounds atenolol, caffeine, cyclamate, ibuprofen and paracetamol (also known as acetaminophen). The breakthrough of the tracers was monitored at a karst spring at a distance of ca. 3 km. The breakthrough curves of the reactive compounds were interpreted relative to the reference substances. No significant retardation was found for any of the investigated micropollutants. The determined half-lives of the reactive compounds range from 38 to 1,400 h (i.e. persistent within the investigation period) in the following order (from high to no observed attenuation): paracetamol>atenolol≈ibuprofen>caffeine≫cyclamate. The attenuation rates are generally in agreement with studies from other environmental compartments. The occurrence of the biotransformation product atenolol acid served as evidence for in-situ biodegradation within the aquifer system. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Analysis of some pharmaceuticals in municipal wastewater of Almadinah Almunawarah

    KAUST Repository

    Shraim, Amjad

    2012-11-29

    The chemical pollution of water resources is a major challenge facing the humanity in this century. Pharmaceuticals and personal care products (PPCPs) are a group of emerging environmental chemical pollutants distinguished by their bioactivity and high solubility. They may also cause health complications to humans and living organisms. Pharmaceuticals enter the environment, mainly via wastewater and can eventually reach the surface and ground water. Despite this, PPCPs received less attention as environmental pollutants than other chemical pollutants (e.g. heavy metals and pesticides). The purpose of this work was to investigate the presence of some of the most frequently dispensed drugs for the residents of Almadinah Almunawarah, Saudi Arabia in the municipal wastewater before and after treatment. For this purpose, wastewater samples were collected biweekly from the city’s sewage treatment plant for a period of 4 months and analyzed the targeted drugs using tandem LC–MS. Out of the 19 investigated drugs, 5 pharmaceuticals have been found in concentrations greater than the limit of detection in both the influents and effluents of the sewage treatment plant. As expected, the concentrations of investigated pharmaceuticals in the wastewater were found to be low. These drugs and their average concentrations (in ng mL−1) in the influents were: acetaminophen (38.9), metformin (15.2), norfluoxetine (7.07), atenolol (2.04), and cephalexin (1.88). Meanwhile, the effluents contained slightly lower levels (in ng mL−1) than those of influents: acetaminophen (31.2), metformin (3.19), norfluoxetine (7.25), atenolol (0.545), and cephalexin (1.53). The results of this study supported by many other investigations indicate the inefficiency of current conventional wastewater treatment protocols in eliminating such a group of active and potentially hazardous pollutants from the wastewater.

  19. Quantifying the impoverishing effects of purchasing medicines: a cross-country comparison of the affordability of medicines in the developing world.

    Science.gov (United States)

    Niëns, Laurens M; Cameron, Alexandra; Van de Poel, Ellen; Ewen, Margaret; Brouwer, Werner B F; Laing, Richard

    2010-08-31

    Increasing attention is being paid to the affordability of medicines in low- and middle-income countries (LICs and MICs) where medicines are often highly priced in relation to income levels. The impoverishing effect of medicine purchases can be estimated by determining pre- and postpayment incomes, which are then compared to a poverty line. Here we estimate the impoverishing effects of four medicines in 16 LICs and MICs using the impoverishment method as a metric of affordability. Affordability was assessed in terms of the proportion of the population being pushed below US$1.25 or US$2 per day poverty levels because of the purchase of medicines. The prices of salbutamol 100 mcg/dose inhaler, glibenclamide 5 mg cap/tab, atenolol 50 mg cap/tab, and amoxicillin 250 mg cap/tab were obtained from facility-based surveys undertaken using a standard measurement methodology. The World Bank's World Development Indicators provided household expenditure data and information on income distributions. In the countries studied, purchasing these medicines would impoverish large portions of the population (up to 86%). Originator brand products were less affordable than the lowest-priced generic equivalents. In the Philippines, for example, originator brand atenolol would push an additional 22% of the population below US$1.25 per day, whereas for the lowest priced generic equivalent this demographic shift is 7%. Given related prevalence figures, substantial numbers of people are affected by the unaffordability of medicines. Comparing medicine prices to available income in LICs and MICs shows that medicine purchases by individuals in those countries could lead to the impoverishment of large numbers of people. Action is needed to improve medicine affordability, such as promoting the use of quality assured, low-priced generics, and establishing health insurance systems. Please see later in the article for the Editors' Summary.

  20. Quantifying the impoverishing effects of purchasing medicines: a cross-country comparison of the affordability of medicines in the developing world.

    Directory of Open Access Journals (Sweden)

    Laurens M Niëns

    Full Text Available BACKGROUND: Increasing attention is being paid to the affordability of medicines in low- and middle-income countries (LICs and MICs where medicines are often highly priced in relation to income levels. The impoverishing effect of medicine purchases can be estimated by determining pre- and postpayment incomes, which are then compared to a poverty line. Here we estimate the impoverishing effects of four medicines in 16 LICs and MICs using the impoverishment method as a metric of affordability. METHODS AND FINDINGS: Affordability was assessed in terms of the proportion of the population being pushed below US$1.25 or US$2 per day poverty levels because of the purchase of medicines. The prices of salbutamol 100 mcg/dose inhaler, glibenclamide 5 mg cap/tab, atenolol 50 mg cap/tab, and amoxicillin 250 mg cap/tab were obtained from facility-based surveys undertaken using a standard measurement methodology. The World Bank's World Development Indicators provided household expenditure data and information on income distributions. In the countries studied, purchasing these medicines would impoverish large portions of the population (up to 86%. Originator brand products were less affordable than the lowest-priced generic equivalents. In the Philippines, for example, originator brand atenolol would push an additional 22% of the population below US$1.25 per day, whereas for the lowest priced generic equivalent this demographic shift is 7%. Given related prevalence figures, substantial numbers of people are affected by the unaffordability of medicines. CONCLUSIONS: Comparing medicine prices to available income in LICs and MICs shows that medicine purchases by individuals in those countries could lead to the impoverishment of large numbers of people. Action is needed to improve medicine affordability, such as promoting the use of quality assured, low-priced generics, and establishing health insurance systems. Please see later in the article for the Editors

  1. Removal of beta-blockers from aqueous media by adsorption onto graphene oxide

    Energy Technology Data Exchange (ETDEWEB)

    Kyzas, George Z. [Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, GR-541 24 Thessaloniki (Greece); Koltsakidou, Anastasia [Laboratory of Environmental Pollution Control, Department of Chemistry, Aristotle University of Thessaloniki, GR–541 24 Thessaloniki (Greece); Nanaki, Stavroula G.; Bikiaris, Dimitrios N. [Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, GR-541 24 Thessaloniki (Greece); Lambropoulou, Dimitra A., E-mail: dlambro@chem.auth.gr [Laboratory of Environmental Pollution Control, Department of Chemistry, Aristotle University of Thessaloniki, GR–541 24 Thessaloniki (Greece)

    2015-12-15

    The aim of the present study is the evaluation of graphene oxide (GhO) as adsorbent material for the removal of beta-blockers (pharmaceutical compounds) in aqueous solutions. The composition and morphology of prepared materials were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). Atenolol (ATL) and propranolol (PRO) were used as model drug molecules and their behavior were investigated in terms of GhO dosage, contact time, temperature and pH. Adsorption mechanisms were proposed and the pH-effect curves after adsorption were discussed. The kinetic behavior of GhO-drugs system was analyzed after fitting to pseudo-first and -second order equations. The adsorption equilibrium data were fitted to Langmuir, Freundlich and Langmuir–Freundlich model calculating the maximum adsorption capacity (67 and 116 mg/g for PRO and ATL (25 °C), respectively). The temperature effect on adsorption was tested carrying out the equilibrium adsorption experiments at three different temperatures (25, 45, 65 °C). Then, the thermodynamic parameters of enthalpy, free energy and entropy were calculated. Finally, the desorption of drugs from GhO was evaluated by using both aqueous eluants (pH 2–10) and organic solvents. - Highlights: • Removal of beta-blockers by graphene oxide (GhO) from aqueous samples • Detailed adsorbent characterization and adsorption studies • Kinetic studies are performed and adsorption isotherms are determined and modeled. • GhO was proved to be an effective adsorbent for removal of atenolol and propranolol.

  2. Impact of sludge stabilization processes and sludge origin (urban or hospital) on the mobility of pharmaceutical compounds following sludge landspreading in laboratory soil-column experiments.

    Science.gov (United States)

    Lachassagne, Delphine; Soubrand, Marilyne; Casellas, Magali; Gonzalez-Ospina, Adriana; Dagot, Christophe

    2015-11-01

    This study aimed to determine the effect of sludge stabilization treatments (liming and anaerobic digestion) on the mobility of different pharmaceutical compounds in soil amended by landspreading of treated sludge from different sources (urban and hospital). The sorption and desorption potential of the following pharmaceutical compounds: carbamazepine (CBZ), ciprofloxacin (CIP), sulfamethoxazole (SMX), salicylic acid (SAL), ibuprofen (IBU), paracetamol (PAR), diclofenac (DIC), ketoprofen (KTP), econazole (ECZ), atenolol (ATN), and their solid-liquid distribution during sludge treatment (from thickening to stabilization) were investigated in the course of batch testing. The different sludge samples were then landspread at laboratory scale and leached with an artificial rain simulating 1 year of precipitation adapted to the surface area of the soil column used. The quality of the resulting leachate was investigated. Results showed that ibuprofen had the highest desorption potential for limed and digested urban and hospital sludge. Ibuprofen, salicylic acid, diclofenac, and paracetamol were the only compounds found in amended soil leachates. Moreover, the leaching potential of these compounds and therefore the risk of groundwater contamination depend mainly on the origin of the sludge because ibuprofen and diclofenac were present in the leachates of soils amended with urban sludge, whereas paracetamol and salicylic acid were found only in the leachates of soils amended with hospital sludge. Although carbamazepine, ciprofloxacin, sulfamethoxazole, ketoprofen, econazole, and atenolol were detected in some sludge, they were not present in any leachate. This reflects either an accumulation and/or (bio)degradation of these compounds (CBZ, CIP, SMX, KTP, ECZ, and ATN ), thus resulting in very low mobility in soil. Ecotoxicological risk assessment, evaluated by calculating the risk quotients for each studied pharmaceutical compound, revealed no high risk due to the

  3. Structural basis of drugs that increase cardiac inward rectifier Kir2.1 currents.

    Science.gov (United States)

    Gómez, Ricardo; Caballero, Ricardo; Barana, Adriana; Amorós, Irene; De Palm, Sue-Haida; Matamoros, Marcos; Núñez, Mercedes; Pérez-Hernández, Marta; Iriepa, Isabel; Tamargo, Juan; Delpón, Eva

    2014-11-01

    We hypothesize that some drugs, besides flecainide, increase the inward rectifier current (IK1) generated by Kir2.1 homotetramers (IKir2.1) and thus, exhibit pro- and/or antiarrhythmic effects particularly at the ventricular level. To test this hypothesis, we analysed the effects of propafenone, atenolol, dronedarone, and timolol on Kir2.x channels. Currents were recorded with the patch-clamp technique using whole-cell, inside-out, and cell-attached configurations. Propafenone (0.1 nM-1 µM) did not modify either IK1 recorded in human right atrial myocytes or the current generated by homo- or heterotetramers of Kir2.2 and 2.3 channels recorded in transiently transfected Chinese hamster ovary cells. On the other hand, propafenone increased IKir2.1 (EC50 = 12.0 ± 3.0 nM) as a consequence of its interaction with Cys311, an effect which decreased inward rectification of the current. Propafenone significantly increased mean open time and opening frequency at all the voltages tested, resulting in a significant increase of the mean open probability of the channel. Timolol, which interacted with Cys311, was also able to increase IKir2.1. On the contrary, neither atenolol nor dronedarone modified IKir2.1. Molecular modelling of the Kir2.1-drugs interaction allowed identification of the pharmacophore of drugs that increase IKir2.1. Kir2.1 channels exhibit a binding site determined by Cys311 that is responsible for drug-induced IKir2.1 increase. Drug binding decreases channel affinity for polyamines and current rectification, and can be a mechanism of drug-induced pro- and antiarrhythmic effects not considered until now. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  4. Impact of wastewater treatment plants on receiving surface waters and a tentative risk evaluation: the case of estrogens and beta blockers.

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    Gabet-Giraud, V; Miège, C; Jacquet, R; Coquery, M

    2014-02-01

    Five estrogenic hormones (unconjugated + conjugated fractions) and 10 beta blockers were analyzed in three wastewater treatment plant (WWTP) effluents and receiving river waters in the area of Lyon, France. In the different samples, only two estrogens were quantified: estrone and estriol. Some beta blockers, such as atenolol, acebutolol, and sotalol, were almost always quantified, but others, e.g., betaxolol, nadolol, and oxprenolol were rarely quantified. Concentrations measured in river waters were in the nanogram per liter range for estrogens and between 0.3 and 210 ng/L for beta blockers depending on the substance and the distance from the WWTP outfall. The impact of the WWTP on the receiving rivers was studied and showed a clear increase in concentrations near the WWTP outfall. For estrogens, the persistence in surface waters was not evaluated given the low concentrations levels (around 1 ng/L). For beta blockers, concentrations measured downstream of the WWTP outfall were up to 16 times higher than those measured upstream. Also, the persistence of metoprolol, nadolol, and propranolol was noted even 2 km downstream of the WWTP outfall. The comparison of beta blocker fingerprints in the samples collected in effluent and in the river also showed the impact of WWTP outfall on surface waters. Finally, a tentative environmental risk evaluation was performed on 15 sites by calculating the ratio of receiving water concentrations to predicted non-effect concentrations (PNEC). For estrogens, a total PNEC of 5 ng/L was considered and these substances were not linked to any potential environmental risk (only one site showed an environmental risk ratio above 1). Unfortunately, few PNECs are available and risk evaluation was only possible for 4 of the 10 beta blockers studied: acebutolol, atenolol, metoprolol, and propranolol. Only propranolol presented a ratio near or above 1, showing a possible environmental risk for 4 receiving waters out of 15.

  5. The high frequency relationship: implications for torsadogenic hERG blockers.

    Science.gov (United States)

    Champeroux, P; Le Guennec, J Y; Jude, S; Laigot, C; Maurin, A; Sola, M L; Fowler, J S L; Richard, S; Thireau, J

    2016-02-01

    Ventricular arrhythmias induced by human ether-a-go-go related gene (hERG; Kv 11.1 channel) blockers are a consequence of alterations in ventricular repolarisation in association with high-frequency (HF) oscillations, which act as a primary trigger; the autonomic nervous system plays a modulatory role. In the present study, we investigated the role of β1 -adrenoceptors in the HF relationship between magnitude of heart rate and QT interval changes within discrete 10 s intervals (sorted into 5 bpm heart rate increments) and its implications for torsadogenic hERG blockers. The HF relationship was studied under conditions of autonomic blockade with atenolol (β1 -adrenoceptor blocker) in the absence or presence of five hERG blockers in beagle dogs. In total, the effects of 14 hERG blockers on the HF relationship were investigated. All the torsadogenic hERG blockers tested caused a vertical shift in the HF relationship, while hERG blockers associated with a low risk of Torsades de Pointes did not cause any vertical shift. Atenolol completely prevented the effects four torsadogenic agents (quinidine, thioridazine, risperidone and terfenadine) on the HF relationship, but only partially reduced those of dofetilide, leading to the characterization of two types of torsadogenic agent. Analysis of the vertical shift in the HF relationship demonstrated that signs of transient sympathetic activation during HF oscillations in the presence of torsadogenic hERG blockers are mediated by β1 -adrenoceptors. We suggest the HF relationship as a new biomarker for assessing Torsades de pointes liability, with potential implications in both preclinical studies and the clinic. © 2015 The British Pharmacological Society.

  6. Occurrence, ecotoxicological effects and risk assessment of antihypertensive pharmaceutical residues in the aquatic environment--A review.

    Science.gov (United States)

    Godoy, Aline A; Kummrow, Fábio; Pamplin, Paulo Augusto Z

    2015-11-01

    This study presents a review of the investigated antihypertensives in different aquatic compartments. It aims to compare these data with those regarding ecotoxicity effects in order to find out ecotoxicological data gaps for these pharmaceuticals and to point out the need for future studies. In addition, part of this article is dedicated to the risk assessment of the parent compounds atenolol, metoprolol, propranolol and verapamil, which are of great environmental concern in terms of contamination levels and for which there are sufficient ecotoxicological data available. 79 articles were retrieved presenting quantization data for 34 different antihypertensives and/or their metabolites. Only 43 articles were found regarding acute and chronic ecotoxicological effects of antihypertensive drugs. The results indicated that the beta-blockers atenolol, metoprolol and propranolol are the antihypertensives most frequently detected in the aquatic environment. They are also the drugs which reached the highest maximum concentrations in surface waters in the data reported in the literature. The highest percentages of ecotoxicity data regarding antihypertensives were also related to these beta-blockers. On the other hand, there is clearly a lack of ecotoxicity data, especially the chronic ones, regarding other antihypertensives. The environmental risk assessment (ERA) showed that all three of the evaluated beta-blockers can pose a potential long-term risk for non-target organisms of both fresh and marine water species. However, more meaningful ecotoxicity data for antihypertensives, including saltwater species, are required to refine and enlarge these results. Additional studies focusing on potential interactions between pharmaceutical mixtures, including antihypertensives, are also an urgent need. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. The Effect of Sympathetic Antagonists on the Antidepressant Action of Alprazolam

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    Gorash ZM

    2008-01-01

    Full Text Available Alprazolam is an anti-anxiety drug shown to be effective in the treatment of depression. In this study, the effect of sympathetic receptor antagonists on alprazolam–induced antidepressant action was studied using a mouse model of forced swimming behavioral despair. The interaction of three sympathetic receptor antagonists with benzodiazepines, which may impact the clinical use of alprazolam, was also studied. Behavioral despair was examined in six groups of albino mice. Drugs were administered intraperitoneally. The control group received only a single dose of 1% Tween 80. The second group received a single dose of alprazolam, and the third group received an antagonist followed by alprazolam. The fourth group was treated with imipramine, and the fifth group received an antagonist followed by imipramine. The sixth group was treated with a single dose of an antagonist alone (atenolol, a β1-selective adrenoceptor antagonist; propranolol, a non selective β-adrenoceptor antagonist; and prazocin, an α1-adrenoceptor antagonist. Results confirmed the antidepressant action of alprazolam and imipramine. Prazocin treatment alone produced depression, but it significantly potentiated the antidepressant actions of imipramine and alprazolam. Atenolol alone produced an antidepressant effect and potentiated the antidepressant action of alprazolam. Propranolol treatment alone produced depression, and antagonized the effects of alprazolam and imipramine, even producing depression in combined treatments. In conclusion, our results reveal that alprazolam may produce antidepressant effects through the release of noradrenaline, which stimulates β2 receptors to produce an antidepressant action. Imipramine may act by activating β2 receptors by blocking or down-regulating β1 receptors.

  8. Isoflurane depresses baroreflex control of heart rate in decerebrate rats.

    Science.gov (United States)

    Lee, Jong S; Morrow, Don; Andresen, Michael C; Chang, Kyoung S K

    2002-05-01

    Isoflurane inhibits baroreflex control of heart rate (HR) by poorly understood mechanisms. The authors examined whether suprapontine central nervous system cardiovascular regulatory sites are required for anesthetic depression. The effects of isoflurane (1 and 2 rat minimum alveolar concentration [MAC]) on the baroreflex control of HR were determined in sham intact and midcollicular-transected decerebrate rats. Intravenous phenylephrine (0.2-12 microg/kg) and nitroprusside (1-60 microg/kg) were used to measure HR responses to peak changes in mean arterial pressure (MAP). Sigmoidal logistic curve fits to HR-MAP data assessed baroreflex sensitivity (HR/MAP), HR range, lower and upper HR plateau, and MAP at half the HR range (BP50). Four groups (two brain intact and two decerebrate) were studied before, during, and after isoflurane. To assess sympathetic and vagal contributions to HR baroreflex, beta-adrenoceptor (1 mg/kg atenolol) or muscarinic (0.5 mg/kg methyl atropine) antagonists were administered systemically. Decerebration did not alter resting MAP and HR or baroreflex parameters. Isoflurane depressed baroreflex slope and HR range in brain-intact and decerebrate rats. In both groups, 1 MAC reduced HR range by depressing peak reflex tachycardia. Maximal reflex bradycardia during increases in blood pressure was relatively preserved. Atenolol during 1 MAC did not alter maximum reflex tachycardia. In contrast, atropine during 1 MAC fully blocked reflex bradycardia. Therefore, 1 MAC predominantly depresses sympathetic components of HR baroreflex. Isoflurane at 2 MAC depressed both HR plateaus and decreased BP50 in both groups. Isoflurane depresses HR baroreflex control by actions that do not require suprapontine central nervous system sites. Isoflurane actions seem to inhibit HR baroreflex primarily by the sympathetic nervous system.

  9. Photochemical fate of beta-blockers in NOM enriched waters.

    Science.gov (United States)

    Wang, Ling; Xu, Haomin; Cooper, William J; Song, Weihua

    2012-06-01

    Beta-blockers, prescribed for the treatment of high blood pressure and for long-term use after a heart attack, have been detected in surface and ground waters. This study examines the photochemical fate of three beta-blockers, atenolol, metoprolol, and nadolol. Hydrolysis accounted for minor losses of these beta-blockers in the pH range 4-10. The rate of direct photolysis at pH 7 in a solar simulator varied from 6.1 to 8.9h(-1) at pH 7. However, the addition of a natural organic matter (NOM) isolate enhanced the photochemical loss of all three compounds. Indirect photochemical fate, generally described by reactions with hydroxyl radical (OH) and singlet oxygen ((1)ΔO(2)), and, the direct reaction with the triplet excited state, (3)NOM(⁎), also varied but collectively appeared to be the major loss factor. Bimolecular reaction rate constants of the three beta-blockers with (1)ΔO(2) and OH were measured and accounted for 0.02-0.04% and 7.2-38.9% of their loss, respectively. These data suggest that the (3)NOM(⁎) contributed 50.6-85.4%. Experiments with various (3)NOM(⁎) quenchers supported the hypothesis that it was singly the most important reaction. Atenolol was chosen for more detailed investigation, with the photoproducts identified by LC-MS analysis. The results suggested that electron-transfer could be an important mechanism in photochemical fate of beta-blockers in the presence of NOM. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Uptake and effects of a mixture of widely used therapeutic drugs in Eruca sativa L. and Zea mays L. plants.

    Science.gov (United States)

    Marsoni, Milena; De Mattia, Fabrizio; Labra, Massimo; Bruno, Antonia; Bruno, Antonella; Bracale, Marcella; Vannini, Candida

    2014-10-01

    Pharmaceutically active compounds (PACs) are continuously dispersed into the environment due to human and veterinary use, giving rise to their potential accumulation in edible plants. In this study, Eruca sativa L. and Zea mays L. were selected to determine the potential uptake and accumulation of eight different PACs (Salbutamol, Atenolol, Lincomycin, Cyclophosphamide, Carbamazepine, Bezafibrate, Ofloxacin and Ranitidine) designed for human use. To mimic environmental conditions, the plants were grown in pots and irrigated with water spiked with a mixture of PACs at concentrations found in Italian wastewaters and rivers. Moreover, 10× and 100× concentrations of these pharmaceuticals were also tested. The presence of the pharmaceuticals was tested in the edible parts of the plants, namely leaves for E. sativa and grains for Z. mays. Quantification was performed by liquid chromatography mass spectroscopy (LC/MS/MS). In the grains of 100× treated Z. mays, only atenolol, lincomycin and carbamazepine were above the limit of detection (LOD). At the same concentration in E. sativa plants the uptake of all PACs was >LOD. Lincomycin and oflaxacin were above the limit of quantitation in all conditions tested in E. sativa. The results suggest that uptake of some pharmaceuticals from the soil may indeed be a potential transport route to plants and that these environmental pollutants can reach different edible parts of the selected crops. Measurements of the concentrations of these pharmaceuticals in plant materials were used to model potential adult human exposure to these compounds. The results indicate that under the current experimental conditions, crops exposed to the selected pharmaceutical mixture would not have any negative effects on human health. Moreover, no significant differences in the growth of E. sativa or Z. mays plants irrigated with PAC-spiked vs. non-spiked water were observed. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. MÉTODO DE ESCOLHA DE MEDICAMENTOS ANTI-HIPERTENSIVOS POR GESTORES DA ÁREA DE SAÚDE

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    Rondinelli de Carvalho LADEIRA

    2016-06-01

    Full Text Available Um problema enfrentado pelos gestores de saúde é a aquisição de medicamentos que, para o abastecimento do SUS, deve-se levar em consideração a efetividade, os custos e a segurança dos mesmos. A análise farmacoeconômica pode ser vista como a descrição e a análise dos custos da terapia farmacêutica para os sistemas de assistência à saúde e para a sociedade. O presente trabalho faz a análise de custo-efetividade de cinco betabloqueadores adrenérgicos usados no tratamento de hipertensão arterial (atenolol, carvedilol, metoprolol, propranolol e sotalol através de auxílio multicritério à decisão. Tendo em vista gestores de saúde como agentes da decisão, foram testados os métodos de Borda para definição dos pesos dos critérios por especialistas e AHP para escolha do medicamento através do software IPE 1.0. Questionários foram aplicados a sete profissionais médicos especialistas em cardiologia para a comparação dos critérios (efetividade, custo, experiência com o fármaco e segurança, sub-critérios (agravamento da insuficiência cardíaca congestiva, agravamento da doença arterial periférica, broncoespasmo, bradicardia e alterações metabólicas, relativos ao critério segurança e alternativas à luz dos critérios estudados. O betabloqueador que se apresentou como melhor escolha foi o atenolol (32,38%.

  12. Monitoring one-year compliance to antihypertension medication in the Seychelles.

    Science.gov (United States)

    Bovet, Pascal; Burnier, Michel; Madeleine, George; Waeber, Bernard; Paccaud, Fred

    2002-01-01

    To examine the compliance to medication among newly diagnosed hypertensive patients screened from the general population of the Seychelles, a rapidly developing country. Among the 1067 participants to a population-based survey for cardiovascular risk factors, hypertension was discovered in 50 (previously unaware of having hypertension and having blood pressure > or = 160/95 mmHg over 3 visits). These 50 patients were placed on a daily one-pill regimen of medication (bendrofluazide, atenolol, or a combination of hydrochlorothiazide and atenolol) and compliance to the regimen was assessed over 12 months using electronic pill containers. Satisfactory compliance was defined as taking the medication on 6 or 7 days a week on average (which corresponds to a mean compliance level of > or = 86%). In the first month, fewer than half (46%) of the new hypertension patients achieved satisfactory compliance, and only about one-quarter (26%) achieved this level by the twelfth month. Compliance was better among the 23 participants who regularly attended medical follow-up, with nearly three-quarters of these patients (74%) achieving satisfactory compliance during the first month and over one-half (55%) by the twelfth month. There was a direct association between mean 12-month compliance level and having a highly skilled occupation; having good health awareness; and regularly attending medical appointments. In contrast, there was an inverse relationship between mean compliance level and heavy drinking. The low proportion of people selected from the general population who were capable of sustaining satisfactory compliance to antihypertension medication may correspond to the maximum effectiveness of medication interventions based on a screening and treatment strategy in the general population. The results stress the need for both high-risk and population approaches to improve hypertension control.

  13. Evaluation Of Prescription Pattern And Medication Adherence Of Antihypertensive Drugs In Stage 1 Essential Hypertensive Patients At Rural Tertiary Care Teaching Hospital Of Central India.

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    Chetan S. Urade

    2016-09-01

    Full Text Available Objectives- To study the prescription pattern of antihypertensive drugs and analyze the medication adherence to antihypertensive drugs at rural tertiary care teaching hospital.Materials and Methods- Prospective, observational, 12 weeks, questionnaire based study, conducted in rural tertiary care teaching hospital of central India. 214 antihypertensive prescriptions were analyzed by Morisky medication adherence scale. Statistical analysis was done by MS Excel and Graph pad prism 6.0.Results- 28.03% patients were not aware about the medicines taken, 29.90% patients were unacquainted about dose and route of administration whereas 32.71% patients were unfamiliar about frequency of administration of medicines. 53.27% patients were unaware about precautions to be taken while consuming medicines.  58.68% & 12.67% patients consumed amlodipine & atenolol respectively. In 16.43% patients, atenolol + amlodipine combination therapy was prescribed.  Amongst 214 patients 12, 58 & 144 showed high, medium & low adherence respectively.  No significant difference was found on gender basis at any level of adherence.Conclusion- In this study, physicians given preference to amlodipine than other antihypertensive drugs. However, thiazide is a first line drug in stage 1 hypertension, recommended by JNC VII guideline. This indicates that there is need of creating awareness about current management of hypertension to clinicians by organizing various workshops. We observed only 5.60% patients showed high adherence to antihypertensive therapy. Therefore educational strategies must be carried out for physicians focusing on causes for nonadherence to antihypertensive medications. Also raising patient trust in their physicians may improve patient motivation to prescribed medication. 

  14. Analysis of some pharmaceuticals in municipal wastewater of Almadinah Almunawarah

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    Amjad Shraim

    2017-02-01

    Full Text Available The chemical pollution of water resources is a major challenge facing the humanity in this century. Pharmaceuticals and personal care products (PPCPs are a group of emerging environmental chemical pollutants distinguished by their bioactivity and high solubility. They may also cause health complications to humans and living organisms. Pharmaceuticals enter the environment, mainly via wastewater and can eventually reach the surface and ground water. Despite this, PPCPs received less attention as environmental pollutants than other chemical pollutants (e.g. heavy metals and pesticides. The purpose of this work was to investigate the presence of some of the most frequently dispensed drugs for the residents of Almadinah Almunawarah, Saudi Arabia in the municipal wastewater before and after treatment. For this purpose, wastewater samples were collected biweekly from the city's sewage treatment plant for a period of 4 months and analyzed the targeted drugs using tandem LC–MS. Out of the 19 investigated drugs, 5 pharmaceuticals have been found in concentrations greater than the limit of detection in both the influents and effluents of the sewage treatment plant. As expected, the concentrations of investigated pharmaceuticals in the wastewater were found to be low. These drugs and their average concentrations (in ng mL−1 in the influents were: acetaminophen (38.9, metformin (15.2, norfluoxetine (7.07, atenolol (2.04, and cephalexin (1.88. Meanwhile, the effluents contained slightly lower levels (in ng mL−1 than those of influents: acetaminophen (31.2, metformin (3.19, norfluoxetine (7.25, atenolol (0.545, and cephalexin (1.53. The results of this study supported by many other investigations indicate the inefficiency of current conventional wastewater treatment protocols in eliminating such a group of active and potentially hazardous pollutants from the wastewater.

  15. Methimazole-Induced Goitrogenesis in an Adult Patient With the Syndrome of Resistance to Thyroid Hormone

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    Kathleen Glymph DO

    2014-10-01

    Full Text Available Patients with the syndrome of resistance to thyroid hormone (RTH have clinical (tachycardia and anxiety and biochemical (elevated thyroid hormones level features of hyperthyroidism. Based on previous reports in pediatric patients with the RTH, antithyroid treatment in these patients is not indicated. Clinical and biochemical sequel of antithyroid therapy in an adult patient with RTH was not previously reported. A 63-year-old African American female with history of RTH was treated with a therapy consisting of methimazole 15 mg daily and atenolol. Methimazole treatment resulted in reduction in thyroid hormone level while the patient’s TSH increased with a peak of 24.88 mIU/L. Having achieved biochemical euthyroidism, the patient developed thyroid gland enlargement associated with progressive symptoms of dysphagia and dyspnea. Examination demonstrated globally enlarged firm thyroid gland with areas of nodularity in both lobes. A computed tomography of the neck showed enlarged thyroid gland with extension around bilateral sternocleidomastoid muscles and compression onto the trachea. Methimazole therapy was discontinued and patient was treated just on atenolol. Over 12 months following discontinuation of methimazole, the patient experienced marked clinical and radiographic improvement of the goiter size associated with TSH reduction to 1.26 mIU/L and modest free thyroxine increase as expected in RTH. It seems appealing to treat patients with the RTH with antithyroid medications. However, in these patients decrease in thyroid hormone levels will stimulate TSH production, which can, in turn, predispose to goiter formation. Our report supports prior observations in children with RTH that treatment with methimazole is not indicated in adult patients with RTH.

  16. Field and action potential recordings in heart slices: correlation with established in vitro and in vivo models

    Science.gov (United States)

    Himmel, Herbert M; Bussek, Alexandra; Hoffmann, Michael; Beckmann, Rolf; Lohmann, Horst; Schmidt, Matthias; Wettwer, Erich

    2012-01-01

    BACKGROUND AND PURPOSE Action potential (AP) recordings in ex vivo heart preparations constitute an important component of the preclinical cardiac safety assessment according to the ICH S7B guideline. Most AP measurement models are sensitive, predictive and informative but suffer from a low throughput. Here, effects of selected anti-arrhythmics (flecainide, quinidine, atenolol, sotalol, dofetilide, nifedipine, verapamil) on field/action potentials (FP/AP) of guinea pig and rabbit ventricular slices are presented and compared with data from established in vitro and in vivo models. EXPERIMENTAL APPROACH Data from measurements of membrane currents (hERG, INa), AP/FP (guinea pig and rabbit ventricular slices), AP (rabbit Purkinje fibre), haemodynamic/ECG parameters (conscious, telemetered dog) were collected, compared and correlated to complementary published data (focused literature search). KEY RESULTS The selected anti-arrhythmics, flecainide, quinidine, atenolol, sotalol, dofetilide, nifedipine and verapamil, influenced the shape of AP/FP of guinea pig and rabbit ventricular slices in a manner similar to that observed for rabbit PF. The findings obtained from slice preparations are in line with measurements of membrane currents in vitro, papillary muscle AP in vitro and haemodynamic/ECG parameters from conscious dogs in vivo, and were also corroborated by published data. CONCLUSION AND IMPLICATIONS FP and AP recordings from heart slices correlated well with established in vitro and in vivo models in terms of pharmacology and predictability. Heart slice preparations yield similar results as papillary muscle but offer enhanced throughput for mechanistic investigations and may substantially reduce the use of laboratory animals. PMID:22074238

  17. S-oxiracetam protect against ischemic stroke via alleviating blood brain barrier dysfunction in rats.

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    Huang, Liangliang; Shang, Erxin; Fan, Wenxiang; Li, Xiang; Li, Binbin; He, Shucheng; Fu, Yuxin; Zhang, Yizhi; Li, Yunman; Fang, Weirong

    2017-11-15

    The blood brain barrier (BBB) maintains the basic stability of the brain tissue under physiological conditions, while destroys and exaggerates brain edema and inflammatory response after ischemic stroke. In this study, we researched S-oxiracetam (S-ORC), a nootropic drug, alleviates BBB dysfunction and protects against ischemic stroke in rats. Middle cerebral artery occlusion(MCAO)/reperfusion in rats is applied to mimic ischemic stroke. One hour after reperfusion, rats are administered intravenously with different dose (0.12, 0.24, or 0.48g/kg) of S-ORC for continuative three days. Seventy-two hours after MCAO, TTC staining, hematoxylin and eosin (H&E) staining, brain water content, immunohistochemical staining, EB extravasation, western blot are provided to evaluate the protective effect and possible mechanism of S-ORC on BBB dysfunction. Furthermore, brain concentration of verapamil (P-glycoprotein substrate) and atenolol (paracellular transport marker) were assayed by UPLC-MS/MS co administration with or without S-ORC. The results show that post-treatment of S-ORC decreases cerebral infarct size, lessens brain edema, inhibits neutrophil infiltration and cytokines releasing. Furthermore, S-ORC treatment decreases EB leakage, downregulates MMP-9, upregulates occludin and claudin-5, and decreases brain concentration of verapamil and atenolol after MCAO surgery. In conclusion, the present study demonstrates that post-treatment of S-ORC alleviates BBB dysfunction by regulating tight junction proteins (TJPs), upregulating P-glycoprotein function, and protects against ischemic stroke as result. Copyright © 2017. Published by Elsevier B.V.

  18. Combinação de anlodipino e enalaprila em pacientes hipertensos com doença coronariana Combinación de amlodipino y enalapril en pacientes hipertensos con enfermedad coronaria Combination of amlodipine and enalapril in hypertensive patients with coronary disease

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    Marcos Rienzo

    2009-03-01

    Full Text Available FUNDAMENTO: Pacientes (pts com doença coronariana (DAC estável podem se beneficiar de menor pressão arterial (PA, conforme estudos recentes. OBJETIVO: Avaliar a eficácia e a tolerabilidade da combinação fixa anlodipino + enalaprila, comparada a anlodipino na normalização da PA diastólica (PAD ( 90 e 110 mmHg durante o wash-out de quatro semanas, em uso só de atenolol. Após wash-out randomizamos para combinação (A ou anlodipino (B e seguimos de quatro em quatro semanas até 98 dias. As doses (mg iniciais foram, respectivamente: A- 2,5/10 e B- 2,5, sendo incrementadas se PAD> 85mmHg, nas visitas. Estatística com χ2, Fischer e análise de variância, para pFUNDAMENTO: Pacientes (pts con enfermedad coronaria (EAC estable pueden beneficiarse con una menor presión arterial (PA, de acuerdo con estudios recientes. OBJETIVO: Evaluar la eficacia y la tolerancia de la combinación fija amlodipino + enalapril, comparada a el amlodipino en la normalización de la PA diastólica (PAD (90 y 110 mmHg durante el wash-out de cuatro semanas, en uso sólo de atenolol. Después del wash-out randomizamos para combinación (A o amlopidino (B y seguimos de cuatro en cuatro semanas hasta 98 días. Las dosis (mg iniciales fueron, respectivamente: A- 2,5/10 y B- 2,5, siendo incrementadas si PAD> 85mmHg, en las visitas. Estadística con χ2, Fischer y análisis de varianza, para pBACKGROUND: Patients (pts with stable coronary artery disease (CAD can benefit from a decrease in the blood pressure (BP, according to recent studies. OBJECTIVE: To evaluate the efficacy and tolerability of the fixed combination: amlodipine + enalapril, when compared to amlodipine in the normalization of the diastolic arterial pressure (DAP (90 and 110 mmHg during the four-week wash-out with atenolol treatment alone, were excluded. After the wash-out, pts were randomly distributed for the use of the combination (A or amlodipine (B and were followed every four weeks up to 98 days

  19. Uso incorreto de medicamentos por pacientes após acidente vascular cerebral Uso incorrecto de medicamentos por pacientes después de un accidente cerebro vascular Incorrect use of medicines by patients post cerebrovascular accident

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    Lolita Dopico da Silva

    2011-07-01

    Full Text Available Objetivo. Avaliar o emprego de medicamentos no lar pelos pacientes vítimas de um acidente vascular cerebral (AVC. Metodologia. Estudo transversal de uma mostra representativa de 30 pacientes que recebiam atendimento público domiciliário no Rio de Janeiro (Brasil em 2008. Por meio de entrevista estruturada aos pacientes se tomou informação sobre os fatores de risco para AVC, os medicamentos que estavam tomando e o uso correto ou incorreto dos mesmos, utilizando para isto a classificação de DRUGDEX® System. Resultados. Os participantes de idade avançada e com predomínio de mulheres. A média de medicamentos por foi 3.3. As causas do erro mais comuns foram: a tomada do medicamento com alimentos e com outras medicações. As proporções mais altas de uso incorreto de medicamento em mais de 50% das doses foram: espironolactona, glibenclamida e atenolol (a cada uma com 100.0%, sinvastatina (87.5%, furosemida (83.3%, captropril (72.5% e insulina NPH (66.7%. Conclusão. Uma grande proporção de pacientes depois de um AVC usam incorretamente os medicamentos prescritos para o tratamento no lar.Objetivo. Evaluar el empleo de medicamentos en el hogar por los pacientes víctimas de un accidente cerebrovascular (ACV. Metodología. Estudio transversal de una muestra representativa de 30 pacientes que recibían atención pública domiciliario en Río de Janeiro (Brasil en 2008. En la muestra predominaron las mujeres y los pacientes de edad avanzada. Por medio de entrevista estructurada a los pacientes se tomó información sobre los factores de riesgo para ACV, los medicamentos que estaban tomando y el uso correcto o incorrecto de los mismos, utilizando para esto la clasificación de DRUGDEX® System. Resultados. El promedio de medicamentos por fue 3.3. Las causas más comunes de error fueron la toma del medicamento con alimentos y con otras medicaciones. Las proporciones más altas de uso incorrecto de medicamento en más del 50% de las dosis

  20. THE EFFECT OF NEBIVOLOL ON BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN WITH MILD HYPERTENSION

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    I. L. Tepoyan

    2015-09-01

    Full Text Available Aim. To study the effects of nebivolol on bone mineral density (BMD in postmenopausal women with mild hypertension (HT and osteopenia.Material and methods. Postmenopausal women (n=56 aged 50-65 years with mild HT фтв osteopenia were included into the randomized controlled study and divided in two groups (28 patients in each. During 12 months patients of the main group received treatment with nebivolol (5-7.5 mg/day and patients of the control group received treatment with atenolol (12.5-25 mg/day. Clinical and anthropometric examinations, blood pressure measurements, ECG registrations were performed in all patients initially and after 12 months of treatment. Quantitative estimation of BMD was performed by dual energy X-ray absorptiometry with osteodensitometry DELPHI W manufactured by HOLOGIC company (USA in the lumbar spine (L1-L4, femoral neck and proximal femur in the anterior-posterior projection. In addition, calcium and bone metabolism indices were determined: ionized calcium, total alkaline phosphatase, C-telopeptide of type I collagen (CTX.Results. Therapy of mild HT with nebivolol during 12 months showed increase in BMD in the spine according to the T-test from -1.7±0.4 SD to -1.4±0.53 SD (p<0.001, while in atenolol group this index decreased from -1.5±0.7 SD to -1.6±0.64 SD (p<0.001. When evaluating T-test of the femoral neck the index changed in the main group from - 1.4±0.44 SD to -1.27±0.5 SD (p=0.015, in the control group - from -1.3±0.64 SD to -1.5±0.65 SD (p=0.0005. In the study group T-test of proximal femur changed from -0.58±0.4 SD to -0.49±0.4 SD (p=0.003, and in the control group - from -0.8±0.84 SD to -0.83±0.93 SD (p=0.3. The dynamics of the BMD due to 12 month therapy in all investigated bone segments distinguished significantly between study and control groups. Nebivolol therapy group showed reduction in CTX level from 0.367±0.16 to 0.294±0.12 ng/ml (p<0.001, whereas the control group showed increase in

  1. Relative Importance of Aortic Stiffness and Volume as Predictors of Treatment-Induced Improvement in Left Ventricular Mass Index in Dialysis.

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    Panagiotis I Georgianos

    Full Text Available This study aimed to explore the relative contribution of aortic stiffness and volume in treatment-induced change of left ventricular mass in dialysis. Hypertension in Hemodialysis Patients Treated with Atenolol or Lisinopril trial compared the effect of lisinopril versus atenolol in reducing left ventricular mass index; 179 patients with echo measurements of aortic pulse wave velocity and left ventricular mass at baseline were included. In unadjusted analysis, overall reductions of 26.24 g/m2 (95% CI: -49.20, -3.29 and 35.67 g/m2 (95% CI: -63.70, -7.64 in left ventricular mass index were noted from baseline to 6 and 12 months respectively. Volume control emerged as an important determinant of regression of left ventricular mass index due to the following reasons: (i additional control for change in ambulatory systolic blood pressure mitigated the reduction in left ventricular mass index in the statistical model above [6-month visit: -18.6 g/m2 (95% CI: -43.7, 6.5; 12-month visit: -22.1 g/m2 (95% CI: -52.2, 8.0] (ii regression of left ventricular hypertrophy was primarily due to reduction in left ventricular chamber and not wall thickness and (iii adjustment for inferior vena cava diameter (as a proxy for volume removed the effect of time on left ventricular mass index reduction [6-month visit: -6.6 g/m2 (95% CI: (-41.6, 28.4; 12-month visit: 0.6 g/m2 (95% CI: -39.5, 40.7]. In contrast, aortic pulse wave velocity was neither a determinant of baseline left ventricular mass index nor predictor of its reduction. Among dialysis patients, ambulatory systolic pressure, a proxy for volume expansion, but not aortic stiffness is more important predictor of reduction in left ventricular mass index. Improving blood pressure control via adequate volume management appears as an effective strategy to improve left ventricular hypertrophy in dialysis.

  2. Liver X receptor α gene polymorphisms and variable cardiovascular outcomes in patients treated with antihypertensive therapy: results from the INVEST-GENES study.

    Science.gov (United States)

    Price, Elvin Tyrone; Pacanowski, Michael A; Martin, Michael A; Cooper-DeHoff, Rhonda M; Pepine, Carl J; Zineh, Issam; Johnson, Julie A

    2011-06-01

    Liver X receptor-α (LXRA) is a nuclear receptor that regulates genes important in cholesterol homeostasis and inflammation. Several single nucleotide polymorphisms (SNPs) in the LXRA gene (NR1H3) have been earlier associated with metabolic phenotypes (dyslipidemia and elevated body mass index). Metabolic dysregulation is a major contributor to coronary disease; therefore, we assessed LXRA in International Verapamil Sustained Release SR Trandolapril Study Genetic Substudy (INVEST-GENES), a genetic-substudy of a large clinical trial in patients with hypertension and coronary artery disease. Seven tag SNPs in the LXRA gene region (NR1H3) were selected for study: rs11039149, rs12221497, rs2279238, rs7120118, rs326213, rs11039159, and rs10501321. One thousand fifty-nine patients were genotyped from the INVEST-GENES case-control set (verapamil-sustained release-based or atenolol-based treatment strategies) that comprised of 297 cases frequency matched (approximately 2.5:1) with that of event-free controls by sex and race. The primary outcome was defined as first occurrence of all-cause death, nonfatal myocardial infarction, or nonfatal stroke. Adjusted odds ratios (ORs) were calculated using logistic regression. Three of the seven SNPs were associated with significant effects on the primary outcome in nonBlacks. The variant G allele of rs11039149 and the variant A allele of rs12221497 were associated with reduced risk of experiencing the primary outcome [OR: 0.62, confidence interval (CI): 0.45-0.85, P=0.003 and OR: 0.60, CI: 0.39-0.91, P=0.016, respectively]. The rs2279238 genotype was associated with a significant increase in risk for the primary outcome (OR: 1.42, CI: 1.03-1.95, P=0.03). Furthermore, there was a significant genotype-treatment strategy interaction for carriers of the variant T allele of rs2279238 (OR for verapamil-sustained release strategy compared with atenolol strategy: 2.86, CI: 1.50-5.46, P=0.0015). Diplotype analyses showed that the SNPs are

  3. Soil Aquifer Treatment (SAT) and Constructed Wetlands (CW) Applications for Nutrients and Organic Micropollutants (OMPs) Attenuation Using Primary and Secondary Wastewater Effluents

    KAUST Repository

    Hamadeh, Ahmed F.

    2014-06-01

    Constructed wetlands (CW) and soil aquifer treatment (SAT) represent natural wastewater treatment systems (NWTSs). The high costs of conventional wastewater treatment techniques encourage more studies to investigate lower cost treatment methods which make these appropriate for developing and also in developed countries. The main objective of this research was to investigate the removals of nutrients and organic micropollutants (OMPs) through SAT, CW and the CW-SAT hybrid system. CWs are an efficient technology to purify and remove different nutrients as well as OMPs from wastewater. They removed most of the dissolved organic matter (DOC), total nitrogen (TN), ammonium and phosphate. Furthermore, CWs aeration could be used as one of the alternatives to reduce CWs footprint by around 10%. The vegetation in CWs plays an essential role in the treatment especially for nitrogen and phosphate removals, it is responsible for the removal of 15%, 55%, 38%, and 22% for TN, dissolved organic nitrogen (DON), nitrate and phosphate, respectively. CWs achieved a very high removal for some OMPs; they attenuated acetaminophen, caffeine, fluoxetine and trimethoprim (>90%) under different redox conditions. Moreover, it was found that increasing temperature (up to 36 C) could enhance the removals of atenolol, caffeine, DEET and trimethoprim by 17%, 14%, 28% and 45%, respectively. On the other hand, some OMPs, were found to be removed by vegetation such as: acetaminophen, caffeine, fluoxetine, sulfamethoxazole, and trimethoprim. Moreover, atenolol, caffeine, fluoxetine and trimethoprim, showed high removal (>80%) through SAT system. It was also found that, temperature increasing and using primary instead of secondary effluent could enhance the removal of some OMPs. The CWs performance study showed that these systems are adapted to the prevailing extreme arid conditions and the average percent removals are about, 88%, 96%, 98%, 98% and 92%, for COD, BOD and TSS, ammonium and phosphate

  4. Metabolic responses to BRL37344 and clenbuterol in soleus muscle and C2C12 cells via different atypical pharmacologies and β2-adrenoceptor mechanisms

    Science.gov (United States)

    Ngala, R A; O'Dowd, J; Wang, S J; Agarwal, A; Stocker, C; Cawthorne, M A; Arch, J R S

    2008-01-01

    Background and purpose: Picomolar concentrations of the β3-adrenoceptor agonist BRL37344 stimulate 2-deoxyglucose uptake in soleus muscle via undefined receptors. Higher concentrations alter uptake, apparently via β2-adrenoceptors. Effects of BRL37344 and β2-adrenoceptor agonists are compared. Experimental approach: Mouse soleus muscles were incubated with 2-deoxy[1-14C]-glucose, [1-14C]-palmitate or [2-14C]-pyruvate, and BRL37344, β2-adrenoceptor agonists and selective β-adrenoceptor antagonists. Formation of 2-deoxy[1-14C]-glucose-6-phosphate or 14CO2 was measured. 2-Deoxy[1-14C]-glucose uptake and β-adrenoceptor mRNA were measured in C2C12 cells. Key results: 10 pM BRL37344, 10 pM clenbuterol and 100 pM salbutamol stimulated 2-deoxyglucose uptake in soleus muscle by 33–54%. The effect of BRL37344 was prevented by 1 μM atenolol but not by 300 nM CGP20712A or IC3118551, or 1 μM SR59230A; that of clenbuterol was prevented by ICI118551 but not atenolol. 10 nM BRL37344 st4mulated 2-deoxyglucose uptake, whereas 100 nM clenbuterol and salbutamol inhibited uptake. These effects were blocked by ICI118551. Similar results were obtained in C2C12 cells, in which only β2-adrenoceptor mRNA could be detected by RT-PCR. 10 nM BRL37344 and 10 pM clenbuterol stimulated muscle palmitate oxidation. In the presence of palmitate, BRL37344 no longer stimulated 2-deoxyglucose uptake and the effect of clenbuterol was not significant. Conclusions and implications: Stimulation of glucose uptake by 10 pM BRL37344 and clenbuterol involves different atypical pharmacologies. Nanomolar concentrations of BRL37344 and clenbuterol, probably acting via β2-adrenoceptors, have opposite effects on glucose uptake. The agonists preferentially stimulate fat rather than carbohydrate oxidation, but stimulation of endogenous fat oxidation cannot explain why 100 nM clenbuterol inhibited 2-deoxyglucose uptake. PMID:18552870

  5. Metabolic responses to BRL37344 and clenbuterol in soleus muscle and C2C12 cells via different atypical pharmacologies and beta2-adrenoceptor mechanisms.

    Science.gov (United States)

    Ngala, R A; O'Dowd, J; Wang, S J; Agarwal, A; Stocker, C; Cawthorne, M A; Arch, J R S

    2008-10-01

    Picomolar concentrations of the beta3-adrenoceptor agonist BRL37344 stimulate 2-deoxyglucose uptake in soleus muscle via undefined receptors. Higher concentrations alter uptake, apparently via beta2-adrenoceptors. Effects of BRL37344 and beta2-adrenoceptor agonists are compared. Mouse soleus muscles were incubated with 2-deoxy[1-(14)C]-glucose, [1-(14)C]-palmitate or [2-(14)C]-pyruvate, and BRL37344, beta2-adrenoceptor agonists and selective beta-adrenoceptor antagonists. Formation of 2-deoxy[1-(14)C]-glucose-6-phosphate or (14)CO2 was measured. 2-Deoxy[1-(14)C]-glucose uptake and beta-adrenoceptor mRNA were measured in C2C12 cells. 10 pM BRL37344, 10 pM clenbuterol and 100 pM salbutamol stimulated 2-deoxyglucose uptake in soleus muscle by 33-54%. The effect of BRL37344 was prevented by 1 microM atenolol but not by 300 nM CGP20712A or IC3118551, or 1 microM SR59230A; that of clenbuterol was prevented by ICI118551 but not atenolol. 10 nM BRL37344 stimulated 2-deoxyglucose uptake, whereas 100 nM clenbuterol and salbutamol inhibited uptake. These effects were blocked by ICI118551. Similar results were obtained in C2C12 cells, in which only beta2-adrenoceptor mRNA could be detected by RT-PCR. 10 nM BRL37344 and 10 pM clenbuterol stimulated muscle palmitate oxidation. In the presence of palmitate, BRL37344 no longer stimulated 2-deoxyglucose uptake and the effect of clenbuterol was not significant. Stimulation of glucose uptake by 10 pM BRL37344 and clenbuterol involves different atypical pharmacologies. Nanomolar concentrations of BRL37344 and clenbuterol, probably acting via beta2-adrenoceptors, have opposite effects on glucose uptake. The agonists preferentially stimulate fat rather than carbohydrate oxidation, but stimulation of endogenous fat oxidation cannot explain why 100 nM clenbuterol inhibited 2-deoxyglucose uptake.

  6. INFLUENCE OF ANTIHYPERTENSIVE THERAPY ON PSYCHOLOGICAL STATUS OF CHERNOBYL NUCLEAR POWER PLANT ACCIDENT CONSEQUENCES LIQUIDATORS

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    E. M. Manoshkina

    2006-01-01

    Full Text Available Aim. To study psychological status and influence of antihypertensive therapy (AHT on it in Chernobyl nuclear power plant (NPP accident consequences liquidators, who suffer arterial hyper-tension (AH, with controlled treatment compared to the standard treatment in out-patient clinic. Material and methods. 81 liquidators with AH (all men were included into open compara-tive randomized study. Study duration was 12 months. Patients were randomized into main group (MG and control group (CG. Patients of MG received strictly regulated stepped AHT based on ACE inhibitor spirapril 6 mg daily (Quadropril®, Pliva-AVD, hypothiazide was added if necessary (12.5-25 mg daily and afterwards – atenolol (12.5-100 mg daily. In CG AHT and its correction was set by physician in polyclinic. Brief multifactor questionnaire for personality analysis was used to study psychological status. Results. 57 patients completed the study, 28 in MG and 29 in CG. In MG target blood pres-sure (BP levels were reached in 22 (78.6% patients, in CG – in 11 (38% patients (p<0.01. The main feature of psychological status of liquidators with AH was hypochondriac, depressive and anxious disorders. Controlled AHT made it possible to reach improvement in psychological status, i.e. growth of optimism and activity of patients, more often, than standard treatment in out-patient clinics. Increase in number of patients with pronounced anxious changes was observed in CG. Effi-ciency of AHT in liquidators with AH is connected with severity of depressive disturbances: in subgroups with inefficient treatment patients had the highest level of depression. In liquidators with AH, possessing neurotic disturbances, spirapril was efficient both as monotherapy, and in combina-tion with diuretic hydrochlorothiazide and beta-blocker atenolol. Conclusion. Controlled AHT in liquidators with AH has advantages over standard treatment in out-patient clinic and results in more frequent target BP level

  7. A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache

    Science.gov (United States)

    2015-01-01

    Objective To compare the effectiveness and side effects of migraine prophylactic medications. Design We performed a network meta-analysis. Data were extracted independently in duplicate and quality was assessed using both the JADAD and Cochrane Risk of Bias instruments. Data were pooled and network meta-analysis performed using random effects models. Data Sources PUBMED, EMBASE, Cochrane Trial Registry, bibliography of retrieved articles through 18 May 2014. Eligibility Criteria for Selecting Studies We included randomized controlled trials of adults with migraine headaches of at least 4 weeks in duration. Results Placebo controlled trials included alpha blockers (n = 9), angiotensin converting enzyme inhibitors (n = 3), angiotensin receptor blockers (n = 3), anticonvulsants (n = 32), beta-blockers (n = 39), calcium channel blockers (n = 12), flunarizine (n = 7), serotonin reuptake inhibitors (n = 6), serotonin norepinephrine reuptake inhibitors (n = 1) serotonin agonists (n = 9) and tricyclic antidepressants (n = 11). In addition there were 53 trials comparing different drugs. Drugs with at least 3 trials that were more effective than placebo for episodic migraines included amitriptyline (SMD: -1.2, 95% CI: -1.7 to -0.82), -flunarizine (-1.1 headaches/month (ha/month), 95% CI: -1.6 to -0.67), fluoxetine (SMD: -0.57, 95% CI: -0.97 to -0.17), metoprolol (-0.94 ha/month, 95% CI: -1.4 to -0.46), pizotifen (-0.43 ha/month, 95% CI: -0.6 to -0.21), propranolol (-1.3 ha/month, 95% CI: -2.0 to -0.62), topiramate (-1.1 ha/month, 95% CI: -1.9 to -0.73) and valproate (-1.5 ha/month, 95% CI: -2.1 to -0.8). Several effective drugs with less than 3 trials included: 3 ace inhibitors (enalapril, lisinopril, captopril), two angiotensin receptor blockers (candesartan, telmisartan), two anticonvulsants (lamotrigine, levetiracetam), and several beta-blockers (atenolol, bisoprolol, timolol). Network meta-analysis found amitriptyline to be better than several other medications including

  8. β2-Adrenergic receptor-dependent attenuation of hypoxic pulmonary vasoconstriction prevents progression of pulmonary arterial hypertension in intermittent hypoxic rats.

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    Hisashi Nagai

    Full Text Available In sleep apnea syndrome (SAS, intermittent hypoxia (IH induces repeated episodes of hypoxic pulmonary vasoconstriction (HPV during sleep, which presumably contribute to pulmonary arterial hypertension (PAH. However, the prevalence of PAH was low and severity is mostly mild in SAS patients, and mild or no right ventricular hypertrophy (RVH was reported in IH-exposed animals. The question then arises as to why PAH is not a universal finding in SAS if repeated hypoxia of sufficient duration causes cycling HPV. In the present study, rats underwent IH at a rate of 3 min cycles of 4-21% O2 for 8 h/d for 6 w. Assessment of diameter changes in small pulmonary arteries in response to acute hypoxia and drugs were performed using synchrotron radiation microangiography on anesthetized rats. In IH-rats, neither PAH nor RVH was observed and HPV was strongly reversed. Nadolol (a hydrophilic β(1, 2-blocker augmented the attenuated HPV to almost the same level as that in N-rats, but atenolol (a hydrophilic β1-blocker had no effect on the HPV in IH. These β-blockers had almost no effect on the HPV in N-rats. Chronic administration of nadolol during 6 weeks of IH exposure induced PAH and RVH in IH-rats, but did not in N-rats. Meanwhile, atenolol had no effect on morphometric and hemodynamic changes in N and IH-rats. Protein expression of the β1-adrenergic receptor (AR was down-regulated while that of β2AR was preserved in pulmonary arteries of IH-rats. Phosphorylation of p85 (chief component of phosphoinositide 3-kinase (PI3K, protein kinase B (Akt, and endothelial nitric oxide synthase (eNOS were abrogated by chronic administration of nadolol in the lung tissue of IH-rats. We conclude that IH-derived activation of β2AR in the pulmonary arteries attenuates the HPV, thereby preventing progression of IH-induced PAH. This protective effect may depend on the β2AR-Gi mediated PI3K/Akt/eNOS signaling pathway.

  9. Effectiveness of beta-blockers depending on the genotype of congenital long-QT syndrome: A meta-analysis

    Science.gov (United States)

    Lee, Kwang No; Shim, Jaemin; Ahn, Hyeong Sik; Kim, Young-Hoon

    2017-01-01

    Background Beta-blockers are first-line therapy in patients with congenital long-QT syndrome (LQTS). Objective This study sought to determine the differences in effectiveness of beta-blockers on risk reduction according to LQTS genotype. Methods We searched MEDLINE, EMBASE, and CENTRAL databases to investigate the use of beta-blockers (atenolol, nadolol, propranolol, and metoprolol) in patients with LQTS. Hazard ratio (HR) and relative risk (RR) were extracted or calculated from studies reporting cardiac events (syncope, aborted cardiac arrest (ACA), or sudden cardiac death (SCD)). Results Among 2,113 articles searched, 10 studies (7 registry-based cohort studies (Cohort) and 3 interrupted time series studies (ITS)) involving 9,727 patients were included. In a meta-analysis using a random-effect model, the use of beta-blocker was associated with significant risk reduction of all cardiac events (HR 0.49, p<0.001 in Cohort; RR 0.39, p<0.001 in ITS) and serious cardiac events (ACA or SCD) (HR 0.47, p<0.001 in Cohort). In both LQT1 and LQT2, the risk was reduced with beta-blocker therapy in Cohort (HR 0.59 in LQT1; HR 0.39 in LQT2) as well as ITS (RR 0.29 in LQT1; RR 0.48 in LQT2). Among the beta-blockers, nadolol showed a significant risk reduction in both LQT1 and LQT2 (HR 0.47 and 0.27, respectively), whereas atenolol and propranolol decreased the risk only in LQT1 (HR 0.36 and 0.46, respectively). Metoprolol showed no significant reduction in either genotype. In LQT3, beta-blocker therapy was not as effective as LQT1 or LQT2; however, it was inconclusive due to data insufficiency. Conclusion This meta-analysis showed that beta-blockers were effective in reducing risk of cardiac events in patients with LQTS. Among them, nadolol was effective in LQT1 and LQT2, whereas other drugs showed different effectiveness depending on LQT genotype. PMID:29059199

  10. Electrocardiographic strain pattern and prediction of new-onset congestive heart failure in hypertensive patients: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study.

    Science.gov (United States)

    Okin, Peter M; Devereux, Richard B; Nieminen, Markku S; Jern, Sverker; Oikarinen, Lasse; Viitasalo, Matti; Toivonen, Lauri; Kjeldsen, Sverre E; Dahlöf, Björn

    2006-01-03

    The ECG strain pattern of ST depression and T-wave inversion is strongly associated with left ventricular hypertrophy (LVH) independently of coronary heart disease and with an increased risk of cardiovascular morbidity and mortality in hypertensive patients. However, whether ECG strain is an independent predictor of new-onset congestive heart failure (CHF) in the setting of aggressive antihypertensive therapy in unclear. The relationship of ECG strain at study baseline to the development of CHF was examined in 8696 patients with no history of CHF who were enrolled in the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study. All patients had ECG LVH by Cornell product and/or Sokolow-Lyon voltage criteria on a screening ECG, were treated in a blinded manner with atenolol- or losartan-based regimens, and were followed up for a mean of 4.7+/-1.1 years. Strain was defined as a downsloping convex ST segment with inverted asymmetrical T-wave opposite the QRS axis in lead V5 or V6. ECG strain was present in 923 patients (10.6%), and new-onset CHF occurred in 265 patients (3.0%), 26 of whom had a CHF-related death. Compared with patients who did not develop CHF, hypertensive patients who developed CHF were older; were more likely to be black, current smokers, and diabetic; were more like to have a history of myocardial infarction, ischemic heart disease, stroke, or peripheral vascular disease; and had greater baseline severity of LVH by Cornell product and Sokolow-Lyon voltage, higher baseline body mass indexes, higher serum glucose levels and albuminuria, similar baseline systolic and diastolic pressures, and reductions in diastolic pressure with treatment but greater reductions in systolic pressure. In univariate Cox analyses, ECG strain was a significant predictor of new-onset CHF (hazard ratio [HR], 3.27; 95% CI, 2.49 to 4.29) and CHF mortality (HR, 4.74; 95% CI, 2.11 to 10.64). In Cox multivariable analyses adjusting for baseline differences

  11. Comparative effectiveness of antihypertensive medication for primary prevention of cardiovascular disease: systematic review and multiple treatments meta-analysis

    Directory of Open Access Journals (Sweden)

    Fretheim Atle

    2012-04-01

    Full Text Available Abstract Background We conducted a systematic review of evidence from randomized controlled trials to answer the following research question: What are the relative effects of different classes of antihypertensive drugs in reducing the incidence of cardiovascular disease outcomes for healthy people at risk of cardiovascular disease? Methods We searched MEDLINE, EMBASE, AMED (up to February 2011 and CENTRAL (up to May 2009, and reference lists in recent systematic reviews. Titles and abstracts were assessed for relevance and those potentially fulfilling our inclusion criteria were then assessed in full text. Two reviewers made independent assessments at each step. We selected the following main outcomes: total mortality, myocardial infarction and stroke. We also report on angina, heart failure and incidence of diabetes. We conducted a multiple treatments meta-analysis using random-effects models. We assessed the quality of the evidence using the GRADE-instrument. Results We included 25 trials. Overall, the results were mixed, with few significant dif-ferences, and with no drug-class standing out as superior across multiple outcomes. The only significant finding for total mortality based on moderate to high quality evidence was that beta-blockers (atenolol were inferior to angiotensin receptor blockers (ARB (relative risk (RR 1.14; 95% credibility interval (CrI 1.02 to 1.28. Angiotensin converting enzyme (ACE-inhibitors came out inferior to calcium-channel blockers (CCB regarding stroke-risk (RR 1.19; 1.03 to 1.38, but superior regarding risk of heart failure (RR 0.82; 0.69 to 0.94, both based on moderate quality evidence. Diuretics reduced the risk of myocardial infarction compared to beta-blockers (RR 0.82; 0.68 to 0.98, and lowered the risk of heart failure compared to CCB (RR 0.73; 0.62 to 0.84, beta-blockers (RR 0.73; 0.54 to 0.96, and alpha-blockers (RR 0.51; 0.40 to 0.64. The risk of diabetes increased with diuretics compared to ACE

  12. β2-Adrenergic Receptor-Dependent Attenuation of Hypoxic Pulmonary Vasoconstriction Prevents Progression of Pulmonary Arterial Hypertension in Intermittent Hypoxic Rats

    Science.gov (United States)

    Nagai, Hisashi; Kuwahira, Ichiro; Schwenke, Daryl O.; Tsuchimochi, Hirotsugu; Nara, Akina; Inagaki, Tadakatsu; Ogura, Sayoko; Fujii, Yutaka; Umetani, Keiji; Shimosawa, Tatsuo; Yoshida, Ken-ichi; Pearson, James T.; Uemura, Koichi; Shirai, Mikiyasu

    2014-01-01

    In sleep apnea syndrome (SAS), intermittent hypoxia (IH) induces repeated episodes of hypoxic pulmonary vasoconstriction (HPV) during sleep, which presumably contribute to pulmonary arterial hypertension (PAH). However, the prevalence of PAH was low and severity is mostly mild in SAS patients, and mild or no right ventricular hypertrophy (RVH) was reported in IH-exposed animals. The question then arises as to why PAH is not a universal finding in SAS if repeated hypoxia of sufficient duration causes cycling HPV. In the present study, rats underwent IH at a rate of 3 min cycles of 4–21% O2 for 8 h/d for 6w. Assessment of diameter changes in small pulmonary arteries in response to acute hypoxia and drugs were performed using synchrotron radiation microangiography on anesthetized rats. In IH-rats, neither PAH nor RVH was observed and HPV was strongly reversed. Nadolol (a hydrophilic β1, 2-blocker) augmented the attenuated HPV to almost the same level as that in N-rats, but atenolol (a hydrophilic β1-blocker) had no effect on the HPV in IH. These β-blockers had almost no effect on the HPV in N-rats. Chronic administration of nadolol during 6 weeks of IH exposure induced PAH and RVH in IH-rats, but did not in N-rats. Meanwhile, atenolol had no effect on morphometric and hemodynamic changes in N and IH-rats. Protein expression of the β1-adrenergic receptor (AR) was down-regulated while that of β2AR was preserved in pulmonary arteries of IH-rats. Phosphorylation of p85 (chief component of phosphoinositide 3-kinase (PI3K)), protein kinase B (Akt), and endothelial nitric oxide synthase (eNOS) were abrogated by chronic administration of nadolol in the lung tissue of IH-rats. We conclude that IH-derived activation of β2AR in the pulmonary arteries attenuates the HPV, thereby preventing progression of IH-induced PAH. This protective effect may depend on the β2AR-Gi mediated PI3K/Akt/eNOS signaling pathway. PMID:25350545

  13. Impact of external carbon dose on the removal of micropollutants using methanol and ethanol in post-denitrifying Moving Bed Biofilm Reactors.

    Science.gov (United States)

    Torresi, Elena; Escolà Casas, Mònica; Polesel, Fabio; Plósz, Benedek G; Christensson, Magnus; Bester, Kai

    2017-01-01

    Addition of external carbon sources to post-denitrification systems is frequently used in wastewater treatment plants to enhance nitrate removal. However, little is known about the fate of micropollutants in post-denitrification systems and the influence of external carbon dosing on their removal. In this study, we assessed the effects of two different types and availability of commonly used carbon sources -methanol and ethanol- on the removal of micropollutants in biofilm systems. Two laboratory-scale moving bed biofilm reactors (MBBRs), containing AnoxKaldnes K1 carriers with acclimated biofilm from full-scale systems, were operated in continuous-flow using wastewater dosed with methanol and ethanol, respectively. Batch experiments with 22 spiked pharmaceuticals were performed to assess removal kinetics. Acetyl-sulfadiazine, atenolol, citalopram, propranolol and trimethoprim were easily biotransformed in both MBBRs (biotransformations rate constants kbio between 1.2 and 12.9 L gbiomass-1 d-1), 13 compounds were moderately biotransformed (rate constants between 0.2 and 2 L gbiomass-1 d-1) and 4 compounds were recalcitrant. The methanol-dosed MBBR showed higher kbio (e.g., 1.5-2.5-fold) than in the ethanol-dosed MBBR for 9 out of the 22 studied compounds, equal kbio for 10 compounds, while 3 compounds (i.e., targeted sulfonamides) were biotransformed faster in the ethanol-dosed MBBR. While biotransformation of most of the targeted compounds followed first-order kinetics, removal of venlafaxine, carbamazepine, sulfamethoxazole and sulfamethizole could be described with a cometabolic model. Analyses of the microbial composition in the biofilms using 16S rRNA amplicon sequencing revealed that the methanol-dosed MBBR contained higher microbial richness than the one dosed with ethanol, suggesting that improved biotransformation of targeted compounds could be associated with higher microbial richness. During continuous-flow operation, at conditions representative

  14. A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache.

    Directory of Open Access Journals (Sweden)

    Jeffrey L Jackson

    Full Text Available To compare the effectiveness and side effects of migraine prophylactic medications.We performed a network meta-analysis. Data were extracted independently in duplicate and quality was assessed using both the JADAD and Cochrane Risk of Bias instruments. Data were pooled and network meta-analysis performed using random effects models.PUBMED, EMBASE, Cochrane Trial Registry, bibliography of retrieved articles through 18 May 2014.We included randomized controlled trials of adults with migraine headaches of at least 4 weeks in duration.Placebo controlled trials included alpha blockers (n = 9, angiotensin converting enzyme inhibitors (n = 3, angiotensin receptor blockers (n = 3, anticonvulsants (n = 32, beta-blockers (n = 39, calcium channel blockers (n = 12, flunarizine (n = 7, serotonin reuptake inhibitors (n = 6, serotonin norepinephrine reuptake inhibitors (n = 1 serotonin agonists (n = 9 and tricyclic antidepressants (n = 11. In addition there were 53 trials comparing different drugs. Drugs with at least 3 trials that were more effective than placebo for episodic migraines included amitriptyline (SMD: -1.2, 95% CI: -1.7 to -0.82, -flunarizine (-1.1 headaches/month (ha/month, 95% CI: -1.6 to -0.67, fluoxetine (SMD: -0.57, 95% CI: -0.97 to -0.17, metoprolol (-0.94 ha/month, 95% CI: -1.4 to -0.46, pizotifen (-0.43 ha/month, 95% CI: -0.6 to -0.21, propranolol (-1.3 ha/month, 95% CI: -2.0 to -0.62, topiramate (-1.1 ha/month, 95% CI: -1.9 to -0.73 and valproate (-1.5 ha/month, 95% CI: -2.1 to -0.8. Several effective drugs with less than 3 trials included: 3 ace inhibitors (enalapril, lisinopril, captopril, two angiotensin receptor blockers (candesartan, telmisartan, two anticonvulsants (lamotrigine, levetiracetam, and several beta-blockers (atenolol, bisoprolol, timolol. Network meta-analysis found amitriptyline to be better than several other medications including candesartan, fluoxetine, propranolol, topiramate and valproate and no different than

  15. Influence of microemulsion chirality on chromatographic figures of merit in EKC: results with novel three-chiral-component microemulsions and comparison with one- and two-chiral-component microemulsions.

    Science.gov (United States)

    Kahle, Kimberly A; Foley, Joe P

    2007-08-01

    Novel microemulsion formulations containing all chiral components are described for the enantioseparation of six pairs of pharmaceutical enantiomers (atenolol, ephedrine, metoprolol, N-methyl ephedrine, pseudoephedrine, and synephrine). The chiral surfactant dodecoxycarbonylvaline (DDCV, R- and S-), the chiral cosurfactant S-2-hexanol, and the chiral oil diethyl tartrate (R- and S-) were combined to create four different chiral microemulsions, three of which were stable. Results obtained for enantioselectivity, efficiency, and resolution were compared for the triple-chirality systems and the single-chirality system that contained chiral surfactant only. Improvements in enantioselectivity and resolution were achieved by simultaneously incorporating three chiral components into the aggregate. The one-chiral-component microemulsion provided better efficiencies. Enantioselective synergies were identified for the three-chiral-component nanodroplets using a thermodynamic model. Additionally, two types of dual-chirality systems, chiral surfactant/chiral cosurfactant and chiral surfactant/chiral oil, were examined in terms of chromatographic figures of merit, with the former providing much better resolution. The two varieties of two-chiral-component microemulsions gave similar values for enantioselectivity and efficiency. Lastly, the microemulsion formulations were divided into categories based on the number of chiral microemulsion reagents and the average results for each pair of enantiomers were analyzed for trends. In general, enantioselectivity and resolution were enhanced while efficiency was decreased as more chiral components were used to create the pseudostationary phase (PSP).

  16. Markers of inflammation, endothelial activation, and arterial stiffness in hypertensive heart disease and the effects of treatment: results from the SILVHIA study.

    Science.gov (United States)

    Jekell, Andreas; Malmqvist, Karin; Wallén, N Håkan; Mörtsell, David; Kahan, Thomas

    2013-12-01

    We assessed the contribution of blood pressure (BP), inflammation, and endothelial activation to the development of structural vascular and cardiac changes in hypertension. Furthermore, the effects of antihypertensive therapy were studied. We studied 114 patients with hypertension and left ventricular hypertrophy and 38 matched hypertensive subjects without cardiac hypertrophy and 38 normotensive subjects. The group with hypertension and cardiac hypertrophy were randomized to treatment with an angiotensin receptor blocker (irbesartan) or a beta-adrenergic receptor blocker (atenolol) for 48 weeks. Markers of inflammation (high-sensitive C-reactive protein, interleukin-6, leukocyte counts), vascular function (ambulatory aortic stiffness index, arterial compliance, and pulse pressure), and endothelial activation (E-selectin, intracellular adhesion molecule-1, vascular adhesion molecule-1) were assessed. Markers of inflammation and arterial stiffness were lowest in the normotensive group and highest in patients with hypertensive heart disease; endothelial markers were similar between groups. Inflammation was independently related to BP. Markers of arterial stiffness were independently related to BP and to a lesser extent to left ventricular mass. Antihypertensive treatment improved arterial compliance; inflammatory and endothelial markers remained unchanged. In conclusion, markers of inflammation and arterial stiffness are independently related to BP. Antihypertensive therapy seems to improve arterial stiffness, but effects on markers of inflammation and endothelial activation are small.

  17. Occurrence of micro-organic pollutants on phosphorus recovery from urine.

    Science.gov (United States)

    Kemacheevakul, P; Otani, S; Matsuda, T; Shimizu, Y

    2012-01-01

    Increased population growth and food prices have resulted in more demand for fertilizers, especially phosphorus (P), to be used in agriculture and production of food crops. Phosphorus is one of the important natural resources and will be exhausted in the near future. Nowadays, struvite production is a good method to recover P from urine. However, the natural urines contain high amounts of micro-organic pollutants which may cause health risks. Therefore, in this contribution, we investigated the amount of micro-organic pollutants in struvite from urine. There are various kinds of pharmaceuticals and hormones which are used in the world. Nevertheless, we focused on 10 pharmaceuticals (amoxycillin, carbamazepine, erythromycin, furosemide, atenolol, ibuprofen, norfloxacin, trimethoprim, tetracycline, and acetylsalicylic acid) and one hormone (17β-estradiol) as representatives. The experiments were carried out with synthetic and natural urines. After the production of struvite, the results from synthetic and natural urine samples showed that only tetracycline, erythromycin, and norfloxacin remained in the struvite, and, especially, tetracycline remained in struvite with quite a high amount.

  18. Laparoscopic cholecystectomy due to acute calculouscholecystitis in 16 weeks′ in vitro fertilization and embryo transfer pregnancy: Report of the first case

    Directory of Open Access Journals (Sweden)

    G Augustin

    2012-01-01

    Full Text Available The most common casues of acute abdomen during pregnancy are acute appendicitis followed by acute cholecystitis. The case presented is a 33-year-old patient in 16 weeks′ in vitro fertilization and embryo transfer pregnacy who developed acute cholecystitis. Previously there were two unsuccessful cycles, one complicated with ovarian hyperstimulation syndrome. Due to clinical deterioration during intravenous antibiotic therapy laparoscopic cheolecystecomy was performed and acute cholecystitis found. The postoperative course was uneventful. During the first 24 h tocolysis with intravenous fenoterol in addition to peroral atenolol 2 Χ 50 mg was administered. Postoperative course was uneventuful with further normal pregnancy. Elective cesarean section was made in term pregnancy (39 weeks with singleton with Apgar 10/10. Current guidelines do not recommend prophylactic tocolysis in pregnant population with acute abdomen but there is no mention of the IVF-ET subpopulation of patients. Also, there are no guidelines for thromboprophylaxis in such patients with increased risk of thromboembolic accidents. To our knowledge this is the first case report of a laparoscopic cholecystectomy during IVF-ET gestation.

  19. Sorption of carbamazepine by commercial graphene oxides: a comparative study with granular activated carbon and multiwalled carbon nanotubes.

    Science.gov (United States)

    Cai, Nan; Larese-Casanova, Philip

    2014-07-15

    Graphene nanosheet materials represent a potentially new high surface area sorbent for the treatment of endocrine disrupting compounds (EDCs) in water. However, sorption behavior has been reported only for laboratory graphene prepared by a laborious and hazardous graphite exfoliation process. A careful examination of commercially available, clean, high-volume produced graphene materials should reveal whether they are appropriate for sorbent technologies and which physicochemical properties most influence sorption performance. In this study, three commercially available graphene oxide powders of various particle sizes, specific surface areas, and surface chemistries were evaluated for their sorption performance using carbamazepine and nine other EDCs and were compared to that of conventional granular activated carbon (GAC) and multi-walled carbon nanotubes (MWCNTs). Sorption kinetics of carbamazepine on graphene oxide powders was rapid and reversible with alcohol washing, consistent with π-π interactions. The various sorption extents as described by Freundlich isotherms were best explained by available surface area, and only the highest surface area graphene oxide (771 m(2)/g) out-performed GAC and MWCNTs. Increasing pH caused more negative surface charge, a twofold decrease in sorption of anionic ibuprofen, a onefold increase in sorption of cationic atenolol, and no change for neutral carbamazepine, highlighting the role of electrostatic interactions. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Modifying the Interagency Emergency Health Kit to include treatment for non-communicable diseases in natural disasters and complex emergencies.

    Science.gov (United States)

    Tonelli, Marcello; Wiebe, Natasha; Nadler, Brian; Darzi, Ara; Rasheed, Shahnawaz

    2016-01-01

    The Interagency Emergency Health Kit (IEHK) provides a standard package of medicines and simple medical devices for aid agencies to use in emergencies such as disasters and armed conflicts. Despite the increasing burden of non-communicable diseases (NCDs) in such settings, the IEHK includes few drugs and devices for management of NCDs. Using published data to model the population burden of acute and chronic presentations of NCDs in emergency-prone regions, we estimated the quantity of medications and devices that should be included in the IEHK. NCDs considered were cardiovascular diseases, diabetes, hypertension and chronic respiratory disease. In scenario 1 (the primary scenario), we assumed that resources in the IEHK would only include those needed to manage acute life-threatening conditions. In scenario 2, we included resources required to manage both acute and chronic presentations of NCDs. Drugs and devices that might be required included amlodipine, aspirin, atenolol, beclomethasone, dextrose 50%, enalapril, furosemide, glibenclamide, glyceryl trinitrate, heparin, hydralazine, hydrochlorothiazide, insulin, metformin, prednisone, salbutamol and simvastatin. For scenario 1, the number of units required ranged from 12 (phials of hydralazine) to ∼15 000 (tablets of enalapril). Space and weight requirements were modest and total cost for all drugs and devices was approximately US$2078. As expected, resources required for scenario 2 were much greater. Space and cost requirements increased proportionately: estimated total cost of scenario 2 was $22 208. The resources required to treat acute NCD presentations appear modest, and their inclusion in the IEHK seems feasible.

  1. Comprehensive evaluation of pharmaceuticals and personal care products (PPCPs) in typical highly urbanized regions across China.

    Science.gov (United States)

    Wang, Zhuo; Zhang, Xi-Hui; Huang, Yong; Wang, Hui

    2015-09-01

    This study evaluated the occurrence of 36 PPCPs in urban river water samples collected from Beijing, Changzhou and Shenzhen. Twenty-eight compounds were detected. Compounds found with highest median concentrations included: sulfadimethoxine (164 ng/L), sulpiride (77.3 ng/L), atenolol (52.9 ng/L), and indomethacin (50.9 ng/L). Antibiotic was the predominant class detected and contributed about half of the overall PPCPs contamination level. Effluents from wastewater treatment plants (WWTPs) were demonstrated to be the predominant pathways through which PPCPs entering into aquatic environment in all investigated areas. The ratio of persistent PPCPs like sulpiride and carbamazepine was identified to be feasible in tracing their contamination sources in rivers. Concentrations of most detected PPCPs showed significant positive correlations with total nitrogen and total phosphorus. Two groups of representative PPCPs were selected as the chemical indicators for predicting the overall PPCPs contamination, based on the significant correlations between PPCPs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Cardioversion of a supraventricular tachycardia (SVT) in a 7-year-old using a postural modification of the Valsalva manoeuvre.

    Science.gov (United States)

    Morley-Smith, Edward John; Gagg, James; Appelboam, Andrew

    2017-05-04

    A boy aged 7 years presented with his parents to the emergency department (ED). He had a known diagnosis of paroxysmal supraventricular tachycardia (SVT) and was under the care of paediatricians. He had been suffering episodes of palpitations and chest pain for over a year and had been prescribed atenolol 25 mg ON, though the side effects meant he had not taken it for a month prior to presentation. He had 2 previous confirmed episodes of SVT, one that reverted with Valsalva manoeuvres, and the other with intravenous adenosine. In the ED, an ECG was recorded showing SVT at 180 bpm. Aside from his tachycardia, he was haemodynamically stable. The postural modification of the Valsalva technique was performed within 5 min of arrival, with reversion to sinus rhythm occurring during the leg-lift phase on the first attempt. After 30 min of observation, the child remained stable and was discharged home. 2017 BMJ Publishing Group Ltd.

  3. Impact of microbial physiology and microbial community structure on pharmaceutical fate driven by dissolved oxygen concentration in nitrifying bioreactors.

    Science.gov (United States)

    Stadler, Lauren B; Love, Nancy G

    2016-11-01

    Operation at low dissolved oxygen (DO) concentrations (4 mg/L) DO concentrations to understand how DO growth conditions impacted microbial community structure. Short-term batch experiments using the biomass from the parent reactors were performed under low and high DO conditions to understand how DO concentration impacts microbial physiology. Although the low DO parent biomass had a lower specific activity with respect to ammonia oxidation than the high DO parent reactor biomass, it had faster biotransformation rates of ibuprofen, sulfamethoxazole, 17α-ethinylestradiol, acetaminophen, and atenolol in high DO batch conditions. This was likely because the low DO reactor had a 2x higher biomass concentration, was enriched for ammonia oxidizers (4x higher concentration), and harbored a more diverse microbial community (3x more unique taxa) as compared to the high DO parent reactor. Overall, the results show that there can be indirect benefits from low DO operation over high DO operation that support pharmaceutical biotransformation during wastewater treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Withdrawal reactions following cessation of central alpha-adrenergic receptor agonists.

    Science.gov (United States)

    Reid, J L; Campbell, B C; Hamilton, C A

    1984-01-01

    Interruption of long-term treatment with alpha 2-adrenergic receptor agonists may be associated with reversal of their hemodynamic effects, clinical and biochemical evidence of increased peripheral sympathetic activity, and behavioral responses similar to those seen after narcotic or alcohol withdrawal. Reactions are most commonly observed after short-acting imidazoline drugs such as clonidine and tiamenidine. Reactions are less common after longer acting agents such as guanfacine. A new management approach to withdrawal has been evaluated, which uses a combination of alpha 1-blockade (prazosin) and cardioselective beta-blockade (atenolol) together with a benzodiazepine (chlordiazepoxide). Withdrawal reactions were not observed in eight patients in whom clonidine was withdrawn under cover of these agents. The mechanism of the withdrawal reaction may involve agonist-induced down regulation of alpha 2-adrenergic receptor affinity, number, or both. Experimental studies with the irreversible alpha-antagonist phenoxybenzamine on the turnover of alpha 2-receptors suggest that recovery of receptor number may be much slower in the brain than in the periphery.

  5. Intracoronary gastrin 17 increases cardiac perfusion and function through autonomic nervous system, CCK receptors, and nitric oxide in anesthetized pigs.

    Science.gov (United States)

    Grossini, Elena; Caimmi, Philippe; Molinari, Claudio; Uberti, Francesca; Mary, David; Vacca, Giovanni

    2011-01-01

    The release of gastrointestinal hormones has been reported to modulate reflex cardiovascular responses caused by gastric distension, although the role played by gastrin 17 is as yet unknown. The present study was therefore planned to determine the primary in vivo effect of gastrin 17 on coronary blood flow and cardiac function and the involvement of autonomic nervous system, CCK1/2 receptors, and nitric oxide (NO). In 40 anesthetized pigs, gastrin 17 was infused into the left anterior descending coronary artery at constant heart rate and arterial blood pressure. In 35 of the 40 pigs, the mechanisms of the observed hemodynamic responses were analyzed by repeating gastrin 17 infusion after autonomic nervous system and NO blockade, and after specific CCK receptors agonists/antagonists administration. Intracoronary gastrin 17 administration caused dose-related increases of both coronary blood flow and cardiac function. The intracoronary co-administration of CCK33/pentagastrin and gastrin 17 potentiated the coronary effects observed when the above agents were given alone (P gastrin 17 (P gastrin 17. The cardiac and vascular effects of the hormone were prevented by blockade of β-adrenoceptors (intravenous atenolol and butoxamine), CCK1/2 receptors (intracoronary lorglumide and CAM-1028), and NO synthase (intracoronary Nω-nitro-l-arginine methyl ester). In conclusion, gastrin 17 primarily increased coronary blood flow and cardiac function through the involvement of CCK receptors, β-adrenoceptors, and NO release.

  6. Influence of volumetric reduction factor during ozonation of nanofiltration concentrates for wastewater reuse.

    Science.gov (United States)

    Azaïs, Antonin; Mendret, Julie; Petit, Eddy; Brosillon, Stephan

    2016-12-01

    Global population growth induces increased threat on drinking water resources. One way to address this environmental issue is to reuse water from wastewater treatment plant. The presence of pathogenic microorganisms and potentially toxic organic micropollutants does not allow a direct reuse of urban effluents. Membrane processes such reverse osmosis (RO) or nanofiltration (NF) can be considered to effectively eliminate these pollutants. The integration of membrane processes involves the production of concentrated retentates which require being disposed. To date, no treatment is set up to manage safely this pollution. This work focuses on the application of ozonation for the treatment of NF retentates in the framework of the wastewater reuse. Ozonation is a powerful oxidation process able to react and degrade a wide range of organic pollutants. Four pharmaceutical micropollutants were selected as target molecules: acetaminophen, carbamazepine, atenolol and diatrozic acid. This study highlighted that NF represents a viable alternative to the commonly used RO process ensuring high retention at much lower operating costs. Ozonation appears to be effective to degrade the most reactive pollutants toward molecular ozone but is limited for the reduction of refractory ozone pollutants due to the inhibition of the radical chain by the high content of organic matter in the retentates. The ozonation process appears to be a promising NF retentate treatment, but additional treatments after ozonation are required to lead to a zero liquid discharge treatment scheme. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Study of mesoporous silica/magnetite systems in drug controlled release.

    Science.gov (United States)

    Souza, K C; Ardisson, J D; Sousa, E M B

    2009-02-01

    Ordered mesoporous materials like SBA-15 have a network of channels and pores with well-defined size in the nanoscale range. This particular silica matrix pore architecture makes them suitable for hosting a broad variety of compounds in very promising materials in a range of applications, including drug release magnetic carriers. In this work, magnetic nanoparticles embedded into mesoporous silica were prepared in two steps: first, magnetite was synthesized by oxidation-precipitation method, and next, the magnetic nanoparticles were coated with mesoporous silica by using nonionic block copolymer surfactants as structure-directing agents. The materials were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), N(2) adsorption, and scanning electron microscopy (SEM). The influence of magnetic nanoparticles on drug release kinetics was studied with cisplatin, carboplatin, and atenolol under in vitro conditions in the absence and in the presence of an external magnetic field (0.25 T) by using NdFeB permanent magnet. The constant external magnetic field did not affect drug release significantly. The low-frequency alternating magnetic field had a large influence on the cisplatin release profile.

  8. Combination of anti-hypertensive drugs: a molecular dynamics simulation study.

    Science.gov (United States)

    Yousefpour, Abbas; Modarress, Hamid; Goharpey, Fatemeh; Amjad-Iranagh, Sepideh

    2017-05-01

    The anti-hypertensive drugs amlodipine, atenolol and lisinopril, in ordinary and PEGylated forms, with different combined-ratios, were studied by molecular dynamics simulations using GROMACS software. Twenty simulation systems were designed to evaluate the interactions of drug mixtures with a dimyristoylphosphatidylcholine (DMPC) lipid bilayer membrane, in the presence of water molecules. In the course of simulations, various properties of the systems were investigated, including drug location, diffusion and mass distribution in the membrane; drug orientation; the lipid chain disorder as a result of drug penetration into the DMPC membrane; the number of hydrogen bonds; and drug surface area. According to the results obtained, combined drugs penetrate deeper into the DMPC lipid bilayer membrane, and the lipid chains remain ordered. Also, the combined PEGylated drugs, at a combination ratio of 1:1:1, enhance drug penetration into the DMPC membrane, reduce drug agglomeration, orient the drug in a proper angle for easy penetration into the membrane, and decrease undesirable lipotoxicity due to distorted membrane self-assembly and thickness. Graphical abstract ᅟ.

  9. Removal and seasonal variability of selected analgesics/anti-inflammatory, anti-hypertensive/cardiovascular pharmaceuticals and UV filters in wastewater treatment plant.

    Science.gov (United States)

    Golovko, Oksana; Kumar, Vimal; Fedorova, Ganna; Randak, Tomas; Grabic, Roman

    2014-06-01

    Seasonal removal efficiency of 16 pharmaceuticals and personal care products was monitored in a wastewater treatment plant in České Budějovice, Czech Republic, over a period of 1 year (total amount of samples, n = 272). The studied compounds included four UV filters, three analgesics/anti-inflammatory drugs and nine anti-hypertensive/cardiovascular drugs. In most cases, elimination of the substances was incomplete, and overall removal rates varied strongly from -38 to 100%. Therefore, it was difficult to establish a general trend for each therapeutic group. Based on the removal efficiencies (REs) over the year, three groups of target compounds were observed. A few compounds (benzophenon-1, valsartan, isradipine and furosemide) were not fully removed, but their REs were greater than 50%. The second group of analytes, consisting of 2-phenylbenzimidazole-5-sulfonic acid, tramadol, sotalol, metoprolol, atenolol and diclofenac, showed a very low RE (lower than 50%). The third group of compounds showed extremely variable RE (benzophenon-3 and benzophenon-4, codeine, verapamil, diltiazem and bisoprolol). There were significant seasonal trends in the observed REs, with reduced efficiencies in colder months.

  10. Photocatalytic degradation kinetics and mechanism of environmental pharmaceuticals in aqueous suspension of TiO{sub 2}: A case of {beta}-blockers

    Energy Technology Data Exchange (ETDEWEB)

    Yang Hai [State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Kehua Street, Tianhe District, Guangzhou 510640 (China); Graduate School of Chinese Academy of Sciences, Beijing 100049 (China); An Taicheng, E-mail: antc99@gig.ac.cn [State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Kehua Street, Tianhe District, Guangzhou 510640 (China); Li Guiying [State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Kehua Street, Tianhe District, Guangzhou 510640 (China); Song Weihua; Cooper, William J. [Urban Water Research Center, Department of Civil and Environmental Engineering, University of California, Irvine, CA 92697-2175 (United States); Luo Haiying [State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Kehua Street, Tianhe District, Guangzhou 510640 (China); Graduate School of Chinese Academy of Sciences, Beijing 100049 (China); Guangzhou Product Quality Supervision and Testing Institute, National Centre for Quality Supervision and Testing of Processed Food (Guangzhou), Guangzhou 510110 (China); Guo Xindong [Guangzhou Product Quality Supervision and Testing Institute, National Centre for Quality Supervision and Testing of Processed Food (Guangzhou), Guangzhou 510110 (China)

    2010-07-15

    This study investigated the photocatalytic degradation of three {beta}-blockers in TiO{sub 2} suspensions. The disappearance of the compounds followed pseudo-first-order kinetics according to the Langmuir-Hinshelwood model and the rate constants were 0.075, 0.072 and 0.182 min{sup -1} for atenolol, metoprolol and propranolol, respectively. After 240 min irradiation, the reaction intermediates were completely mineralized to CO{sub 2} and the nitrogen was predominantly as NH{sub 4}{sup +}. The influence of initial pH and {beta}-blocker concentration on the kinetics was also studied. From adsorption studies it appears that the photocatalytic degradation occurred mainly on the surface of TiO{sub 2}. Further studies indicated that surface reaction with {center_dot}OH radical was principally responsible for the degradation of these three {beta}-blockers. The major degradation intermediates were identified by HPLC/MS analysis. Cleavage of the side chain and the addition of the hydroxyl group to the parent compounds were found to be the two main degradation pathways for all three {beta}-blockers.

  11. Severe beta blocker and calcium channel blocker overdose: Role of high dose insulin.

    Science.gov (United States)

    Seegobin, Karan; Maharaj, Satish; Deosaran, Ansuya; Reddy, Pramod

    2018-01-10

    A 54-year-old female presented after taking an overdose of an unknown amount of hydrochlorothiazide, doxazocin, atenolol and amlodipine. She was initially refractory to treatment with conventional therapy (intravenous fluids, activated charcoal, glucagon 5 mg followed with glucagon drip, calcium gluconate 10%, and atropine). Furthermore, insulin at 4 U/kg was not effective in improving her hemodynamics. Shortly after high dose insulin was achieved with 10 U/kg, there was dramatic improvement in hemodynamics resulting in three of five vasopressors being weaned off in 8 h. She was subsequently off all vasopressors after six additional hours. The role of high dose insulin has been documented in prior cases, however it is generally recommended after other conventional therapies have failed. However, there are other reports that suggest it as initial therapy. Our patient failed conventional therapies and responded well only with maximum dose of insulin. Physicians should consider high dose insulin early in severe beta blocker or calcium channel blocker overdose for improvement in hemodynamics. This leads to early discontinuation of vasopressors. It is important that emergency physicians be aware of the beneficial effects of high dose insulin when initiated early as opposed to waiting for conventional therapy to fail; as these patients often present first to the emergency department. Early initiation in the emergency department can be beneficial in these patients. Copyright © 2018. Published by Elsevier Inc.

  12. The Beta-1-Receptor Blocker Nebivolol Elicits Dilation of Cerebral Arteries by Reducing Smooth Muscle [Ca2+]i.

    Science.gov (United States)

    Cseplo, Peter; Vamos, Zoltan; Ivic, Ivan; Torok, Orsolya; Toth, Attila; Koller, Akos

    2016-01-01

    Nebivolol is known to have beta-1 blocker activity, but it was also suggested that it elicits relaxation of the peripheral arteries in part via release of nitric oxide (NO). However, the effect of nebivolol on the vasomotor tone of cerebral arteries is still unclear. To assess the effects of nebivolol on the diameter of isolated rat basilar arteries (BA) in control, in the presence of inhibitors of vasomotor signaling pathways of know action and hemolysed blood. Vasomotor responses were measured by videomicroscopy and the intracellular Ca2+ by the Fura-2 AM ratiometric method. Under control conditions, nebivolol elicited a substantial dilation of the BA (from 216±22 to 394±20 μm; pblocker). Dilatation of BA was also affected by beta-2 receptor blockade with butoxamine, but not by the guanylate cyclase blocker ODQ. Interestingly, beta-1 blockade by atenolol inhibited nebivolol-induced dilation. Also, the BKCa channel blocker iberiotoxin and KCa channel inhibitor TEA significantly reduced nebivolol-induced dilation. Nebivolol significantly reduced smooth muscle Ca2+ level, which correlated with the increases in diameters and moreover it reversed the hemolysed blood-induced constriction of BA. Nebivolol seems to have an important dilator effect in cerebral arteries, which is mediated via several vasomotor mechanisms, converging on the reduction of smooth muscle Ca2+ levels. As such, nebivolol may be effective to improve cerebral circulation in various diseased conditions, such as hemorrhage.

  13. A rational approach to selecting and ranking some pharmaceuticals of concern for the aquatic environment and their relative importance compared with other chemicals.

    Science.gov (United States)

    Donnachie, Rachel L; Johnson, Andrew C; Sumpter, John P

    2016-04-01

    Aquatic organisms can be exposed to thousands of chemicals discharged by the human population. Many of these chemicals are considered disruptive to aquatic wildlife, and the literature on the impacts of these chemicals grows daily. However, because time and resources are not infinite, research must focus on the chemicals that represent the greatest threat. One group of chemicals of increasing concern is pharmaceuticals, for which the primary challenge is to identify which represent the greatest threat. In the present study, a list of 12 pharmaceuticals was compiled based on scoring the prevalence of different compounds from previous prioritization reviews. These included rankings based on prescription data, environmental concentrations, predicted environmental concentration/predicted no-effect concentration (PEC/PNEC) ratios, persistency/bioaccumulation/(eco)toxicity (PBT), and fish plasma model approaches. The most frequently cited were diclofenac, paracetamol, ibuprofen, carbamazepine, naproxen, atenolol, ethinyl estradiol, aspirin, fluoxetine, propranolol, metoprolol, and sulfamethoxazole. For each pharmaceutical, literature on effect concentrations was compiled and compared with river concentrations in the United Kingdom. The pharmaceuticals were ranked by degree of difference between the median effect and median river concentrations. Ethinyl estradiol was ranked as the highest concern, followed by fluoxetine, propranolol, and paracetamol. The relative risk of these pharmaceuticals was compared with those of metals and some persistent organic pollutants. Pharmaceuticals appear to be less of a threat to aquatic organisms than some metals (Cu, Al, Zn) and triclosan, using this ranking approach. © 2015 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC.

  14. Multifunctional Cinnamic Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Aikaterini Peperidou

    2017-07-01

    Full Text Available Our research to discover potential new multitarget agents led to the synthesis of 10 novel derivatives of cinnamic acids and propranolol, atenolol, 1-adamantanol, naphth-1-ol, and (benzylamino ethan-1-ol. The synthesized molecules were evaluated as trypsin, lipoxygenase and lipid peroxidation inhibitors and for their cytotoxicity. Compound 2b derived from phenoxyphenyl cinnamic acid and propranolol showed the highest lipoxygenase (LOX inhibition (IC50 = 6 μΜ and antiproteolytic activity (IC50 = 0.425 μΜ. The conjugate 1a of simple cinnamic acid with propranolol showed the higher antiproteolytic activity (IC50 = 0.315 μΜ and good LOX inhibitory activity (IC50 = 66 μΜ. Compounds 3a and 3b, derived from methoxylated caffeic acid present a promising combination of in vitro inhibitory and antioxidative activities. The S isomer of 2b also presented an interesting multitarget biological profile in vitro. Molecular docking studies point to the fact that the theoretical results for LOX-inhibitor binding are identical to those from preliminary in vitro study.

  15. LMNA gene mutation as a model of cardiometabolic dysfunction: from genetic analysis to treatment response.

    Science.gov (United States)

    Chirico, V; Ferraù, V; Loddo, I; Briuglia, S; Amorini, M; Salpietro, V; Lacquaniti, A; Salpietro, C; Arrigo, T

    2014-06-01

    This report highlights the metabolic, endocrine and cardiovascular comorbidities in a case of familial partial lipodystrophy (FPLD), and also evaluates the efficacy and safety of metformin therapy. Mutational analysis was carried out of the LMNA gene in a teenage girl with an FPLD phenotype. Insulin resistance, sex hormones and metabolic parameters were also evaluated, and echocardiography, electrocardiography and 24-h blood pressure monitoring were also done. The patient showed atypical fat distribution, insulin resistance and hypertrophic cardiomyopathy. Physical examination revealed muscle hypertrophy with a paucity of fat in the extremities, trunk and gluteal regions, yet excess fat deposits in the face, neck and dorsal cervical region. LMNA sequencing revealed a heterozygous missense mutation (c.1543A>G) in exon 9, leading to substitution of lysine by glutamic acid at position 515 (K515E). Moderate hypertension and secondary polycystic ovary syndrome were also assessed. Treatment with metformin resulted in progressive improvement of metabolic status, while blood pressure values normalized with atenolol therapy. Very rapid and good results with no side-effects were achieved with metformin therapy for FPLD. The association of an unusual mutation in the LMNA gene was also described. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  16. Sorption behavior of 20 wastewater originated micropollutants in groundwater — Column experiments with pharmaceutical residues and industrial agents

    Science.gov (United States)

    Burke, Victoria; Treumann, Svantje; Duennbier, Uwe; Greskowiak, Janek; Massmann, Gudrun

    2013-11-01

    Since sorption is an essential process with regard to attenuation of organic pollutants during subsurface flow, information on the sorption properties of each pollutant are essential for assessing their environmental fate and transport behavior. In the present study, the sorption behavior of 20 wastewater originated organic micropollutants was assessed by means of sediment column experiments, since experimentally determined data for these compounds are not or sparsely represented in the literature. Compounds investigated include various psychoactive drugs, phenazone-type pharmaceuticals and β-blockers, as well as phenacetine, N-methylphenacetine, tolyltriazole and para-toluenesulfonamide. While for most of the compounds no or only a low sorption affinity was observed, an elevated tendency to sorb onto aquifer sand was obtained for the β-blockers atenolol, propranolol and metoprolol. A comparison between experimental data and data estimated based on the octanol/water partition coefficient following the QSAR approach demonstrated the limitations of the latter to predict the adsorption behavior in natural systems for the studied compounds.

  17. Advances in aortic disease management: a year in review.

    Science.gov (United States)

    Garg, Vinay; Ouzounian, Maral; Peterson, Mark D

    2016-03-01

    The medical and surgical management of aortic disease is continually changing in search for improved outcomes. Our objective is to highlight recent advances in a few select areas pertaining to aortic disease and aortic surgery: the genetics of aortopathy, medical therapy of aortic aneurysms, advances in cardiac imaging, and operative strategies for the aortic arch. As our understanding of the genetic basis for aortopathy continues to improve, routine genetic testing may be of value in assessing patients with genetically triggered forms of aortic disease. With regard to medical advances, treating patients with Marfan syndrome with either losartan or atenolol at an earlier stage in their disease course improves outcomes. In addition, novel imaging indices such as wall shear stress and aortic stiffness assessed by MRI may become useful markers of aortopathy and warrant further study. With regard to the optimal technique for cerebral perfusion in aortic arch surgery, high-quality data are still lacking. Finally, in patients with complex, multilevel aortic disease, the frozen elephant trunk is a viable single-stage option compared with the conventional elephant trunk, although with an increased risk for spinal cord injury. Based on recent advances, continued studies in genetics, cardiac imaging, and surgical trials will further elucidate the etiology of aortopathy and ultimately guide management, both medically and surgically.

  18. Influence of a compost layer on the attenuation of 28 selected organic micropollutants under realistic soil aquifer treatment conditions: insights from a large scale column experiment.

    Science.gov (United States)

    Schaffer, Mario; Kröger, Kerrin Franziska; Nödler, Karsten; Ayora, Carlos; Carrera, Jesús; Hernández, Marta; Licha, Tobias

    2015-05-01

    Soil aquifer treatment is widely applied to improve the quality of treated wastewater in its reuse as alternative source of water. To gain a deeper understanding of the fate of thereby introduced organic micropollutants, the attenuation of 28 compounds was investigated in column experiments using two large scale column systems in duplicate. The influence of increasing proportions of solid organic matter (0.04% vs. 0.17%) and decreasing redox potentials (denitrification vs. iron reduction) was studied by introducing a layer of compost. Secondary effluent from a wastewater treatment plant was used as water matrix for simulating soil aquifer treatment. For neutral and anionic compounds, sorption generally increases with the compound hydrophobicity and the solid organic matter in the column system. Organic cations showed the highest attenuation. Among them, breakthroughs were only registered for the cationic beta-blockers atenolol and metoprolol. An enhanced degradation in the columns with organic infiltration layer was observed for the majority of the compounds, suggesting an improved degradation for higher levels of biodegradable dissolved organic carbon. Solely the degradation of sulfamethoxazole could clearly be attributed to redox effects (when reaching iron reducing conditions). The study provides valuable insights into the attenuation potential for a wide spectrum of organic micropollutants under realistic soil aquifer treatment conditions. Furthermore, the introduction of the compost layer generally showed positive effects on the removal of compounds preferentially degraded under reducing conditions and also increases the residence times in the soil aquifer treatment system via sorption. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Organic micro-pollutants’ removal via anaerobic membrane bioreactor with ultrafiltration and nanofiltration

    KAUST Repository

    Wei, Chunhai

    2015-12-15

    The removal of 15 organic micro-pollutants (OMPs) in synthetic municipal wastewater was investigated in a laboratory-scale mesophilic anaerobic membrane bioreactor (AnMBR) using ultrafiltration and AnMBR followed by nanofiltration (NF), where powdered activated carbon (PAC) was added to enhance OMPs removal. No significant effects of OMPs spiking and NF connection on bulk organics removal and biogas production were observed. Amitriptyline, diphenhydramine, fluoxetine, sulfamethoxazole, TDCPP and trimethoprim showed readily biodegradable characteristics with consistent biological removal over 80%. Atrazine, carbamazepine, DEET, Dilantin, primidone and TCEP showed refractory characteristics with biological removal below 40%. Acetaminophen, atenolol and caffeine showed a prolonged adaption time of around 45 d, with initial biological removal below 40% and up to 50-80% after this period. Most readily biodegradable OMPs contained a strong electron donating group. Most refractory OMPs contained a strong electron withdrawing group or a halogen substitute. NF showed consistent high rejection of 80-92% with an average of 87% for all OMPs, which resulted in higher OMPs removal in AnMBR-NF than in AnMBR alone, especially for refractory OMPs. Limited sorption performance of PAC for OMPs removal was mainly due to low and batch dosage (100 mg/L) as well as the competitive sorption caused by bulk organics.

  20. Synthesis of [{sup 18}F]-labelled nebivolol as a β{sub 1}-adrenergic receptor antagonist for PET imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Taek Soo; Park, Jeong Hoon; Lee, Jun Young; Yang, Seung Dae [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute (KAERI), Jeongeup (Korea, Republic of); Chang, Dong Jo [College of pharmacy, Sunchon National University, Suncheon (Korea, Republic of)

    2017-02-15

    Selective β{sub 1}-agonist and antagonists are used for the treatment of cardiac diseases including congestive heart failure, angina pectoris and arrhythmia. Selective β{sub 1}-antagonists including nebivolol have high binding affinity on β{sub 1}-adrenergic receptor, not β{sub 2}-receptor mainly expressed in smooth muscle. Nebivolol is one of most selective β{sub 1}-blockers in clinically used β{sub 1}- blockers including atenolol and bisoprolol. We tried to develop clinically useful cardiac PET tracers using a selective β{sub 1}-blocker. Nebivolol is C{sub 2}-symmetric and has two chromane moiety with a secondary amino alcohol and aromatic fluorine. We adopted the general synthetic strategy using epoxide ring opening reaction. Unlike formal synthesis of nebivolol, we prepared two chromane building blocks with fluorine and iodine which was transformed to diaryliodonium salt for labelling of {sup 18}F. Two epoxide building blocks were readily prepared from commercially available chromene carboxylic acids (1, 8). Then, the amino alcohol building block (15) was prepared by ammonolysis of epoxide (14) followed by coupling reaction with the other building block, epoxide (7). Diaryliodonium salt, a precursor for {sup 18}F-aromatic substitution, was synthesized in moderate yield which was readily subjected to {sup 18}F-aromatic substitution to give {sup 18}F-labelled nebivolol.

  1. Nerve growth factor acts with the beta2-adrenoceptor to induce spontaneous nociceptive behavior during temporomandibular joint inflammatory hyperalgesia.

    Science.gov (United States)

    Pelegrini-da-Silva, Adriana; Oliveira, Maria Cláudia G; Parada, Carlos Amílcar; Tambeli, Cláudia Herrera

    2008-12-05

    The aim of this study was to investigate whether the injection of nerve growth factor induces spontaneous nociceptive behavior in the intact or sensitized temporomandibular joint (TMJ) of rats. NGF was injected into the TMJ 1 h after the TMJ injection of saline or carrageenan and the spontaneous nociceptive behavior was quantified. The mechanism involved in this phenomenon was investigated by the injection of NGF into the carrageenan-sensitized TMJ in the presence of indomethacin or of beta-adrenergic antagonists. NGF injected into the TMJ sensitized by a prior TMJ injection of carrageenan but not into the intact TMJ induced a significant nociceptive behavior. Co-injection of the non-specific Trk receptor antagonist k252A with NGF 1 h after the TMJ injection of carrageenan significantly reduced NGF-induced spontaneous nociception supporting the Trk receptor activation in this nociceptive effect. Blockade of prostaglandin synthesis by indomethacin before the TMJ injection of carrageenan did not reduce NGF-induced nociception. Co-administration of carrageenan with the beta2-adrenoceptor antagonist ICI 118.55 but not with the beta1-adrenoceptor antagonist atenolol significantly reduced NGF-induced nociception. The injection of NGF the TMJ sensitized by a previous TMJ injection of epinephrine also induced nociceptive behavior. Taken together, these results indicate that NGF can induce TMJ nociception during TMJ inflammation. Moreover, the expression of this nociceptive response seems to depend on the synergic activity of NGF and sympathetic amines released during TMJ inflammation acting on beta2-adrenergic receptors.

  2. Predicted and measured concentrations of pharmaceuticals in hospital effluents. Examination of the strengths and weaknesses of the two approaches through the analysis of a case study.

    Science.gov (United States)

    Verlicchi, Paola; Zambello, Elena

    2016-09-15

    This study deals with the chemical characterization of hospital effluents in terms of the predicted and measured concentrations of 38 pharmaceuticals belonging to 11 different therapeutic classes. The paper outlines the strengths and weaknesses of the two approaches through an analysis of a case study referring to a large hospital. It highlights the observed (and expected) ranges of variability for the parameters of the adopted model, presents the results of an uncertainty analysis of direct measurements (due to sampling mode and frequency and chemical analysis) and a sensitivity analysis of predicted concentrations (based on the annual consumption of pharmaceuticals, their excretion rate and annual wastewater volume generated by the hospital). Measured concentrations refer to two sampling campaigns carried out in summer and winter in order to investigate seasonal variability of the selected compounds. Predicted concentrations are compared to measured ones in the three scenarios: summer, winter and the whole year. It was found that predicted and measured concentrations are in agreement for a limited number of compounds (namely atenolol, atorvastatin and hydrochlorothiazide), and for most compounds the adoption of the model leads to a large overestimation in all three periods. Uncertainties in predictions are mainly due to the wastewater volume and excretion factor, whereas for measured concentrations, uncertainties are mainly due to sampling mode. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Ozonation as a pretreatment process for nanofiltration brines: Monitoring of transformation products and toxicity evaluation.

    Science.gov (United States)

    Azaïs, Antonin; Mendret, Julie; Cazals, Guillaume; Petit, Eddy; Brosillon, Stephan

    2017-09-15

    Considerable interest has been given to using nanofiltration (NF) in lieu of reverse osmosis for water reclamation schemes due to lower energy consumption, higher flux rates while ensuring good micropollutants rejection. The application NF results in the generation of a large concentrated waste stream. Treatment of the concentrate is a major hurdle for the implementation of membrane technologies since the concentrate is usually unusable due to a large pollutants content. This work focuses on the application of ozonation as pretreatment of urban NF concentrates, the generation of transformation products and their relative toxicity. Three pharmaceutical micropollutants largely encountered in water cycle were selected as target molecules: acetaminophen, carbamazepine and atenolol. Through accurate-mass Q-TOF LC-MS/MS analyses, more than twenty ozonation products were detected, structure proposals and formation pathways were elaborated. Attempts were made to understand the correlation between the transformation products and acute toxicity on Vibrio fischeri strain. It is the first time that an integrated study reported on the ozonation of pharmaceuticals in urban membrane concentrates, in terms of transformation products, kinetics, degradation mechanisms, as well as toxicity assessment. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. ECG telemetry in conscious guinea pigs.

    Science.gov (United States)

    Ruppert, Sabine; Vormberge, Thomas; Igl, Bernd-Wolfgang; Hoffmann, Michael

    2016-01-01

    During preclinical drug development, monitoring of the electrocardiogram (ECG) is an important part of cardiac safety assessment. To detect potential pro-arrhythmic liabilities of a drug candidate and for internal decision-making during early stage drug development an in vivo model in small animals with translatability to human cardiac function is required. Over the last years, modifications/improvements regarding animal housing, ECG electrode placement, and data evaluation have been introduced into an established model for ECG recordings using telemetry in conscious, freely moving guinea pigs. Pharmacological validation using selected reference compounds affecting different mechanisms relevant for cardiac electrophysiology (quinidine, flecainide, atenolol, dl-sotalol, dofetilide, nifedipine, moxifloxacin) was conducted and findings were compared with results obtained in telemetered Beagle dogs. Under standardized conditions, reliable ECG data with low variability allowing largely automated evaluation were obtained from the telemetered guinea pig model. The model is sensitive to compounds blocking cardiac sodium channels, hERG K(+) channels and calcium channels, and appears to be even more sensitive to β-blockers as observed in dogs at rest. QT interval correction according to Bazett and Sarma appears to be appropriate methods in conscious guinea pigs. Overall, the telemetered guinea pig is a suitable model for the conduct of early stage preclinical ECG assessment. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Validation of phenol red versus gravimetric method for water reabsorption correction and study of gender differences in Doluisio's absorption technique.

    Science.gov (United States)

    Tuğcu-Demiröz, Fatmanur; Gonzalez-Alvarez, Isabel; Gonzalez-Alvarez, Marta; Bermejo, Marival

    2014-10-01

    The aim of the present study was to develop a method for water flux reabsorption measurement in Doluisio's Perfusion Technique based on the use of phenol red as a non-absorbable marker and to validate it by comparison with gravimetric procedure. The compounds selected for the study were metoprolol, atenolol, cimetidine and cefadroxil in order to include low, intermediate and high permeability drugs absorbed by passive diffusion and by carrier mediated mechanism. The intestinal permeabilities (Peff) of the drugs were obtained in male and female Wistar rats and calculated using both methods of water flux correction. The absorption rate coefficients of all the assayed compounds did not show statistically significant differences between male and female rats consequently all the individual values were combined to compare between reabsorption methods. The absorption rate coefficients and permeability values did not show statistically significant differences between the two strategies of concentration correction. The apparent zero order water absorption coefficients were also similar in both correction procedures. In conclusion gravimetric and phenol red method for water reabsorption correction are accurate and interchangeable for permeability estimation in closed loop perfusion method. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Quality control of tablets by Near Infrared (NIR)-Spectroscopy.

    Science.gov (United States)

    Petri, J; Kaunzinger, A; Niemöller, A; Karas, M

    2005-10-01

    Today, NIR-spectroscopy is an established analytical technique not only in the identification of raw materials but also in the quantification of active ingredients in tablets. In this work calibration models were set up with tablets of the same active ingredient but of miscellaneous origin and manufacturess. Consequently the tablets had different excipients and appearance. The pharmaceutical preparations used included atenolol 100 mg tablets, enalapril 20 mg tablets and acetylsalicylic acid (ASS) tablets of different dosage units. In order to proof if the calibration models set up are generally feasible the assay declared by the manufacturer was used to calculate the partial least square (PLS) calibration. With respect to enalapril tablets simultaneous analysis by HPLC, according to USP 26 was carried out. It was investigated if such methods allow a determination of active ingredients in tablets within limits of +/- 10% of declaration. It was shown that it is possible to set up calibration models to quantify active ingredients in tablets independent of adjuvants or optical appearance. Additionally it could be shown that NIR-spectroscopy is also applicable to determine the concentration of active ingredients in blister-packed tablets.

  7. A novel pure component contribution algorithm (PCCA) for extracting components' contribution from severely overlapped signals; an application to UV-spectrophotometric data.

    Science.gov (United States)

    Hegazy, Maha Abdel Monem

    2015-01-01

    A novel, simple and accurate algorithm capable of extracting the contribution of each component from a mixture signal where the components are completely overlapped was developed. It is based on the development of a coded function which eliminates the signal of interfering components using mean centering as a processing tool; finally the pure contribution of each component is extracted. The algorithm allows the determination of each component as a single one. It was validated by the use of simulated data set of three overlapped signals and tested against simulated random noise. Two fit values were developed and calculated for optimization, one to test that that the absorptivity values of the extracted spectra are within the confidence limits of the slope and the other is the correlation between the pure and extracted spectra. It has been successfully applied to real UV data of binary mixture of Ibuprofen and Paracetamol and ternary mixture of Amiloride hydrochloride, Atenolol and Hydrochlorothiazide in tablets and capsules, respectively. The results were compared to previously reported separation method and no significant difference was found regarding both accuracy and precision. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Carboxymethyl β-cyclodextrin as chiral selector in capillary electrophoresis: Enantioseparation of 16 basic chiral drugs and its chiral recognition mechanism associated with drugs' structural features.

    Science.gov (United States)

    Fang, Linlin; Du, Yueying; Hu, Xiaoyu; Luo, Linda; Guo, Xin; Guo, Xingjie; Yu, Jia

    2017-11-01

    Herein we present the enantioseparation of 10 cardiovascular agents and six bronchiectasis drugs including propranolol, carteolol, metoprolol, atenolol, pindolol, esmolol, bisoprolol, bevantolol, arotinolol, sotalol, clenbuterol, procaterol, bambuterol, tranterol, salbutamol and terbutaline sulfate using carboxymethyl-β-cyclodextrin (CM-β-CD) as chiral selector. To our knowledge, there is no literature about using CM-β-CD for separating carteolol, esmolol, bisoprolol, bevantolol, arotinolol, procaterol, bambuterol and tranterol. During the course of work, changes in pH, CM-β-CD concentration, buffer type and concentration were studied in relation to chiral resolution. Excellent enantiomeric separations were obtained for all 16 compounds, especially for procaterol. An impressive resolution value, up to 17.10, was obtained. In particular, most of them achieved rapid separations within 20 min. Given the fact that enantioseparation results rely on analytes' structural characters, the possible separation mechanisms were discussed. In addition, in order to obtain faster separation for propranolol enantiomers in practical application, the effective length of capillary was innovatively shortened from 45 to 30 cm. After the validation, the method was successfully applied to the enantiomeric purity determination of propranolol in the formulation of drug substances. Copyright © 2017 John Wiley & Sons, Ltd.

  9. Magnetic solid-phase extraction based on magnetic multiwalled carbon nanotubes for the simultaneous enantiomeric analysis of five β-blockers in the environmental samples by chiral liquid chromatography coupled with tandem mass spectrometry.

    Science.gov (United States)

    Wang, Zhaokun; Zhang, Xue; Jiang, Shenmeng; Guo, Xingjie

    2018-04-01

    In this work, the magnetic multiwalled carbon nanotubes (Mag-MWCNTs) were prepared by self-assembly method and characterized by scanning electron microscopy, X-ray powder diffraction, energy dispersive X-ray and vibrating sample magnetometer. Then, these synthetic Mag-MWCNTs were used as sorbents to extract five β-blockers (atenolol, metoprolol, esmolol, pindolol and arotinolol) by magnetic solid-phase extraction. The target analytes adsorbed on Mag-MWCNTs were eluted and determined on a chiral α-acid glycoprotein column coupled with a triple quadrupole mass spectrometry. Eventually, the proposed method was applied to the analysis of the enantiomeric composition of the studied β-blockers in three environmental samples, including river water, influent wastewater and effluent wastewater. Method detection and quantification limits for all enantiomers were in the range of 0.50-1.45 and 1.63-3.75ng/L, respectively. Satisfactory recovery (82.9-95.6%), good intra-day precision (RSD 0.4-10.4%) and inter-day precision (RSD 2.9-7.4%) were also obtained. With numerous advantages such as simplicity of operation, rapidity and high enrichment factor, the newly developed method has potential to assess the enantioselectivity of chiral drugs in ecotoxicity and biodegradation processes, which is also a new expanded application of Mag-MWCNTs in the environmental analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Evidence-based guideline update: Treatment of essential tremor

    Science.gov (United States)

    Zesiewicz, T.A.; Elble, R.J.; Louis, E.D.; Gronseth, G.S.; Ondo, W.G.; Dewey, R.B.; Okun, M.S.; Sullivan, K.L.; Weiner, W.J.

    2011-01-01

    Background: This evidence-based guideline is an update of the 2005 American Academy of Neurology practice parameter on the treatment of essential tremor (ET). Methods: A literature review using MEDLINE, EMBASE, Science Citation Index, and CINAHL was performed to identify clinical trials in patients with ET published between 2004 and April 2010. Results and Recommendations: Conclusions and recommendations for the use of propranolol, primidone (Level A, established as effective); alprazolam, atenolol, gabapentin (monotherapy), sotalol, topiramate (Level B, probably effective); nadolol, nimodipine, clonazepam, botulinum toxin A, deep brain stimulation, thalamotomy (Level C, possibly effective); and gamma knife thalamotomy (Level U, insufficient evidence) are unchanged from the previous guideline. Changes to conclusions and recommendations from the previous guideline include the following: 1) levetiracetam and 3,4-diaminopyridine probably do not reduce limb tremor in ET and should not be considered (Level B); 2) flunarizine possibly has no effect in treating limb tremor in ET and may not be considered (Level C); and 3) there is insufficient evidence to support or refute the use of pregabalin, zonisamide, or clozapine as treatment for ET (Level U). PMID:22013182

  11. Prevalence of carotid atherosclerosis in hypertension: preliminary baseline data from the European Lacidipine Study on Atheroscelerosis (ELSA).

    Science.gov (United States)

    Zanchetti, A

    1996-01-01

    In the ELSA trial, the effects of lacidipine-based treatment and beta-blocker (atenolol)-based treatment on the development and progression of carotid wall alterations are assessed in hypertensive patients. The primary endpoint of this study is the rate of change in the intima-media thickness of the carotid artery wall, measured with B-mode ultrasound. About 2300 hypertensive patients have been recruited and randomized to either of the antihypertensive agents. Baseline data for 1965 patients are available, showing a high prevalence of carotid wall lesions: about 82% of the subjects have an intima-media thickness > or = 1.3 mm, defined as plaque in the ELSA protocol; 16% of the subjects have intima-media thickening (> or = 1.0 mm, < 1.3 mm) and only about 1% have normal carotid artery walls. Analysis of demographic data and risk factor prevalence in ELSA patients, and comparison of these preliminary observations with data from other intervention or observational studies indicate that high blood pressure is a very important risk factor for carotid atherosclerosis.

  12. β-Blockers in hypertension, diabetes, heart failure and acute myocardial infarction: a review of the literature.

    Science.gov (United States)

    DiNicolantonio, James J; Fares, Hassan; Niazi, Asfandyar K; Chatterjee, Saurav; D'Ascenzo, Fabrizio; Cerrato, Enrico; Biondi-Zoccai, Giuseppe; Lavie, Carl J; Bell, David S; O'Keefe, James H

    2015-01-01

    β-Blockers (BBs) are an essential class of cardiovascular medications for reducing morbidity and mortality in patients with heart failure (HF). However, a large body of data indicates that BBs should not be used as first-line therapy for hypertension (HTN). Additionally, new data have questioned the role of BBs in the treatment of stable coronary heart disease (CHD). However, these trials mainly tested the non-vasodilating β1 selective BBs (atenolol and metoprolol) which are still the most commonly prescribed BBs in the USA. Newer generation BBs, such as the vasodilating BBs carvedilol and nebivolol, have been shown not only to be better tolerated than non-vasodilating BBs, but also these agents do not increase the risk of diabetes mellitus (DM), atherogenic dyslipidaemia or weight gain. Moreover, carvedilol has the most evidence for reducing morbidity and mortality in patients with HF and those who have experienced an acute myocardial infarction (AMI). This review discusses the cornerstone clinical trials that have tested BBs in the settings of HTN, HF and AMI. Large randomised trials in the settings of HTN, DM and stable CHD are still needed to establish the role of BBs in these diseases, as well as to determine whether vasodilating BBs are exempt from the disadvantages of non-vasodilating BBs.

  13. Optimal use of β-blockers in high-risk hypertension: A guide to dosing equivalence

    Directory of Open Access Journals (Sweden)

    Janet B McGill

    2010-05-01

    Full Text Available Janet B McGillDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri, USAAbstract: Hypertension is the number one diagnosis made by primary care physicians, placing them in a unique position to prescribe the antihypertensive agent best suited to the individual patient. In individuals with diabetes mellitus, blood pressure (BP levels > 130/80 mmHg confer an even higher risk for cardiovascular and renal disease, and these patients will benefit from aggressive antihypertensive treatment using a combination of agents. β‑blockers are playing an increasingly important role in the management of hypertension in high-risk patients. β‑blockers are a heterogeneous class of agents, and this review presents the differences between β‑blockers and provides evidence-based protocols to assist in understanding dose equivalence in the selection of an optimal regimen in patients with complex needs. The clinical benefits provided by β‑blockers are only effective if patients adhere to medication treatment long term. β‑blockers with proven efficacy, once-daily dosing, and lower side effect profiles may become instrumental in the treatment of hypertensive diabetic and nondiabetic patients.Keywords: antihypertensive, blood pressure, atenolol, carvedilol, labetalol, metoprolol, nebivolol

  14. Carvedilol in hypertension treatment

    Directory of Open Access Journals (Sweden)

    Panagiotis C Stafylas

    2008-02-01

    Full Text Available Panagiotis C Stafylas, Pantelis A Sarafidis1st Department of Medicine, AHEPA University Hospital, Aristotle University, Thessaloniki, GreeceAbstract: Although β-blockers have been previously shown to effectively reduce blood pressure (BP and have been used for hypertension treatment for over 40 years, their effect on cardiovascular morbidity and mortality in hypertensive patients remains controversial and its use in uncomplicated hypertension is currently under debate. However, data on the above field derive mainly from studies which were conducted with older agents, such as atenolol and metoprolol, while considerable pharamacokinetic and pharmacodynamic heterogeneity is present within the class of β-blockers. Carvedilol, a vasodilating non-cardioselective β-blocker, is a compound that seems to give the opportunity to the clinician to use a cardioprotective agent without the concerning hemodynamic and metabolic actions of traditional β-blocker therapy. In contrast with conventional β-blockers, carvedilol maintains cardiac output, has a less extended effect on heart rate and reduces BP by decreasing vascular resistance. Further, several studies has shown that carvedilol has a beneficial or at least neutral effect on metabolic parameters, such as glycemic control, insulin sensitivity, and lipid metabolism, suggesting that they could be used in subjects with the metabolic syndrome or diabetes without negative consequences. This article summarizes the distinct pharmacologic, hemodynamic, and metabolic properties of carvedilol in relation to conventional β-blockers, attempting to examine the potential use of this agent for hypertension treatment.Keywords: carvedilol, β-blockers, hypertension treatment

  15. An investigation into the presence of a vagal tachycardia and the effect of vasoactive intestinal polypeptide on rat heart rate in vitro.

    Science.gov (United States)

    Hogan, K; Markos, F

    2006-01-01

    The presence of the vagal tachycardia and the effect of vasoactive intestinal polypeptide in the isolated innervated rat atrium were investigated. The right vagus, or cardiac branch, were stimulated at 4, 8, 16 and 32 Hz, pulse duration 1 ms, 20 V, 30 s before atropine and for 1 min after atropine (3 micromol/l), experiments were carried out in the presence of atenolol (4 micromol/l). No significant vagal tachycardia was observed in the presence of atropine, the greatest increase in heart rate was at 16 Hz which was 3+/-1 beats/min (n = 12 rats) (p = 0.052). Baseline heart rates for the control, 226+/-11 beats/min (n = 12 rats) and atropine experiments, 210+/-8 beats/min (n = 12 rats), were not significantly different (p = 0.24). VIP (0.06, 0.12, 0.24 micromol/l) caused a maximum increase of 27+/-13 beats/min (n = 5 rats) after 6 micromol/l VIP which was not significant, two higher concentrations of VIP failed to increase heart rate further. These results show that the vagal tachycardia is not present and that VIP does not cause a significant tachycardia in the rat. Copyright (c) 2006 S. Karger AG, Basel.

  16. Amlodipine-induced bilateral upper extremity edema.

    Science.gov (United States)

    Ganeshalingham, Anusha; Wong, William

    2007-09-01

    To report a case of bilateral upper extremity edema associated with amlodipine use in a child. A previously well and normotensive 6-year-old girl presented with a generalized vasculitis of unknown origin and severe hypertension. Large vessels predominantly affecting the neck, chest, and abdomen were found to be involved, resulting in abnormal arterial circulation and significant blood pressure differences between the upper and lower extremities. Multiple antihypertensive agents were initially required to control blood pressure. She was stabilized and discharged on amlodipine 10 mg each evening, atenolol 50 mg/day, and warfarin. Three days later she was noted to have facial and bilateral upper extremity pitting edema. Laboratory and radiologic assessments for possible etiologies were negative. Discontinuation of amlodipine resulted in resolution of edema. As of June 2007, there had been no cases of bilateral upper extremity edema associated with amlodipine use reported in the English literature. Adverse effects of amlodipine, a widely used antihypertensive, have been well reported. These include flushing, headache, and peripheral edema. Lower limb edema is the most common, while periocular and perioral edema have occurred less frequently. Anasarca edema has been described only once in the English literature. According to the Naranjo probability scale, amlodipine was a probable cause of bilateral upper extremity edema in this child. Bilateral upper extremity edema has been associated with amlodipine use in a child with an abnormal arterial circulation. The edema resolved upon discontinuation of the drug.

  17. Short-limb dwarfism and hypertrophic cardiomyopathy in a patient with paternal isodisomy 14: 45,XYidic(14)(p11)

    Energy Technology Data Exchange (ETDEWEB)

    Walter, C.A.; Moore, C.M.; Kaye, C.I. [Univ. of Texas Health Science Center, San Antonio, TX (United States)] [and others

    1996-11-11

    Uniparental disomy (UPD) has been shown to result in specific disorders either due to imprinting and/or homozygosity of mutant alleles. Here we present the findings in a child with paternal UPD14. Ultrasound evaluation was performed at 30 weeks of gestation because of abnormally large uterine size. Pertinent ultrasound findings included polyhydramnios, short limbs, abnormal position of hands, small thorax, and nonvisualization of the fetal stomach. Postnatally the infant was found to have a low birth weight, short birth length, contractures, short limbs, and a small thorax with upslanting ribs. Assisted ventilation and gastrostomy were required. At age 6 months, the infant required hospitalization for hypertrophic cardiomyopathy which responded to Atenolol{reg_sign}. Initial cytogenetic studies demonstrated an apparently balanced de novo Robertsonian translocation involving chromosomes 14 and a karyotype designation of 45,XY,t(14q14q). No indication of mosaicism for trisomy 14 was observed in metaphase spreads prepared from peripheral blood lymphocytes or skin-derived fibroblasts. C-band and fluorescence in situ hybridization results demonstrated that the chromosome was dicentric. DNA analyses showed paternal uniparental isodisomy for chromosome 14. Based on the cytogenetic and DNA results a final karyotype designation of 45,XY,idic(14)(p11) was assigned to this infant with paternal isodisomy of chromosome 14. 41 refs., 5 figs., 2 tabs.

  18. Perioperative Hypertension Management during Facelift under Local Anesthesia with Intravenous Hypnotics

    Directory of Open Access Journals (Sweden)

    Ki Ho Chung

    2017-07-01

    Full Text Available Perioperative hypertension is a phenomenon in which a surgical patient’s blood pressure temporarily increases throughout the preoperative and postoperative periods and remains high until the patient’s condition stabilizes. This phenomenon requires immediate treatment not only because it is observed in a majority of patients who are not diagnosed with high blood pressure, but also because occurs in patients with underlying essential hypertension who show a sharp increase in their blood pressure. The most common complication following facelift surgery is hematoma, and the most critical risk factor that causes hematoma is elevated systolic blood pressure. In general, a systolic blood pressure goal of 65 mm Hg are recommended. This article discusses the causes of increased blood pressure and the treatment methods for perioperative hypertension during the preoperative, intraoperative, and postoperative periods, in order to find ways to maintain normal blood pressure in patients during surgery. Further, in this paper, we review the causes of perioperative hypertension, such as anxiety, epinephrine, pain, and postoperative nausea and vomiting. The treatment methods for perioperative hypertension are analyzed according to the following 3 operative periods, with a review of the characteristics and interactions of each drug: preoperative antihypertensive medicine (atenolol, clonidine, and nifedipine, intraoperative intravenous (IV hypnotics (propofol, midazolam, ketamine, and dexmedetomidine, and postoperative antiemetic medicine (metoclopramide and ondansetron. This article focuses on the knowledge necessary to safely apply local anesthesia with IV hypnotics during facelift surgery without the assistance of an anesthesiologist.

  19. Perioperative Hypertension Management during Facelift under Local Anesthesia with Intravenous Hypnotics.

    Science.gov (United States)

    Chung, Ki Ho; Cho, Myeong Soo; Jin, Hoon

    2017-07-01

    Perioperative hypertension is a phenomenon in which a surgical patient's blood pressure temporarily increases throughout the preoperative and postoperative periods and remains high until the patient's condition stabilizes. This phenomenon requires immediate treatment not only because it is observed in a majority of patients who are not diagnosed with high blood pressure, but also because occurs in patients with underlying essential hypertension who show a sharp increase in their blood pressure. The most common complication following facelift surgery is hematoma, and the most critical risk factor that causes hematoma is elevated systolic blood pressure. In general, a systolic blood pressure goal of 65 mm Hg are recommended. This article discusses the causes of increased blood pressure and the treatment methods for perioperative hypertension during the preoperative, intraoperative, and postoperative periods, in order to find ways to maintain normal blood pressure in patients during surgery. Further, in this paper, we review the causes of perioperative hypertension, such as anxiety, epinephrine, pain, and postoperative nausea and vomiting. The treatment methods for perioperative hypertension are analyzed according to the following 3 operative periods, with a review of the characteristics and interactions of each drug: preoperative antihypertensive medicine (atenolol, clonidine, and nifedipine), intraoperative intravenous (IV) hypnotics (propofol, midazolam, ketamine, and dexmedetomidine), and postoperative antiemetic medicine (metoclopramide and ondansetron). This article focuses on the knowledge necessary to safely apply local anesthesia with IV hypnotics during facelift surgery without the assistance of an anesthesiologist.

  20. Physicochemical characterisation and investigation of the bonding mechanisms of API-titanate nanotube composites as new drug carrier systems.

    Science.gov (United States)

    Sipos, Barbara; Pintye-Hódi, Klára; Kónya, Zoltán; Kelemen, András; Regdon, Géza; Sovány, Tamás

    2017-02-25

    Titanate nanotube (TNT) has recently been explored as a new carrier material for active pharmaceutical ingredients (API). The aim of the present work was to reveal the physicochemical properties of API-TNT composites, focusing on the interactions between the TNTs and the incorporated APIs. Drugs belonging to different Biopharmaceutical Classification System (BCS) classes were loaded into TNTs: diltiazem hydrochloride (BCS I.), diclofenac sodium (BCS II.), atenolol (BCS III.) and hydrochlorothiazide (BCS IV.). Experimental results demonstrated that it is feasible for spiral cross-sectioned titanate nanotubes to carry drugs and maintain their bioactivity. The structural properties of the composites were characterized by a range of analytical techniques, including FT-IR, DSC, TG-MS, etc. The interactions between APIs and TNTs were identified as electrostatic attractions, mainly dominated by hydrogen bonds. Based on the results, it can be stated that the strength of the association depends on the hydrogen donor strength of the API. The drug release of incorporated APIs was evaluated from compressed tablets and compared to that of pure APIs. Differences noticed in the dissolution profiles due to incorporation showed a correlation with the strength of interactions between the APIs and the TNTs observed in the above analytical studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. A primary fish gill cell culture model to assess pharmaceutical uptake and efflux: evidence for passive and facilitated transport.

    Science.gov (United States)

    Stott, Lucy C; Schnell, Sabine; Hogstrand, Christer; Owen, Stewart F; Bury, Nic R

    2015-02-01

    The gill is the principle site of xenobiotic transfer to and from the aqueous environment. To replace, refine or reduce (3Rs) the large numbers of fish used in in vivo uptake studies an effective in vitro screen is required that mimics the function of the teleost gill. This study uses a rainbow trout (Oncorhynchus mykiss) primary gill cell culture system grown on permeable inserts, which tolerates apical freshwater thus mimicking the intact organ, to assess the uptake and efflux of pharmaceuticals across the gill. Bidirectional transport studies in media of seven pharmaceuticals (propranolol, metoprolol, atenolol, formoterol, terbutaline, ranitidine and imipramine) showed they were transported transcellularly across the epithelium. However, studies conducted in water showed enhanced uptake of propranolol, ranitidine and imipramine. Concentration-equilibrated conditions without a concentration gradient suggested that a proportion of the uptake of propranolol and imipramine is via a carrier-mediated process. Further study using propranolol showed that its transport is pH-dependent and at very low environmentally relevant concentrations (ng L(-1)), transport deviated from linearity. At higher concentrations, passive uptake dominated. Known inhibitors of drug transport proteins; cimetidine, MK571, cyclosporine A and quinidine inhibited propranolol uptake, whilst amantadine and verapamil were without effect. Together this suggests the involvement of specific members of SLC and ABC drug transporter families in pharmaceutical transport. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Spectrophotometric determination of some beta-blockers in dosage forms based on complex formation with Cu(II) and Co(II).

    Science.gov (United States)

    Gölcü, Ayşegül; Yücesoy, Cem; Serin, Selahattin

    2004-06-01

    Four sensitive and accurate spectrophotometric methods have been developed for the assay of Acebutolol Hydrochloride (ACH), Atenolol (ATE) and Propranolol Hydrochloride (PRH), which are based on the complexation of drugs with copper(II) (Cu(II)) and cobalt(II) (Co(II)). The coloured products are measured at 613, 694, 548 and 614 nm for ACH-Co(II), ATE-Cu(II), PRH-Cu(II) and PRH-Co(II) method, respectively. The optimization of various experimental conditions is described. Conformity with Beer's Law was evident over a concentration range in the of 2 x 10(-5) - 1 x 10(-2) mol/L. The molar absorptivity, detection and quantification limits are calculated. The results obtained showed good recoveries of 100.2 +/- 1.1, 100.3 +/- 1.2, 100.75 +/- 1.0 and 99.55 +/- 1.1 % with relative standard deviations of 0.410, 0.490, 0.161 and 0.140 % for ACH-Co(II), ATE-Cu(II), PRH-Cu(II) and PRH-Co(II) method, respectively. They were applied to the analysis of tablet forms of the drugs and the results were statistically compared with those obtained by official and literature methods using t- and F-tests. There were no significant difference among the mean values and precisions of the methods at 95% confidence level.

  3. Anti-hypertensive effects of probenecid via inhibition of the α-adrenergic receptor.

    Science.gov (United States)

    Park, Jin Baek; Kim, Sung-Jin

    2011-01-01

    Probenecid has long been used in the treatment of gout. Its anti-gout mechanisms consist of uric acid reuptake inhibition and the consequent facilitation of uric acid excretion. In the present study, we investigated whether probenecid could exert an anti-hypertensive effect in spontaneously hypertensive rats (SHR). The noninvasive indirect tail cuff method was employed to measure blood pressure and heart rate. The administration of probenecid (50 mg/kg, ip) induced a significant systolic blood pressure (SBP) decrease, from 167 mmHg to 141 mmHg, within 120 min. In contrast, probenecid had little effect on normotensive control Wistar Kyoto rats (WKY). The anti-hypertensive effects of probenecid are almost as potent as those of atenolol. In a further exploration of the anti-hypertensive mechanisms of probenecid, its effects on phenylephrine-induced blood vessel contraction were tested. Our results suggest that probenecid significantly inhibited the contractions of rat aorta. This effect was also observed with endothelium-removed rat aorta, suggesting that probenecid can directly interact with the α-adrenergic receptor. Moreover, probenecid inhibited the α-adrenergic-receptor-mediated activation of ERK I/II in MC3TC-E1 cells. Therefore, our results indicate that probenecid might alleviate high blood pressure in SHR via inhibition of the α-adrenergic receptor and ERK I/II.

  4. Comparison of the Usefulness of SPE Cartridges for the Determination of β-Blockers and β-Agonists (Basic Drugs in Environmental Aqueous Samples

    Directory of Open Access Journals (Sweden)

    Magda Caban

    2015-01-01

    Full Text Available Even though the methodology used for the determination of β-blockers and β-agonists in environmental samples is based mainly on solid-phase extraction (SPE and gas chromatography or liquid chromatography with mass spectrometric detection, the available literature data on the applied SPE procedures is rather sparse. In this paper such comparison is presented. Moreover, the usefulness of the eight SPE cartridges for the determination of five β-blockers (acebutolol, atenolol, metoprolol, nadolol, and propranolol and two β-agonists (salbutamol and terbutaline in environmental aqueous samples using GC techniques is tested. Among them, three (the trifunction sorbent Strata Screen C, the copolymers LiChrolut EN, and the functionalized copolymer Isolute ENV+ were used for the first time for this purpose. It was confirmed that polystyrene-divinylbenzene-N-vinylpyrrolidone copolymers (PS-DVB-VP, Strata-X, and Oasis HLB cartridges have a better potential than a cation-exchange sorbent for the extraction of the target drugs from environmental water samples. However, it should be stressed out that the direct application of the tested SPE conditions for the analysis of real environmental water samples is not possible, and such parameters, like volume of loading sample, appropriate solvents for washing and elution steps, and so forth, must be optimized again in order to achieve satisfactory recovery values for the target compounds.

  5. Occurrence and persistence of organic emerging contaminants and priority pollutants in five sewage treatment plants of Spain: two years pilot survey monitoring.

    Science.gov (United States)

    Bueno, M J Martínez; Gomez, M J; Herrera, S; Hernando, M D; Agüera, A; Fernández-Alba, A R

    2012-05-01

    This work summarized all results obtained during almost two-years of a monitoring programme carried out in five municipal sewage treatment plants (STPs) located in the north, centre and south-east of Spain. The study evaluated the occurrence and persistence of a group of 100 organic compounds belonging to several chemical groups (pharmaceuticals, personal care products, pesticides and metabolites). The average removal efficiencies of the STPs studied varied from 20% (erythromycin) to 99% (acetaminophen). In analysed samples, we identified a large number of compounds at mean range concentrations between 7-59,495 ng/L and 5-32,720 ng/L for influent and effluent samples, respectively. This study also identified 20 of the mostly detected and persistent compounds in wastewater effluent, of which hydrochlorothiazide, atenolol, gemfibrozil, galaxolide and three metabolites (fenofibric acid, 4-AAA and 4-FAA), presented the highest average contribution percentages, in relation to the total load of contaminants for the different STPs effluent studied. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Effect of adrenergic receptor ligands on metaiodobenzylguanidine uptake and storage in neuroblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Babich, J.W. [Division of Nuclear Medicine, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts (United States)]|[Department of Radiology, Harvard Medical School, Boston, Massachusetts (United States); Graham, W. [Division of Nuclear Medicine, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts (United States); Fischman, A.J. [Division of Nuclear Medicine, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts (United States)]|[Department of Radiology, Harvard Medical School, Boston, Massachusetts (United States)

    1997-05-01

    The effects of adrenergic receptor ligands on uptake and storage of the radiopharmaceutical [{sup 125}I]metaiodobenzylguanidine (MIBG) were studied in the human neuroblastoma cell line SK-N-SH. For uptake studies, cells were with varying concentrations of {alpha}-agonist (clonidine, methoxamine, and xylazine), {alpha}-antagonist (phentolamine, tolazoline, phenoxybenzamine, yohimbine, and prazosin), {beta}-antagonist (propranolol, atenolol), {beta}-agonist (isoprenaline and salbutamol), mixed {alpha}/{beta} antagonist (labetalol), or the neuronal blocking agent guanethidine, prior to the addition of [{sup 125}I]MIBG (0.1 {mu}M). The incubation was continued for 2 h and specific cell-associated radioactivity was measured. For the storage studies, cells were incubated with [{sup 125}I]MIBG for 2 h, followed by replacement with fresh medium with or without drug (MIBG, clonidine, or yohimbine). Cell-associated radioactivity was measured at various times over the next 20 h. Propanolol reduced [{sup 125}I]MIBG uptake by approximately 30% (P<0.01) at all concentrations tested, most likely due to nonspecific membrane changes. In conclusion, the results of this study establish that selected adrenergic ligands can significantly influence the pattern of uptake and storage of MIBG in cultured neuroblastoma cells, most likely through inhibition of uptake or through noncompetitive inhibition. The potential inplications of these findings justify further study. (orig./VHE). With 4 figs., 1 tab.

  7. Activation of peripheral chemoreceptors causes positive inotropic effects in a working heart-brainstem preparation of the rat.

    Science.gov (United States)

    Braga, Valdir A; Zoccal, Daniel B; Soriano, Renato N; Antunes, Vagner R; Paton, Julian F; Machado, Benedito H; Nalivaiko, Eugene

    2007-11-01

    1. The aim of the present study was to evaluate the effects of peripheral chemoreceptor activation on myocardial contractility in an anaesthetic-free decerebrated rat preparation. 2. In the decerebrated and retrogradely perfused working heart-brainstem preparation, we recorded phrenic nerve activity, left ventricular (LV) pressure (microtip Millar catheter), LV dP/dT, heart rate and aortic perfusion pressure before and after activating peripheral chemoreceptors with bolus intra-arterial injections of KCN. 3. Without cardiac pacing, chemoreflex activation caused falls in heart rate (-108 +/- 21 b.p.m.) and complex polyphasic changes in LV pressure and LV dP/dT. If the heart was paced, chemoreflex activation caused significant rises in LP pressure (+16 +/- 3 mmHg) and LV dP/dt (+778 +/- 93 mmHg/s). These positive inotropic effects were significantly and substantially attenuated by beta-adrenoceptor blockade with atenolol. In all instances, chemoreflex activation elicited potent tachypnoeic responses. 4. In conclusion, activation of peripheral chemoreceptors in non-anaesthetized rats evokes a positive inotropic response that is sympathetically mediated. This observation may be relevant for the evaluation of neurally induced effects of acute hypoxia on the ventricular myocardium.

  8. EXCESS PRESSURE INTEGRAL PREDICTS CARDIOVASCULAR EVENTS INDEPENDENT OF OTHER RISK FACTORS IN THE CONDUIT ARTERY FUNCTIONAL EVALUATION (CAFE) SUB-STUDY OF ANGLO-SCANDINAVIAN CARDIAC OUTCOMES TRIAL (ASCOT)

    Science.gov (United States)

    Davies, Justin E; Lacy, Peter; Tillin, Therese; Collier, David; Cruickshank, J Kennedy; Francis, Darrel P; Malaweera, Anura; Mayet, Jamil; Stanton, Alice; Williams, Bryan; Parker, Kim H; McG Thom, Simon A; Hughes, Alun D

    2014-01-01

    Excess pressure integral (XSPI), a new index of surplus work performed by the left ventricle, can be calculated from blood pressure (BP) waveforms and may indicate circulatory dysfunction. We investigated whether XSPI predicted future cardiovascular (CV) events and target organ damage in treated hypertensive individuals. Radial BP waveforms were acquired by tonometry in 2069 individuals (63±8y) in the Conduit Artery Functional Evaluation sub-study of the Anglo-Scandinavian Cardiac Outcomes trial. Measurements of left ventricular mass index (LVMI; n = 862) and common carotid artery intima media thickness (cIMT; n = 923) were also performed. XSPI and the integral of reservoir pressure (PRI) were lower in people treated with amlodipine ± perindopril than atenolol ± bendroflumethiazide, although brachial systolic BP was similar. A total of 134 CV events accrued over a median 3.4 years of follow-up; XSPI was a significant predictor of CV events after adjustment for age and sex and this relationship was unaffected by adjustment for conventional CV risk factors or Framingham risk score. XSPI, central systolic BP, central augmentation pressure (AP), central pulse pressure (cPP) and PRI were correlated with LVMI, but only XSPI, AP and cPP were positively associated with cIMT. Associations between LVMI and XSPI and PRI, and cIMT and XSPI were unaffected by multivariable adjustment for other covariates. XSPI is a novel indicator of CV dysfunction and independently predicts CV events and target organ damage in a prospective clinical trial. PMID:24821941

  9. Potentially inappropriate prescribing in elderly population: A study in medicine out-patient department

    Directory of Open Access Journals (Sweden)

    Ajit Kumar Sah

    2017-03-01

    Full Text Available Background & Objectives: Older individuals often suffer from multiple systemic diseases and are particularly more vulnerable to potentially inappropriate medicine prescribing. Inappropriate medication can cause serious medical problem for the elderly. The study was conducted with objectives to determine the prevalence of potentially inappropriate medicine (PIM prescribing in older Nepalese patients in a medicine outpatient department.Materials & Methods: A prospective observational analysis of drugs prescribed in medicine out-patient department (OPD of a tertiary hospital of central Nepal was conducted during November 2012 to October 2013 among 869 older adults aged 65 years and above. The use of potentially inappropriate medications (PIM in elderly patients was analysed using Beer’s Criteria updated to 2013. Results: In the 869 patients included, the average number of drugs prescribed per prescription was 5.56. The most commonly used drugs were atenolol (24.3%, amlodipine (23.16%, paracetamol (17.6%, salbutamol (15.72% and vitamin B complex (13.26%. The total number of medications prescribed was 4833. At least one instance of PIM was experienced by approximately 26.3% of patients when evaluated using the Beers criteria. Conclusion: Potentially inappropriate medications are highly prevalent among older patients attending medical OPD and are associated with number of medications prescribed. Further research is warranted to study the impact of PIMs towards health related outcomes in these elderly.

  10. Algal cultivation in urban wastewater: an efficient way to reduce pharmaceutical pollutants.

    Science.gov (United States)

    Gentili, Francesco G; Fick, Jerker

    2017-01-01

    The purpose of this study was to investigate whether pharmaceutical pollutants in urban wastewater can be reduced during algal cultivation. A mixed population of wild freshwater green algal species was grown on urban wastewater influent in a 650 L photobioreactor under natural light and with the addition of flue gases. Removal efficiencies were very high (>90 %), moderate (50-90 %), low (10-50 %), and very low or non-quantifiable (pharmaceuticals, respectively, over a 7-day period. High reduction was found in the following pharmaceuticals: the beta-blockers atenolol, bispropol, and metoprolol; the antibiotic clarithromycine; the antidepressant bupropion; the muscle relaxant atracurium; hypertension drugs diltiazem and terbutaline used to relive the symptoms of asthma. Regression analysis did not detect any relationship between the reduction in pharmaceutical contents and light intensity reaching the water surface of the algal culture. However, the reduction was positively correlated with light intensity inside the culture and stronger when data collected during the night were excluded. Algae cultivation can remove partially or totally pharmaceutical pollutants from urban wastewater, and this opens up new possibilities for treating urban wastewater.

  11. [Early cellular alterations induced by myocardial hypoxia: possible role of cyclic AMP (author's transl)].

    Science.gov (United States)

    de Leiris, J; Bégué, J M; Gauduel, Y; Feuvray, D

    1980-01-01

    The ability of endogenous myocardial catecholamines to participate in the development of myocardial cellular alterations during a short period of severe hypoxia (30 min) was studied in isolated, Langendorff-perfused rat heart preparation, arrested by a high potassium concentration (16 mM) and perfused in the absence of exogenous substrate (Table I). Tyramine, which accelerated catecholamine depletion, also increased myocardial cell damage as assessed by a higher lactate dehydrogenase (LDH) release and a more marked reduction in cellular levels of high energy phosphates and glycogen (Table II). On the other hand, under conditions of beta-blockade (atenolol), hypoxia-induced tissular damage was reduced (Table II). These changes could be related to modifications in the cellular content of cyclic AMP (cAMP) since cAMP was consistently higher during the first 30 min of hypoxic perfusion than in control normoxic hearts (Table III) whereas cyclic GMP content remained unchanged. Moreover, interventions increasing cellular content of cAMP (theophylline, dibutyryl-cAMP) also increased hypoxic damage (Table IV), whereas N-methyl imidazole which reduced cellular content of cAMP lessened hypoxia-induced cellular alterations (Table IV). It is concluded that cellular lesions developing during the first 30 min of hypoxia in isolated arrested rat heart preparation perfused without exogenous substrate could be related to intracellular accumulation of cAMP occurring under the effect of endogenous catecholamine release.

  12. A Dual-Functional [SBA-15/Fe3O4/P(N-iPAAm] Hybrid System as a Potential Nanoplatform for Biomedical Application

    Directory of Open Access Journals (Sweden)

    Andreza de Sousa

    2014-01-01

    Full Text Available The synthesis strategy of a multifunctional system of [SBA-15/Fe3O4/P(N-iPAAm] hybrids of interest for bioapplications was explored. Magnetite nanoparticles coated by mesoporous silica were prepared by an alternative chemical route using neutral surfactant and without the application of any functionalization method. Monomer adsorption followed by in situ polymerization initiated by a radical was the adopted procedure to incorporate the hydrogel into the pore channels of silica nanocomposite. Characterization of the materials was carried out by using X-ray diffraction (XRD, Fourier-transform infrared spectroscopy (FTIR, N2 adsorption, transmission electron microscopy (TEM, and Temperature programmed reduction studies (TPR. Their application as drug delivery system using atenolol as a model drug to assess the influence of the application of low frequency alternating magnetic fields on drug release was evaluated. The structural characteristics of the magnetic hybrid nanocomposite, including the effect of the swelling behavior on heating by the application of an alternating magnetic field, are presented and discussed.

  13. [General awareness and use of generic medication among citizens of Tubarão, state of Santa Catarina, Brazil].

    Science.gov (United States)

    Blatt, Carine Raquel; Trauthman, Silvana Cristina; Schmidt, Edegar Henrique; Marchesan, Samuel; da Silva, Luana May; Martins, João Luiz

    2012-01-01

    Although generic medication has been introduced in the country to offer an accessible alternative to brand-name medication, it represents only 14% of sales in number of units within the pharmaceutical market. The aim of this work was to research the level of awareness and the use of generic products among residents of the municipality of Tubarão, State of Santa Catarina, Brazil. A transversal study was carried out with a sample of 234 interviewees, distributed among municipal areas. With regard to use, the majority of those interviewed had used generic medication, and half of them had at least one such product in their home. To verify awareness of different types of medication, pictures with the generic, brand name and similar packaging for paracetamol and atenolol were shown and 91% were able to identify all products correctly. To be of higher economic standing, already having used generic products, believing that the generic medication has the same effect as the brand name medication, finding generic products in drugstores easily and being accustomed to buy generic products, were factors that were positively associated with the correct identification.

  14. Active modulation of drug release by ionic field effect transistor for an ultra-low power implantable nanofluidic system

    Science.gov (United States)

    Bruno, Giacomo; Canavese, Giancarlo; Liu, Xuewu; Filgueira, Carly S.; Sacco, Adriano; Demarchi, Danilo; Ferrari, Mauro; Grattoni, Alessandro

    2016-01-01

    We report an electro-nanofluidic membrane for tunable, ultra-low power drug delivery employing an ionic field effect transistor. Therapeutic release from a drug reservoir was successfully modulated, with high energy efficiency, by actively adjusting the surface charge of slit-nanochannels 50, 110, and 160 nm in size, by the polarization of a buried gate electrode and the consequent variation of the electrical double layer in the nanochannel. We demonstrated control over the transport of ionic species, including two relevant hypertension drugs, atenolol and perindopril, that could benefit from such modulation. By leveraging concentration-driven diffusion, we achieve a 2 to 3 order of magnitude reduction in power consumption as compared to other electrokinetic phenomena. The application of a small gate potential (±5 V) in close proximity (150 nm) of 50 nm nanochannels generated a sufficiently strong electric field, which doubled or blocked ionic flux depending on the polarity of the voltage applied. These compelling findings can lead to next generation, more reliable, smaller, and longer lasting drug delivery implants with ultra-low power consumption. PMID:27787528

  15. The active modulation of drug release by an ionic field effect transistor for an ultra-low power implantable nanofluidic system.

    Science.gov (United States)

    Bruno, Giacomo; Canavese, Giancarlo; Liu, Xuewu; Filgueira, Carly S; Sacco, Adriano; Demarchi, Danilo; Ferrari, Mauro; Grattoni, Alessandro

    2016-11-10

    We report an electro-nanofluidic membrane for tunable, ultra-low power drug delivery employing an ionic field effect transistor. Therapeutic release from a drug reservoir was successfully modulated, with high energy efficiency, by actively adjusting the surface charge of slit-nanochannels 50, 110, and 160 nm in size, by the polarization of a buried gate electrode and the consequent variation of the electrical double layer in the nanochannel. We demonstrated control over the transport of ionic species, including two relevant hypertension drugs, atenolol and perindopril, that could benefit from such modulation. By leveraging concentration-driven diffusion, we achieve a 2 to 3 order of magnitude reduction in power consumption as compared to other electrokinetic phenomena. The application of a small gate potential (±5 V) in close proximity (150 nm) of 50 nm nanochannels generated a sufficiently strong electric field, which doubled or blocked the ionic flux depending on the polarity of the voltage applied. These compelling findings can lead to next generation, more reliable, smaller, and longer lasting drug delivery implants with ultra-low power consumption.

  16. Removal of pharmaceuticals and personal care products in a membrane bioreactor wastewater treatment plant.

    Science.gov (United States)

    Kim, M; Guerra, P; Shah, A; Parsa, M; Alaee, M; Smyth, S A

    2014-01-01

    Ninety-nine pharmaceuticals and personal care products (PPCPs) were analyzed in influent, final effluent, and biosolids samples from a wastewater treatment plant employing a membrane bioreactor (MBR). High concentrations in influent were found for acetaminophen, caffeine, metformin, 2-hydroxy-ibuprofen, paraxanthine, ibuprofen, and naproxen (10(4)-10(5) ng/L). Final effluents contained clarithromycin, metformin, atenolol, carbamazepine, and trimethoprim (>500 ng/L) at the highest concentrations, while triclosan, ciprofloxacin, norfloxacin, triclocarban, metformin, caffeine, ofloxacin, and paraxanthine were found at high concentrations in biosolids (>10(3) ng/g dry weight). PPCP removals varied from -34% to >99% and 23 PPCPs had ≥90% removal. Of the studied PPCPs, 26 compounds have been rarely or never studied in previous membrane bioreactor (MBR) investigations. The removal pathway showed that acetaminophen, 2-hydroxy-ibuprofen, naproxen, ibuprofen, codeine, metformin, enalapril, atorvastatin, caffeine, paraxanthine, and cotinine exhibited high degradation/transformation. PPCPs showing strong sorption to solids included triclocarban, triclosan, miconazole, tetracycline, 4-epitetracycline, norfloxacin, ciprofloxacin, doxycycline, paroxetine, and ofloxacin. Trimethoprim, oxycodone, clarithromycin, thiabendazole, hydrochlorothiazide, erythromycin-H2O, carbamazepine, meprobamate, and propranolol were not removed during treatment, and clarithromycin was even formed during treatment. This investigation extended our understanding of the occurrence and fate of PPCPs in an MBR process through the analysis of the largest number of compounds in an MBR study to date.

  17. Occurrence and distribution of selected pharmaceuticals and personal care products in aquatic environments: a comparative study of regions in China with different urbanization levels.

    Science.gov (United States)

    Chen, Hong; Li, Xiaojuan; Zhu, Saichang

    2012-07-01

    We analyzed and compared the distributions of 13 target pharmaceuticals in different water samples from the Hangzhou metropolitan area and Linan County, Southeast China. Sampling was conducted in five hospitals, two wastewater treatment plants (WWTPs), and Qiantang River. Samples were concentrated by solid-phase extraction and PPCP concentrations were determined by UPLC-MS/MS. Trimethoprim, erythromycin A dihydrate, norfloxacin, ofloxacin, diclofenac sodium, and atenolol were the most frequently detected pharmaceuticals in hospital effluents. Most of the pharmaceutical concentrations in hospital effluents were higher than those in the WWTP influents. Although both WWTPs adopt the anaerobic-aerobic-anoxic treatment process, the removal rates for pharmaceuticals, such as trimethoprim and diclofenac sodium, were completely different. Meanwhile, erythromycin A dihydrate, ofloxacin, penicillin-G, cephalexin, cefazolin, ibuprofen, and diclofenac sodium were detected in Qiantang River. These results indicate that hospitals are more concentrated sources of pharmaceuticals than WWTPs, and the WWTPs are not the only route of entry of pharmaceuticals into aquatic environments in these two regions.

  18. Equilibrium partitioning of organic compounds to OASIS HLB® as a function of compound concentration, pH, temperature and salinity.

    Science.gov (United States)

    Jeong, Yoonah; Schäffer, Andreas; Smith, Kilian

    2017-05-01

    Oasis hydrophilic lipophilic balance® (Oasis HLB) is commonly employed in solid phase extraction (SPE) of environmental contaminants and within polar organic chemical integrative passive samplers (POCIS). In this study batch experiments were carried out to evaluate the relative affinity of a range of relevant organic pollutants to Oasis HLB in aqueous systems. The influence of sorbate concentration, temperature, pH, and salinity on the equilibrium sorption was investigated. Equilibrium partition ratios (KD) of 28 compounds were determined, ranging over three orders of magnitude from 1.16 × 103 L/kg (atenolol) to 1.07 × 106 L/kg (isoproturon). The Freundlich model was able to describe the equilibrium partitioning to Oasis HLB, and an analysis of the thermodynamic parameters revealed the spontaneous and exothermic nature of the partitioning process. Ionic strength had only a minor effect on the partitioning, whereas pH had a considerable effect but only for ionizable compounds. The results show that apolar interactions between the Oasis HLB and analyte mainly determine the equilibrium partitioning. These research findings can be used to optimize the application of SPE and POCIS for analyses of environmental contaminants even in complex mixtures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. eNOS-dependent antisenscence effect of a calcium channel blocker in human endothelial cells.

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    Toshio Hayashi

    Full Text Available Senescence of vascular endothelial cells is an important contributor to the pathogenesis of age-associated vascular disorders such as atherosclerosis. We investigated the effects of antihypertensive agents on high glucose-induced cellular senescence in human umbilical venous endothelial cells (HUVECs. Exposure of HUVECs to high glucose (22 mM for 3 days increased senescence-associated- β-galactosidase (SA-β-gal activity, a senescence marker, and decreased telomerase activity, a replicative senescence marker. The calcium channel blocker nifedipine, but not the β1-adrenergic blocking agent atenolol or the angiotensin-converting enzyme inhibitor perindopril, reduced SA-β-gal positive cells and prevented a decrease in telomerase activity in a high-glucose environment. This beneficial effect of nifedipine was associated with reduced reactive oxygen species (ROS and increased endothelial nitric oxide synthase (eNOS activity. Thus, nifedipine prevented high glucose-induced ROS generation and increased basal eNOS phosphorylation level at Ser-1177. Treatment with N (G-nitro-L-arginine (L-NAME and transfection of small interfering RNA (siRNA targeting eNOS eliminated the anti-senscence effect of nifedipine. These results demonstrate that nifedipine can prevent endothelial cell senescence in an eNOS-dependent manner. The anti-senescence action of nifedipine may represent a novel mechanism by which it protects against atherosclerosis.

  20. Evaluation of pharmacy and therapeutics committee drug evaluation reports.

    Science.gov (United States)

    Majercik, P L; May, J R; Longe, R L; Johnson, M H

    1985-05-01

    Pharmacy and therapeutics (P & T) committee drug evaluation reports prepared by pharmacies and drug information centers (DICs) and product package inserts were compared with standard guidelines to evaluate their quality. Letters were sent to 143 hospital pharmacies asking them to submit a previously prepared drug evaluation report on temazepam, moxalactam disodium, or atenolol. The reports and package inserts for these three drugs were evaluated by the presence of 40 elements derived from the published ASHP guidelines for drug evaluation report preparation. Responses were obtained from 124 (87%) pharmacies; however, only 80 reports (60 DIC-prepared and 20 pharmacy-prepared) were received. The reports contained a mean of 28 of the 40 (70%) possible elements. The most frequently omitted elements were AHFS number, potential unlabeled uses, drug-drug interactions, drug-disease-laboratory test interactions, risk and benefit data, prevention and treatment of side effects, comparisons with established treatment, and disadvantages of the drug under consideration. Although the reports prepared by the DICs and pharmacies contained the same amount of information, the DIC-prepared reports included data more frequently on supply sources, therapeutic indications, approved labeling, comparison with established treatment, bioavailability and pharmacokinetics, and recommendations. Most of the reports contained more elements than the corresponding package inserts. The product package inserts did not contain the comparative elements required for P & T committee decisions. Both the pharmacy- and DIC-prepared reports failed to contain all 40 elements recommended in the standard guidelines, suggesting the need for more thorough reports.

  1. Enfermedad de Graves: Presentación tardía de síndrome de reconstitución inmune en VIH/SIDA.: Reporte de casos y revisión de la literatura.

    Directory of Open Access Journals (Sweden)

    Miguel Eduardo Pinto Valdivia

    2007-10-01

    Full Text Available Se reportan dos casos de enfermedad de Graves relacionados con sindrome de Reconstitución Inmune en dos pacientes infectados con VIH luego de iniciar la terapia antiretroviral de gran actividad (TARGA. Se revisaron las historias clínicas de los pacientes y se hizo una revisión bibliográfica. Dos pacientes con historia de infección por VIH desarrollaron pérdida de peso, taquicardia, tremor en la manos y diarrea, luego de 30 y 48 meses después de iniciado tratamiento TARGA con zidovudina, lamivudina y atazanavir. Al momento de desarrollar este problema su conteo de células CD4 estaba en rangos de normalidad y su carga viral estaba en niveles indetectables. En el examen Físico se detectó un aumento de volumen de la glándula tiroides. Los niveles de tirotropina estaban suprimidos y los niveles de tiroxina libre elevados; se detectó niveles positivos de anticuerpos anti-TPO. Ambos pacientes mejoraron con el tratamiento metimazol y atenolol. La enfermedad de Graves ha sido reportada como complicación inusual en pacientes VIH como reconstitución Inmune luego del inicio de TARGA. Estos dos pacientes muestran un cuadro compatible.

  2. Nanocarriers and the delivered drug: effect interference due to intravenous administration.

    Science.gov (United States)

    Vlasova, Maria A; Rytkönen, Jussi; Riikonen, Joakim; Tarasova, Olga S; Mönkäre, Juha; Kovalainen, Miia; Närvänen, Ale; Salonen, Jarno; Herzig, Karl-Heinz; Lehto, Vesa-Pekka; Järvinen, Kristiina

    2014-10-15

    Intravenously administered nanocarriers are widely studied to improve the delivery of various therapeutic agents. However, recent in vivo studies have demonstrated that intravenously administered nanocarriers that do not contain any drug may affect cardiovascular function. Here we provide an example where the drug and the nanocarrier both affect the same cardiovascular parameters following intravenous administration. The peptide ghrelin antagonist (GhA) increases arterial pressure, while thermally hydrocarbonized porous silicon nanoparticles (THCPSi) transiently decrease it, as assessed with radiotelemetry in conscious rats. As a result, intravenous administration of GhA-loaded THCPSi nanoparticles partially antagonized GhA activity: arterial pressure was not increased. When the cardiovascular effects of GhA were blocked with atenolol pretreatment, GhA-loaded nanoparticles reduced arterial pressure to similar extent as drug-free nanoparticles. These data indicate that the biological activity of a drug delivered within a nanocarrier may be obscured by the biological responses induced by the nanocarrier itself. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Characterization of Pharmacokinetics in the Göttingen Minipig with Reference Human Drugs: An In Vitro and In Vivo Approach.

    Science.gov (United States)

    Lignet, Floriane; Sherbetjian, Eva; Kratochwil, Nicole; Jones, Russell; Suenderhauf, Claudia; Otteneder, Michael B; Singer, Thomas; Parrott, Neil

    2016-10-01

    This study aims to expand our understanding of the mechanisms of drug absorption, distribution, metabolism and excretion in the Göttingen minipig to aid a knowledge-driven selection of the optimal species for preclinical pharmaceutical research. The pharmacokinetics of seven reference compounds (antipyrine, atenolol, cimetidine, diazepam, hydrochlorothiazide, midazolam and theophylline) was investigated after intravenous and oral dosing in minipigs. Supportive in vitro data were generated on hepatocellularity, metabolic clearance in hepatocytes, blood cell and plasma protein binding and metabolism routes. Systemic plasma clearance for the seven drugs ranged from low (1.1 ml/min/kg, theophylline) to close to liver blood flow (37.4 ml/min/kg, cimetidine). Volume of distribution in minipigs ranged from 0.7 L/kg for antipyrine to 3.2 L/kg for hydrochlorothiazide. A gender-related difference of in vivo metabolic clearance was observed for antipyrine. The hepatocellularity for minipig was determined as 124 Mcells/g liver, similar to the values reported for human. Based on these data a preliminary in vitro to in vivo correlation (IVIVC) for metabolic clearance measured in hepatocytes was investigated. Metabolite profiles of diazepam and midazolam compared well between minipig and human. The results of the present study support the use of in vitro metabolism data for the evaluation of minipig in preclinical research and safety testing.

  4. Aqueous chlorination of acebutolol: kinetics, transformation by-products, and mechanism.

    Science.gov (United States)

    Khalit, Wan Nor Adira Wan; Tay, Kheng Soo

    2016-02-01

    This study investigated the reaction kinetics and the transformation by-products of acebutolol during aqueous chlorination. Acebutolol is one of the commonly used β-blockers for the treatment of cardiovascular diseases. It has been frequently detected in the aquatic environment. In the kinetics study, the second-order rate constant for the reaction between acebutolol and chlorine (k app) was determined at 25 ± 0.1 °C. The degradation of acebutolol by free available chlorine was highly pH dependence. When the pH increased from 6 to 8, it was found that the k app for the reaction between acebutolol and free available chlorine was increased from 1.68 to 11.2 M(-1) min(-1). By comparing with the reported k app values, the reactivity of acebutolol toward free available chlorine was found to be higher than atenolol and metoprolol but lower than nadolol and propranolol. Characterization of the transformation by-products formed during the chlorination of acebutolol was carried out using liquid chromatography-quadrupole time-of-flight high-resolution mass spectrometry. Seven major transformation by-products were identified. These transformation by-products were mainly formed through dealkylation, hydroxylation, chlorination, and oxidation reactions.

  5. Taste acceptability of pulverized brand-name and generic drugs containing amlodipine or candesartan.

    Science.gov (United States)

    Uestuener, Peter; Ferrarini, Alessandra; Santi, Maristella; Mardegan, Chiara; Bianchetti, Mario G; Simonetti, Giacomo D; Milani, Gregorio P; Lava, Sebastiano A G

    2014-07-01

    Trials with pulverized brand-name antihypertensive drugs suggest that, from the perspective of taste acceptability, crushed candesartan, chlortalidon, hydrochlorothiazide, lercanidipine and lisinopril should be preferred to pulverized amlodipine, atenolol, bisoprolol, enalapril, irbesartan, losartan, ramipril, telmisartan and valsartan. Brand-name antihypertensive drugs and the corresponding generic medicines have never been compared with respect to their taste acceptability. We therefore investigated among healthy health care workers the taste acceptability of a pulverized 1 mg-test dose of the brand-name and two generics containing either the dihydropyridine calcium-channel blocker amlodipine (Norvasc(®), Amlodipin-Mepha(®) and Amlodipin Pfizer(®)) or the angiotensin receptor antagonist candesartan (Atacand(®), Cansartan-Mepha(®) and Pemzek(®)). For this purpose, a smiley-face scale depicting four degrees of pleasure was used. Between November and December 2013, the taste test was performed among 19 nurses (15 female and 4 male subjects) and 12 physicians (5 female and 7 male subjects) aged between 25 and 49 years. Pulverized brand-names and generics containing either amlodipine or candesartan did not differ with respect to their taste acceptability. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Emerging organic contaminants in coastal waters: anthropogenic impact, environmental release and ecological risk.

    Science.gov (United States)

    Jiang, Jheng-Jie; Lee, Chon-Lin; Fang, Meng-Der

    2014-08-30

    This study provides a first estimate of the sources, distribution, and risk presented by emerging organic contaminants (EOCs) in coastal waters off southwestern Taiwan. Ten illicit drugs, seven nonsteroidal anti-inflammatory drugs (NSAIDs), five antibiotics, two blood lipid regulators, two antiepileptic drugs, two UV filters, caffeine, atenolol, and omeprazole were analyzed by solid-phase extraction and liquid chromatography coupled to tandem mass spectrometry (SPE-LC-MS/MS). Thirteen EOCs were detected in coastal waters, including four NSAIDs (acetaminophen, ibuprofen, ketoprofen, and codeine), three antibiotics (ampicillin, erythromycin, and cefalexin), three illicit drugs (ketamine, pseudoephedrine, and MDMA), caffeine, carbamazepine, and gemfibrozil. The median concentrations for the 13 EOCs ranged from 1.47 ng/L to 156 ng/L. Spatial variation in concentration of the 13 EOCs suggests discharge into coastal waters via ocean outfall pipes and rivers. Codeine and ampicillin have significant pollution risk quotients (RQ>1), indicating potentially high risk to aquatic organisms in coastal waters. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. ANTIHYPERTENSIVE DRUG THERAPY FOR HYPERTENSIVE DISORDERS IN PREGNANCY

    Directory of Open Access Journals (Sweden)

    Slobodan Jankovic

    2008-10-01

    Full Text Available Hypertension in pregnancy is associated with increased maternal and fetal mortality and morbidity. About 8 % of all pregnancies are complicated with hypertensive disorders. There is concordance that severe hypertension should be treated without delay to reduce maternal risks of acute cerebrovascular complications. Intravenous labetalol and oral nifedipine are as effective as intravenous hydralazine in control of severe hypertension, with less adverse effects. Still, there is no consensus as to whether mild-to-moderate hypertension in pregnancy should be treated, considering that there are no definitive conclusions which can be made about the relative maternal or perinatal benefits/risks of antihypertensive treatment. Considering their safe usage during pregnancy, methyldopa, labetalol and nifedipine are commonly used blood-pressure lowering drugs for pregnant women with hypertension. The cardio-selective β- blocker atenolol should be avoided in pregnancy, because it has been associated with lower birth weights and fetal growth impairment. ACE inhibitors and angiotensin receptor blockers are contraindicated in pregnancy.

  8. The review of identification and assay methods of β-blockers

    Directory of Open Access Journals (Sweden)

    Ольга Олександрівна Віслоус

    2015-10-01

    Full Text Available Every year the number of β-blockers on the pharmaceutical market is increasing, requiring systematization of their standardization methods.Aim of research. The aim of our research is to study literature data about identification and assay methods of β-blockers with different direction of action – selective (praktolol, metoprolol, atenolol, acebutolol, betaxolol, bevantolol, bisoprolol, celiprolol, esmolol, epanolol, esatenolol, nebivolol, Talinolol, non-selective (alprenolol, Oxprenololum, pindolol, propranolol, timolol, sotalol, nadolol, mepindolol, karteol, tertatolol, bopindolol, bupranolol, penbutolol, kloranolol and combined (labetalol, carvedilol.Methods. The analytical review of literature sources about β-blockers analysis by physical, chemical, and physicochemical methods.Results. After literature sources’ analyzing it was found that physical and physicochemical constants are basically used for β-blockers pharmacopoeial analysis; both physicochemical values and chemical reactions are used in forensic analysis, resulting in the article.It was founded that titration methods, mostly acid-base titration method, are used for β-blockers assay in the analysis of substances. For β-blockers detection in biological fluids and dosage forms, active pharmaceutical ingredients and metabolites mixture separation one should prefer physicochemical methods, such as gas chromatography and liquid chromatography, absorption UV-Visible spectroscopy, fluorometry, etc.Conclusion. The results have shown can be used for the further search of the identification and assay optimal methods of β-blockers both pure and mixed with other active substances and excipients

  9. Pharmacologic treatment of chronic pediatric hypertension.

    Science.gov (United States)

    Robinson, Renee F; Nahata, Milap C; Batisky, Donald L; Mahan, John D

    2005-01-01

    Improved recognition of the relationship between childhood and adult blood pressures and identification of end-organ damage in children, adolescents, and young adults with hypertension has led to increased focus by pediatricians and general practitioners on the detection, evaluation, and treatment of hypertension. Notably, detection, evaluation, and treatment of pediatric hypertension has increased significantly since the first Task Force Report on High Blood Pressure in Children and Adolescents in 1977 with advances in both nonpharmacologic and pharmacologic treatments.Angiotensin-converting enzyme inhibitors (e.g. captopril, enalapril, lisinopril, ramipril) and calcium channel antagonists (e.g. nifedipine, amlodipine, felodipine, isradipine) are the most commonly prescribed antihypertensive medications in children due to their low adverse-effect profiles. Diuretics (e.g. thiazide diuretics, loop diuretics, and potassium-sparing diuretics) are usually reserved as adjunct therapy. Newer agents, such as angiotensin receptor antagonists (e.g. irbesartan), are currently being studied in children and adolescents. These agents may be an option in children with chronic cough secondary to angiotensin-converting enzyme inhibitors. beta-Adrenoreceptor antagonists (e.g. propranolol, atenolol, metoprolol, and labetalol), alpha-adrenoreceptor antagonists, alpha-adrenoreceptor agonists, direct vasodilators, peripheral adrenoreceptor neuron agonists, and combination products are less commonly used in pediatric patients because of adverse events but may be an option in children unresponsive to calcium channel blockers, angiotensin converting-enzyme inhibitors, or angiotensin receptor blockers.

  10. Treatment Strategies for Paradoxical Hypertension Following Surgical Correction of Coarctation of the Aorta in Children.

    Science.gov (United States)

    Roeleveld, Peter P; Zwijsen, Eline G

    2017-05-01

    Paradoxical hypertension after repair of coarctation of the aorta is a well-known phenomenon. The pathogenesis involves the activation of the sympathetic nervous system (first phase) and renin-angiotensin system (second phase). Only a limited number of different treatment strategies have been published in the literature, without any comparative studies. Our aim was to describe the current international practice variation surrounding pharmacological treatment currently being employed to treat paradoxical hypertension following the repair of coarctation of the aorta in children. We performed an online survey among 197 members of the Pediatric Cardiac Intensive Care Society. We also conducted a systematic review of the literature regarding the treatment of paradoxical hypertension. Eighty-eight people (45%), from 62 different centers, responded and answered the questions regarding blood pressure control. Nitroprusside is the first drug of choice for initial blood pressure control in 66% of respondents, esmolol in 11%, labetalol in 11%, and angiotensin-converting enzyme inhibitors (ACEIs) are used by 3% of respondents. For oral blood pressure control after discharge from the pediatric intensive care unit, 75% of respondents use ACEIs, 18% use labetalol, and 12% use other beta-blockers (propranolol, carvedilol, atenolol, metoprolol). The systematic review identified 14 articles reporting pharmacological treatment of direct postoperative hypertension following coarctation repair. There is wide practice variability, due to the lack of sufficient compelling evidence. The majority (66%) of caregivers use nitroprusside to control blood pressure in the acute postoperative phase. The ACEIs are the drug of choice for chronic blood pressure control.

  11. Comparison of Mass Transfer Models for Determination of the Intestinal Permeability

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    P Zakeri-Milani

    2008-09-01

    Full Text Available Background and the purpose of the study: In determination of the permeability of the intestinal wall by external perfusion techniques, several models have been proposed. In the present study three models were used for experimental results that differ in their convection and diffusion assumptions. Material and Methods: Permeability coefficients for 13 compounds (metoprolol, propranolol, naproxen, ketoprofen, furosemide, hydrochlorothiazide, cimetidine, ranitidine, atenolol, piroxicam, antipyrine, ibuprofen and carbamazepine with known human intestinal permeability values were determined in anaesthetized rats by different mass transfer models and plotted versus the observed human intestinal permeabilities. Results: The calculated dimensionless wall permeability values were in the range of 0.37 - 4.85, 0.38-6.54 and 0.41-16.59 for complete radial mixing, mixing tank and laminar flow models respectively. The results indicated that all of the models work relatively well for our data despite fundamentally different assumptions. The wall permeabilities were in the order laminar flow > mixing tank > complete radial mixing. Conclusion: Although laminar flow model provides the most direct measure of the intrinsic wall permeability, it has limitations for highly permeable drugs such as ibuprofen. The normal physiological hydrodynamics is more complex and more investigation is required to find out the real hydrodynamics.

  12. [Biotransformation by human intestinal flora and absorption-transportation characteristic in a model of Caco-2 cell monolayer of d-corydaline and tetrahydropalmatine].

    Science.gov (United States)

    Liu, Yang-Zi; Yang, Xin-Bao; Yang, Xiu-Wei; Yao, Chun-Mei; Ran, Li; Wu, Shuai; Xu, Wei; Liu, Jian-Xun

    2013-01-01

    To study the biotransformation by human intestinal flora, and the absorption and transportation characteristic in a model of human colon adenocarcinoma cell lines (Caco-2 cell) monolayer of d-corydaline (CDL) and tetrahydropalmatine (THP). CDL or THP was incubated with crude enzymes of human intestinal flora under the anaerobic environment and 37 degrees C conditions to transform CDL or THP. Caco-2 cell monolayer was used as an intestinal epithelial cell model for determination of the permeability of CDL or THP from apical side (AP side) to basolateral side (BL side) or from BL side to AP side. Transportation parameters and permeability coefficients (P(app)) were then calculated, and P(app) values were compared with the reported values for model compounds, propranolol as a well absorbed drug and atenolol as a poor absorbed drug. The concentration of CDL or THP was measured by HPLC coupled with photodiode array detector. CDL or THP in the human intestinal flora incubation system did not happen biotransformation. In the Caco-2 cell monolayer model, the P(app) magnitudes of both CDL and THP were 1 x 10(-5) cm x s(-1) in the bi-directional transport, which were identical with propranolol. And their transports were concentration dependent between 0-180 min. Both CDL and THP may be stable in the human intestinal flora incubation system, and their absorption and transportation in the human Caco-2 cell monolayer model are mainly via passive diffusion mechanism.

  13. Pacing for Vasovagal Syncope

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    Nevin T Wijesekera

    2002-10-01

    Full Text Available Vasovagal syncope is a common condition, usually associated with a benign prognosis. Most sufferers experience only occasional symptoms, and can be treated with reassurance and lifestyle advice. However, a minority of patients are debilitated by frequent fainting that can infringe on daily living, or even mimic sudden death. This has been termed "malignant" vasovagal syncope because of the associated falls and physical injury. In these cases, a more interventional approach may be appropriate. Pharmacological measures have been the mainstay of treatment for recurrent vasovagal syncope: beta-blockers (e.g. atenolol, serotonin reuptake inhibitors (e.g. paroxetine, certain vasoconstricting drugs (e.g. midodrine and fluid retaining agents (e.g. fludrocortisone have been of particular interest. However, there is only mixed support from randomised controlled trials for the efficacy of these agents in preventing vasovagal syncope. 1,2,3 In the last few years, cardiac pacing has been advocated for the treatment of some forms of vasovagal syncope. This article reviews the literature and discusses the indications for pacing in vasovagal syncope.

  14. O tratamento farmacológico da fobia social Pharmacologic treatment of social phobia

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    Antonio Egidio Nardi

    1999-12-01

    Full Text Available A fobia social é o medo acentuado e persistente de comer, beber, tremer, enrubescer, falar, escrever, enfim, de agir de forma ridícula ou inadequada na presença de outras pessoas. A fobia social apresenta-se em dois tipos básicos: a circunscrita, restrita a apenas um tipo de situação social, e a generalizada, caracterizada pelo temor a todas ou quase todas situações sociais. As características clínicas da fobia social são a ansiedade antecipatória, os sintomas físicos, a esquiva e a baixa auto-estima. Conforme o rigor diagnóstico, estima-se que 5% a 13% da população geral apresentem sintomas fóbicos sociais que resultem em diferentes graus de incapacitação e limitações sociais e ocupacionais. O tratamento médico de escolha é o uso de medicamentos associados à psicoterapia cognitivo-comportamental. Beta-bloqueadores (atenolol, propranolol, antidepressivos inibidores da monoamino oxidase (IMAO (fenelzine, tanilcipromina, inibidores reversíveis da monoamino oxidase tipo-A (RIMA (moclobemida, brofaromina, benzodiazepínicos (clonazepam, bromazepam, alprazolam e antidepressivos inibidores seletivos de serotonina (ISRS (paroxetina, sertralina, fluoxetina e fluvoxamina e alguns outros (venlafaxina, nefazodone, gabapentina, clonidina têm demonstrado eficácia em inúmeros estudos com diferentes metodologias. Os antidepressivos tricíclicos (imipramina, clomipramina, o ácido valproico e a buspirona têm apresentado resultados negativos. A paroxetina é o medicamento mais estudado com metodologia duplo-cega, com melhores resultados e com boa tolerância. Atualmente, os indivíduos que têm sua vida prejudicada pela fobia social podem, com o tratamento eficaz, adquirir uma postura mais segura em situações sociais.Social phobia is a marked and persistent fear of eating, drinking, trembling, blushing, speaking, writing or doing almost everything in front of people due to concerns about embarrassment or being scrutinized by others

  15. Reacciones adversas a medicamentos como causa de abandono del tratamiento farmacológico en hipertensos Adverse reactions to drugs as leaving drug therapy cause in hypertensive persons

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    Ana Julia García Milián

    2009-03-01

    Full Text Available INTRODUCCIÓN: los fallos al seguir las prescripciones médicas exacerban los problemas de salud y la progresión de las enfermedades, e imposibilitan estimar los efectos y el valor de un determinado tratamiento. OBJETIVO: caracterizar las causas que generan la no adherencia al tratamiento farmacológico en hipertensos. MÉTODOS: estudio observacional descriptivo de corte transversal, constituido por 241 hipertensos inscriptos por algún fármaco antihipertensivo en farmacias comunitarias seleccionadas de Guantánamo, Las Tunas, Camagüey, Cienfuegos, Villa Clara, Granma, Santiago de Cuba y Ciego de Ávila. El método de recogida de la información fue la encuesta. RESULTADOS: los antihipertensivos más consumidos fueron el captopril, la hidroclorotiacida y el atenolol, y fue el primero, con el 31,9 %, el medicamento que tuvo un mayor porcentaje de incumplidores y productor de evento adverso. El cumplimiento fue mayor en los pacientes menores de 30 años. Dentro de los motivos las reacciones adversas ocuparon el 2do. lugar, con el 16,9 %. Las reacciones que causaron abandono terapéutico fueron la tos, las reacciones cutáneas y el decaimiento. CONCLUSIONES: las reacciones adversas se ubican dentro de las causas más frecuentes de abandono de tratamiento antihipertensivo, y fueron el captopril y la hidroclorotiacida los que con mayor frecuencia la provocaron. Las reacciones adversas referidas, en su mayoría, son consideradas como leves.INTRODUCTION: failures to follow medical prescriptions increase health problems and diseases progression, and make it impossible for to estimate effects and value of a specific treatment. AIM: to characterize causes generating the non-adherence to pharmacologic treatment in hypertensive patients. METHODS: cross-sectional descriptive and observational study including 241 hypertensive patients registered by some anti-hypertensive drug in selected community drugstore In Guantánamo, Las Tunas, Camaguey, Villa Clara

  16. Conhecimento popular e utilização dos medicamentos genéricos na população do município de Tubarão, SC General awareness and use of generic medication among citizens of Tubarão, state of Santa Catarina, Brazil

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    Carine Raquel Blatt

    2012-01-01

    Full Text Available Embora os genéricos tenham sido introduzidos no país para oferecer alternativa mais acessível aos medicamentos de referência, representam apenas 14% das vendas em unidades no conjunto do mercado farmacêutico. O objetivo deste trabalho foi pesquisar o nível de conhecimento e o grau de utilização de genéricos em residentes do município de Tubarão, SC. Para isso, realizou-se um estudo transversal com uma amostra de 234 entrevistados, estratificada por bairro. Quanto ao grau de utilização, a maioria dos entrevistados já havia utilizado genéricos, e metade possuía pelo menos um exemplar dessa opção em casa. Para verificar o conhecimento sobre os diferentes tipos de medicamentos, realizou-se um teste de identificação de figuras de embalagens representativas das versões genérico, de referência e similar do paracetamol e do atenolol, 91,0% dos sujeitos identificaram corretamente todas as figuras. Ser de classe econômica mais elevada, já ter utilizado medicamento genérico, acreditar que o genérico tem o mesmo efeito que o medicamento de referência, encontrar medicamentos genéricos nas farmácias com facilidade e costumar comprar o genérico foram fatores associados positivamente com a identificação correta.Although generic medication has been introduced in the country to offer an accessible alternative to brand-name medication, it represents only 14% of sales in number of units within the pharmaceutical market. The aim of this work was to research the level of awareness and the use of generic products among residents of the municipality of Tubarão, State of Santa Catarina, Brazil. A transversal study was carried out with a sample of 234 interviewees, distributed among municipal areas. With regard to use, the majority of those interviewed had used generic medication, and half of them had at least one such product in their home. To verify awareness of different types of medication, pictures with the generic, brand name and

  17. The Role of Beta-Blockers in the Treatment of Hypertension.

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    Cruickshank, John M

    2017-01-01

    angiotensin receptor blockers (ARBs)) do not decrease (and may increase) the risk of myocardial infarction, and are therefore inappropriate first-line agents in this age-group. By contrast, in younger/middle-aged hypertensive subjects (less than 60 years old), meta-analysis has shown that beta-blockers are significantly superior to randomised placebo, and at least as effective as randomised comparator agents, in reducing death/stroke/myocardial infarction. In this younger/middle-aged hypertensive group beta-blockers have been shown (vs randomised placebo or diuretics) to reduce the risk of myocardial infarction by 35-50 %, and stroke by 50-55 % (vs placebo), in non-smoker men. Atenolol was at least as effective as ACE-inhibition (captopril) in reducing all 7 cardiovascular endpoints (including stroke which was reduced by 50 %), vs less tight control of blood pressure, in obese hypertensive subjects with type-2 diabetes (UKPDS study); and after 20 years follow-up, atenolol was significantly (23 %) superior to the ACE-inhibitor in reducing the risk of all-cause death (beta-blockers have anti-cancer properties, which maybe relevant). Primary/essential hypertension in younger/middle-age is underpinned by high sympathetic nerve activity. In this age-group high resting heart rates and high plasma norepinephrine levels (independent of blood pressure) are linked to premature cardiovascular events and death. Thus, anti-hypertensive agents that increase sympathetic nerve activity ie diuretics, dihydropyridine calcium blockers, and ARBs, are inappropriate first-line choices in this younger age-group. Beta-blockers perform well vs randomised placebo and other antihypertensive agents regarding reduced risk of death/stroke/myocardial infarction in younger (<60 years) hypertensive subjects, and are a reasonable first-line choice of therapy (certainly in men). These facts should be reflected in the recommendations of guideline committees around the world.

  18. The release of wastewater contaminants in the Arctic: A case study from Cambridge Bay, Nunavut, Canada.

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    Chaves-Barquero, Luis G; Luong, Kim Hoang; Mundy, C J; Knapp, Charles W; Hanson, Mark L; Wong, Charles S

    2016-11-01

    The treatment of municipal wastewater in the Arctic is challenging due to a variety of financial, operational, climatic and technical issues. To better understand the efficacy of current wastewater treatment in this region and the hazard posed to receiving waters, we assessed the occurrence of nutrients and contaminants (i.e., pharmaceuticals, antibiotic resistance genes) as they moved through a lagoon-based treatment system in Cambridge Bay, Nunavut, Canada. Wastewater treatment in this community is performed by the use of a lagoon-tundra wetland system that is discharged into the marine environment and is representative of current common practices throughout the region. In 2014, samples were collected before and during lagoon discharge from two locations in the main lagoon, one location downstream from the lagoon effluent and three locations offshore. Grab samples were collected to measure nutrients (e.g., total nitrogen and phosphorus) and the presence of antibiotic resistance gene-bearing microbes, and Polar Organic Chemical Integrative Samplers (POCIS) were deployed to collect passively organic contaminants in all locations. A total of six pharmaceuticals were detected from a screen of twenty-eight analytes during the study: atenolol, carbamazepine, clarithromycin, metoprolol, sulfamethoxazole and trimethoprim. The greatest concentrations of nutrients, antibiotic resistance genes (ARGs), and pharmaceuticals were found in sampling locations within the treatment lagoon. Offshore of the release point, we observed limited to no detection of pharmaceuticals and ARGs, but no change in total nitrogen and phosphorus from pre-release. We conclude that the current concentrations of monitored pharmaceuticals do not pose a significant hazard at this time to aquatic organisms in Cambridge Bay. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. [The mechanism of change in speed of agglutination of human erythrocytes under the influence of adrenaline].

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    Volodchenko, A I; Tsirkin, V I; Kostiaev, A A

    2014-01-01

    In the study of red blood cells of 80 men found that adrenaline (10(-10) - 10(-6) g/mL) and phenylephrine (10-(10) - 10(-6) g/mL) dose-dependently increase the speed of agglutination of red blood cells, according to the decrease in agglutination of the start time and ginipral (10(-10) - 10(-7) g/mL), on the contrary, decreases it. The effect of adrenaline and phenylephrine is blocked by nicergoline (10(-6) g/mL), increased obzidan (10(-6) g/mL) and does not change under the action ofyohimbine (10(-6) g/mL) and atenolol (10(-6) g/mL). These data indicate that the speed of agglutination increases with activation alpha1-adrenergic receptor (AR) and decreases in the activation of beta2-AR, while the activation of alpha2- and beta1-AR does not affect it. Trifluoperazine (10(-6) g/mL) as the calmodulin antagonist, barium chloride (10(-6) g/mL) as a blocked of Ca(2+)-dependent K(+)-channels and indomethacine (10(-6) g/mL) as an inhibitor of cyclooxygenase and phospholipase A2 inhibit the ability of adrenaline to increases the speed of agglutination of red blood cells. This suggests that the effect of adrenaline caused an increase in erythrocyte entry of Ca2+, activation of calmodulin, cyclooxygenase, phospholipase A2 and the release of K+ from red blood cell through the Ca(2+)-dependent K+ channels, which is regarded as a manifestation of eryptosis. Indirectly, this means that more efficient activation of alpha1-AR and beta2-AR, respectively, increases or, conversely, decreases the rate of eryptosis.

  20. Treatment of severe neutropenia with high-dose pyridoxine in a patient with chronic graft versus host disease and squamous cell carcinoma: a case report

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    Rauf Mariam

    2011-08-01

    Full Text Available Abstract Introduction The differential diagnosis of neutropenia includes medications, infections, autoimmune diseases, and deficiencies of Vitamin B12 and folate. The association of Vitamin B6 deficiency with severe neutropenia is a rare finding. Case presentation A 51-year-old Caucasian woman presented with fever and profound neutropenia (48 neutrophils/uL. Her clinical history included non-Hodgkin lymphoma, in remission following treatment with allogeneic bone marrow transplantation, quiescent chronic graft-versus-host disease, and squamous cell carcinoma of the skin metastatic to cervical lymph nodes. Medications included atenolol, topical clobetasol, Ditropan (oxybutynin, prophylactic voriconazole, prophylactic valganciclovir, Soriatane (acitretin, and Carac (fluorouracil cream. The bone marrow was hypocellular without metastatic cancer or myelodysplasia. Neutropenia did not respond to stopping medications that have been associated with neutropenia (valganciclovir, voriconazole and Soriatane or treatment with antibiotics or granulocyte colony stimulating factor. Blood tests revealed absence of antineutrophil antibodies, normal folate and B12 levels, moderate zinc deficiency and severe Vitamin B6 deficiency. Replacement therapy with oral Vitamin B6 restored blood vitamin levels to the normal range and corrected the neutropenia. Her cervical adenopathy regressed clinically and became negative on scintography following Vitamin B6 therapy and normalization of the blood neutrophil count. Conclusion Severe pyridoxine deficiency can lead to neutropenia. Screening for Vitamin B6 deficiency, along with folate and Vitamin B12 levels, is recommended in patients with refractory neutropenia, especially those with possible malabsorption syndromes, or a history of chronic-graft-versus host disease. Severe neutropenia may facilitate progression of squamous cell carcinoma.

  1. Regulation of catecholamine release in human adrenal chromaffin cells by β-adrenoceptors.

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    Cortez, Vera; Santana, Magda; Marques, Ana Patrícia; Mota, Alfredo; Rosmaninho-Salgado, Joana; Cavadas, Cláudia

    2012-03-01

    The adrenal gland plays a fundamental role in the response to a variety of stress situations. After a stress condition, adrenal medullary chromaffin cells release, by exocytosis, high quantities of catecholamine (epinephrine, EP; norepinephrine, NE), especially EP. Once in the blood stream, catecholamines reach different target organs, and induce their biological actions through the activation of different adrenoceptors. Adrenal gland cells may also be activated by catecholamines, through hormonal, paracrine and/or autocrine system. The presence of functional adrenoceptors on human adrenal medulla and their involvement on catecholamines secretion was not previously evaluated. In the present study we investigated the role of β(1)-, β(2)- and β(3)-adrenoceptors on catecholamine release from human adrenal chromaffin cells in culture. We observed that the β-adrenoceptor agonist (isoproterenol) and β(2)-adrenoceptor agonist (salbutamol) stimulated catecholamine (NE and EP) release from human adrenal chromaffin cells. Furthermore, the β(2)-adrenoceptor antagonist (ICI 118,551; 100 nM) and β(3)-adrenoceptor antagonist (SR 59230A; 100 nM) inhibited the catecholamine release stimulated by isoproterenol and nicotine in chromaffin cells. The β(1)-adrenoceptor antagonist (atenolol; 100 nM) did not change the isoproterenol- neither the nicotine-evoked catecholamine release from human adrenal chromaffin cells. Moreover, our results show that the protein kinase A (PKA), protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and phospholipase C (PLC) are intracellular mechanisms involved in the catecholamine release evoked by salbutamol. In conclusion, our data suggest that the activation of β(2)- and β(3)-adrenoceptors modulate the basal and evoked catecholamine release, NE and EP, via an autocrine positive feedback loop in human adrenal chromaffin cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Pro-survival function of MEF2 in cardiomyocytes is enhanced by β-blockers

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    Hashemi, S; Salma, J; Wales, S; McDermott, JC

    2015-01-01

    β1-Adrenergic receptor (β1-AR) stimulation increases apoptosis in cardiomyocytes through activation of cAMP/protein kinase A (PKA) signaling. The myocyte enhancer factor 2 (MEF2) proteins function as important regulators of myocardial gene expression. Previously, we reported that PKA signaling directly represses MEF2 activity. We determined whether (a) MEF2 has a pro-survival function in cardiomyocytes, and (b) whether β-adrenergic/PKA signaling modulates MEF2 function in cardiomyocytes. Initially, we observed that siRNA-mediated gene silencing of MEF2 induces cardiomyocyte apoptosis as indicated by flow cytometry. β1-AR activation by isoproterenol represses MEF2 activity and promotes apoptosis in cultured neonatal cardiomyocytes. Importantly, β1-AR mediated apoptosis was abrogated in cardiomyocytes expressing a PKA-resistant form of MEF2D (S121/190A). We also observed that a β1-blocker, Atenolol, antagonizes isoproterenol-induced apoptosis while concomitantly enhancing MEF2 transcriptional activity. β-AR stimulation modulated MEF2 cellular localization in cardiomyocytes and this effect was reversed by β-blocker treatment. Furthermore, Kruppel-like factor 6, a MEF2 target gene in the heart, functions as a downstream pro-survival factor in cardiomyocytes. Collectively, these data indicate that (a) MEF2 has an important pro-survival role in cardiomyocytes, and (b) β-adrenergic signaling antagonizes the pro-survival function of MEF2 in cardiomyocytes and β-blockers promote it. These observations have important clinical implications that may contribute to novel strategies for preventing cardiomyocyte apoptosis associated with heart pathology. PMID:27551452

  3. Availability, price and affordability of cardiovascular medicines: A comparison across 36 countries using WHO/HAI data

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    Cameron Alexandra

    2010-06-01

    Full Text Available Abstract Background The global burden of cardiovascular disease (CVD continues to rise. Successful treatment of CVD requires adequate pharmaceutical management. The aim was to examine the availability, pricing and affordability of cardiovascular medicines in developing countries using the standardized data collected according to the World Health Organization/Health Action International methodology. Methods The following medicines were included: atenolol, captopril, hydrochlorothiazide, losartan and nifedipine. Data from 36 countries were analyzed. Outcome measures were percentage availability, price ratios to international reference prices and number of day's wages needed by the lowest-paid unskilled government worker to purchase one month of chronic treatment. Patient prices were adjusted for inflation and purchasing power, procurement prices only for inflation. Data were analyzed for both generic and originator brand products and the public and private sector and summarized by World Bank Income Groups. Results For all measures, there was great variability across surveys. The overall availability of cardiovascular medicines was poor (mean 26.3% in public sector, 57.3% private sector. Procurement prices were very competitive in some countries, whereas others consistently paid high prices. Patient prices were generally substantially higher than international references prices; some countries, however, performed well. Chronic treatment with anti-hypertensive medication cost more than one day's wages in many cases. In particular when monotherapy is insufficient, treatment became unaffordable. Conclusions The results of this study emphasize the need of focusing attention and financing on making chronic disease medicines accessible, in particular in the public sector. Several policy options are suggested to reach this goal.

  4. Adverse drug reactions induced by cardiovascular drugs in outpatients

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    Gholami K

    2008-03-01

    Full Text Available Considering increased use of cardiovascular drugs and limitations in pre-marketing trials for drug safety evaluation, post marketing evaluation of adverse drug reactions (ADRs induced by this class of medicinal products seems necessary.Objectives: To determine the rate and seriousness of adverse reactions induced by cardiovascular drugs in outpatients. To compare sex and different age groups in developing ADRs with cardiovascular agents. To assess the relationship between frequencies of ADRs and the number of drugs used. Methods: This cross-sectional study was done in cardiovascular clinic at a teaching hospital. All patients during an eight months period were evaluated for cardiovascular drugs induced ADRs. Patient and reaction factors were analyzed in detected ADRs. Patients with or without ADRs were compared in sex and age by using chi-square test. Assessing the relationship between frequencies of ADRs and the number of drugs used was done by using Pearson analysis. Results: The total number of 518 patients was visited at the clinic. ADRs were detected in 105 (20.3% patients. The most frequent ADRs were occurred in the age group of 51-60. The highest rate of ADRs was recorded to be induced by Diltiazem (23.5% and the lowest rate with Atenolol (3%. Headache was the most frequent detected ADR (23%. Assessing the severity and preventability of ADRs revealed that 1.1% of ADRs were detected as severe and 1.9% as preventable reactions. Women significantly developed more ADRs in this study (chi square = 3.978, P<0.05. ADRs more frequently occurred with increasing age in this study (chi square = 15.871, P<0.05. With increasing the number of drugs used, the frequency of ADRs increased (Pearson=0.259, P<0.05. Conclusion: Monitoring ADRs in patients using cardiovascular drugs is a matter of importance since this class of medicines is usually used by elderly patients with critical conditions and underlying diseases.

  5. Polypharmacy among older adults in Tehran

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    B. Ahmadi

    2006-08-01

    Full Text Available Background: Multiple drug use is frequently considered to be hazardous for the elderly because of their greater vulnerability to the complications. The purpose of this study was to determine the prevalence of polypharmacy in Tehran and to assess the relative demographic characteristics of patients. Methods: In a cross-sectional study 400 persons aging 55 years and older were interviewed in order to determine the presence of polypharmacy (daily intake of three or more drugs. The cases were randomly selected and asked to answer a questionnaire through interview at home. The questionnaire contained questions about all taking drugs, pattern of using each drug and also patients' personal, social and medical history. Chi-square and fisher exact tests and determination of odds ratios were used in order to data analysis. Results: Medium number of drugs used was 3.4 ± 1.9 in studied cases and %39.6 of cases were exposed to polypharmacy. The prevalence of physician prescribed drug usage was observed to be increased by increasing number of total used drugs in each case (P<0.002. The most commonly used drugs were A.S.A, Atenolol and propranolol and these drugs were prescribed by physician in over than %90 of cases. There was a positive correlations between polypharmacy with referring to multiple physicians (OR=1.96, CI 95%, 1.28-2.98 (P<0.002 and adverse drug reactions (OR=2.44, CI 95%, 1.47-4.05 (P<0.001. Polypharmacy was more prevalent in the age group of 65-75 years (P<0.04 and lower levels of education (P<0.004 and less prevalent in the group with moderate income (P<0.001. Conclusion: Polypharmacy is common among adults aging 55 years and more in Tehran and is affected by age, education level and economic status.

  6. Noradrenaline increases intracellular glutathione in human astrocytoma U-251 MG cells by inducing glutamate-cysteine ligase protein via β3-adrenoceptor stimulation.

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    Yoshioka, Yasuhiro; Kadoi, Hisatsugu; Yamamuro, Akiko; Ishimaru, Yuki; Maeda, Sadaaki

    2016-02-05

    Glutathione (GSH) plays a critical role in protecting cells from oxidative damage. Since neurons rely on the supply of GSH from astrocytes to maintain optimal intracellular GSH concentrations, the GSH concentration of astrocytes is important for the survival of neighboring neurons against oxidative stress. The neurotransmitter noradrenaline is known to modulate the functions of astrocytes and has been suggested to have neuroprotective properties in neurodegenerative diseases. To elucidate the mechanisms underlying the neuroprotective properties of noradrenaline, in this study, we investigated the effect of noradrenaline on the concentrations of intracellular GSH in human U-251 malignant glioma (MG; astrocytoma) cells. Treatment of the cells with noradrenaline for 24h concentration-dependently increased their intracellular GSH concentration. This increase was inhibited by a non-selective β-adrenoceptor antagonist propranolol and by a selective β3-adrenoceptor antagonist SR59230A, but not by a non-selective α-adrenoceptor antagonist phenoxybenzamine, or by a selective β1-adrenoceptor antagonist atenolol or by a selective β2-adrenoceptor antagonist butoxamine. In addition, the selective β3-adrenoceptor agonist CL316243 increased the intracellular GSH in U-251 MG cells. Treatment of the cells with noradrenaline (10μM) for 24h increased the protein level of the catalytic subunit of glutamate-cysteine ligase (GCLc), the rate-limiting enzyme of GSH synthesis; and this increase was inhibited by SR59230A. These results thus suggest that noradrenaline increased the GSH concentration in astrocytes by inducing GCLc protein in them via β3-adrenoceptor stimulation. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Combined fibroblast growth factor receptor 4 cell membrane chromatography online with high performance liquid chromatography/mass spectrometry to screen active compounds in Brassica albla.

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    Zhang, Tao; Han, Shengli; Huang, Jing; Wang, Sicen

    2013-01-01

    We investigated an analytical method for the recognition separation, and identification of active components from the traditional Chinese medicinal plant Brassica albla L. using fibroblast growth factor receptor 4 cell membrane chromatography (FGFR4/CMC) with high performance liquid chromatography/mass spectrometry (HPLC/MS). HEK293-FGFR4 cells were obtained by stable transfection of the HEK293 cell line with pcDNA3.1 vector containing the FGFR4 gene. Crude extracts of B. albla L. were firstly subjected to FGFR4/CMC column, and the retain contents on the FGFR4/CMC column were then transferred and enriched using a pre-column, and a ten port column switcher were used between FGFR4/CMC column and HPLC. The retained components on FGFR4/CMC column were then directly delivered to the HPLC/MS system for separation and identification. Gefitinib, nicotine, atenolol, and nimodipine were used in order to verify FGFR4/CMC-HPLC/MS system specificity. Subsequently, we investigated the reproducibility and reliability of the FGFR4/CMC-HPLC/MS system. Finally, sinapine was identified as an active component of B. albla L. The MTT colorimetric assay revealed sinapine could inhibit the proliferation of HEK293-FGFR4 cells with dose dependence. Competitive displacement assay approved getitinib could occupy binding site of sinapine with competition way. And FleX dock simulation further exhibited sinapine and gefitinib could bind with the FGFR4 tyrosine active domain. Thus, sinapine is a potential tumor antagonist that acts on the tyrosine kinase domain. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Olmesartan medoxomil combined with hydrochlorothiazide for the treatment of hypertension

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    Mark Greathouse

    2006-12-01

    Full Text Available Mark GreathouseSouth Hills Cardiology Associates of Pittsburgh, Pittsburgh, PA, USAAbstract: In most patients with hypertension, especially Stage 2 hypertension, adequate control of blood pressure (BP is only achieved with combination drug therapy. When using combination therapy, antihypertensive agents with complementary mechanisms of action are recommended, for example, an angiotensin receptor blocker (ARB in combination with hydrochlorothiazide (HCTZ, a β-blocker + HCTZ, an ACE inhibitor + HCTZ, or a calcium channel blocker + an ACE inhibitor. One such combination is olmesartan medoxomil + HCTZ, which is available as fixed-dose, single-tablet combinations for once-daily administration. In clinical trials, olmesartan medoxomil/HCTZ reduced systolic BP (SBP and diastolic BP (DBP to a greater extent than either component as monotherapy. A clinical study in patients with Stage 1 or 2 hypertension showed that olmesartan medoxomil/HCTZ achieved a similar mean reduction in DBP, but a significantly greater mean reduction in SBP and higher rate of BP control (<140/90 mmHg than observed with losartan/HCTZ, at US/European-approved starting doses. In a non-inferiority trial, the antihypertensive efficacy of olmesartan medoxomil/HCTZ was comparable to that of atenolol/HCTZ. Furthermore, indirect comparisons have shown that olmesartan medoxomil/HCTZ compares favorably with other antihypertensive combination therapies, including other ARB/HCTZ combinations and amlodipine besylate/benazepril. Olmesartan medoxomil/HCTZ is generally well tolerated. In conclusion, olmesartan medoxomil/HCTZ is an effective and well-tolerated combination antihypertensive therapy that results in significant BP reductions and BP control in many patients. Keywords: olmesartan medoxomil, hydrochlorothiazide, angiotensin II receptor blocker, hypertension

  9. A pharmacodynamic study on clenbuterol-induced toxicity: beta1- and beta2-adrenoceptors involvement in guinea-pig tachycardia in an in vitro model.

    Science.gov (United States)

    Mazzanti, Gabriela; Di Sotto, Antonella; Daniele, Claudia; Battinelli, Lucia; Brambilla, Gianfranco; Fiori, Maurizio; Loizzo, Stefano; Loizzo, Alberto

    2007-09-01

    Beta(2)-receptor adrenergic agonists as clenbuterol and analogues are illegally used as growth promoters in cattle, in Europe, as well as in other countries. Following consumption of meat or liver, intoxication cases were described, and cardiovascular toxic effects (tachycardia, hypertension) were of clinical relevance. Therefore, we investigated whether heart rate increase induced by clenbuterol could depend upon stimulation of beta(1)- and/or beta(2)-adrenergic receptors, and in which ratio. We used in vitro guinea-pig atria, a model in which beta(1)-/beta(2)-receptors ratio is similar to that found in men. In our experiments both beta(1)- and beta(2)-receptors contributed to clenbuterol-induced heart rate increase, but with a different potency. The selective beta(2)-antagonist ICI-118,551 competitively antagonized responses to clenbuterol with high affinity (pA(2) 9.47+/-0.28, SchildSlope 0.98+/-0.20 not significantly different from unity, K(B) 0.34 nM). The selective beta(1)-antagonist atenolol antagonized clenbuterol with a relatively lower affinity (pA(2)=7.59+/-0.14), the SchildSlope=1.97+/-0.33 was significantly different from unity (Pclenbuterol stimulates guinea-pig heart rate by acting chiefly on beta(2)-adrenoceptor, although responses to clenbuterol apparently are mediated by an inter-play between both beta-adrenoceptors. Further experiments are necessary to understand which beta-adrenergic antagonists are of effectiveness to counteract cardiovascular effects in case of intoxication following clenbuterol, or other beta-adrenergic stimulants.

  10. Do results from major clinical trials indicate a change in management in the acute phase of myocardial infarction?

    Science.gov (United States)

    Hjalmarson, A

    1987-01-01

    Since introduction of modern Coronary Care Units, hospital mortality has been reduced by about 50%. This is most likely due to a number of treatments that today are well established. Those include detection and treatment of serious arrhythmias with antiarrhythmic agents and electrical conversion, and more aggressive early treatment of congestive heart failure, of chest pain, and of atrioventricular (AV) block and bradyarrhythmias. The new goals in early management of suspected acute myocardial infarction must aim at prevention and limitation of ischemic damage. The use of beta-blockers has been widely studied. Data from 27 randomized trials with a total of about 27,000 patients have convincingly shown that early beta-blockade reduces mortality, prevents and limits infarct development and arrhythmias, and reduces infarct complications. Three large trials, the Göteborg and MIAMI Trials on metoprolol and the ISIS Trial on atenolol, have demonstrated significant beneficial effects and good tolerance. Thrombolytic therapy in patients with signs of acute myocardial infarction, mainly streptokinase, has demonstrated significant reduction of short-term mortality. The large Italian GISSI Trial, including almost 12,000 patients, showed very significant reduction in 21 day mortality by streptokinase, and the earlier treatment started, the better the reduction. Pooling all published studies in the literature also shows the same favorable effects on mortality. Early treatment with thrombolytic therapy might also prevent and limit infarct development and preserve myocardial function. Recent large scale studies have convincingly demonstrated the value of early beta-blockade and of thrombolytic therapy in selected patients with signs of acute myocardial infarction. It seems reasonable to change the management in the acute phase of myocardial infarction based upon recent major clinical trials.

  11. Evaluation of microwave oven heating for prediction of drug-excipient compatibilities and accelerated stability studies.

    Science.gov (United States)

    Schou-Pedersen, Anne Marie V; Østergaard, Jesper; Cornett, Claus; Hansen, Steen Honoré

    2015-05-15

    Microwave ovens have been used extensively in organic synthesis in order to accelerate reaction rates. Here, a set up comprising a microwave oven combined with silicon carbide (SiC) plates for the controlled microwave heating of model formulations has been applied in order to investigate, if a microwave oven is applicable for accelerated drug stability testing. Chemical interactions were investigated in three selected model formulations of drug and excipients regarding the formation of ester and amide reaction products. In the accelerated stability studies, a design of experiments (DoE) approach was applied in order to be able to rank excipients regarding reactivity: Study A: cetirizine with PEG 400, sorbitol, glycerol and propylene glycol. Study B: 6-aminocaproic acid with citrate, acetate, tartrate and gluconate. Study C: atenolol with citric, tartaric, malic, glutaric, and sorbic acid. The model formulations were representative for oral solutions (co-solvents), parenteral solutions (buffer species) and solid dosage forms (organic acids applicable for solubility enhancement). The DoE studies showed overall that the same impurities were generated by microwave oven heating leading to temperatures between 150°C and 180°C as compared to accelerated stability studies performed at 40°C and 80°C using a conventional oven. Ranking of the reactivity of the excipients could be made in the DoE studies performed at 150-180°C, which was representative for the ranking obtained after storage at 40°C and 80°C. It was possible to reduce the time needed for drug-excipient compatibility testing of the three model formulations from weeks to less than an hour in the three case studies. The microwave oven is therefore considered to be an interesting alternative to conventional thermal techniques for the investigation of drug-excipient interactions during preformulation. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Pharmacologic differences between beta blockers.

    Science.gov (United States)

    Wood, A J

    1984-10-01

    All of the beta blockers act by antagonizing the actions of the endogenous adrenergic agonists epinephrine and norepinephrine at the beta-adrenergic receptors. However, a number of pharmacologic differences exist between the various agents. Some drugs, such as atenolol and metoprolol, are relatively selective for the beta-1-adrenergic receptors, requiring higher concentrations to block beta-2-adrenergic receptors than are required to block beta-1 receptors. It should be noted, however, that these selective beta blockers all block beta-2 receptors when their concentrations are high enough. When patients with asthma must receive a beta blocker, low doses of a selective drug should be used. Recent studies, however, have suggested that the use of a nonselective beta blocker may be desirable to antagonize some beta-2-mediated metabolic effects, such as hypokalemia, induced by epinephrine. Pindolol is the only beta-receptor antagonist available in the United States with intrinsic sympathomimetic, or partial agonist, activity. Such drugs, because of their partial agonist activity, cause some sympathetic stimulation under conditions of low endogenous sympathetic tone, such as while subjects are at rest in the supine position. Under conditions of higher sympathetic tone, pindolol blocks the effects of the endogenous agonists, producing the characteristic effects of a beta blocker. Membrane-stabilizing activity was first recognized with propranolol, and the value of this property has been a source of controversy ever since, but recent studies suggest that propranolol may induce electrophysiologic effects by mechanisms other than beta blockade. Pharmacokinetic differences between the drugs are also of importance.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Effect of changing heart rate during treatment of hypertension on incidence of heart failure.

    Science.gov (United States)

    Okin, Peter M; Kjeldsen, Sverre E; Julius, Stevo; Hille, Darcy A; Dahlöf, Björn; Devereux, Richard B

    2012-03-01

    An elevated heart rate (HR) at rest at baseline is associated with an increased risk of incident heart failure (HF) and with greater cardiovascular event rates in patients with chronic HF. However, despite the high attributable risk of hypertension for HF, whether the in-treatment HR predicts incident HF in patients with treated hypertension has not been evaluated. The HR was evaluated on annual electrocardiograms from 9,024 patients with hypertension without HF who were treated with losartan- or atenolol-based regimens. During a mean follow-up of 4.7 ± 1.1 years, HF developed in 285 patients (3.2%). On multivariate Cox analyses adjusted for randomized treatment, the baseline risk factors for HF, baseline and in-treatment blood pressure, QRS duration, and electrocardiographic left ventricular hypertrophy, a greater in-treatment HR predicted a 45% greater adjusted risk of new HF for every 10-beats/min increase in the HR (95% confidence interval [CI] 34% to 57%) or a 159% greater risk of HF in patients with the persistence or development of a HR of ≥84 beats/min (95% CI 88% to 257%). In contrast, with adjustment for the same covariates, the baseline HR as a continuous variable was a significantly less powerful predictor of new HF (hazard ratio 1.15 per 10 beats/min, 95% CI 1.03 to 1.28) and a baseline HR of ≥84 beats/min did not predict new HF (hazard ratio 1.00, 95% CI 0.63 to 1.58). In conclusion, a greater in-treatment HR on the serial electrocardiograms predicts a greater risk of incident HF during antihypertensive treatment, independent of the covariates, in patients with hypertension with electrocardiographic left ventricular hypertrophy. These findings support serial HR assessment to improve the risk stratification of patients with hypertension. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Mass loading and removal of pharmaceuticals and personal care products including psychoactives, antihypertensives, and antibiotics in two sewage treatment plants in southern India.

    Science.gov (United States)

    Subedi, Bikram; Balakrishna, Keshava; Joshua, Derrick Ian; Kannan, Kurunthachalam

    2017-01-01

    Environmental contamination by pharmaceuticals and personal care products (PPCPs) is barely studied in India despite being one of the largest global producers and consumers of pharmaceuticals. In this study, 29 pharmaceuticals and six metabolites were determined in sewage treatment plants (STPs) in Udupi (STPU: population served ∼150,000) and Mangalore (STPM: population served ∼450,000); the measured mean concentrations ranged from 12 to 61,000 ng/L and 5.0 to 31,000 ng/L, respectively. Atorvastatin (the most prescribed antihypercholesterolemic in India), mefenamic acid, and paraxanthine were found for the first time in wastewater in India at the mean concentrations of 395 ng/L, 1100 ng/L, and 13,000 ng/L, respectively. Select pharmaceutical metabolites (norverapamil and clopidogrel carboxylic acid) were found at concentrations of upto 7 times higher than their parent drugs in wastewater influent and effluent. This is the first study in India to report mass loading and emission of PPCPs and their select metabolites in STPs. The total mass load of all PPCPs analyzed in this study at STPU (4.97 g/d/1000 inhabitants) was 3.6 times higher than calculated for STPM. Select recalcitrant PPCPs (carbamazepine, diazepam, and clopidogrel) were found to have negative or no removal from STPU while additional treatment with upflow anaerobic sludge blanket reactor at STPM removed (up to 95%) these PPCPs from STPM. Overall, 5.1 kg of caffeine, 4.1 kg of atenolol, 2.7 kg of ibuprofen, and 1.9 kg of triclocarban were discharged annually from STPU. The PPCP contamination profile in the Indian STP was compared with a similar study in the USA. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Mapping genetic variants associated with beta-adrenergic responses in inbred mice.

    Directory of Open Access Journals (Sweden)

    Micha Hersch

    Full Text Available β-blockers and β-agonists are primarily used to treat cardiovascular diseases. Inter-individual variability in response to both drug classes is well recognized, yet the identity and relative contribution of the genetic players involved are poorly understood. This work is the first genome-wide association study (GWAS addressing the values and susceptibility of cardiovascular-related traits to a selective β(1-blocker, Atenolol (ate, and a β-agonist, Isoproterenol (iso. The phenotypic dataset consisted of 27 highly heritable traits, each measured across 22 inbred mouse strains and four pharmacological conditions. The genotypic panel comprised 79922 informative SNPs of the mouse HapMap resource. Associations were mapped by Efficient Mixed Model Association (EMMA, a method that corrects for the population structure and genetic relatedness of the various strains. A total of 205 separate genome-wide scans were analyzed. The most significant hits include three candidate loci related to cardiac and body weight, three loci for electrocardiographic (ECG values, two loci for the susceptibility of atrial weight index to iso, four loci for the susceptibility of systolic blood pressure (SBP to perturbations of the β-adrenergic system, and one locus for the responsiveness of QTc (p<10(-8. An additional 60 loci were suggestive for one or the other of the 27 traits, while 46 others were suggestive for one or the other drug effects (p<10(-6. Most hits tagged unexpected regions, yet at least two loci for the susceptibility of SBP to β-adrenergic drugs pointed at members of the hypothalamic-pituitary-thyroid axis. Loci for cardiac-related traits were preferentially enriched in genes expressed in the heart, while 23% of the testable loci were replicated with datasets of the Mouse Phenome Database (MPD. Altogether these data and validation tests indicate that the mapped loci are relevant to the traits and responses studied.

  16. Phototransformation of wastewater-derived trace organic contaminants in open-water unit process treatment wetlands.

    Science.gov (United States)

    Jasper, Justin T; Sedlak, David L

    2013-10-01

    Open-water cells in unit process treatment wetlands can be used to exploit sunlight photolysis to remove trace organic contaminants from municipal wastewater effluent. To assess the performance of these novel systems, a photochemical model was calibrated using measured photolysis rates for atenolol, carbamazepine, propranolol, and sulfamethoxazole in wetland water under representative conditions. Contaminant transformation by hydroxyl radical ((•)OH) and carbonate radical ((•)CO3(-)) were predicted from steady-state radical concentrations measured at pH values between 8 and 10. Direct photolysis rates and the effects of light screening by dissolved organic matter on photolysis rates were estimated using solar irradiance data, contaminant quantum yields, and light screening factors. The model was applied to predict the land area required for 90% removal of a suite of wastewater-derived organic contaminants by sunlight-induced reactions under a variety of conditions. Results suggest that during summer, open-water cells that receive a million gallons of water per day (i.e., about 4.4 × 10(-2) m(3) s(-1)) of nitrified wastewater effluent can achieve 90% removal of most compounds in an area of about 15 ha. Transformation rates were strongly affected by pH, with some compounds exhibiting faster transformation rates under the high pH conditions associated with photosynthetic algae at the sediment-water interface and other contaminants exhibiting faster transformation rates at the circumneutral pH values characteristic of algae-free cells. Lower dissolved organic carbon concentrations typically resulted in increased transformation rates.

  17. Fruit juice inhibition of uptake transport: a new type of food-drug interaction.

    Science.gov (United States)

    Bailey, David G

    2010-11-01

    A new type of interaction in which fruit juices diminish oral drug bioavailability through inhibition of uptake transport is the focus of this review. The discovery was based on an opposite to anticipated finding when assessing the possibility of grapefruit juice increasing oral fexofenadine bioavailability in humans through inhibition of intestinal MDR1-mediated efflux transport. In follow-up investigations, grapefruit or orange juice at low concentrations potentially and selectively inhibited in vitro OATP1A2-mediated uptake compared with MDR1-caused efflux substrate transport. These juices at high volume dramatically depressed oral fexofenadine bioavailability. Grapefruit was the representative juice to characterize the interaction subsequently. A volume-effect relationship study using a normal juice amount halved average fexofenadine absorption. Individual variability and reproducibility data indicated the clinical interaction involved direct inhibition of intestinal OATP1A2. Naringin was a major causal component suggesting that other flavonoids in fruits and vegetables might also produce the effect. Duration of juice clinical inhibition of fexofenadine absorption lasted more than 2 h but less than 4 h indicating the interaction was avoidable with appropriate interval of time between juice and drug consumption. Grapefruit juice lowered the oral bioavailability of several medications transported by OATP1A2 (acebutolol, celiprolol, fexofenadine, talinolol, L-thyroxine) while orange juice did the same for others (atenolol, celiprolol, ciprofloxacin, fexofenadine). Juice clinical inhibition of OATP2B1 was unresolved while that of OATP1B1 seemed unlikely. The interaction between grapefruit juice and etoposide also seemed relevant. Knowledge of both affected uptake transporter and drug hydrophilicity assisted prediction of the clinical interaction with grapefruit or orange juice. © 2010 The Author. British Journal of Clinical Pharmacology © 2010 The British

  18. β-Adrenergic receptor antagonists inhibit vasculogenesis of embryonic stem cells by downregulation of nitric oxide generation and interference with VEGF signalling.

    Science.gov (United States)

    Sharifpanah, Fatemeh; Saliu, Fatjon; Bekhite, Mohamed M; Wartenberg, Maria; Sauer, Heinrich

    2014-11-01

    The β-adrenoceptor antagonist Propranolol has been successfully used to treat infantile hemangioma. However, its mechanism of action is so far unknown. The hypothesis of this research was that β-adrenoceptor antagonists may interfere with endothelial cell differentiation of stem cells. Specifically, the effects of the non-specific β-adrenergic receptor (β-adrenoceptor) antagonist Propranolol, the β1-adrenoceptor-specific antagonist Atenolol and the β2-adrenoceptor-specific antagonist ICI118,551 on vasculogenesis of mouse embryonic stem (ES) cells were investigated. All three β-blockers dose-dependently downregulated formation of capillary structures in ES cell-derived embryoid bodies and decreased the expression of the vascular cell markers CD31 and VE-cadherin. Furthermore, β-blockers downregulated the expression of fibroblast growth factor-2 (FGF-2), hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor 165 (VEGF165), VEGF receptor 2 (VEGF-R2) and phospho VEGF-R2, as well as neuropilin 1 (NRP1) and plexin-B1 which are essential modulators of embryonic angiogenesis with additional roles in vessel remodelling and arteriogenesis. Under conditions of β-adrenoceptor inhibition, the endogenous generation of nitric oxide (NO) as well as the phosphorylation of endothelial nitric oxide synthase (eNOS) was decreased in embryoid bodies, whereas an increase in NO generation was observed with the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP). Consequently, vasculogenesis of ES cells was restored upon treatment of differentiating ES cells with β-adrenoceptor antagonists in the presence of NO donor. In summary, our data suggest that β-blockers impair vasculogenesis of ES cells by interfering with NO generation which could be the explanation for their anti-angiogenic effects in infantile hemangioma.

  19. Development of a Paper Spray Mass Spectrometry Cartridge with Integrated Solid Phase Extraction for Bioanalysis.

    Science.gov (United States)

    Zhang, Chengsen; Manicke, Nicholas E

    2015-06-16

    A novel paper spray cartridge with an integrated solid phase extraction (SPE) column is described. The cartridge performs extraction and pre-concentration, as well as sample ionization by paper spray, from complex samples such as plasma. The cartridge allows for selective enrichment of target molecules from larger sample volumes and removal of the matrix, which significantly improved the signal intensity of target compounds in plasma samples by paper spray ionization. Detection limits, quantitative performance, recovery, ionization suppression, and the effects of sample volume were evaluated for five drugs: carbamazepine, atenolol, sulfamethazine, diazepam, and alprazolam. Compared with direct paper spray analysis of dried plasma spots, paper spray analysis using the integrated solid phase extraction improved the detection limits significantly by a factor of 14-70, depending on the drug. The improvement in detection limits was, in large part, due to the capability of analyzing larger sample volumes. In addition, ionization suppression was found to be lower and recovery was higher for paper spray with integrated SPE, as compared to direct paper spray analysis. By spiking an isotopically labeled internal standard into the plasma sample, a linear calibration curve for the drugs was obtained from the limit of detection (LOD) to 1 μg/mL, indicating that this method can be used for quantitative analysis. The paper spray cartridge with integrated SPE could prove valuable for analytes that ionize poorly, in applications where lower detection limits are required, or on portable mass spectrometers. The improved performance comes at the cost of requiring a more complex paper spray cartridge and requiring larger sample volumes than those used in typical direct paper spray ionization.

  20. Power to identify a genetic predictor of antihypertensive drug response using different methods to measure blood pressure response

    Directory of Open Access Journals (Sweden)

    Turner Stephen T

    2012-03-01

    Full Text Available Abstract Background To determine whether office, home, ambulatory daytime and nighttime blood pressure (BP responses to antihypertensive drug therapy measure the same signal and which method provides greatest power to identify genetic predictors of BP response. Methods We analyzed office, home, ambulatory daytime and nighttime BP responses in hypertensive adults randomized to atenolol (N = 242 or hydrochlorothiazide (N = 257 in the Pharmacogenomic Evaluation of Antihypertensive Responses Study. Since different measured BP responses may have different predictors, we tested the "same signal" model by using linear regression methods to determine whether known predictors of BP response depend on the method of BP measurement. We estimated signal-to-noise ratios and compared power to identify a genetic polymorphism predicting BP response measured by each method separately and by weighted averages of multiple methods. Results After adjustment for pretreatment BP level, known predictors of BP response including plasma renin activity, race, and sex were independent of the method of BP measurement. Signal-to-noise ratios were more than 2-fold greater for home and ambulatory daytime BP responses than for office and ambulatory nighttime BP responses and up to 11-fold greater for weighted averages of all four methods. Power to identify a genetic polymorphism predicting BP response was directly related to the signal-to-noise ratio and, therefore, greatest with the weighted averages. Conclusion Since different methods of measuring BP response to antihypertensive drug therapy measure the same signal, weighted averages of the BP responses measured by multiple methods minimize measurement error and optimize power to identify genetic predictors of BP response.

  1. Oxidative transformation of micropollutants during municipal wastewater treatment: comparison of kinetic aspects of selective (chlorine, chlorine dioxide, ferrate VI, and ozone) and non-selective oxidants (hydroxyl radical).

    Science.gov (United States)

    Lee, Yunho; von Gunten, Urs

    2010-01-01

    Chemical oxidation processes have been widely applied to water treatment and may serve as a tool to minimize the release of micropollutants (e.g. pharmaceuticals and endocrine disruptors) from municipal wastewater effluents into the aquatic environment. The potential of several oxidants for the transformation of selected micropollutants such as atenolol, carbamazepine, 17 alpha-ethinylestradiol (EE2), ibuprofen, and sulfamethoxazole was assessed and compared. The oxidants include chlorine, chlorine dioxide, ferrate(VI), and ozone as selective oxidants versus hydroxyl radicals as non-selective oxidant. Second-order rate constants (k) for the reaction of each oxidant show that the selective oxidants react only with some electron-rich organic moieties (ERMs), such as phenols, anilines, olefins, and deprotonated-amines. In contrast, hydroxyl radicals show a nearly diffusion-controlled reactivity with almost all organic moieties (k>or=10(9)M(-1) s(-1)). Due to a competition for oxidants between a target micropollutant and wastewater matrix (i.e. effluent organic matter, EfOM), a higher reaction rate with a target micropollutant does not necessarily translate into more efficient transformation. For example, transformation efficiencies of EE2, a phenolic micropollutant, in a selected wastewater effluent at pH 8 varied only within a factor of 7 among the selective oxidants, even though the corresponding k for the reaction of each selective oxidant with EE2 varied over four orders of magnitude. In addition, for the selective oxidants, the competition disappears rapidly after the ERMs present in EfOM are consumed. In contrast, for hydroxyl radicals, the competition remains practically the same during the entire oxidation. Therefore, for a given oxidant dose, the selective oxidants were more efficient than hydroxyl radicals for transforming ERMs-containing micropollutants, while hydroxyl radicals are capable of transforming micropollutants even without ERMs. Besides Ef

  2. Exploring the occurrence and distribution of contaminants of emerging concern through unmanned sampling from ships of opportunity in the North Sea

    Science.gov (United States)

    Brumovský, Miroslav; Bečanová, Jitka; Kohoutek, Jiří; Thomas, Henrike; Petersen, Wilhelm; Sørensen, Kai; Sáňka, Ondřej; Nizzetto, Luca

    2016-10-01

    Chemical pollution is of concern for the marine environment. New European regulation demands exposure and impact assessment to be conducted in coastal environments in order to define and ensure fulfillment of environmental quality standards. A cost-effective approach for monitoring the over 100,000 km of European coasts is necessary. This proof-of-concept study focuses on the use of unmanned water sampling from a commercial ship of opportunity to implement monitoring of marine contaminants of emerging concern. Marine areas that are not directly affected by river plumes or other direct sources were covered in order to provide information on background pollution. 14 currently used pesticides, 11 pharmaceuticals and personal care products and 3 food additives were detected in water samples through targeted analysis at sub-ng to tenths of ng/L levels in both coastal and offshore areas of the North Sea. Among contaminants, 6 pesticides (dimethoate, fenpropimorph, pendimethalin, propiconazole, tebuconazole and temephos), 3 pharmaceuticals (acetaminophen, naproxen and ketoprofen) and 2 food additives (acesulfame and saccharine) have never been detected before in offshore areas. 4 pesticides (diuron, isoproturon, metazachlor and terbuthylazine), 4 pharmaceuticals (carbamazepine, atenolol, ibuprofen and ketoprofen) and 2 food additives (sucralose and acesulfame) were detected in over 90% of the samples. The antibiotic sulfamethoxazole was detected in 50% of the samples at tenths of pg/L levels, including some offshore areas. Our study highlights that the use of ships of opportunity can provide a key support for the development and cost-effective implementation of marine monitoring of chemical pollutants in Europe and elsewhere.

  3. Comparison of contaminants of emerging concern removal, discharge, and water quality hazards among centralized and on-site wastewater treatment system effluents receiving common wastewater influent.

    Science.gov (United States)

    Du, Bowen; Price, Amy E; Scott, W Casan; Kristofco, Lauren A; Ramirez, Alejandro J; Chambliss, C Kevin; Yelderman, Joe C; Brooks, Bryan W

    2014-01-01

    A comparative understanding of effluent quality of decentralized on-site wastewater treatment systems, particularly for contaminants of emerging concern (CECs), remains less understood than effluent quality from centralized municipal wastewater treatment plants. Using a novel experimental facility with common influent wastewater, effluent water quality from a decentralized advanced aerobic treatment system (ATS) and a typical septic treatment system (STS) coupled to a subsurface flow constructed wetland (WET) were compared to effluent from a centralized municipal treatment plant (MTP). The STS did not include soil treatment, which may represent a system not functioning properly. Occurrence and discharge of a range of CECs were examined using isotope dilution liquid chromatography-tandem mass spectrometry during fall and winter seasons. Conventional parameters, including total suspended solids, carbonaceous biochemical oxygen demand and nutrients were also evaluated from each treatment system. Water quality of these effluents was further examined using a therapeutic hazard modeling approach. Of 19 CECs targeted for study, the benzodiazepine pharmaceutical diazepam was the only CEC not detected in all wastewater influent and effluent samples over two sampling seasons. Diphenhydramine, codeine, diltiazem, atenolol, and diclofenac exhibited significant (ptreatment systems was generally not influenced by season. However, significant differences (ptreatment technologies. For example, removal of most CECs by ATS was generally comparable to MTP. Lowest removal of most CECs was observed for STS; however, removal was improved when coupling the STS to a WET. Across the treatment systems examined, the majority of pharmaceuticals observed in on-site and municipal effluent discharges were predicted to potentially present therapeutic hazards to fish. © 2013.

  4. An observational study of hypertension treatment and patient outcomes in a primary care setting.

    Science.gov (United States)

    Thinyane, Keneuoe Hycianth; Mothebe, Tumelo; Sooro, Mopa; Namole, Lekotoane David; Cooper, Varsay

    2015-01-01

    Evaluation and treatment of high blood pressure are vital to reducing hypertension-related morbidity. There are limited data on treatment of hypertension in Lesotho. The aim of this study was to investigate hypertension treatment and control in a primary care setting in Lesotho. A cross-sectional study was conducted among hypertensive patients treated at Domiciliary Health Clinic in Maseru, Lesotho between April and May 2013. We reviewed medical records and evaluated hypertension treatment and blood pressure control in the past 12 months. Patients were interviewed to assess adherence to hypertension treatment. Logistic regression analysis was used to identify factors associated with poor blood pressure control. 70 patients were enrolled in the study; 90.0% were female, the mean age was 57.7 years, 80.0% were overweight/obese and 27.1% had diabetes mellitus. 90.0% of the patients received combination antihypertensive therapy; the most frequently prescribed drugs were hydrochlorothiazide (90.0%), captopril (67.1%) and atenolol (51.4%). The majority of the patients had chronic uncontrolled hypertension. 67.2% of the patients had continuous access to antihypertensive drugs in the past 12 months; adherence to medication, diet and exercise was 64.3%, 37.1% and 7.1% respectively. Age ≥65 was the strongest independent predictor of poor blood pressure control (AOR = 10.3, 95% CI: 1.21-88.98, p = 0.033). There is a need for interventions to improve hypertension care and outcomes in this setting. Efforts should be made to improve assessment of hypertensive patients, optimise antihypertensive therapy and promote patient adherence to treatment.

  5. Development of Fluorescence Surrogates to Predict the Photochemical Transformation of Pharmaceuticals in Wastewater Effluents.

    Science.gov (United States)

    Yan, Shuwen; Yao, Bo; Lian, Lushi; Lu, Xinchen; Snyder, Shane A; Li, Rui; Song, Weihua

    2017-03-07

    The photochemical transformation of pharmaceutical and personal care products (PPCPs) in wastewater effluents is an emerging concern for environmental scientists. In the current study, the photodegradation of 29 PPCPs was examined in effluents under simulated solar irradiation. Direct photodegradation, triplet state effluent organic matter ( 3 EfOM*)-mediated and hydroxyl radical (HO • )-mediated degradation are three major pathways in the removal process. With the photodegradation of trace levels of PPCPs, the excitation-emission matrix (EEM) fluorescence intensities of the effluents were also gradually reduced. Therefore, fluorescence peaks have been identified, for the first time, as appropriate surrogates to assess the photodegradation of PPCPs. The humic-like fluorescence peak is linked to direct photolysis-labile PPCPs, such as naproxen, ronidazole, diclofenac, ornidazole, tinidazole, chloramphenicol, flumequine, ciprofloxacin, methadone, and dimetridazole. The tyrosine-like EEM peak is associated with HO • /CO 3 •- -labile PPCPs, such as trimethoprim, ibuprofen, gemfibrozil, atenolol, carbamazepine, and cephalexin. The tryptophan-like peak is associated with 3 EfOM*-labile PPCPs, such as clenbuterol, metoprolol, venlafaxine, bisphenol A, propranolol, ractopamine, salbutamol, roxithromycin, clarithromycin, azithromycin, famotidine, terbutaline, and erythromycin. The reduction in EEM fluorescence correlates well with the removal of PPCPs, allowing a model to be constructed. The solar-driven removal of EEM fluorescence was applied to predict the attenuation of 11 PPCPs in five field samples. A close correlation between the predicted results and the experimental results suggests that fluorescence may be a suitable surrogate for monitoring the solar-driven photodegradation of PPCPs in effluents.

  6. High performance liquid chromatographic separation of thirteen drugs collected in Chinese Pharmacopoeia 2010(Ch.P2010 on cellulose ramification chiral stationary phase

    Directory of Open Access Journals (Sweden)

    Ying Zhou

    2012-02-01

    Full Text Available The enantiomers separation of thirteen drugs collected in Ch.P2010 was performed on chiral stationary phase of cellulose ramification (chiralpak OD and chiralpak OJ by high performance liquid chromatographic (HPLC methods, which included ibuprofen (C1, ketoprofen (C2, nitrendipine (C3, nimodipine (C4, felodipine (C5, omeprazole (C6, praziquantel (C7, propranolol hydrochloride (C8, atenolol (C9, sulpiride (C10, clenbuterol hydrochloride (C11, verapamil hydrochloride (C12, and chlorphenamine maleate (C13. The mobile phase consisted of isopropanol and n-hexane. The detection wavelength was set at 254 nm and the flow rate was 0.7 mL/min. The enantiomers separation of these thirteen racemates on chiralpak OD column and chiralpak OJ column was studied, while the effects of proportion of organic additives, alcohol displacer and temperature on the separation were studied. And the mechanism of some of racemates was discussed. The results indicated that thirteen chiral drugs could be separated on chiral stationary phase of cellulose ramification in normal phase chromatographic system. The chromatographic retention and resolution of enantiomers could be adjusted by factors including column temperature and the concentration of alcohol displacer and organic alkaline modifier in mobile phase. It was shown that the resolution was improved with reducing concentration of alcohol displacer. When concentration of organic alkaline modifier was 0.2% (v/v, the resolution and the peak shape were fairly good. Most racemates mentioned above had better resolution at column temperature of 25 °C. When racemates were separated, the temperature should be kept so as to obtain stable separation results. Keywords: HPLC, Chiral stationary phase, Optical enantiomers, Cellulose ramification

  7. Managing hypertension in diabetic patients – focus on trandolapril/verapamil combination

    Directory of Open Access Journals (Sweden)

    Sanjib Kumar Sharma

    2007-09-01

    Full Text Available Sanjib Kumar Sharma1,3, Piero Ruggenenti1,2, Giuseppe Remuzzi1,2, 1Clinical Research Centre for Rare Diseases “Aldo e Cele Daccò”, Mario Negri Institute for Pharmacological Research, Villa Camozzi, Ranica, Italy; 2Unit of Nephrology, Azienda Ospedaliera, Ospedali Riuniti, Bergamo, Italy; 3Department of Medicine, BP Koirala Institute of Health Sciences, Dharan, NepalAbstract: Hypertensive diabetes individuals are at higher risk for cardiovascular events and progression to end stage renal disease. Several well conducted clinical trials indicate that aggressive treatment of hypertension in individual with diabetes reduces these complications. Combinations of two or more antihypertensive drugs are frequently required to reach the target blood pressure and to improve the cardiovascular and renal outcomes in these patients. There are physiological and clinical rationales for renin-angiotensin system blockade in hypertensive diabetics. Trandolapril/verapamil sustained released (SR is a fixed-dose combination of trandolapril and a sustained release formulation of verapamil and indicated in treatment of hypertension in patients who require more than one drug to reach target blood pressure. The antihypertensive efficacy of trandolapril/verapamil SR has been evaluated extensively in large trials. In the INVEST trial, a verapamil SR-based treatment strategy that included trandolapril in most patients was effective in reducing the primary outcome in hypertensive patients with coronary artery disease. The new onset of diabetes was also significantly lower in the verapamil SR/trandolapril treatment group in comparison with those on the atenolol/hydroclorothiazide treatment group. The BErgamo NEphrologic DIabetes Complications Trial (BENEDICT documented that in hypertensive diabetes and normoalbuminuria, trandolapril plus verapamil or trandolapril alone delayed the onset of microalbuminuria independent of their blood pressurereducing effect. Thus

  8. A pragmatic randomized trial of a polypill-based strategy to improve use of indicated preventive treatments in people at high cardiovascular disease risk.

    Science.gov (United States)

    Patel, Anushka; Cass, Alan; Peiris, David; Usherwood, Tim; Brown, Alex; Jan, Stephen; Neal, Bruce; Hillis, Graham S; Rafter, Natasha; Tonkin, Andrew; Webster, Ruth; Billot, Laurent; Bompoint, Severine; Burch, Carol; Burke, Hugh; Hayman, Noel; Molanus, Barbara; Reid, Christopher M; Shiel, Louise; Togni, Samantha; Rodgers, Anthony

    2015-07-01

    Most individuals at high cardiovascular disease (CVD) risk worldwide do not receive any or optimal preventive drugs. We aimed to determine whether fixed dose combinations of generic drugs ('polypills') would promote use of such medications. We conducted a randomized, open-label trial involving 623 participants from Australian general practices. Participants had established CVD or an estimated five-year CVD risk of ≥15%, with indications for antiplatelet, statin and ≥2 blood pressure lowering drugs ('combination treatment'). Participants randomized to the 'polypill-based strategy' received a polypill containing aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg. Participants randomized to 'usual care' continued with separate medications and doses as prescribed by their doctor. Primary outcomes were self-reported combination treatment use, systolic blood pressure and total cholesterol. After a median of 18 months, the polypill-based strategy was associated with greater use of combination treatment (70% vs. 47%; relative risk 1.49, (95% confidence interval (CI) 1.30 to 1.72) p study end, 17% and 67% of participants in polypill and usual care groups, respectively, were taking atorvastatin or rosuvastatin. Provision of a polypill improved self-reported use of indicated preventive treatments. The lack of differences in blood pressure and cholesterol may reflect limited study power, although for cholesterol, improved statin use in the polypill group counter-balanced use of more potent statins with usual care. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  9. Comparison of the packaging and labeling of Target ClearRx with conventional prescription drug packaging and labeling.

    Science.gov (United States)

    Soller, R William; Lightwood, James M

    2007-01-01

    To compare consumer preferences for Target pharmacy's clearrx packaging and labeling with conventional prescription drug packaging and labeling. Prospective, hands-on comparison of packaging and labeling formats. Two suburban shopping malls in northern California in February and March 2006. Volunteer participants from local communities. Self-administered questionnaire. Participants were asked to compare ClearRx bottles with conventional cylindrical prescription bottles (both labeled as containing fluoxetine). They also were asked their opinions on three ClearRx bottles (labeled as containing albuterol, amoxicillin, or atenolol) with different color rings corresponding to three fictitious family members. Consumer preference for ClearRx or conventional packaging and labeling, consumer ability to differentiate between two types of packaging and labeling, consumer perception of safety design, and reasons for consumer preferences. The majority of consumers (85%) preferred ClearRx packaging and labeling over the conventional format (10%; 5% uncertain; P Consumers described distinct differences between the packaging and labeling formats, citing ClearRx as better designed for safety, easier to read, and having better organized warnings with larger type size. The ClearRx patient information card was rated by the majority of consumers as easy or very easy to access (91%; P designed to avoid medication mix-ups (i.e., color rings, large type face for medication name) allowed consumers to easily distinguish among bottles of ClearRx. These findings were consistent across various demographic categories. ClearRx represents an important advance in meeting consumer needs for patient-centered designs in prescription packaging and labeling.

  10. Evaluation of cardiac function in unrestrained dogs and monkeys using left ventricular dP/dt.

    Science.gov (United States)

    Buchanan, Lewis V; Warner, William A; Arthur, Susan R; Gleason, Carol R; Lewen, Geoff; Levesque, Paul C; Gill, Michael W

    2016-01-01

    Preclinical assessment for alterations in cardiac ventricular function for drug candidates has not been a focus of ICH S7b guidelines for cardiovascular safety studies, but there is growing interest given that the cardiovascular risk is associated with positive and negative inotropes. From 2003 through 2013, 163 telemetry studies with left-ventricular function analyses were conducted in dogs and monkeys at Bristol Myers Squibb (BMS) in support for drug development programs. The ability of the telemetry system to detect changes in cardiac contractility was verified with positive control agents pimobendan and atenolol. Control data from a subset of studies were analyzed to determine dP/dt reference range values, and minimum detectable mean differences (control vs. treated) for statistical significance. Median minimum detectable differences for dogs ranged from 14 to 21% for positive dP/dt and 11 to 21% for negative dP/dt. For monkeys, median minimum detectable differences were 25 and 14% for positive and negative dP/dt, respectively. For BMS programs, 15 drug candidates were identified that produced primary effects on contractility. Changes in contractility that were associated with, and potentially secondary to, drug-related effects on heart rate or systemic blood pressure were observed with an additional 29 drug candidates. Changes in contractility have been observed in large animals during drug development studies at BMS over the past 10years. Model sensitivity has been demonstrated and a dP/dt beat-to-beat cloud analysis tool has been developed to help distinguish primary effects from those potentially secondary to systemic hemodynamic changes. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. A cost-minimization analysis of diuretic-based antihypertensive therapy reducing cardiovascular events in older adults with isolated systolic hypertension

    Directory of Open Access Journals (Sweden)

    Moran William P

    2005-01-01

    Full Text Available Abstract Background Hypertension is among the most common chronic condition in middle-aged and older adults. Approximately 50 million Americans are currently diagnosed with this condition, and more than $18.7 billion is spent on hypertension management, including $3.8 billion for medications. There are numerous pharmacological agents that can be chosen to treat hypertension by physicians in clinical practices. The purpose of this study was to assess the cost of alternative antihypertensive treatments in older adults with isolated systolic hypertension (ISH. Method Using the Systolic Hypertension in the Elderly Program (SHEP and other data, a cost-minimization analysis was performed. The cost was presented as the cost of number-needed-to treat (NNT of patients for 5 years to prevent one adverse event associated with cardiovascular disease (CVD. Result It was found that the cost of 5 year NNT to prevent one adverse CVD event ranged widely from $6,843 to $37,408 in older patients with ISH. The incremental cost of the 5 year NNT was lower to treat older patients in the very high CVD risk group relative to patients in the lower CVD risk group, ranging from $456 to $15,511. Compared to the cost of the 5 year NNT of other commonly prescribed antihypertensive drugs, the cost of SHEP-based therapy is the lowest. The incremental costs of the 5 year NNT would be higher if other agents were used, ranging from $6,372 to $38,667 to prevent one CVD event relative to SHEP-based drug therapy. Conclusion Antihypertensive therapy that is diuretic-based and that includes either low-dose reserpine or atenolol is an effective and relatively inexpensive strategy to prevent cardiovascular events in older adults with isolated systolic hypertension. Use of the diuretic-based therapy is the most cost-effective in patients at high risk for developing cardiovascular disease.

  12. Chemometric evaluation of the combined effect of temperature, pressure, and co-solvent fractions on the chiral separation of basic pharmaceuticals using actual vs set operational conditions.

    Science.gov (United States)

    Forss, Erik; Haupt, Dan; Stålberg, Olle; Enmark, Martin; Samuelsson, Jörgen; Fornstedt, Torgny

    2017-05-26

    The need to determine the actual operational conditions, instead of merely using the set operational conditions, was investigated for in packed supercritical fluid chromatography (SFC) by design of experiments (DoE) using a most important type of compounds, pharmaceutical basics, as models. The actual values of temperature, pressure, and methanol levels were recorded and calculated from external sensors, while the responses in the DoE were the retention factors and selectivity. A Kromasil CelluCoat column was used as the stationary phase, carbon dioxide containing varying methanol contents as the mobile phase, and the six racemates of alprenolol, atenolol, metoprolol, propranolol, clenbuterol, and mianserin were selected as model solutes. For the retention modeling, the most important term was the methanol fraction followed by the temperature and pressure. Significant differences (p<0.05) between most of the coefficients in the retention models were observed when comparing models from set and actual conditions. The selectivity was much less affected by operational changes, and therefore was not severely affected by difference between set and actual conditions. The temperature differences were usually small, maximum ±1.4°C, whereas the pressure differences were larger, typically approximately +10.5bar. The set and actual fractions of methanol also differed, usually by ±0.4 percentage points. A cautious conclusion is that the primary reason for the discrepancy between the models is a mismatch between the set and actual methanol fractions. This mismatch is more serious in retention models at low methanol fractions. The study demonstrates that the actual conditions should almost always be preferred. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Chronic mercury exposure impairs the sympathovagal control of the rat heart.

    Science.gov (United States)

    Simões, M R; Azevedo, B F; Fiorim, J; Jr Freire, D D; Covre, E P; Vassallo, D V; Dos Santos, L

    2016-11-01

    Mercury is known to cause harmful neural effects affecting the cardiovascular system. Here, we evaluated the chronic effects of low-dose mercury exposure on the autonomic control of the cardiovascular system. Wistar rats were treated for 30 days with HgCl2 (1st dose 4.6 μg/kg followed by 0.07 μg/kg per day, intramuscular) or saline. The femoral artery and vein were then cannulated for evaluation of autonomic control of the hemodynamic function, which was evaluated in awake rats. The following tests were performed: baroreflex sensitivity, Von Bezold-Jarisch reflex, heart rate variability (HRV) and pharmacological blockade with methylatropine and atenolol to test the autonomic tone of the heart. Exposure to HgCl2 for 30 days slightly increased the mean arterial pressure and heart rate (HR). There was a significant reduction in the baroreflex gain of animals exposed to HgCl2 . Moreover, haemodynamic responses to the activation of the Von Bezold-Jarisch reflex were also reduced. The changes in the spectral analysis of HRV suggested a shift in the sympathovagal balance toward a sympathetic predominance after mercury exposure, which was confirmed by autonomic pharmacological blockade in the HgCl2 group. This group also exhibited reduced intrinsic HR after the double block suggesting that the pacemaker activity of the sinus node was also affected. These findings suggested that the autonomic modulation of the heart was significantly altered by chronic mercury exposure, thus reinforcing that even at low concentrations such exposure might be associated with increased cardiovascular risk. © 2016 John Wiley & Sons Australia, Ltd.

  14. Excess pressure integral predicts cardiovascular events independent of other risk factors in the conduit artery functional evaluation substudy of Anglo-Scandinavian Cardiac Outcomes Trial.

    Science.gov (United States)

    Davies, Justin E; Lacy, Peter; Tillin, Therese; Collier, David; Cruickshank, J Kennedy; Francis, Darrel P; Malaweera, Anura; Mayet, Jamil; Stanton, Alice; Williams, Bryan; Parker, Kim H; McG Thom, Simon A; Hughes, Alun D

    2014-07-01

    Excess pressure integral (XSPI), a new index of surplus work performed by the left ventricle, can be calculated from blood pressure waveforms and may indicate circulatory dysfunction. We investigated whether XSPI predicted future cardiovascular events and target organ damage in treated hypertensive individuals. Radial blood pressure waveforms were acquired by tonometry in 2069 individuals (aged, 63±8 years) in the Conduit Artery Functional Evaluation (CAFE) substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Measurements of left ventricular mass index (n=862) and common carotid artery intima media thickness (n=923) were also performed. XSPI and the integral of reservoir pressure were lower in people treated with amlodipine±perindopril than in those treated with atenolol±bendroflumethiazide, although brachial systolic blood pressure was similar. A total of 134 cardiovascular events accrued during a median 3.4 years of follow-up; XSPI was a significant predictor of cardiovascular events after adjustment for age and sex, and this relationship was unaffected by adjustment for conventional cardiovascular risk factors or Framingham risk score. XSPI, central systolic blood pressure, central augmentation pressure, central pulse pressure, and integral of reservoir pressure were correlated with left ventricular mass index, but only XSPI, augmentation pressure, and central pulse pressure were associated positively with carotid artery intima media thickness. Associations between left ventricular mass index, XSPI, and integral of reservoir pressure and carotid artery intima media thickness and XSPI were unaffected by multivariable adjustment for other covariates. XSPI is a novel indicator of cardiovascular dysfunction and independently predicts cardiovascular events and targets organ damage in a prospective clinical trial. © 2014 American Heart Association, Inc.

  15. Muscle pain induced by static contraction in rats is modulated by peripheral inflammatory mechanisms.

    Science.gov (United States)

    Santos, Diogo Francisco da Silva Dos; Melo Aquino, Bruna de; Jorge, Carolina Ocanha; Azambuja, Graciana de; Schiavuzzo, Jalile Garcia; Krimon, Suzy; Neves, Juliana Dos Santos; Parada, Carlos Amilcar; Oliveira-Fusaro, Maria Claudia Gonçalves

    2017-09-01

    Muscle pain is an important health issue and frequently related to static force exertion. The aim of this study is to evaluate whether peripheral inflammatory mechanisms are involved with static contraction-induced muscle pain in rats. To this end, we developed a model of muscle pain induced by static contraction performed by applying electrical pulses through electrodes inserted into muscle. We also evaluated the involvement of neutrophil migration, bradykinin, sympathetic amines and prostanoids. A single session of sustained static contraction of gastrocnemius muscle induced acute mechanical muscle hyperalgesia without affecting locomotor activity and with no evidence of structural damage in muscle tissue. Static contraction increased levels of creatine kinase but not lactate dehydrogenase, and induced neutrophil migration. Dexamethasone (glucocorticoid anti-inflammatory agent), DALBK (bradykinin B1 antagonist), Atenolol (β1 adrenoceptor antagonist), ICI 118,551 (β2 adrenoceptor antagonist), indomethacin (cyclooxygenase inhibitor), and fucoidan (non-specific selectin inhibitor) all reduced static contraction-induced muscle hyperalgesia; however, the bradykinin B2 antagonist, bradyzide, did not have an effect on static contraction-induced muscle hyperalgesia. Furthermore, an increased hyperalgesic response was observed when the selective bradykinin B1 agonist des-Arg9-bradykinin was injected into the previously stimulated muscle. Together, these findings demonstrate that static contraction induced mechanical muscle hyperalgesia in gastrocnemius muscle of rats is modulated through peripheral inflammatory mechanisms that are dependent on neutrophil migration, bradykinin, sympathetic amines and prostanoids. Considering the clinical relevance of muscle pain, we propose the present model of static contraction-induced mechanical muscle hyperalgesia as a useful tool for the study of mechanisms underlying static contraction-induced muscle pain. Copyright © 2017 IBRO

  16. Beta blocker use and colorectal cancer risk: population-based case-control study.

    Science.gov (United States)

    Jansen, Lina; Below, Janina; Chang-Claude, Jenny; Brenner, Hermann; Hoffmeister, Michael

    2012-08-15

    Recently, it has been postulated that long-term use of beta blockers might decrease the risk of certain types of cancer because of weakening of norepinephrine signaling. Previous studies on colorectal cancer (CRC) yielded inconsistent results, but lacked information on covariates. Thus, the authors investigated the association of beta blocker use and CRC risk in a large population-based case-control study (DACHS study). Between 2003 and 2007, information on beta blocker use and potential confounders was collected by personal interviews for 1762 CRC cases and 1708 control individuals from Germany. The association of CRC risk and beta blocker use and subclasses of beta blockers was estimated by multiple logistic regression. In addition, site- and stage-specific analyses were performed. After adjustment for covariates, no association was observed with beta blocker use (odds ratio [OR], 1.05; 95% confidence interval [CI], 0.86-1.29) or with duration of beta blocker use. Also, the analysis by subclasses of beta blockers (cardioselectivity) and active ingredients (metoprolol, bisoprolol, carvedilol, and atenolol) or by CRC subsite showed no associations. In stage-specific analyses, long-term beta blocker use (6+ years) was associated with a significantly higher risk of stage IV CRC (OR, 2.02; 95% CI, 1.25-3.27). Our adjusted results do not support the hypothesis that beta blocker use is associated with decreased risk of CRC. In contrast, we found a positive association of long-term beta blocker use and risk of stage IV CRC. The latter result should be further evaluated in future studies. Copyright © 2012 American Cancer Society.

  17. Profile of diseases prevalent in a tribal locality in Jharkhand, India: A family medicine practitioner′s perspective

    Directory of Open Access Journals (Sweden)

    Sumit Kumar

    2015-01-01

    , ramipril, hydrochlorothiazide, atenolol, salbutamol, etophyline, metformin, glimepiride, fluoxetine, flavoxate, tamsulosin, iron-folic acid, etc. The fact that three or more drugs are given in most of the prescriptions, can be justified due to multiple morbidity and the severity of disease than to irresponsible prescribing.

  18. Beta-blockers in hypertension.

    Science.gov (United States)

    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. Copyright © 2010 Elsevier Inc. All rights reserved.

  19. Arterial stiffness, hypertension, and rational use of nebivolol

    Directory of Open Access Journals (Sweden)

    Enrico Agabiti-Rosei

    2009-05-01

    Full Text Available Enrico Agabiti-Rosei, Enzo Porteri, Damiano RizzoniClinica Medica, Department of Medical and Surgical Sciences, University of Brescia, ItalyAbstract: Arterial stiffness plays a key role in the pathophysiology of the cardiovascular system. Some indices of arterial stiffness (pulse wave velocity, augmentation index, characteristics of central blood pressure waveform may be presently calculated and evaluated in the clinical setting. Age and blood pressure are the two major clinical determinants of increased arterial stiffness, while molecular determinants of arterial stiffness are related to fibrotic components of the extracellular matrix, mainly elastin, collagen and fibronectin. Increased arterial stiffness has been consistently observed in conditions such as hypertension, dyslipidemia and diabetes. Arterial stiffness evaluated by means of carotid-femoral pulse wave velocity yielded prognostic significance beyond and above traditional risk factors. A more favorable effect of calcium channel blockers, diuretics and ACE inhibitors compared with β-blockers on indices of arterial stiffness was observed in several studies. It is conceivable that newer β-blockers with additional vasodilating properties, such as nebivolol, which has favorable effects on carbohydrate and lipid metabolism, as well as on endothelial function and on oxidative stress, may have favorable effects on arterial stiffness, compared with atenolol. In fact, in recent studies, nebivolol was demonstrated to improve artery stiffness to a greater extent than older β-blockers. Because endothelial dysfunction and increased arterial stiffness play an important role in the early atherosclerotic processes and are associated with poor outcomes and increased mortality, independently of blood pressure, the ability of nebivolol to enhance release of endothelium-derived nitric oxide, and consequently improve endothelial function and arterial stiffness, may have significant clinical

  20. Current role of beta-blockers in the treatment of hypertension.

    Science.gov (United States)

    Aronow, Wilbert S

    2010-11-01

    It is important to know which patients with hypertension will benefit from beta-blocker therapy and which beta-blockers should be used in the treatment of hypertension to reduce cardiovascular events and mortality. Studies between 1981 and 2009 using a Medline search are reported. Beta-blockers should be used to treat hypertension in patients with previous myocardial infarction, acute coronary syndromes, angina pectoris, congestive heart failure, ventricular arrhythmias, supraventricular tachyarrhythmias, diabetes mellitus, after coronary artery bypass graft surgery, and in patients who are pregnant, have thyrotoxicosis, glaucoma, migraine, essential tremor, perioperative hypertension, or an excessive blood pressure response after exercise. The use of beta-blockers as first-line therapy in patients with primary hypertension has been controversial. However, the 2009 guidelines of the European Society of Hypertension state that large-scale meta-analyses of available data confirm that diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and calcium channel blockers do not significantly differ in their ability to lower blood pressure and to exert cardiovascular protection both in elderly and in younger patients. The key message of this paper is that atenolol should not be used as an antihypertensive drug and that the degree of reduction of mortality, myocardial infarction, stroke and congestive heart failure by antihypertensive therapy is dependent on the degree of lowering of aortic blood pressure. Newer vasodilator beta-blockers such as carvedilol and nebivolol may be more effective in reducing cardiovascular events than traditional beta-blockers, but this needs to be investigated by controlled clinical trials.

  1. Association of the pattern of use of perioperative β-blockade and postoperative mortality.

    Science.gov (United States)

    Wallace, Arthur W; Au, Selwyn; Cason, Brian A

    2010-10-01

    The 1996 atenolol study provided evidence that perioperative β-adrenergic receptor blockade (β-blockade) reduced postsurgical mortality. In 1998, the indications for perioperative β-blockade were codified as the Perioperative Cardiac Risk Reduction protocol and implemented at the San Francisco Veterans Administration Medical Center, San Francisco, California. The present study analyzed the association of the pattern of use of perioperative β-blockade with perioperative mortality since introduction of the Perioperative Cardiac Risk Reduction protocol. Epidemiologic analysis of the operations undertaken since 1996 at the San Francisco Veterans Administration Medical Center was performed. The pattern of use of perioperative β-blockade was divided into four groups: None, Addition, Withdrawal, and Continuous. Logistic regression, survival analysis, and propensity analysis were performed. A total of 38,779 operations were performed between 1996 and 2008. In patients meeting Perioperative Cardiac Risk Reduction indications for perioperative β-blockade, Addition is associated with a reduction in 30-day (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.33 to 0.83; P = 0.006) and 1-yr mortality (OR, 0.64; 95%, CI 0.51 to 0.79; P < 0.0001). Continuous is associated with a reduction in 30-day (OR, 0.68; 95% CI, 0.47 to 0.98; P = 0.04) and 1-yr mortality (OR, 0.82; 95% CI, 0.67 to 1.0; P = 0.05). Withdrawal is associated with an increase in 30-day (OR 3.93, 95% CI, 2.57 to 6.01; P less than 0.0001) and 1-yr mortality (OR, 1.96; 95% CI, 1.49 to 2.58; P < 0.0001). Perioperative β-blockade administered according to the Perioperative Cardiac Risk Reduction protocol is associated with a reduction in 30-day and 1-yr mortality. Perioperative withdrawal of β-blockers is associated with increased mortality.

  2. Echocardiographic methods, quality review, and measurement accuracy in a randomized multicenter clinical trial of Marfan syndrome.

    Science.gov (United States)

    Selamet Tierney, Elif Seda; Levine, Jami C; Chen, Shan; Bradley, Timothy J; Pearson, Gail D; Colan, Steven D; Sleeper, Lynn A; Campbell, M Jay; Cohen, Meryl S; De Backer, Julie; Guey, Lin T; Heydarian, Haleh; Lai, Wyman W; Lewin, Mark B; Marcus, Edward; Mart, Christopher R; Pignatelli, Ricardo H; Printz, Beth F; Sharkey, Angela M; Shirali, Girish S; Srivastava, Shubhika; Lacro, Ronald V

    2013-06-01

    The Pediatric Heart Network is conducting a large international randomized trial to compare aortic root growth and other cardiovascular outcomes in 608 subjects with Marfan syndrome randomized to receive atenolol or losartan for 3 years. The authors report here the echocardiographic methods and baseline echocardiographic characteristics of the randomized subjects, describe the interobserver agreement of aortic measurements, and identify factors influencing agreement. Individuals aged 6 months to 25 years who met the original Ghent criteria and had body surface area-adjusted maximum aortic root diameter (ROOTmax) Z scores > 3 were eligible for inclusion. The primary outcome measure for the trial is the change over time in ROOTmaxZ score. A detailed echocardiographic protocol was established and implemented across 22 centers, with an extensive training and quality review process. Interobserver agreement for the aortic measurements was excellent, with intraclass correlation coefficients ranging from 0.921 to 0.989. Lower interobserver percentage error in ROOTmax measurements was independently associated (model R(2) = 0.15) with better image quality (P = .002) and later study reading date (P < .001). Echocardiographic characteristics of the randomized subjects did not differ by treatment arm. Subjects with ROOTmaxZ scores ≥ 4.5 (36%) were more likely to have mitral valve prolapse and dilation of the main pulmonary artery and left ventricle, but there were no differences in aortic regurgitation, aortic stiffness indices, mitral regurgitation, or left ventricular function compared with subjects with ROOTmaxZ scores < 4.5. The echocardiographic methodology, training, and quality review process resulted in a robust evaluation of aortic root dimensions, with excellent reproducibility. Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

  3. Mechanisms underlying the nociceptive responses induced by platelet-activating factor (PAF) in the rat paw.

    Science.gov (United States)

    Marotta, Denise M; Costa, Robson; Motta, Emerson M; Fernandes, Elizabeth S; Medeiros, Rodrigo; Quintão, Nara L M; Campos, Maria M; Calixto, João B

    2009-04-01

    Platelet-activating factor (PAF) is an inflammatory mediator widely known to exert relevant pathophysiological functions. However, the relevance of PAF in nociception has received much less attention. Herein, we have investigated the mechanisms underlying PAF-induced spontaneous nociception and mechanical hypersensitivity in the rat paw. PAF injection (1- 30 nmol/paw) resulted in a dose-related overt nociception, whilst only the dose of 10 nmol/ paw produced a significant and time-related mechanical hypersensitivity. Local coinjection of PAF antagonist WEB2086 significantly inhibited both spontaneous nociception and mechanical hypersensitivity. Moreover, the coinjection of the natural IL-1beta receptor antagonist (IRA) notably prevented both PAF-induced nociceptive responses, whilst these responses were not altered by anti-TNFalpha coinjection. Interestingly, pretreatment with the ultrapotent vaniloid agonist resiniferotoxin, coinjection of the TRPV1 receptor antagonist SB366791, or mast cell depletion with compound 48/80 markedly prevented PAF-induced spontaneous nociception. Conversely, PAF-elicited mechanical hypersensitivity was strikingly susceptible to distinct antineutrophil-related strategies, namely the antineutrophil antibody, the selectin blocker fucoidin, the chemokine CXCR2 receptor antagonist SB225002, and the C5a receptor antibody anti-CD88. Notably, the same antineutrophil migration strategies significantly prevented the increase of myeloperoxidase activity induced by PAF. The mechanical hypersensitivity caused by PAF was also prevented by the cyclooxygenase inhibitors indomethacin or celecoxib, and by the selective beta(1) adrenergic receptor antagonist atenolol. Collectively, the present results provide consistent evidence indicating that distinct mechanisms are involved in the spontaneous nociception and mechanical hypersensitivity caused by PAF. They also support the concept that selective PAF receptor antagonists might constitute interesting

  4. [Preparation and performance characterization of gold nanoparticles modified chiral capillary electrochromatography stationary phase].

    Science.gov (United States)

    Xiong, Lele; Li, Ruijun; Ji, Yibing

    2017-07-08

    Gold nanoparticles (GNPs, 15 nm) were prepared and introduced to amino groups derived silica monolithic column. Bovine serum albumin (BSA) was immobilized via covalent modification method onto the carboxylic functionalized GNPs to afford chiral stationary phase (CSP) for enantioseparation. GNPs were well dispersed and successfully incorporated onto the columns with the contents as high as 17.18% by characterization method such as transmission electron microscopy (TEM), ultraviolet (UV)-visible absorption spectra and scanning electron microscopy (SEM). The preparation conditions of the BSA modified CSP were optimized and 10% (v/v) 3-aminopropyltriethoxysilane (APTES) and 15 g/L BSA were selected as appropriate reaction conditions. The enantioseparation performance of the BSA modified CSP has been investigated by capillary electrochromatography (CEC). Enantiomers of tryptophan, ephedrine and atenolol were resolved, and the baseline separation of tryptophan was achieved. Meanwhile, the influences of pH value, buffer concentrations and applied voltages used on the chiral separation were studied, and the optimal separation conditions were 10 mmol/L phosphate buffer at pH 7.4 and 15 kV applied voltages. In comparison with the BSA modified CSP prepared by physical adsorption, the CSP prepared by covalent modification method had better separation results, and the analytes could be separated directly without pre-column derivatization. In addition, the prepared BSA modified CSP exhibited good run to run repeatability with relative standard deviations (RSDs) of the migration times and selectivity factors not more than 2.3% and 0.96%, respectively. This work offers a good thinking for modification with other proteins or other types of chiral selectors.

  5. New standards in hypertension and cardiovascular risk management: focus on telmisartan

    Directory of Open Access Journals (Sweden)

    Domenico Galzerano

    2010-03-01

    Full Text Available Domenico Galzerano1, Cristina Capogrosso4, Sara Di Michele2, Antonio Galzerano1, Paola Paparello1, Diana Lama3, Carlo Gaudio21Department of Cardiology, San Gennaro Hospital, Naples, Italy; 2Department of Heart and Great Vessels, A. Reale, La Sapienza University, Rome, Italy; 3V Division of Internal Medicine, II University, Naples, Italy; 4Cardiology Division, San Giovanni Bosco Hospital, Naples, ItalyAbstract: Blockade of the renin–angiotensin system is an important approach in managing high blood pressure, and has increasingly been shown to affect cardiovascular disease processes mediated by angiotensin II throughout the cardiovascular and renal continua. Telmisartan is an angiotensin II receptor blocker (ARB displaying unique pharmacologic properties, including a longer half life than any other ARB, that result in large and sustained reductions of blood pressure. In patients with mild-to-moderate hypertension, telmisartan has proved superior to other antihypertensive agents (valsartan, losartan, ramipril, perindopril, and atenolol in controlling blood pressure particularly towards the end of the dosing interval. There is also clinical evidence that telmisartan reduces left ventricular hypertrophy, reduces arterial stiffness and the recurrence of atrial fibrillation, and confers renoprotection. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET® study has demonstrated that telmisartan has similar cardiovascular protective effects to ramipril in a large, high-risk patient population but was better tolerated. The powerful and sustained blood pressure control apparent in clinical trials, together with cardiovascular protection and tolerability demonstrated in ONTARGET® means that telmisartan may be a preferred option for patients with hypertension.Keywords: angiotensin II receptor blocker, cardiovascular disease, hypertension, renin–angiotensin system, telmisartan

  6. Molecular Modeling Study of Chiral Separation and Recognition Mechanism of β-Adrenergic Antagonists by Capillary Electrophoresis

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    Yifeng Chai

    2012-01-01

    Full Text Available Chiral separations of five β-adrenergic antagonists (propranolol, esmolol, atenolol, metoprolol, and bisoprolol were studied by capillary electrophoresis using six cyclodextrins (CDs as the chiral selectors. Carboxymethylated-β-cyclodextrin (CM-β-CD exhibited a higher enantioselectivity power compared to the other tested CDs. The influences of the concentration of CM-β-CD, buffer pH, buffer concentration, temperature, and applied voltage were investigated. The good chiral separation of five β-adrenergic antagonists was achieved using 50 mM Tris buffer at pH 4.0 containing 8 mM CM-β-CD with an applied voltage of 24 kV at 20 °C. In order to understand possible chiral recognition mechanisms of these racemates with CM-β-CD, host-guest binding procedures of CM-β-CD and these racemates were studied using the molecular docking software Autodock. The binding free energy was calculated using the Autodock semi-empirical binding free energy function. The results showed that the phenyl or naphthyl ring inserted in the hydrophobic cavity of CM-β-CD and the side chain was found to point out of the cyclodextrin rim. Hydrogen bonding between CM-β-CD and these racemates played an important role in the process of enantionseparation and a model of the hydrogen bonding interaction positions was constructed. The difference in hydrogen bonding formed with the –OH next to the chiral center of the analytes may help to increase chiral discrimination and gave rise to a bigger separation factor. In addition, the longer side chain in the hydrophobic phenyl ring of the enantiomer was not beneficial for enantioseparation and the chiral selectivity factor was found to correspond to the difference in binding free energy.

  7. Propranolol sensitizes thyroid cancer cells to cytotoxic effect of vemurafenib.

    Science.gov (United States)

    Wei, Wei-Jun; Shen, Chen-Tian; Song, Hong-Jun; Qiu, Zhong-Ling; Luo, Quan-Yong

    2016-09-01

    Treatment options for advanced metastatic or progressive thyroid cancers are limited. Although targeted therapy specifically inhibiting intracellular kinase signaling pathways has markedly changed the therapeutic landscape, side-effects and resistance of single agent targeted therapy often leads to termination of the treatment. The objective of the present study was to identify the antitumor property of the non-selective β-adrenergic receptor antagonist propranolol for thyroid cancers. Human thyroid cancer cell lines 8505C, K1, BCPAP and BHP27 were used in the present study. Broad β-blocker propranolol and β2-specific antagonist ICI118551, but not β1-specific antagonist atenolol, inhibited the growth of 8505C and K1 cells. Propranolol treatment inhibited growth and induced apoptosis of 8505C cells in vitro and in vivo, which are closely associated with decreased expressions of cyclin D1 and anti-apoptotic Bcl-2. Expression of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) also decreased following propranolol intervention. 18F-FDG PET/CT imaging of the 8505C xenografts validated shrinkage of the tumors in the propranolol-treated group when compared to the phosphate‑buffered saline treated group. Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib. Our present results suggest that propranolol has potential activity against thyroid cancers and investigation of the combination with targeted molecular therapy for progressive thyroid cancers could be beneficial.

  8. Direct Enantiomeric Resolution of Betaxolol with Application to Analysis of Pharmaceutical Products

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    Mona M. Al-Shehri

    2006-01-01

    Full Text Available A high-performance liquid chromatographic (HPLC method has been developed for the separation and determination of S- and R-enantiomers of betaxolol in tablets and ophthalmic preparations. Baseline resolution was achieved by using teicoplanin macrocyclic antibiotic chiral stationary phase (CSP known as Chirobiotic T with fl uorescence detection at excitation/emission wavelengths 275/305 nm. The polar ionic mobile phase (PIM consists of methanol-glacial acetic acid-triethylamine, (100:0.020:0.025, v/v/v has been used at a fl ow rate of 1.5 ml/min. All analytes with S-(--atenolol as internal standard were conducted at ambient temperature. The method is highly specific where another coformulated compounds did not interfere. The stability of betaxolol enantiomers under different degree of temperature also studied. The results showed that it is stable for at least 7 days at 70oC. The method validated for its linearity, accuracy, precision and robustness. Experimental design was used during validation to evaluate method robustness. Using the chromatographic conditions described, S- and R-betaxolol were well resolved with mean retention times of 11.3 and 12.6 min, respectively.Linear response (r > 0.997 was observed over the range of 10-500 ng/ml of betaxolol enantiomers, with detection limit of 5 ng/ml. The recoveries of S- and R-betaxolol from tablets and ophthalmic preparation ranged from 97.4 to 101.4% and 98.0 to 102.0%, respectively. The mean relative standard deviation (R.S.D.% for both enantiomers were 1.1-1.4% and 1.3-1.7% in tablets and ophthalmic solution, respectively.

  9. Effects of adrenaline in human colon adenocarcinoma HT-29 cells.

    Science.gov (United States)

    Wong, Helen P S; Ho, Judy W C; Koo, Marcel W L; Yu, Le; Wu, William K K; Lam, Emily K Y; Tai, Emily K K; Ko, Joshua K S; Shin, Vivian Y; Chu, Kent Man; Cho, Chi Hin

    2011-06-20

    Stress has been implicated in the development of cancers. Adrenaline levels are increased in response to stress. The effects of adrenaline on colon cancer are largely unknown. The aims of the study are to determine the effects of adrenaline in human colon adenocarcinoma HT-29 cells and the possible underlying mechanisms involved. The effect of adrenaline on HT-29 cell proliferation was determined by [(3)H] thymidine incorporation assay. Expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) were detected by Western blot. Matrix metalloproteinase-9 (MMP-9) activity and prostaglandin E(2) (PGE(2)) release were determined by zymography and enzyme immunoassay, respectively. Adrenaline stimulated HT-29 cell proliferation. This was accompanied by the enhanced expression of COX-2 and VEGF in HT-29 cells. Adrenaline also upregulated MMP-9 activity and PGE(2) release. Adrenaline stimulated HT-29 cell proliferation which was reversed by COX-2 inhibitor sc-236. COX-2 inhibitor also reverted the action of adrenaline on VEGF expression and MMP-9 activity. Further study was performed to determine the involvement of β-adrenoceptors. The stimulatory action of adrenaline on colon cancer growth was blocked by atenolol and ICI 118,551, a β(1)- and β(2)-selective antagonist, respectively. This signified the role of β-adrenoceptors in this process. In addition, both antagonists also abrogated the stimulating actions of adrenaline on COX-2, VEGF expression, MMP-9 activity and PGE(2) release in HT-29 cells. These results suggest that adrenaline stimulates cell proliferation of HT-29 cells via both β(1)- and β(2)-adrenoceptors by a COX-2 dependent pathway. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Synthesis, analytical characterization and capillary electrophoretic use of the single-isomer heptakis-(6-O-sulfobutyl)-beta-cyclodextrin.

    Science.gov (United States)

    Malanga, Milo; Fejős, Ida; Varga, Erzsébet; Benkovics, Gábor; Darcsi, András; Szemán, Julianna; Béni, Szabolcs

    2017-09-08

    This contribution reports the synthesis, characterization and capillary electrophoretic application of heptakis-(6-O-sulfobutyl-ether)-β-cyclodextrin sodium salt, (6-(SB)7-β-CD). The compound was obtained through a five-steps synthesis and it represents the first example of single-isomer sulfobutylated cyclodextrin that carries the negatively charged functions exclusively on its primary side and it is unmodified on the lower rim. The purity of each intermediate was determined by appropriate liquid chromatographic methods, while the isomeric purity of the final product was established by an ad-hoc developed HPLC method based on a CD-Screen-IEC column. The structural identification of 6-(SB)7-β-CD was carried out by 1D, 2D NMR spectroscopy and ESI-MS. The chiral separation ability of 6-(SB)7-β-CD was studied by chiral capillary electrophoresis using the single-isomer host as a background electrolyte additive to separate the enantiomers of a representative set of pharmacologically significant model compounds such as verapamil, dapoxetine, ondansetron, propranolol, atenolol, metoprolol, carvedilol, terbutaline, amlodipine and tadalafil. The enantiomer migration order and the effects of the selector concentration on the enantiorecognition properties were investigated. NMR spectroscopy was applied to deepen and further confirm the host-guest interactions and in the case of the model compound dapoxetine a potential representation for the supramolecular assembly was developed based on the dataset collected by the extensive 2D NMR analysis. This single-isomer chiral selector offers a new alternative to the widely applied randomly sulfobutylated- and sulfated-beta-cylodextrins as well as to the single-isomer sulfated and carboxymethylated derivatives in chiral separations. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Role of wetland organic matters as photosensitizer for degradation of micropollutants and metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eunkyung [Department of Civil and Environmental Engineering, Yonsei University, Yonsei-ro 50, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Shon, Ho Kyong [School of Civil and Environmental Engineering, University of Technology, Sydney (UTS), PO Box 123, Broadway, Sydney 2007, NSW (Australia); Cho, Jaeweon, E-mail: chojw@yonsei.ac.kr [Department of Civil and Environmental Engineering, Yonsei University, Yonsei-ro 50, Seodaemun-gu, Seoul 120-749 (Korea, Republic of)

    2014-07-15

    Highlights: • Photodegradation of PPCPs was investigated in various NOM enriched solutions. • Direct and indirect photolysis experiments were conducted upon UV irradiation. • PPCPs showed different levels of photodegradation rates depending on their photoreactivity. • Allochthonous NOM inhibited the photolysis of target PPCPs. • Wetland NOM enhanced photodegradation of some conservative PPCPs. - Abstract: Overall photodegradation of pharmaceuticals, personal care products (PPCPs) and pharmaceutical metabolites were investigated in order to evaluate their photochemical fate in aquatic environments in various natural organic matter (NOM) enriched solutions. Tested PPCPs exhibited different rates of loss during direct and indirect photolysis. Here, only ultraviolet (UV) light source was used for direct photolysis and UV together with {sup 3}DOM{sup *}for indirect photolysis. Diclofenac and sulfamethoxazole were susceptible to photodegradation, whereas carbamazepine, caffeine, paraxanthine and tri(2-chloroethyl) phosphate (TCEP) showed low levels of photodegradation rate, reflecting their conservative photoreactivity. During indirect photodegradation, in contrast to the hydrophilic autochthonous NOM, allochthonous NOM with relatively high molecular weight (MW), specific ultraviolet absorbance (SUVA) and hydrophobicity (e.g., Suwannee River humic acid (SRHA)) revealed to significantly inhibit the photolysis of target micropollutants. The presence of Typha wetland NOM enhanced the indirect photolysis of well-known conservative micopollutants (carbamazepine and paraxanthine). And atenolol, carbamazepine, glimepiride, and N-acetyl-sulfamethoxazole were found to be sensitive to the triplet excited state of dissolved organic matter ({sup 3}DOM{sup *}) with Typha wetland NOM under deoxygenated condition. This suggests that photolysis in constructed wetlands connected to the wastewater treatment plant can enhance the degradation of some anthropogenic micropollutants

  12. Occurrence and removal of pharmaceuticals, hormones, personal care products, and endocrine disrupters in a full-scale water reclamation plant.

    Science.gov (United States)

    Tran, Ngoc Han; Gin, Karina Yew-Hoong

    2017-12-01

    This study provided the first comprehensive data on the occurrence and removal of twenty-five target emerging contaminants (ECs) in a full-scale water reclamation plant (WRP) in the Southeast Asian region. Nineteen out of the twenty-five ECs were ubiquitously detected in raw influent samples. Concentrations of the detected ECs in raw influent samples ranged substantially from 44.3 to 124,966ng/L, depending upon the compound and sampling date. The elimination of ECs in full-scale conventional activated sludge (CAS) and membrane bioreactor (MBR) systems at a local WRP was evaluated and compared. Several ECs, such as acetaminophen, atenolol, fenoprofen, indomethacin, ibuprofen, and oxybenzone, exhibited excellent removal efficiencies (>90%) in biological wastewater treatment processes, while some of the investigated compounds (carbamazepine, crotamiton, diclofenac, and iopamidol) appeared to be persistent in the both CAS and MBR systems. Field-based monitoring results showed that MBR outperformed CAS in the elimination of most target ECs. The relationship between molecular characteristics of ECs (i.e. physicochemical properties and structural features) and their removal efficiencies during biological wastewater treatment was also elucidated. Excellent removal efficiencies (>90%) were often noted for ECs with the sole presence of electron donating groups (i.e. phenolic [OH], amine [NH2], methoxy [OCH3], phenoxy [OC6H5], or alkyl groups). Conversely, ECs with the absence of electron donating groups or the predominance of strong electron withdrawing groups (e.g. halogenated, carbonyl, carboxyl, and sulfonamide) tended to show poor removal efficiencies (<30%) in biological wastewater treatment processes. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Heterozygous disruption of activin receptor-like kinase 1 is associated with increased arterial pressure in mice

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    María González-Núñez

    2015-11-01

    Full Text Available The activin receptor-like kinase 1 (ALK-1 is a type I cell-surface receptor for the transforming growth factor-β (TGF-β family of proteins. Hypertension is related to TGF-β1, because increased TGF-β1 expression is correlated with an elevation in arterial pressure (AP and TGF-β expression is upregulated by the renin-angiotensin-aldosterone system. The purpose of this study was to assess the role of ALK-1 in regulation of AP using Alk1 haploinsufficient mice (Alk1+/−. We observed that systolic and diastolic AP were significantly higher in Alk1+/− than in Alk1+/+ mice, and all functional and structural cardiac parameters (echocardiography and electrocardiography were similar in both groups. Alk1+/− mice showed alterations in the circadian rhythm of AP, with higher AP than Alk1+/+ mice during most of the light period. Higher AP in Alk1+/− mice is not a result of a reduction in the NO-dependent vasodilator response or of overactivation of the peripheral renin-angiotensin system. However, intracerebroventricular administration of losartan had a hypotensive effect in Alk1+/− and not in Alk1+/+ mice. Alk1+/− mice showed a greater hypotensive response to the β-adrenergic antagonist atenolol and higher concentrations of epinephrine and norepinephrine in plasma than Alk1+/+ mice. The number of brain cholinergic neurons in the anterior basal forebrain was reduced in Alk1+/− mice. Thus, we concluded that the ALK-1 receptor is involved in the control of AP, and the high AP of Alk1+/− mice is explained mainly by the sympathetic overactivation shown by these animals, which is probably related to the decreased number of cholinergic neurons.

  14. The quantal secretion of catecholamines is impaired by the accumulation of β-adrenoceptor antagonists into chromaffin cell vesicles

    Science.gov (United States)

    Montesinos, Mónica S; Camacho, Marcial; Machado, J David; Viveros, O Humberto; Beltrán, Beatriz; Borges, Ricardo

    2010-01-01

    Background and purpose: The delayed onset of certain effects of antagonists of β-adrenoceptors (β-blockers), such as lowering arterial blood pressure (several days), cannot be explained solely by their effects on β-adrenoceptors, an action that occurs within minutes. Although several mechanisms have been proposed, none of them explain this temporal delay. This work aimed at providing a new explanation based on the interference of these drugs with the functional accumulation of catecholamines within neurosecretory vesicles. Experimental approach: We used the simultaneous on-line monitoring of catecholamine and labetalol release from bovine isolated chromaffin cells and from rat perfused adrenal glands, as well as single cell amperometry, intracellular electrochemistry, patch amperometry and HPLC. Key results: Using amperometry, three β-blockers, labetalol, atenolol and propranolol, reduced the quantal size of secretory events in chromaffin cells, accompanied by a slowing down of exocytosis. By patch amperometry, we found that treatment with β-blockers also increases the chromaffin vesicle volume, thereby creating a functional dilution of catecholamines. Experiments with intracellular electrochemistry show that vesicles cannot uptake new catecholamines. There was progressive accumulation of labetalol in secretory vesicles of bovine adrenal chromaffin cells, and this β-blocker was co-released with catecholamines from rat and bovine chromaffin tissues. Conclusions and implications: We propose that β-blockers are progressively concentrated into sympathetic secretory vesicles, and interfere with the storage of catecholamines and are co-released with the natural transmitters, resulting in a decrease in the sympathetic tone. This could explain the delayed onset of the hypotensive effects of β-blockers. PMID:20233226

  15. The corporate bias and the molding of prescription practices: the case of hypertension

    Directory of Open Access Journals (Sweden)

    F.D. Fuchs

    2009-03-01

    Full Text Available Drug management of hypertension has been a noticeable example of the influence of the pharmaceutical industry on prescription practices. The worldwide leading brands of blood pressure-lowering agents are angiotensin receptor-blocking agents, although they are considered to be simply substitutes of angiotensin-converting enzyme (ACE inhibitors. Commercial strategies have been based on the results of clinical trials sponsored by drug companies. Most of them presented distortions in their planning, presentation or interpretation that favored the drugs from the sponsor, i.e., corporate bias. Atenolol, an ineffective blood pressure agent in elderly individuals, was the comparator drug in several trials. In a re-analysis of the INSIGHT trial, deaths appeared to have been counted twice. The LIFE trial appears in the title of more than 120 reproductions of the main and flawed trial, as a massive strategy of scientific marketing. Most guidelines have incorporated the corporate bias from the original studies, and the evidence from better designed studies, such as the ALLHAT trial, have been largely ignored. In trials published recently corporate influences have touched on ethical limits. In the ADVANCE trial, elderly patients with type 2 diabetes and cardiovascular disease or risk factors, allocated to placebo, were not allowed to use diuretic and full doses of an ACE inhibitor, despite the sound evidence of benefit demonstrated in previous trials. As a consequence, they had a 14% higher mortality rate than the participants allocated to the active treatment arm. This reality should be modified immediately, and a greater independence of the academy from the pharmaceutical industry is necessary.

  16. Application in the STRATHE trial of a score system to compare the efficacy and the tolerability of different therapeutic strategies in the management of hypertension

    Directory of Open Access Journals (Sweden)

    Bernard Waeber

    2008-02-01

    Full Text Available Bernard Waeber1, Jean-Jacques Mourad21Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland; 2Hôpital Avicienne, Bobigny, FranceAbstract: A score system integrating the evolution of efficacy and tolerability over time was applied to a subpopulation of the STRATHE trial, a trial performed according to a parallel group design, with a double-blind, random allocation to either a fixed-dose combination strategy (perindopril/indapamide 2 mg/0.625 mg, with the possibility to increase the dose to 3 mg/0.935 mg, and 4 mg/1.250 mg if needed, n = 118, a sequential monotherapy approach (atenolol 50 mg, followed by losartan 50 mg and amlodipine 5 mg if needed, n = 108, or a stepped-care strategy (valsartan 40 mg, followed by valsartan 80 mg and valsartan 80 mg+ hydrochlorothiazide 12.5 mg if needed, n = 103. The aim was to lower blood pressure below 140/90 mmHg within a 9-month period. The treatment could be adjusted after 3 and 6 months. Only patients in whom the study protocol was strictly applied were included in this analysis. At completion of the trial the total score averaged 13.1 ± 70.5 (mean ± SD using the fixed-dose combination strategy, compared with –7.2 ± 81.0 using the sequential monotherapy approach and –17.5 ± 76.4 using the stepped-care strategy. In conclusion, the use of a score system allows the comparison of antihypertensive therapeutic strategies, taking into account at the same time efficacy and tolerability. In the STRATHE trial the best results were observed with the fixed-dose combination containing low doses of an angiotensin enzyme converting inhibitor (perindopril and a diuretic (indapamide.Keywords: antihypertensive therapy, tolerability, antihypertensive efficacy, fixed-dose combination, sequential monotherapy, stepped-care treatment

  17. MODERN VIEWS ON THE VARIABILITY OF BLOOD PRESSURE

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    V. M. Gorbunov

    2012-01-01

    Full Text Available Nowadays conception of blood pressure (BP variability (BPV includes a number of indicators related to various physiological factors. All the indexes are calculated with the standard deviation (SD or more complex formulas, including SD. BPV main varieties are considered a 24-hour BPV (measured by ambulatory BP monitoring – ABPM, midterm BPV (BP self-control or home BP – HBP, and long-term, visit-to-visit, BPV (traditional BP measurement or office BP – OBP. The 24-hour BPV was the main subject of study for many years. Recently significant attention has been paid to the visit-to-visit BPV assessment. Retrospective meta-analysis showed that in a cohort of patients after stroke or transient ischemic attack, this index was a strong and independent (from the average BP level predictor of stroke. In ASCOT-BPLA study visit-to-visit systolic BPV also was a strong predictor of stroke and coronary events. Long-term BPV in patients of amlodipine/perindopril treatment group was significantly lower than this in patients of atenolol/diuretic group during the follow-up that was associated with a lower risk of cardiovascular complications. However , the concept of visit-to-visit BPV use for risk stratification and monitoring of antihypertensive therapy efficacy is associated with significant limitations (basic data is obtained in the post hoc analysis, difficulties in objective evaluation of prognostic significance of indicators, their dependence on medication adherence, etc.. The HBP self-control is a promising approach to the BPV analysis; it may be the "happy medium" between ABPM and OPB. New-designed prospective comparative studies are needed to evaluate the clinical significance of the various BPV parameters.

  18. The role of the anaesthetised guinea-pig in the preclinical cardiac safety evaluation of drug candidate compounds

    Energy Technology Data Exchange (ETDEWEB)

    Marks, Louise, E-mail: louise.marks@astrazeneca.com [Safety Assessment UK, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG (United Kingdom); Borland, Samantha; Philp, Karen; Ewart, Lorna; Lainée, Pierre; Skinner, Matthew [Safety Assessment UK, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG (United Kingdom); Kirk, Sarah [Innovative Medicines, Discovery Sciences, AstraZeneca, Alderley Park, Macclesfield, Cheshire, SK10 4TG (United Kingdom); Valentin, Jean-Pierre [Safety Assessment UK, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG (United Kingdom)

    2012-09-01

    Despite rigorous preclinical and clinical safety evaluation, adverse cardiac effects remain a leading cause of drug attrition and post-approval drug withdrawal. A number of cardiovascular screens exist within preclinical development. These screens do not, however, provide a thorough cardiac liability profile and, in many cases, are not preventing the progression of high risk compounds. We evaluated the suitability of the anaesthetised guinea-pig for the assessment of drug-induced changes in cardiovascular parameters. Sodium pentobarbitone anaesthetised male guinea-pigs received three 15 minute intravenous infusions of ascending doses of amoxicillin, atenolol, clonidine, dobutamine, dofetilide, flecainide, isoprenaline, levosimendan, milrinone, moxifloxacin, nifedipine, paracetamol, verapamil or vehicle, followed by a 30 minute washout. Dose levels were targeted to cover clinical exposure and above, with plasma samples obtained to evaluate effect/exposure relationships. Arterial blood pressure, heart rate, contractility function (left ventricular dP/dt{sub max} and QA interval) and lead II electrocardiogram were recorded throughout. In general, the expected reference compound induced effects on haemodynamic, contractility and electrocardiographic parameters were detected confirming that all three endpoints can be measured accurately and simultaneously in one small animal. Plasma exposures obtained were within, or close to the expected clinical range of therapeutic plasma levels. Concentration–effect curves were produced which allowed a more complete understanding of the margins for effects at different plasma exposures. This single in vivo screen provides a significant amount of information pertaining to the cardiovascular risk of drug candidates, ultimately strengthening strategies addressing cardiovascular-mediated compound attrition and drug withdrawal. -- Highlights: ► Evaluation of the anaesthetised guinea-pig to determine cardiac liability.

  19. Impact of heart rate on central aortic pressures and hemodynamics: analysis from the CAFE (Conduit Artery Function Evaluation) study: CAFE-Heart Rate.

    Science.gov (United States)

    Williams, Bryan; Lacy, Peter S

    2009-08-18

    The CAFE (Conduit Artery Function Evaluation) study showed less effective central aortic pressure lowering with atenolol-based therapy versus amlodipine-based therapy in people with hypertension. The present study examined the importance of heart rate (HR) as a determinant of this effect. Recent analyses have suggested that beta-blockers are less effective at reducing cardiovascular events than alternative blood pressure (BP)-lowering therapies. There has been much debate about the mechanism for this shortfall in benefit and specifically the role of HR lowering by beta-blockers. Central pressures were derived from brachial pressure and radial pulse wave analysis in 2,073 patients, and 7,146 measurements were recorded and analyzed over follow-up for up to 4 years. There was no impact of HR on brachial systolic or pulse pressures; however, there was a highly significant inverse relationship between HR and central aortic systolic and pulse pressures (p < 0.001). This was dependent on a strong inverse relationship between HR and augmentation index, indicative of increased wave reflection at lower HRs. Multiple regression, adjusted for brachial BP, showed HR to be the major determinant of central pressures. Moreover, HR and brachial BP accounted for 92% of the variability in central systolic and pulse pressures. Consequently, drug-related differences in central aortic pressures were markedly attenuated after adjustment for HR. When comparing beta-blocker-based treatments with other BP-lowering strategies, HR reduction with beta-blockers is a major mechanism accounting for less effective central aortic pressure reduction per unit change in brachial pressure.

  20. Evidence-based management for preeclampsia.

    Science.gov (United States)

    von Dadelszen, Peter; Menzies, Jennifer; Gilgoff, Sarah; Xie, Fang; Douglas, M Joanne; Sawchuck, Diane; Magee, Laura A

    2007-05-01

    This review reflects both the variable presentation and the systemic nature of preeclampsia. Recommendations for the comprehensive evaluation and management of organ dysfunction associated with pre-eclampsia are included. The main points in the review are that: (1) Preeclampsia is a systemic disorder that may affect many organ systems. (2) For preeclampsia remote from term (management improves perinatal outcomes, but requires obsessive surveillance to mitigate maternal risks and is a "package." (3) Initial assessment and ongoing surveillance of women with preeclampsia should include assessment of all vulnerable maternal organs as well as of the fetus. (4) Initiate antihypertensive drug treatment immediately if sBP >160 mmHg or dBP more than 110 mmHg, or if sBP 140-159 mmHg and/or dBP 85-109 mmHg (prepregnancy renal disease or diabetes). (5) The treatment of nonsevere pregnancy hypertension should include a treatment goal of dBP 80-105 mmHg (depending on practitioner preference), with one of the following agents, Methyldopa, Labetalol, Nifedipine, or, with special indications (renal or cardiac diseases), diuretics. (6) Drugs to avoid: angiotensin-converting enzyme inhibitors; angiotensin II receptor antagonists; and atenolol. (7) For the acute management of severe hypertension, initially reduce dBP by 10 mmHg and maintain the blood pressure at or below that level with either Nifedipine or Labetalol. (8) For both prophylaxis against and treatment of eclampsia, MgSO4 (4 g IV stat, then 1 g/hr). (9) For recurrent seizures, MgSO4 (2g IV stat, then increase to 1.5 g/hr). (10) Total fluid intake should not exceed 80 ml/hr; tolerate urine outputs as low as 10 ml/hr. (11) Early-onset and/or severe preeclampsia predict later cardiovascular morbidity and mortality; it would seem prudent to offer such women screening and lipid lowering interventions.

  1. Does selective beta-1 blockade provide bone marrow protection after trauma/hemorrhagic shock?

    Science.gov (United States)

    Pasupuleti, Latha V; Cook, Kristin M; Sifri, Ziad C; Kotamarti, Srinath; Calderon, Gabriel M; Alzate, Walter D; Livingston, David H; Mohr, Alicia M

    2012-09-01

    Previously, nonselective beta-blockade (BB) with propranolol demonstrated protection of the bone marrow (BM) after trauma and hemorrhagic shock (HS). Because selective beta-1 blockers are used commonly for their cardiac protection, the aim of this study was to more clearly define the role of specific beta adrenergic receptors in BM protection after trauma and HS. Male Sprague-Dawley rats underwent unilateral lung contusion (LC) followed by HS for 45 minutes. After resuscitation, animals were injected with a selective beta-blocker, atenolol (B1B), butoxamine (B2B), or SR59230A (B3B). Animals were killed at 3 hours or 7 days. Heart rate and blood pressure were measured throughout the study period. BM cellularity, growth of hematopoietic progenitor cells (HPCs) in BM, and hemoglobin levels (Hb) were assessed. Treatment with a B2B or B3B after LCHS restored both BM cellularity and BM HPC colony growth at 3 hours and 7 days. In contrast, treatment with a B1B had no effect on BM cellularity or HPC growth but did decrease heart effectively rate throughout the study. Treatment with a B3B after LCHS increased Hb as compared with LCHS alone. After trauma and HS, protection of BM for 7 days was seen with use of either a selective beta-2 or beta-3 blocker. Use of a selective beta-1 blocker was ineffective in protecting the BM despite a physiologic decrease in heart rate. Therefore, the protection of BM is via the beta-2 and beta-3 receptors and it is not via a direct cardiovascular effect. Published by Mosby, Inc.

  2. Pharmacological mechanisms underlying the cardiovascular effects of the "bath salt" constituent 3,4-methylenedioxypyrovalerone (MDPV).

    Science.gov (United States)

    Schindler, Charles W; Thorndike, Eric B; Suzuki, Masaki; Rice, Kenner C; Baumann, Michael H

    2016-12-01

    3,4-Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone with stimulatory cardiovascular effects that can lead to serious medical complications. Here, we examined the pharmacological mechanisms underlying these cardiovascular actions of MDPV in conscious rats. Male Sprague-Dawley rats had telemetry transmitters surgically implanted for the measurement of BP and heart rate (HR). On test days, rats were placed individually in standard isolation cubicles. Following drug treatment, cardiovascular parameters were monitored for 3 h sessions. Racemic MDPV (0.3-3.0 mg·kg -1 ) increased BP and HR in a dose-dependent manner. The S(+) enantiomer (0.3-3.0 mg·kg -1 ) of MDPV produced similar effects, while the R(-) enantiomer (0.3-3.0 mg·kg -1 ) had no effects. Neither of the hydroxylated phase I metabolites of MDPV altered cardiovascular parameters significantly from baseline. Pretreatment with the ganglionic blocker chlorisondamine (1 and 3 mg·kg -1 ) antagonized the increases in BP and HR produced by 1 mg·kg -1 MDPV. The α 1 -adrenoceptor antagonist prazosin (0.3 mg·kg -1 ) attenuated the increase in BP following MDPV, while the β-adrenoceptor antagonists propranolol (1 mg·kg -1 ) and atenolol (1 and 3 mg·kg -1 ) attenuated the HR increases. The S(+) enantiomer appeared to mediate the cardiovascular effects of MDPV, while the metabolites of MDPV did not alter BP or HR significantly; MDPV increased BP and HR through activation of central sympathetic outflow. Mixed-action α/β-adrenoceptor antagonists may be useful as treatments in counteracting the adverse cardiovascular effects of MDPV. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  3. Pharmacological mechanisms underlying the cardiovascular effects of the “bath salt” constituent 3,4‐methylenedioxypyrovalerone (MDPV)

    Science.gov (United States)

    Thorndike, Eric B; Suzuki, Masaki; Rice, Kenner C; Baumann, Michael H

    2016-01-01

    Background and Purpose 3,4‐Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone with stimulatory cardiovascular effects that can lead to serious medical complications. Here, we examined the pharmacological mechanisms underlying these cardiovascular actions of MDPV in conscious rats. Experimental Approach Male Sprague–Dawley rats had telemetry transmitters surgically implanted for the measurement of BP and heart rate (HR). On test days, rats were placed individually in standard isolation cubicles. Following drug treatment, cardiovascular parameters were monitored for 3 h sessions. Key Results Racemic MDPV (0.3–3.0 mg·kg−1) increased BP and HR in a dose‐dependent manner. The S(+) enantiomer (0.3–3.0 mg·kg−1) of MDPV produced similar effects, while the R(−) enantiomer (0.3–3.0 mg·kg−1) had no effects. Neither of the hydroxylated phase I metabolites of MDPV altered cardiovascular parameters significantly from baseline. Pretreatment with the ganglionic blocker chlorisondamine (1 and 3 mg·kg−1) antagonized the increases in BP and HR produced by 1 mg·kg−1 MDPV. The α1‐adrenoceptor antagonist prazosin (0.3 mg·kg−1) attenuated the increase in BP following MDPV, while the β‐adrenoceptor antagonists propranolol (1 mg·kg−1) and atenolol (1 and 3 mg·kg−1) attenuated the HR increases. Conclusions and Implications The S(+) enantiomer appeared to mediate the cardiovascular effects of MDPV, while the metabolites of MDPV did not alter BP or HR significantly; MDPV increased BP and HR through activation of central sympathetic outflow. Mixed‐action α/β‐adrenoceptor antagonists may be useful as treatments in counteracting the adverse cardiovascular effects of MDPV. PMID:27714779

  4. Uncovering the Molecular Mechanism of Actions between Pharmaceuticals and Proteins on the AD Network.

    Directory of Open Access Journals (Sweden)

    Shujuan Cao

    Full Text Available This study begins with constructing the mini metabolic networks (MMNs of beta amyloid (Aβ and acetylcholine (ACh which stimulate the Alzheimer's Disease (AD. Then we generate the AD network by incorporating MMNs of Aβ and ACh, and other MMNs of stimuli of AD. The panel of proteins contains 49 enzymes/receptors on the AD network which have the 3D-structure in PDB. The panel of drugs is formed by 5 AD drugs and 5 AD nutraceutical drugs, and 20 non-AD drugs. All of these complexes formed by these 30 drugs and 49 proteins are transformed into dyadic arrays. Utilizing the prior knowledge learned from the drug panel, we propose a statistical classification (dry-lab. According to the wet-lab for the complex of amiloride and insulin degrading enzyme, and the complex of amiloride and neutral endopeptidase, we are confident that this dry-lab is reliable. As the consequences of the dry-lab, we discover many interesting implications. Especially, we show that possible causes of Tacrine, donepezil, galantamine and huperzine A cannot improve the level of ACh which is against to their original design purpose but they still prevent AD to be worse as Aβ deposition appeared. On the other hand, we recommend Miglitol and Atenolol as the safe and potent drugs to improve the level of ACh before Aβ deposition appearing. Moreover, some nutrients such as NADH and Vitamin E should be controlled because they may harm health if being used in wrong way and wrong time. Anyway, the insights shown in this study are valuable to be developed further.

  5. Impact of APCI ionization source in liquid chromatography tandem mass spectrometry based tissue distribution studies.

    Science.gov (United States)

    Khatal, Laxman; Gaur, Ashwani; Naphade, Ashish; Kandikere, Vishwottam; Mookhtiar, Kasim

    2016-10-01

    Measurement of test article concentration in tissue samples has been an important part of pharmacokinetic study and has helped to co-relate pharmacokinetic/pharmacodynamic relationships since the 1950s. Bioanalysis of tissue samples using LC-MS/MS comes with unique challenges in terms of sample handling and inconsistent analyte response owing to nonvolatile matrix components. Matrix effect is a phenomenon where the target analyte response is either suppressed or enhanced in the presence of matrix components. Based on previous reports electrospray ionization (ESI) mode of ionization is believed to be more affected by matrix components than atmospheric pressure chemical ionization (APCI) or atmospheric pressure photoionization. To explore the impact of ionization source with respect to bioanalysis of tissue samples, five structurally diverse compounds - atenolol, verapamil, diclofenac, propranolol and flufenamic acid - were selected. Quality control standards were spiked into 10 different biological matrices like whole blood, liver, heart, brain, spleen, kidney, skeletal muscle, eye and skin tissue and were quantified against calibration standards prepared in rat plasma. Quantitative bioanalysis was performed utilizing both APCI and ESI mode and results were compared. Quality control standards when analyzed with APCI mode were found to be more consistent in terms of accuracy and precision as compared with ESI mode. Additionally, for some instances, up to 20-fold broader dynamic linearity range was observed with APCI mode as compared with ESI mode. As phospholid interferences have poor response in APCI mode, protein precipitation extraction technique can be used for multimatrix quantitation, which is more amenable to automation. The approach of multiple biological matrix quantitation against a single calibration curve helps bioanalysts to reduce turnaround time. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  6. [Beta-blocker intoxication].

    Science.gov (United States)

    Joye, F

    2000-05-20

    Beta-blocker intoxication is not frequent but can produce particularly severe or fatal conditions which must not be underestimated. Severity of beta-blocker intoxication varies from one compound to another. The more toxic drugs are propranolol, sotalol, oxprenolol, metoprolol, atenolol, acebutolol, labetalol, and carvedilol. Besides the drug type, history taking can provide a precise assessment of risk, particularly important in when elderly patients with a cardiovascular history have taken more than 20 tablets, when emergency care is provided late, and when other cardiotoxic or psychotoxic drugs have been coingested. The diagnosis of beta-blocker intoxication must be suspected in any case associating hypotension and bradycardia. The main cardiovascular complications are cardiogenic shock, atrio-ventricular conduction disorders, and obviously life-threatening ventricular arrhythmia with cardiac arrest. Centrally induced respiratory arrest is a rare but dreadful consequence which can occur suddenly even without hemodynamic failure. Neurologic toxicity is mainly expressed by consciousness disorders and more sporadically by seizures. Laboratory tests show variable serum potassium, lactic acidosis, hypoxia-hypercapnia resulting from hypoventilation, and rarely hypoglycemia. The ECG should be recorded early because electrocardiographic signs usually appear before clinical signs and QRS enlargement is a factor predictive of severe ventricular arrhythmia. The patient must be placed in an intensive care unit for continuous multiparametric monitoring. Besides gastric evacuation and symptomatic measures, treatment essentially requires glucagon for its positive inotropic effect after high intravenous doses. If glucagon infusion is ineffective or unavailable, an alternative would be to use high doses of vasoactive agents, choosing isoproterenol or epinephrine as the first intention drugs.

  7. On-line sensor monitoring for chemical contaminant attenuation during UV/H2O2 advanced oxidation process.

    Science.gov (United States)

    Yu, Hye-Weon; Anumol, Tarun; Park, Minkyu; Pepper, Ian; Scheideler, Jens; Snyder, Shane A

    2015-09-15

    A combination of surrogate parameters and indicator compounds were measured to predict the removal efficiency of trace organic compounds (TOrCs) using low pressure (LP)-UV/H2O2 advanced oxidation process (AOP), engaged with online sensor-based monitoring system. Thirty-nine TOrCs were evaluated in two distinct secondary wastewater effluents in terms of estimated photochemical reactivity, as a function of the rate constants of UV direct photolysis (kUV) and hydroxyl radical (OH) oxidation (kOH). The selected eighteen TOrCs were classified into three groups that served as indicator compounds: Group 1 for photo-susceptible TOrCs but with minor degradation by OH oxidation (diclofenac, fluoxetine, iohexol, iopamidol, iopromide, simazine and sulfamethoxazole); Group 2 for TOrCs susceptible to both direct photolysis and OH oxidation (benzotriazole, diphenhydramine, ibuprofen, naproxen and sucralose); and Group 3 for photo-resistant TOrCs showing dominant degradation by OH oxidation (atenolol, carbamazepine, DEET, gemfibrozil, primidone and trimethoprim). The results indicate that TOC (optical-based measurement), UVA254 or UVT254 (UV absorbance or transmittance at 254 nm), and total fluorescence can all be used as suitable on-line organic surrogate parameters to predict the attenuation of TOrCs. Furthermore, the automated real-time monitoring via on-line surrogate sensors and equipped with the developed degradation profiles between sensor response and a group of TOrCs removal can provide a diagnostic tool for process control during advanced treatment of reclaimed waters. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Air-assisted liquid-liquid microextraction using floating organic droplet solidification for simultaneous extraction and spectrophotometric determination of some drugs in biological samples through chemometrics methods

    Science.gov (United States)

    Farahmand, Farnaz; Ghasemzadeh, Bahar; Naseri, Abdolhossein

    2018-01-01

    An air assisted liquid-liquid microextraction by applying the solidification of a floating organic droplet method (AALLME-SFOD) coupled with a multivariate calibration method, namely partial least squares (PLS), was introduced for the fast and easy determination of Atenolol (ATE), Propanolol (PRO) and Carvedilol (CAR) in biological samples via a spectrophotometric approach. The analytes would be extracted from neutral aqueous solution into 1-dodecanol as an organic solvent, using AALLME. In this approach a low-density solvent with a melting point close to room temperature was applied as the extraction solvent. The emulsion was immediately formed by repeatedly pulling in and pushing out the aqueous sample solution and extraction solvent mixture via a 10-mL glass syringe for ten times. After centrifugation, the extractant droplet could be simply collected from the aqueous samples by solidifying the emulsion at a lower than the melting point temperature. In the next step, analytes were back extracted simultaneously into the acidic aqueous solution. Derringer and Suich multi-response optimization were utilized for simultaneous optimizing the parameters of three analytes. This method incorporates the benefits of AALLME and dispersive liquid-liquid microextraction considering the solidification of floating organic droplets (DLLME-SFOD). Calibration graphs under optimized conditions were linear in the range of 0.30-6.00, 0.32-2.00 and 0.30-1.40 μg mL- 1 for ATE, CAR and PRO, respectively. Other analytical parameters were obtained as follows: enrichment factors (EFs) were found to be 11.24, 16.55 and 14.90, and limits of detection (LODs) were determined to be 0.09, 0.10 and 0.08 μg mL- 1 for ATE, CAR and PRO, respectively. The proposed method will require neither a highly toxic chlorinated solvent for extraction nor an organic dispersive solvent in the application process; hence, it is more environmentally friendly.

  9. Anestesia para cesariana em paciente portadora de cardiomiopatia hipertrófica familiar: relato de caso Anestesia para cesária en paciente portadora de cardiomiopatía hipertrófica familiar: relato de caso Anesthesia for cesarean section in a patient with familiar hypertrophic cardiomyopathy: case report

    Directory of Open Access Journals (Sweden)

    Renato Mestriner Stocche

    2007-12-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A cardiomiopatia hipertrófica familiar (CHF é uma doença cardíaca rara, com transmissão hereditária, caracterizada por hipertrofia do septo ventricular e grau variável de estenose aórtica subvalvar. Nessa doença, o aumento da contratilidade do miocárdio e a diminuição da resistência vascular periférica podem agravar a obstrução da via de saída do VE, produzindo disritmia e isquemia cardíaca. Este relato objetivou discutir o manuseio anestésico para cesariana em paciente com CHF. RELATO DO CASO: Paciente com 33 semanas de gestação e diagnóstico prévio de CHF apresentou no holter de 24 horas 22 episódios de taquicardia ventricular não-sustentada (TVNS e dois episódios de taquicardia ventricular sustentada (TVS. Referia episódios de palpitação, dispnéia e dor precordial de curta duração. A paciente foi medicada com atenolol e apresentou controle dos sintomas e das disritmias cardíacas. Com 38 semanas e 5 dias de gestação a paciente foi submetida à cesariana eletiva. Além do habitual a monitorização contou com análise de segmento ST e pressão arterial invasiva. Utilizou-se anestesia raquiperidural com injeção de 5 µg de sunfentanil na raqui seguida de administração de bupivacaína a 0,375% em doses de incremento até atingir altura de T6 (total de 16 mL. Utilizou-se metaraminol como vasopressor. Não houve hipotensão arterial materna ou outras complicações no perioperatório. CONCLUSÕES: A anestesia geral é freqüentemente utilizada para cesarianas de pacientes com CHF. A anestesia raquiperidural com instalação lenta do bloqueio foi uma alternativa segura. Nessas pacientes, o aumento da contratilidade miocárdica deve ser evitado, devendo-se, se necessário, utilizar-se um a-agonista para correção de hipotensão arterial materna.JUSTIFICATIVA Y OBJETIVOS: La cardiomiopatía hipertrófica familiar (CHF es una enfermedad cardiaca rara con transmisión hereditaria

  10. Anestesia para salpingectomia parcial bilateral em paciente com miocardiopatia hipertrófica idiopática: relato de um caso e revisão da literatura Anestesia para salpingectomía parcial bilateral en paciente con miocardiopatía hipertrófica idiopática: relato de un caso y revisión del literatura Anesthesia for partial bilateral salpingectomy in a patient with idiopathic hypertrophic cardiomyopathy: case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Ana Sofia Del Castillo Sardi

    2010-02-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A miocardiopatia hipertrófica é uma doença cardíaca rara, com transmissão autossômica dominante e que se caracteriza pela hipertrofia do septo ventricular e pelas anormalidades da valva mitral. RELATO DO CASO: Paciente secundípara, de 25 anos, com diagnóstico de miocardiopatia hipertrófica há quatro anos e antecedente de asma leve intermitente controlada com inalações esporádicas de corticosteroides. Apresentava sopro holossistólico IV/VI plurifocal e importante escoliose, com os espaços intervertebrais palpáveis. Acusou palpitações esporádicas durante toda a gravidez e recebia medicação de 100 mg de atenolol por dia. Apresentava hemograma, creatinina e eletrólitos dentro dos limites normais, ecocardiograma com miocardiopatia hipertrófica de predomínio septal, com fração de ejeção sistólica de 0,76%. A paciente entrou em trabalho de parto de rápida evolução e nasceu criança viva, do sexo feminino, com APGAR 9/9 sem complicações maternas nem fetais. Foi realizada a programação para a realização de salpingectomia parcial bilateral. Em consulta, a paciente negou-se a receber anestesia para o procedimento. A técnica anestésica de eleição foi a regional combinada. O procedimento cirúrgico durou 20 minutos e as mudanças de pressão arterial junto com a frequência cardíaca foram 10% menores que as dos valores iniciais, sem complicações hemodinâmicas nem cirúrgicas imediatas. CONCLUSÕES: A mortalidade absoluta materna com miocardiopatia hipertrófica (MH é muito baixa e costuma aparecer em mulheres com fatores de alto risco. Não há evidências de que a anestesia regional aumente o risco em mulheres com MH quando é utilizada para o parto vaginal. Tanto a anestesia geral como a regional foram utilizadas com sucesso e sem complicações em cesarianas de parturientes com MH.JUSTIFICATIVA Y OBJETIVOS: La cardiomiopatía hipertrófica es enfermedad cardíaca rara, con transmisi

  11. Generic-reference and generic-generic bioequivalence of forty-two, randomly-selected, on-market generic products of fourteen immediate-release oral drugs.

    Science.gov (United States)

    Hammami, Muhammad M; De Padua, Sophia J S; Hussein, Rajaa; Al Gaai, Eman; Khodr, Nesrine A; Al-Swayeh, Reem; Alvi, Syed N; Binhashim, Nada

    2017-12-08

    The extents of generic-reference and generic-generic average bioequivalence and intra-subject variation of on-market drug products have not been prospectively studied on a large scale. We assessed bioequivalence of 42 generic products of 14 immediate-release oral drugs with the highest number of generic products on the Saudi market. We conducted 14 four-sequence, randomized, crossover studies on the reference and three randomly-selected generic products of amlodipine, amoxicillin, atenolol, cephalexin, ciprofloxacin, clarithromycin, diclofenac, ibuprofen, fluconazole, metformin, metronidazole, paracetamol, omeprazole, and ranitidine. Geometric mean ratios of maximum concentration (Cmax) and area-under-the-concentration-time-curve, to last measured concentration (AUCT), extrapolated to infinity (AUCI), or truncated to Cmax time of reference product (AUCReftmax) were calculated using non-compartmental method and their 90% confidence intervals (CI) were compared to the 80.00%-125.00% bioequivalence range. Percentages of individual ratios falling outside the ±25% range were also determined. Mean (SD) age and body-mass-index of 700 healthy volunteers (28-80/study) were 32.2 (6.2) years and 24.4 (3.2) kg/m2, respectively. In 42 generic-reference comparisons, 100% of AUCT and AUCI CIs showed bioequivalence, 9.5% of Cmax CIs barely failed to show bioequivalence, and 66.7% of AUCReftmax CIs failed to show bioequivalence/showed bioinequivalence. Adjusting for 6 comparisons, 2.4% of AUCT and AUCI CIs and 21.4% of Cmax CIs failed to show bioequivalence. In 42 generic-generic comparisons, 2.4% of AUCT, AUCI, and Cmax CIs failed to show bioequivalence, and 66.7% of AUCReftmax CIs failed to show bioequivalence/showed bioinequivalence. Adjusting for 6 comparisons, 2.4% of AUCT and AUCI CIs and 14.3% of Cmax CIs failed to show bioequivalence. Average geometric mean ratio deviation from 100% was ≤3.2 and ≤5.4 percentage points for AUCI and Cmax, respectively, in both generic

  12. Removal of Organic Micropollutants by Aerobic Activated Sludge

    KAUST Repository

    Wang, Nan

    2013-06-01

    The study examined the removal mechanism of non-acclimated and acclimated aerobic activated sludge for 29 target organic micropollutants (OMPs) at low concentration. The selection of the target OMPs represents a wide range of physical-chemical properties such as hydrophobicity, charge state as well as a diverse range of classes, including pharmaceuticals, personal care products and household chemicals. The removal mechanisms of OMPs include adsorption, biodegradation, hydrolysis, and vaporization. Adsorption and biodegradation were found to be the main routes for OMPs removal for all target OMPs. Target OMPs responded to the two dominant removal routes in different ways: (1) complete adsorption, (2) strong biodegradation and weak adsorption, (3) medium biodegradation and adsorption, and (4) weak sorption and weak biodegradatio. Kinetic study showed that adsorption of atenolol, mathylparaben and propylparaben well followed first-order model (R2: 0.939 to 0.999) with the rate constants ranging from 0.519-7.092 h-1. For biodegradation kinetics, it was found that benzafibrate, bisphenol A, diclofenac, gemfibrozil, ibuprofen, caffeine and DEET followed zero-order model (K0:1.15E-4 to 0.0142 μg/Lh-1, R2: 0.991 to 0.999), while TCEP, naproxen, dipehydramine, oxybenzone and sulfamethoxazole followed first-order model (K1:1.96E-4 to 0.101 h-1, R2: 0.912 to 0.996). 4 Inhibition by sodium azide (NaN3)and high temperature sterilization was compared, and it was found that high temperature sterilization will damage cells and change the sludge charge state. For the OMPs adaptation removal study, it was found that some of OMPs effluent concentration decreased, which may be due to the slow adaptation of the sludge or the increase of certain bacteria culture; some increased due to chromic toxicity of the chemicals; most of the OMPs had stable effluent concentration trend, it was explained that some of the OMPs were too difficutl to remove while other showed strong quick adaptation

  13. Financial Burden and Impoverishment Due to Cardiovascular Medications in Low and Middle Income Countries: An Illustration from India.

    Directory of Open Access Journals (Sweden)

    Kiran Raj Pandey

    Full Text Available Health expenditures are a major financial burden for many persons in low and middle-income countries, where individuals often lack health insurance. We estimate the effect of purchasing cardiovascular medicines on poverty in low and middle-income populations using rural and urban India as an example.We created step-up treatment regimens for prevention of ischemic heart disease for the most common cardiovascular medications in India based on their cost and relative risk reduction. Cost was measured by Government of India mandated ceiling prices in rupees (Rs. 1 = $0·016 for essential medicines plus taxes. We calculated step-wise projected incidence and intensity of impoverishment due to medicine purchase. To do this we measured the resources available to individuals as daily per-capita expenditures from the latest National Sample Survey, subtracted daily medication costs, and compared this to 2014 poverty thresholds recommended by an expert group.Analysis of cost-effectiveness resulted in five primary prevention drug regimens, created by progressive addition of Aspirin 75 mg, Hydrochlorothiazide 12.5mg, Losartan 25 mg, and Atorvastatin 10 mg or 40mg. Daily cost from steps 1 to 5 increased from Rs. 0·13, Rs. 1.16, Rs. 3.81, Rs. 10.07, to Rs. 28.85. At baseline, 31% of rural and 27% percent of urban Indian population are poor at the designated poverty thresholds. The Rs. 28.85 regimen would be unaffordable to 81% and 58% of rural and urban people. A secondary prevention regimen with aspirin, hydrochlorothiazide, atenolol and atorvastatin could be unaffordable to 81% and 57% rural and urban people respectively. According to our estimates, 17% of the rural 32% of the urban adult population could benefit with these medications, and their out of pocket purchase could impoverish 17 million rural and 10 million urban people in India and increase respective poverty gaps by 2.9%.Medication costs for cardiovascular disease have the potential to cause

  14. Financial Burden and Impoverishment Due to Cardiovascular Medications in Low and Middle Income Countries: An Illustration from India.

    Science.gov (United States)

    Pandey, Kiran Raj; Meltzer, David O

    2016-01-01

    Health expenditures are a major financial burden for many persons in low and middle-income countries, where individuals often lack health insurance. We estimate the effect of purchasing cardiovascular medicines on poverty in low and middle-income populations using rural and urban India as an example. We created step-up treatment regimens for prevention of ischemic heart disease for the most common cardiovascular medications in India based on their cost and relative risk reduction. Cost was measured by Government of India mandated ceiling prices in rupees (Rs. 1 = $0·016) for essential medicines plus taxes. We calculated step-wise projected incidence and intensity of impoverishment due to medicine purchase. To do this we measured the resources available to individuals as daily per-capita expenditures from the latest National Sample Survey, subtracted daily medication costs, and compared this to 2014 poverty thresholds recommended by an expert group. Analysis of cost-effectiveness resulted in five primary prevention drug regimens, created by progressive addition of Aspirin 75 mg, Hydrochlorothiazide 12.5mg, Losartan 25 mg, and Atorvastatin 10 mg or 40mg. Daily cost from steps 1 to 5 increased from Rs. 0·13, Rs. 1.16, Rs. 3.81, Rs. 10.07, to Rs. 28.85. At baseline, 31% of rural and 27% percent of urban Indian population are poor at the designated poverty thresholds. The Rs. 28.85 regimen would be unaffordable to 81% and 58% of rural and urban people. A secondary prevention regimen with aspirin, hydrochlorothiazide, atenolol and atorvastatin could be unaffordable to 81% and 57% rural and urban people respectively. According to our estimates, 17% of the rural 32% of the urban adult population could benefit with these medications, and their out of pocket purchase could impoverish 17 million rural and 10 million urban people in India and increase respective poverty gaps by 2.9%. Medication costs for cardiovascular disease have the potential to cause financial burden to

  15. Inhibition of a TREK-like K+ channel current by noradrenaline requires both β1- and β2-adrenoceptors in rat atrial myocytes.

    Science.gov (United States)

    Bond, Richard C; Choisy, Stéphanie C M; Bryant, Simon M; Hancox, Jules C; James, Andrew F

    2014-10-01

    Noradrenaline plays an important role in the modulation of atrial electrophysiology. However, the identity of the modulated channels, their mechanisms of modulation, and their role in the action potential remain unclear. This study aimed to investigate the noradrenergic modulation of an atrial steady-state outward current (IKss). Rat atrial myocyte whole-cell currents were recorded at 36°C. Noradrenaline potently inhibited IKss (IC50 = 0.90 nM, 42.1 ± 4.3% at 1 µM, n = 7) and potentiated the L-type Ca(2+) current (ICaL, EC50 = 136 nM, 205 ± 40% at 1 µM, n = 6). Noradrenaline-sensitive IKss was weakly voltage-dependent, time-independent, and potentiated by the arachidonic acid analogue, 5,8,11,14-eicosatetraynoic acid (EYTA; 10 µM), or by osmotically induced membrane stretch. Noise analysis revealed a unitary conductance of 8.4 ± 0.42 pS (n = 8). The biophysical/pharmacological properties of IKss indicate a TREK-like K(+) channel. The effect of noradrenaline on IKss was abolished by combined β1-/β2-adrenoceptor antagonism (1 µM propranolol or 10 µM β1-selective atenolol and 100 nM β2-selective ICI-118,551 in combination), but not by β1- or β2-antagonist alone. The action of noradrenaline could be mimicked by β2-agonists (zinterol and fenoterol) in the presence of β1-antagonist. The action of noradrenaline on IKss, but not on ICaL, was abolished by pertussis toxin (PTX) treatment. The action of noradrenaline on ICaL was mediated by β1-adrenoceptors via a PTX-insensitive pathway. Noradrenaline prolonged APD30 by 52 ± 19% (n = 5; P Noradrenaline inhibits a rat atrial TREK-like K(+) channel current via a PTX-sensitive mechanism involving co-operativity of β1-/β2-adrenoceptors that contributes to atrial APD prolongation. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

  16. Stress-associated cardiovascular reaction masks heart rate dependence on physical load in mice.

    Science.gov (United States)

    Andreev-Andrievskiy, A A; Popova, A S; Borovik, A S; Dolgov, O N; Tsvirkun, D V; Custaud, M; Vinogradova, O L

    2014-06-10

    When tested on the treadmill mice do not display a graded increase of heart rate (HR), but rather a sharp shift of cardiovascular indices to high levels at the onset of locomotion. We hypothesized that under test conditions cardiovascular reaction to physical load in mice is masked with stress-associated HR increase. To test this hypothesis we monitored mean arterial pressure (MAP) and heart rate in C57BL/6 mice after exposure to stressful stimuli, during spontaneous locomotion in the open-field test, treadmill running or running in a wheel installed in the home cage. Mice were treated with β1-adrenoblocker atenolol (2mg/kg ip, A), cholinolytic ipratropium bromide (2mg/kg ip, I), combination of blockers (A+I), anxiolytic diazepam (5mg/kg ip, D) or saline (control trials, SAL). MAP and HR in mice increased sharply after handling, despite 3weeks of habituation to the procedure. Under stressful conditions of open field test cardiovascular parameters in mice were elevated and did not depend on movement speed. HR values did not differ in I and SAL groups and were reduced with A or A+I. HR was lower at rest in D pretreated mice. In the treadmill test HR increase over speeds of 6, 12 and 18m/min was roughly 1/7-1/10 of HR increase observed after placing the mice on the treadmill. HR could not be increased with cholinolytic (I), but was reduced after sympatholytic (A) or A+I treatment. Anxiolytic (D) reduced heart rate at lower speeds of movement and its overall effect was to unmask the dependency of HR on running speed. During voluntary running in non-stressful conditions of the home cage HR in mice linearly increased with increasing running speeds. We conclude that in test situations cardiovascular reactions in mice are governed predominantly by stress-associated sympathetic activation, rendering efforts to evaluate HR and MAP reactions to workload unreliable. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Corticotropin-Releasing Factor in the Basolateral Amygdala Enhances Memory Consolidation via an Interaction with the β-Adrenoceptor-cAMP Pathway: Dependence on Glucocorticoid Receptor Activation

    Science.gov (United States)

    Roozendaal, Benno; Schelling, Gustav; McGaugh, James L.

    2008-01-01

    Extensive evidence indicates that stress hormone effects on the consolidation of emotionally influenced memory involve noradrenergic activation of the basolateral complex of the amygdala (BLA). The present experiments examined whether corticotropin-releasing factor (CRF) modulates memory consolidation via an interaction with the β-adrenoceptor-adenosine 3′,5′-cyclic monophosphate (cAMP) system in the BLA. In a first experiment, male Sprague-Dawley rats received bilateral infusions of the CRF-binding protein ligand inhibitor CRF6-33 into the BLA either alone or together with the CRF receptor antagonist α-helical CRF9-41 immediately after inhibitory avoidance training. CRF6-33 induced dose-dependent enhancement of 48-h retention latencies, which was blocked by co-administration of α-helical CRF9-41, suggesting that CRF6-33 enhances memory consolidation by displacing CRF from its binding protein, thereby increasing ‘free’ endogenous CRF concentrations. In a second experiment, intra-BLA infusions of atenolol (β-adrenoceptor antagonist) and Rp-cAMPS (cAMP inhibitor), but not prazosin (α1-adrenoceptor antagonist), blocked CRF6-33-induced retention enhancement. In a third experiment, the CRF receptor antagonist α-helical CRF9-41 administered into the BLA immediately after training attenuated the dose-response effects of concurrent intra-BLA infusions of clenbuterol (β-adrenoceptor agonist). In contrast, α-helical CRF9-41 did not alter retention enhancement induced by posttraining intra-BLA infusions of either cirazoline (α1-adrenoceptor agonist) or 8-br-cAMP (cAMP analog). These findings suggest that CRF facilitates the memory-modulatory effects of noradrenergic stimulation in the BLA via an interaction with the β-adrenoceptor-cAMP cascade, at a locus between the membrane-bound β-adrenoceptor and the intracellular cAMP formation site. Moreover, consistent with evidence that glucocorticoids enhance memory consolidation via a similar interaction with the

  18. Use of common migraine treatments in breast-feeding women: a summary of recommendations.

    Science.gov (United States)

    Hutchinson, Susan; Marmura, Michael J; Calhoun, Anne; Lucas, Sylvia; Silberstein, Stephen; Peterlin, B Lee

    2013-04-01

    Breast-feeding has important health and emotional benefits for both mother and infant, and should be encouraged. While there are some data to suggest migraine may improve during breast-feeding, more than half of women experience migraine recurrence with 1 month of delivery. Thus, a thorough knowledge base of the safety and recommended use of common acute and preventive migraine drugs during breast-feeding is vital to clinicians treating migraine sufferers. Choice of treatment should take into account the balance of benefit and risk of medication. For some of the medications commonly used during breast-feeding, there is not good evidence about benefits. A list of commonly used migraine medications was agreed upon by the 6 authors, who treat migraine and other headaches on a regular basis and are members of the Women's Special Interest Section of the American Headache Society. Each medication was researched by the first author utilizing widely accepted data sources, such as the American Academy of Pediatrics publication "The Transfer of Drugs and Other Chemicals Into Human Milk; Thomas Hale's manual Medications and Mothers Milk; Briggs, Freeman, and Yaffe's reference book Drugs in Pregnancy and Lactation; and the National Library of Medicine's Drugs and Lactation Database (LactMed) - a peer-reviewed and fully referenced database available online. Many commonly used migraine medications may be compatible with breast-feeding based on expert recommendations. Ibuprofen, diclofenac, and eletriptan are among acute medications with low levels in breast milk, but studies of triptans are limited. Toxicity is a concern with aspirin due to an association with Reye's syndrome; sedation or apnea is a concern with opioids. Finally, preventive medications not recommended include zonisamide, atenolol, and tizanidine. Several excellent resources are available for clinicians making treatment decisions in breast-feeding women. Clinicians treating migraine should discuss both acute and

  19. Mirabegron relaxes urethral smooth muscle by a dual mechanism involving β3 -adrenoceptor activation and α1 -adrenoceptor blockade.

    Science.gov (United States)

    Alexandre, E C; Kiguti, L R; Calmasini, F B; Silva, F H; da Silva, K P; Ferreira, R; Ribeiro, C A; Mónica, F Z; Pupo, A S; Antunes, E

    2016-02-01

    This article is commented on by Michel, M. C., pp. 429-430 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.13379. Mirabegron is the first β3 -adrenoceptor agonist approved for treatment of overactive bladder syndrome. This study aimed to investigate the effects of β3 -adrenoceptor agonist mirabegron in mouse urethra. The possibility that mirabegron also exerts α1 -adrenoceptor antagonism was also tested in rat smooth muscle preparations presenting α1A - (vas deferens and prostate), α1D - (aorta) and α1B -adrenoceptors (spleen). Functional assays were carried out in mouse and rat isolated tissues. Competition assays for the specific binding of [(3) H]prazosin to membrane preparations of HEK-293 cells expressing each of the human α1 -adrenoceptors, as well as β-adrenoceptor mRNA expression and cyclic AMP measurements in mouse urethra, were performed. Mirabegron produced concentration-dependent urethral relaxations that were shifted to the right by the selective β3 -adrenoceptor antagonist L-748,337 but unaffected by β1 - and β2 -adrenoceptor antagonists (atenolol and ICI-118,551 respectively). Mirabegron-induced relaxations were enhanced by the PDE4 inhibitor rolipram, and the agonist stimulated cAMP synthesis. Mirabegron also produced rightward shifts in urethral contractions induced by the α1 -adrenoceptor agonist phenylephrine. Schild regression analysis revealed that mirabegron behaves as a competitive antagonist of α1 -adrenoceptors in urethra, vas deferens and prostate (α1A -adrenoceptor, pA2  ≅ 5.6) and aorta (α1D -adrenoceptor, pA2  ≅ 5.4) but not in spleen (α1B -adrenoceptor). The affinities estimated for mirabegron in functional assays were consistent with those estimated in radioligand binding with human recombinant α1A - and α1D -adrenoceptors (pKi  ≅ 6.0). The effects of mirabegron in urethral smooth muscle are the result of β3 -adrenoceptor agonism together with α1A and α1D -adrenoceptor

  20. Impact of Beta-Blocker Initiation Timing on Mortality Risk in Patients With Diabetes Mellitus Undergoing Noncardiac Surgery: A Nationwide Population-Based Cohort Study.

    Science.gov (United States)

    Chen, Ray-Jade; Chu, Hsi; Tsai, Lung-Wen

    2017-01-10

    Relevant clinical studies have been small and have not convincingly demonstrated whether the perioperative initiation of beta-blockers should be considered in patients with diabetes mellitus undergoing noncardiac surgery. In this nationwide propensity score-matched study, we included patients with diabetes mellitus undergoing noncardiac surgery between 2000 and 2011 from Taiwan's National Health Insurance Research Database. Patients were classified as beta-blocker and non-beta-blocker cohorts. We further stratified beta-blocker users into cardioprotective beta-blocker (atenolol, bisoprolol, metoprolol, or carvedilol) and other beta-blocker users. To investigate time of initiation of beta-blocker use, initiation time was stratified into 2 periods (>30 and ≤30 days preoperatively). The outcomes of interest were in-hospital and 30-day mortality. After propensity score matching, we identified 50 952 beta-blocker users and 50 952 matched controls. Compared with non-beta-blocker users, cardioprotective beta-blocker users were associated with lower risks of in-hospital (odds ratio 0.75, 95% CI 0.68-0.82) and 30-day (odds ratio 0.75, 95% CI 0.70-0.81) mortality. Among initiation times, only the use of cardioprotective beta-blockers for >30 days was associated with decreased risk of in-hospital (odds ratio 0.72, 95% CI 0.65-0.78) and 30-day (odds ratio 0.72, 95% CI 0.66-0.78) mortality. Of note, use of other beta-blockers for ≤30 days before surgery was associated with increased risk of both in-hospital and 30-day mortality. The use of cardioprotective beta-blockers for >30 days before surgery was associated with reduced mortality risk, whereas short-term use of beta-blockers was not associated with differences in mortality in patients with diabetes mellitus. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  1. Beta-blockers for hypertension

    Science.gov (United States)

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

    2017-01-01

    close to that of the estimate of effect), moderate (if the true effect is likely to be close to the estimate of effect), low (if the true effect may be substantially different from the estimate of effect), and very low (if we are very uncertain about the estimate of effect). Main results Thirteen RCTs met inclusion criteria. They compared beta-blockers to placebo (4 RCTs, 23,613 participants), diuretics (5 RCTs, 18,241 participants), calcium-channel blockers (CCBs: 4 RCTs, 44,825 participants), and renin-angiotensin system (RAS) inhibitors (3 RCTs, 10,828 participants). These RCTs were conducted between the 1970s and 2000s and most of them had a high risk of bias resulting from limitations in study design, conduct, and data analysis. There were 40,245 participants taking beta-blockers, three-quarters of them taking atenolol. We found no outcome trials involving the newer vasodilating beta-blockers (e.g. nebivolol). There was no difference in all-cause mortality between beta-blockers and placebo (RR 0.99, 95% CI 0.88 to 1.11), diuretics or RAS inhibitors, but it was higher for beta-blockers compared to CCBs (RR 1.07, 95% CI 1.00 to 1.14). The evidence on mortality was of moderate-certainty for all comparisons. Total CVD was lower for beta-blockers compared to placebo (RR 0.88, 95% CI 0.79 to 0.97; low-certainty evidence), a reflection of the decrease in stroke (RR 0.80, 95% CI 0.66 to 0.96; low-certainty evidence) since there was no difference in coronary heart disease (CHD: RR 0.93, 95% CI 0.81 to 1.07; moderate-certainty evidence). The effect of beta-blockers on CVD was worse than that of CCBs (RR 1.18, 95% CI 1.08 to 1.29; moderate-certainty evidence), but was not different from that of diuretics (moderate-certainty) or RAS inhibitors (low-certainty). In addition, there was an increase in stroke in beta-blockers compared to CCBs (RR 1.24, 95% CI 1.11 to 1.40; moderate-certainty evidence) and RAS inhibitors (RR 1.30, 95% CI 1.11 to 1.53; moderate-certainty evidence

  2. Type of Beta-blocker Use Among Patients with Versus without Diabetes after Myocardial Infarction

    Science.gov (United States)

    Arnold, Suzanne V.; Spertus, John A.; Lipska, Kasia J.; Lanfear, David E.; Tang, Fengming; Grodzinsky, Anna; McGuire, Darren K.; Gore, M. Odette; Goyal, Abhinav; Maddox, Thomas M.; Kosiborod, Mikhail

    2014-01-01

    Background Discharge beta-blocker prescription after myocardial infarction (MI) is recommended for all eligible patients. Numerous beta-blocker choices are presently available with variable glycometabolic effects, which could be an important consideration in patients with diabetes mellitus (DM). Whether patients with DM preferentially receive beta-blockers with favorable metabolic effects after MI and if this choice is associated with better glycemic control post-discharge is unknown. Methods Among patients from 24 US hospitals enrolled in an MI registry (2005–08), we investigated the frequency of “DM-friendly” beta-blocker prescription at discharge by DM status. Beta-blockers were classified as DM-friendly (e.g., carvedilol, labetalol), or non-DM-friendly (e.g., metoprolol, atenolol), based on their effects on glycemic control. Hierarchical, multivariable logistic regression examined the association of DM with DM-friendly beta-blocker use. Among DM patients, we examined the association of DM-friendly beta-blockers with worsened glycemic control at 6 months after MI. Results Of 4031 MI patients, 1382 (34%) had DM. Beta-blockers were prescribed at discharge in 93% of patients. DM-friendly beta-blocker use was low regardless of DM status, although patients with DM were more likely to be discharged on a DM-friendly beta-blocker compared with patients without DM (13.5% vs. 10.3%, p=0.003), an association that remained after multivariable adjustment (OR 1.41, 95% CI 1.13–1.77). There was a trend toward a lower risk of worsened glucose control at 6 months in DM patients prescribed DM-friendly vs. non-friendly beta-blockers (RR 0.80, 95% CI 0.60–1.08). Conclusion The vast majority of DM patients were prescribed non-DM friendly beta-blockers—a practice that was associated with a trend towards worse glycemic control post-discharge. While in need of further confirmation in larger studies, our findings highlight an opportunity to improve current practices of beta

  3. Estudio de las fracciones lipídicas de colesterol y triglicéridos en pacientes de dos consultorios médicos de la familia

    Directory of Open Access Journals (Sweden)

    José Luis Cusidó Carralero

    2014-11-01

    Full Text Available La segunda causa de muerte en la provincia de Las Tunas son las enfermedades del corazón, estas se asocian a múltiples factores de riesgo, como, por ejemplo, los niveles elevados de colesterol y triglicéridos. La alta frecuencia de valores patológicos de colesterol y triglicéridos en pacientes de los Consultorios Médicos de la Familia (CMF 19-01 y 20-01 en el Policlínico Docente “Manuel Fajardo Rivero” motivó a la realización de este trabajo, que tiene como objetivo evaluar el comportamiento de las fracciones lipídicas de colesterol y triglicéridos en pacientes de estos CMF, durante el período comprendido entre enero y junio de 2014. Las variables analizadas fueron: rango de valores de colesterol y triglicéridos, edad, sexo, antecedentes patológicos personales, diagnóstico clínico y tratamiento médico. Se incluyeron los pacientes mayores de 20 años de ambos consultorios, los diabéticos, hipertensos, cardiópatas; se excluyeron de la investigación las gestantes, enfermos hospitalizados o con ingreso domiciliario. Se obtuvo como resultado que casi la mitad de los pacientes presentó valores elevados en las fracciones lipídicas de colesterol y triglicéridos, las edades más afectadas fueron los adultos de 41 a 60 años, con predominio del sexo masculino. En la revisión de historias clínicas se tabularon como principales antecedentes patológicos personales que más de la mitad de los pacientes con alteraciones lipídicas son fumadores y un cuarto de ellos consumen alcohol. En el diagnóstico clínico y tratamiento médico registrado en la historia clínica de los pacientes afectados se constató que dos tercios de ellos son hipertensos y utilizan el captopril, enalapril y atenolol y casi un tercio son diabéticos, que se medican con los hipoglucemiantes, insulina y glibenclamida

  4. Ventricular action potential adaptation to regular exercise: role of β-adrenergic and KATPchannel function.

    Science.gov (United States)

    Wang, Xinrui; Fitts, Robert H

    2017-08-01

    Regular exercise training is known to affect the action potential duration (APD) and improve heart function, but involvement of β-adrenergic receptor (β-AR) subtypes and/or the ATP-sensitive K + (K ATP ) channel is unknown. To address this, female and male Sprague-Dawley rats were randomly assigned to voluntary wheel-running or control groups; they were anesthetized after 6-8 wk of training, and myocytes were isolated. Exercise training significantly increased APD of apex and base myocytes at 1 Hz and decreased APD at 10 Hz. Ca 2+ transient durations reflected the changes in APD, while Ca 2+ transient amplitudes were unaffected by wheel running. The nonselective β-AR agonist isoproterenol shortened the myocyte APD, an effect reduced by wheel running. The isoproterenol-induced shortening of APD was largely reversed by the selective β 1 -AR blocker atenolol, but not the β 2 -AR blocker ICI 118,551, providing evidence that wheel running reduced the sensitivity of the β 1 -AR. At 10 Hz, the K ATP channel inhibitor glibenclamide prolonged the myocyte APD more in exercise-trained than control rats, implicating a role for this channel in the exercise-induced APD shortening at 10 Hz. A novel finding of this work was the dual importance of altered β 1 -AR responsiveness and K ATP channel function in the training-induced regulation of APD. Of physiological importance to the beating heart, the reduced response to adrenergic agonists would enhance cardiac contractility at resting rates, where sympathetic drive is low, by prolonging APD and Ca 2+ influx; during exercise, an increase in K ATP channel activity would shorten APD and, thus, protect the heart against Ca 2+ overload or inadequate filling. NEW & NOTEWORTHY Our data demonstrated that regular exercise prolonged the action potential and Ca 2+ transient durations in myocytes isolated from apex and base regions at 1-Hz and shortened both at 10-Hz stimulation. Novel findings were that wheel running shifted the

  5. PRESCRIBING OF ANTIHYPERTENSIVE AGENTS IN PUBLIC PRIMARY CARE CLINICS – IS IT IN ACCORDANCE WITH CURRENT EVIDENCE?

    Directory of Open Access Journals (Sweden)

    SAJARI J

    2010-01-01

    Full Text Available Background: Large population surveys in Malaysia have consistently shown minimal improvement of blood pressure control rates over the last 10 years. Poor adherence to antihypertensive medication has been recognized as a major reason for poor control of hypertension. This study aimed to describe the prescribing pattern of antihypertensive agents in 2 public primary care clinics and assess its appropriateness in relation to current evidence and guidelines. Methods: A cross-sectional survey to describe the prescribing pattern of antihypertensive agents was carried out in 2 publicprimary care clinics in Selangor from May to June 2009. Hypertensive patients on pharmacological treatment for ≥1 year who attended the clinics within the study period of 7 weeks were selected. Appropriate use of antihypertensive agents was defined based on current evidence and the recommendations by the Malaysian Clinical Practice Guidelines (CPG on the Management of Hypertension, 2008. Data were obtained from patients’ medical records and were analysed using the SPSS software version 16.0. Results: A total of 400 hypertensive patients on treatment were included. Mean age was 59.5 years (SD ±10.9, range 28 to91 years, of which 52.8% were females and 47.2% were males. With regards to pharmacotherapy, 45.7% were on monotherapy,43.3% were on 2 agents and 11.0% were on ≥3 agents. Target blood pressure of <140/90mmHg was achieved in 51.4% of patients on monotherapy, and 33.2% of patients on combination of ≥2 agents. The commonest monotherapy agents being prescribed were β-blockers (atenolol or propranolol, followed by the short-acting calcium channel blocker (nifedipine. The commonest combination of 2-drug therapy prescribed was β-blockers and short-acting calcium channel blocker. Conclusion: This study shows that the prescribing pattern of antihypertensive agents in the 2 primary care clinics was not in accordance with current evidence and guidelines.

  6. Air-assisted liquid-liquid microextraction using floating organic droplet solidification for simultaneous extraction and spectrophotometric determination of some drugs in biological samples through chemometrics methods.

    Science.gov (United States)

    Farahmand, Farnaz; Ghasemzadeh, Bahar; Naseri, Abdolhossein

    2018-01-05

    An air assisted liquid-liquid microextraction by applying the solidification of a floating organic droplet method (AALLME-SFOD) coupled with a multivariate calibration method, namely partial least squares (PLS), was introduced for the fast and easy determination of Atenolol (ATE), Propanolol (PRO) and Carvedilol (CAR) in biological samples via a spectrophotometric approach. The analytes would be extracted from neutral aqueous solution into 1-dodecanol as an organic solvent, using AALLME. In this approach a low-density solvent with a melting point close to room temperature was applied as the extraction solvent. The emulsion was immediately formed by repeatedly pulling in and pushing out the aqueous sample solution and extraction solvent mixture via a 10-mL glass syringe for ten times. After centrifugation, the extractant droplet could be simply collected from the aqueous samples by solidifying the emulsion at a lower than the melting point temperature. In the next step, analytes were back extracted simultaneously into the acidic aqueous solution. Derringer and Suich multi-response optimization were utilized for simultaneous optimizing the parameters of three analytes. This method incorporates the benefits of AALLME and dispersive liquid-liquid microextraction considering the solidification of floating organic droplets (DLLME-SFOD). Calibration graphs under optimized conditions were linear in the range of 0.30-6.00, 0.32-2.00 and 0.30-1.40μg mL-1 for ATE, CAR and PRO, respectively. Other analytical parameters were obtained as follows: enrichment factors (EFs) were found to be 11.24, 16.55 and 14.90, and limits of detection (LODs) were determined to be 0.09, 0.10 and 0.08μg mL-1 for ATE, CAR and PRO, respectively. The proposed method will require neither a highly toxic chlorinated solvent for extraction nor an organic dispersive solvent in the application process; hence, it is more environmentally friendly. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Pharmacological characteristics of Artemisia vulgaris L. in isolated porcine basilar artery.

    Science.gov (United States)

    Nguyen, Ha Thi Thanh; Nguyen, Hai Thanh; Islam, Md Zahorul; Obi, Takeshi; Pothinuch, Pitchaya; Zar, Phyu Phyu Khine; Hou, De Xing; Van Nguyen, Thanh; Nguyen, Tuong Manh; Van Dao, Cuong; Shiraishi, Mitsuya; Miyamoto, Atsushi

    2016-04-22

    . Captopril (an angiotensin converting enzyme inhibitor), atenolol (a β1 receptor antagonist) and cimetidine (a H2 receptor antagonist) had no effect on this relaxation. In Ca(2+)-free 60mM KCl-containing solution, pretreatment with AVL significantly inhibited CaCl2-induced contraction. For the first time, the present study has demonstrated that AVL has two opposite effects, contraction and relaxation, on isolated artery, which may help to explain the conflicting indications for AVL in traditional herbalism. 5-HT is a significant factor affecting artery contraction in the presence of AVL. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Regression of electrocardiographic left ventricular hypertrophy or strain is associated with lower incidence of cardiovascular morbidity and mortality in hypertensive patients independent of blood pressure reduction - A LIFE review.

    Science.gov (United States)

    Bang, Casper N; Devereux, Richard B; Okin, Peter M

    2014-01-01

    Cornell product criteria, Sokolow-Lyon voltage criteria and electrocardiographic (ECG) strain (secondary ST-T abnormalities) are markers for left ventricular hypertrophy (LVH) and adverse prognosis in population studies. However, the relationship of regression of ECG LVH and strain during antihypertensive therapy to cardiovascular (CV) risk was unclear before the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study. We reviewed findings on ECG LVH regression and strain over time in 9193 hypertensive patients with ECG LVH at baseline enrolled in the LIFE study. The composite endpoint of CV death, nonfatal MI, or stroke occurred in 1096 patients during 4.8±0.9years follow-up. In Cox multivariable models adjusting for randomized treatment, known risk factors including in-treatment blood pressure, and for severity ECG LVH by Cornell product and Sokolow-Lyon voltage, baseline ECG strain was associated with a 33% higher risk of the LIFE composite endpoint (HR. 1.33, 95% CI [1.11-1.59]). Development of new ECG strain between baseline and year-1 was associated with a 2-fold increased risk of the composite endpoint (HR. 2.05, 95% CI [1.51-2.78]), whereas the risk associated with regression or persistence of ECG strain was attenuated and no longer statistically significant (both p>0.05). After controlling for treatment with losartan or atenolol, for baseline Framingham risk score, Cornell product, and Sokolow-Lyon voltage, and for baseline and in-treatment systolic and diastolic blood pressure, 1 standard deviation (SD) lower in-treatment Cornell product was associated with a 14.5% decrease in the composite endpoint (HR. 0.86, 95% CI [0.82-0.90]). In a parallel analysis, 1 SD lower in-treatment Sokolow-Lyon voltage was associated with a 16.6% decrease in the composite endpoint (HR. 0.83, 95% CI [0.78-0.88]). The LIFE study shows that evaluation of both baseline and in-study ECG LVH defined by Cornell product criteria, Sokolow-Lyon voltage criteria or

  9. Use of Common Migraine Treatments in Breast-Feeding Women: A Summary of Recommendations

    Science.gov (United States)

    Hutchinson, Susan; Marmura, Michael J.; Calhoun, Anne; Lucas, Sylvia; Silberstein, Stephen; Peterlin, B. Lee

    2014-01-01

    Background Breast-feeding has important health and emotional benefits for both mother and infant, and should be encouraged. While there are some data to suggest migraine may improve during breast-feeding, more than half of women experience migraine recurrence with 1 month of delivery. Thus, a thorough knowledge base of the safety and recommended use of common acute and preventive migraine drugs during breast-feeding is vital to clinicians treating migraine sufferers. Choice of treatment should take into account the balance of benefit and risk of medication. For some of the medications commonly used during breast-feeding, there is not good evidence about benefits. Methods A list of commonly used migraine medications was agreed upon by the 6 authors, who treat migraine and other headaches on a regular basis and are members of the Women's Special Interest Section of the American Headache Society. Each medication was researched by the first author utilizing widely accepted data sources, such as the American Academy of Pediatrics publication “The Transfer of Drugs and Other Chemicals Into Human Milk; Thomas Hale's manual Medications and Mothers Milk; Briggs, Freeman, and Yaffe's reference book Drugs in Pregnancy and Lactation; and the National Library of Medicine's Drugs and Lactation Database (LactMed) – a peer-reviewed and fully referenced database available online. Results Many commonly used migraine medications may be compatible with breast-feeding based on expert recommendations. Ibuprofen, diclofenac, and eletriptan are among acute medications with low levels in breast milk, but studies of triptans are limited. Toxicity is a concern with aspirin due to an association with Reye's syndrome; sedation or apnea is a concern with opioids. Finally, preventive medications not recommended include zonisamide, atenolol, and tizanidine. Conclusions Several excellent resources are available for clinicians making treatment decisions in breast-feeding women. Clinicians

  10. Effect of right atrial pacing, intravenous amiodarone and beta blockers for suppression of atrial fibrillation after coronary artery bypass surgery: a pilot study.

    Science.gov (United States)

    Cardona, Francisco; Seide, Hanscy; Cox, Rafael A; Pérez, Cynthia M

    2003-06-01

    This pilot study aimed to compare right atrial pacing, intravenous amiodarone and oral beta-blockers in the prevention, time to onset, duration and effect on hospital stay of postoperative atrial fibrillation (AF) after coronary artery bypass graft surgery (CABG) at our center. AF is the most common arrhythmic complication after CABG and is related to increased morbidity, length of hospital stay and costs. Trials with different drugs and other therapeutic modalities including beta-blockers, intravenous amiodarone and override suppression of automatic atrial foci by atrial pacing have shown partial success as preventive measures. However, a comparison between those three interventions has not been reported. Thirty-six consecutive patients that underwent CABG at our institution were randomly assigned to atrial pacing (18 patients) and intravenous amiodarone (18 patients) after baseline clinical, electrocardiographic and hemodynamic assessment. All patients received concomitant oral metoprolol or atenolol right after extubation. Thirty-three patients who had CABG at our center in the previous two months and that only received beta-blockers during their perioperative period served as a control group. The majority of baseline clinical and hemodynamic characteristics were similar in all groups. Only one patient (5.6%) developed AF in the atrial pacing group versus five (27.8%) on amiodarone and six (18.2%) who only received beta-blockers. That finding, however, did not attain statistical significance (p > 0.05). After adjusting for potential confounders, the odds of occurrence of AF was 77% lower in atrial pacing patients (OR = 0.23; 95% CI: 0.02, 2.20; p = 0.09) and 2.36 times higher in those on amiodarone (95% CI: 0.55, 10.24; P = 0.053) when compared to patients which only received beta blockers. Since only one patient on right atrial pacing developed atrial fibrillation, the analysis of the median time to onset and median duration of atrial fibrillation was

  11. Metoprolol-induced visual hallucinations: a case series

    Directory of Open Access Journals (Sweden)

    Goldner Jonathan A

    2012-02-01

    Full Text Available Abstract Introduction Metoprolol is a widely used beta-adrenergic blocker that is commonly prescribed for a variety of cardiovascular syndromes and conditions. While central nervous system adverse effects have been well-described with most beta-blockers (especially lipophilic agents such as propranolol, visual hallucinations have been only rarely described with metoprolol. Case presentations Case 1 was an 84-year-old Caucasian woman with a history of hypertension and osteoarthritis, who suffered from visual hallucinations which she described as people in her bedroom at night. They would be standing in front of the bed or sitting on chairs watching her when she slept. Numerous medications were stopped before her physician realized the metoprolol was the causative agent. The hallucinations resolved only after discontinuation of this medication. Case 2 was a 62-year-old Caucasian man with an inferior wall myocardial infarction complicated by cardiac arrest, who was successfully resuscitated and discharged from the hospital on metoprolol. About 18 months after discharge, he related to his physician that he had been seeing dead people at night. He related his belief that since he 'had died and was brought back to life', he was now seeing people from the after-life. Upon discontinuation of the metoprolol the visual disturbances resolved within several days. Case 3 was a 68 year-old Caucasian woman with a history of severe hypertension and depression, who reported visual hallucinations at night for years while taking metoprolol. These included awakening during the night with people in her bedroom and seeing objects in her room turn into animals. After a new physician switched her from metoprolol to atenolol, the visual hallucinations ceased within four days. Conclusion We suspect that metoprolol-induced visual hallucinations may be under-recognized and under-reported. Patients may frequently fail to acknowledge this adverse effect believing that they

  12. Sorption of structurally different ionized pharmaceutical and illicit drugs to a mixed-mode coated microsampler.

    Science.gov (United States)

    Peltenburg, Hester; Timmer, Niels; Bosman, Ingrid J; Hermens, Joop L M; Droge, Steven T J

    2016-05-20

    The mixed-mode (C18/strong cation exchange-SCX) solid-phase microextraction (SPME) fiber has recently been shown to have increased sensitivity for ionic compounds compared to more conventional sampler coatings such as polyacrylate and polydimethylsiloxane (PDMS). However, data for structurally diverse compounds to this (prototype) sampler coating are too limited to define its structural limitations. We determined C18/SCX fiber partitioning coefficients of nineteen cationic structures without hydrogen bonding capacity besides the charged group, stretching over a wide hydrophobicity range (including amphetamine, amitriptyline, promazine, chlorpromazine, triflupromazine, difenzoquat), and eight basic pharmaceutical and illicit drugs (pKa>8.86) with additional hydrogen bonding moieties (MDMA, atenolol, alprenolol, metoprolol, morphine, nicotine, tramadol, verapamil). In addition, sorption data for three neutral benzodiazepines (diazepam, temazepam, and oxazepam) and the anionic NSAID diclofenac were collected to determine the efficiency to sample non-basic drugs. All tested compounds showed nonlinear isotherms above 1mmol/L coating, and linear isotherms below 1mmol/L. The affinity for C18/SCX-SPME for tested organic cations without Hbond capacities increased with longer alkyl chains, ranging from logarithmic fiber-water distribution coefficients (log Dfw) of 1.8 (benzylamine) to 5.8 (triflupromazine). Amines smaller than benzylamine may thus have limited detection levels, while cationic surfactants with alkyl chain lengths >12 carbon atoms may sorb too strong to the C18/SCX sampler which hampers calibration of the fiber-water relationship in the linear range. The log Dfw for these simple cation structures closely correlates with the octanol-water partition coefficient of the neutral form (Kow,N), and decreases with increased branching and presence of multiple aromatic rings. Oxygen moieties in organic cations decreased the affinity for C18/SCX-SPME. Log Dfw values of

  13. Prevalence of Coronary Artery Intramyocardial Course in a Large Population of Clinical Patients Detected by Multislice Computed Tomography Coronary Angiography

    Energy Technology Data Exchange (ETDEWEB)

    De Rosa, R.; Sacco, M.; Tedeschi, C.; Pepe, R.; Capogrosso, P.; Montemarano, E.; Rotondo, A.; Runza, G.; Midiri, M.; Cademartiri, F. (UO di Radiologia, Ospedale San Gennaro, Napoli (Italy))

    2008-10-15

    Background: Intramyocardial course, an inborn coronary anomaly, is defined as a segment of a major epicardial coronary artery that runs intramurally through the myocardium; in particular, we distinguish myocardial bridging, in which the vessel returns to an epicardial position after the muscle bridge, and intramyocardial course, which is described as a vessel running and ending in the myocardium. Purpose: To evaluate the prevalence of myocardial bridging and intramyocardial course of coronary arteries as defined by multidetector computed tomography (MDCT) angiography. Material and Methods: The study population consisted of 242 consecutive patients (211 men, 31 women; mean age 59+-6 years) with atypical chest pain admitted to our hospital between December 2004 and September 2006. All MDCT examinations were performed using a 16-detector-row scanner (Aquilion 16 CFX; Toshiba Medical System, Tokyo, Japan). Patients with heart rate above 65 bpm received 50 mg atenolol orally for 3 days prior to the MDCT scan, or they increased their usual therapy with beta-blockers, in order to obtain a prescan heart rate <60 bpm. Curved multiplanar and 3D volume reconstructions were performed to explore coronary anatomy. Results: In 235 patients, the CT scan was successful and images were appropriate for evaluation. The prevalence of myocardial bridging and intramyocardial course of coronary arteries was 18.7% (47 cases) in our patient population. In 30 segments (63.8%), the vessels ran and ended in the myocardium. In the remaining 17 segments (36.2%), the vessels returned to an epicardial position after the muscle bridge. We found no difference in the prevalence of this inborn coronary anomaly when comparing different clinical characteristics of the study population (sex, age, body-mass index [BMI], etc.). The mean length of the subepicardial artery was 7 mm (range 5-12 mm), and the mean depth in the diastolic phase was 1.9 mm (range 1.2-2.3 mm). There was no significant difference of

  14. Extended-release alfuzosin hydrochloride: a new alpha-adrenergic receptor antagonist for symptomatic benign prostatic hyperplasia.

    Science.gov (United States)

    Guay, David R P

    2004-03-01

    inhibitors of the cytochrome P450 3A4 isozyme (eg, ketoconazole, diltiazem, cimetidine, atenolol) can significantly elevate serum concentrations of alfuzosin and enhance its pharmacodynamic effects. In the absence of direct head-to-head comparative trials, the role of alfuzosin ER in the management of symptomatic BPH relative to that of other AARAs is unclear. Because the effect size (drug response minus placebo response) of alfuzosin ER is comparable to that of other AARAs, marked differences in efficacy are unlikely. Extrapolating from direct comparative trials between these agents and alfuzosin IR/SR, alfuzosin ER would be expected to have better cardiovascular tolerability (eg, in terms of dizziness and orthostasis) than prazosin, terazosin, or doxazosin, and to have similar tolerability to tamsulosin. However, the existing data do not suggest that alfuzosin ER is likely to represent a significant advance over tamsulosin.

  15. Degradation of pharmaceutical beta-blockers by electrochemical advanced oxidation processes using a flow plant with a solar compound parabolic collector.

    Science.gov (United States)

    Isarain-Chávez, Eloy; Rodríguez, Rosa María; Cabot, Pere Lluís; Centellas, Francesc; Arias, Conchita; Garrido, José Antonio; Brillas, Enric

    2011-08-01

    The degradation of the beta-blockers atenolol, metoprolol tartrate and propranolol hydrochloride was studied by electro-Fenton (EF) and solar photoelectro-Fenton (SPEF). Solutions of 10 L of 100 mg L⁻¹ of total organic carbon of each drug in 0.1 M Na₂SO₄ with 0.5 mM Fe²⁺ of pH 3.0 were treated in a recirculation flow plant with an electrochemical reactor coupled with a solar compound parabolic collector. Single Pt/carbon felt (CF) and boron-doped diamond (BDD)/air-diffusion electrode (ADE) cells and combined Pt/ADE-Pt/CF and BDD/ADE-Pt/CF cells were used. SPEF treatments were more potent with the latter cell, yielding 95-97% mineralization with 100% of maximum current efficiency and energy consumptions of about 0.250 kWh g TOC⁻¹. However, the Pt/ADE-Pt/CF cell gave much lower energy consumptions of about 0.080 kWh g TOC⁻¹ with slightly lower mineralization of 88-93%, then being more useful for its possible application at industrial level. The EF method led to a poorer mineralization and was more potent using the combined cells by the additional production of hydroxyl radicals (•OH) from Fenton's reaction from the fast Fe²⁺ regeneration at the CF cathode. Organics were also more rapidly destroyed at BDD than at Pt anode. The decay kinetics of beta-blockers always followed a pseudo first-order reaction, although in SPEF, it was accelerated by the additional production of •OH from the action of UV light of solar irradiation. Aromatic intermediates were also destroyed by hydroxyl radicals. Ultimate carboxylic acids like oxalic and oxamic remained in the treated solutions by EF, but their Fe(III) complexes were photolyzed by solar irradiation in SPEF, thus explaining its higher oxidation power. NO₃⁻ was the predominant inorganic ion lost in EF, whereas the SPEF process favored the production of NH₄⁺ ion and volatile N-derivatives. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Attenuation of trace organic compounds (TOrCs) in bioelectrochemical systems.

    Science.gov (United States)

    Werner, Craig M; Hoppe-Jones, Christiane; Saikaly, Pascal E; Logan, Bruce E; Amy, Gary L

    2015-04-15

    Microbial fuel cells (MFCs) and microbial electrolysis cells (MECs) are two types of microbial bioelectrochemical systems (BESs) that use microorganisms to convert chemical energy in wastewaters into useful energy products such as (bio)electricity (MFC) or hydrogen gas (MEC). These two systems were evaluated for their capacity to attenuate trace organic compounds (TOrCs), commonly found in municipal wastewater, under closed circuit (current generation) and open circuit (no current generation) conditions, using acetate as the carbon source. A biocide was used to evaluate attenuation in terms of biotransformation versus sorption. The difference in attenuation observed before and after addition of the biocide represented biotransformation, while attenuation after addition of a biocide primarily indicated sorption. Attenuation of TOrCs was similar in MFCs and MECs for eight different TOrCs, except for caffeine and trimethoprim where slightly higher attenuation was observed in MECs. Electric current generation did not enhance attenuation of the TOrCs except for caffeine, which showed slightly higher attenuation under closed circuit conditions in both MFCs and MECs. Substantial sorption of the TOrCs occurred to the biofilm-covered electrodes, but no consistent trend could be identified regarding the physico-chemical properties of the TOrCs tested and the extent of sorption. The octanol-water distribution coefficient at pH 7.4 (log DpH 7.4) appeared to be a reasonable predictor for sorption of some of the compounds (carbamazepine, atrazine, tris(2-chloroethyl) phosphate and diphenhydramine) but not for others (N,N-Diethyl-meta-toluamide). Atenolol also showed high levels of sorption despite being the most hydrophilic in the suite of compounds studied (log DpH 7.4 = -1.99). Though BESs do not show any inherent advantages over conventional wastewater treatment, with respect to TOrC removal, overall removals in BESs are similar to that reported for conventional wastewater

  17. Mechanism considerations for photocatalytic oxidation, ozonation and photocatalytic ozonation of some pharmaceutical compounds in water.

    Science.gov (United States)

    Rodríguez, Eva M; Márquez, Gracia; León, Elena A; Álvarez, Pedro M; Amat, Ana M; Beltrán, Fernando J

    2013-09-30

    Aqueous solutions of four pharmaceutical compounds, belonging to the group of emergent contaminants of water: atenolol (ATL), hydrochlorothiazide (HCT), ofloxacin (OFX) and trimethoprim (TMP), have been treated with different oxidation systems, mainly, photocatalytic oxidation, ozonation and photocatalytic ozonation. TiO2 has been used as semiconductor for photocatalytic reactions both in the presence of air, oxygen or ozone-oxygen gas mixtures. Black light lamps mainly emitting at 365 nm were the source of radiation. In all cases, the influence of some variables (concentrations of semiconductor, ozone gas and pharmaceuticals and pH) on the removal of pharmaceuticals, total polyphenol content (TPC) and total organic carbon (TOC) was investigated. A discussion on the possible routes of pharmaceutical and intermediates (as TPC and TOC) elimination has been developed. Thus, OFX TiO2/UVA degradation mechanism seems to develop through the participation of non-hydroxyl free radical species. Furthermore, the presence of OFX inhibits the formation of hydroxyl radicals in the photocatalytic process. The most effective processes were those involving ozone that lead to complete disappearance of parent compounds in less than 30 min for initial pharmaceutical concentrations lower than 2.5 mg L(-1). In the ozonation systems, regardless of the pH and the presence of TiO2, pharmaceuticals are degraded through their direct reaction with ozone. Photocatalytic ozonation was the most efficient process for TPC and TOC removals (≥ 80% and ≥60% elimination after 2 h of treatment, respectively) as well as in terms of the ozone consumption efficiency (1, 5.5 and 4 mol of ozone consumed per mol of TOC mineralized, at pH 4, 7 and 9, respectively). Weakly acid conditions (pH 4) resulted to be the most convenient ones for TPC and TOC removal by photocatalytic ozonation. This was likely due to formation of hydroxyl radicals through the ozonide generated at these conditions. Copyright

  18. Repeated Melatonin Supplementation Improves Sleep in Hypertensive Patients Treated with Beta-Blockers: A Randomized Controlled Trial

    Science.gov (United States)

    Scheer, Frank A.J.L.; Morris, Christopher J.; Garcia, Joanna I.; Smales, Carolina; Kelly, Erin E.; Marks, Jenny; Malhotra, Atul; Shea, Steven A.

    2012-01-01

    Study Objectives: In the United States alone, approximately 22 million people take beta-blockers chronically. These medications suppress endogenous nighttime melatonin secretion, which may explain a reported side effect of insomnia. Therefore, we tested whether nightly melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers. Design: Randomized, double-blind, placebo-controlled, parallel-group design. Setting: Clinical and Translational Research Center at Brigham and Women’s Hospital, Boston. Patients: Sixteen hypertensive patients (age 45-64 yr; 9 women) treated with the beta-blockers atenolol or metoprolol. Interventions: Two 4-day in-laboratory admissions including polysomnographically recorded sleep. After the baseline assessment during the first admission, patients were randomized to 2.5 mg melatonin or placebo (nightly for 3 weeks), after which sleep was assessed again during the second 4-day admission. Baseline-adjusted values are reported. One patient was removed from analysis because of an unstable dose of prescription medication. Measurements and Results: In comparison with placebo, 3 weeks of melatonin supplementation significantly increased total sleep time (+36 min; P = 0.046), increased sleep efficiency (+7.6%; P = 0.046), and decreased sleep onset latency to Stage 2 (-14 min; P = 0.001) as assessed by polysomnography. Compared with placebo, melatonin significantly increased Stage 2 sleep (+41 min; P = 0.037) but did not significantly change the durations of other sleep stages. The sleep onset latency remained significantly shortened on the night after discontinuation of melatonin administration (-25 min; P = 0.001), suggesting a carryover effect. Conclusion: n hypertensive patients treated with beta-blockers, 3 weeks of nightly melatonin supplementation significantly improved sleep quality, without apparent tolerance and without rebound sleep disturbance during withdrawal of melatonin supplementation (in fact, a

  19. The Importance of G Protein-Coupled Receptor Kinase 4 (GRK4 in Pathogenesis of Salt Sensitivity, Salt Sensitive Hypertension and Response to Antihypertensive Treatment

    Directory of Open Access Journals (Sweden)

    Brian Rayner

    2015-03-01

    two major hypertension studies, the 65Leu/142Val heterozygote predicted a significantly decreased response to atenolol treatment, and the 65Leu/142Val heterozygote and 486Val homozygote were associated in an additive fashion with adverse cardiovascular outcomes, independent of BP. In conclusion, there is considerable evidence that GRK4 variants are linked to impaired Na excretion, hypertension in animal models and humans, therapeutic response to dietary Na restriction and response to antihypertensive drugs. It may also underlie the difference in hypertension between different geographically derived population groups, and form a basis for pharmacogenomic approaches to treatment of hypertension.

  20. Development and validation of methodology SPE-LC-MS/MS for pharmaceuticals and illicit drug determination in the waters of Guarapiranga Dam, Sao Paulo, SP, Brazil; Desenvolvimento e validacao de metodologia SPE-LC-MS/MS para a determinacao de farmacos e droga de abuso nas aguas da represa Guarapiranga, Sao Paulo, SP, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Shihomatsu, Helena Miho

    2015-07-01

    This study presents the development of the methodology of solid phase extraction and liquid chromatography - tandem mass spectrometry, SPE-LC-MS/MS, for the determination of 21 (twenty one) pharmaceuticals belonging to different therapeutic groups, 1 (one) illicit drug and its major metabolite, in surface water samples. The chromatographic separation was optimized by studying the performance of different stationary and mobile phases. Quantitation of selected compounds was performed by electrospray ionization (ESI) and the mass spectrometer operating in a multiple reaction monitoring (MRM) mode. The validation of the proposed methodology was performed using the parameters of selectivity, matrix effect, dynamic range, linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, recovery and robustness. The validation of methodology allowed to apply the methodology in the evaluation of the distribution of the 23 (twenty one) selected compounds, in Guarapiranga Dam waters, an of the major producer system of drinking water of the Metropolitan Region of Sao Paulo (MRSP). The presence of these pollutants in aquatic environments is from the direct release of urban sewage from the homes of your surroundings, as a result of poor sanitation system. The waters of Guarapiranga dam were evaluated in 14 (fourteen) locations strategically chosen and sampled in 3 (three) campaigns of sample collection (August 2011, September 2012 and April 2013). In these samples were quantified acetaminophen (9.6 - 254 ng L{sup -1}), atenolol (8.5 - 177 ng L{sup -1}), benzoylecgonine (7.9 - 139 ng L{sup -1}), caffeine (27 - 27386 ng L{sup -1}) carbamazepine (12 - 358 ng L{sup -1}), chlorthalidone (9.4 - 35 ng L{sup -1}), cocaine (12.8 - 2560 ng L{sup -1}), diclofenac (8 - 36 ng L{sup -1}), enalapril (20 ng L{sup -1}), losartan (6.7 - 114 ng L{sup -1}) and valsartan (9.7 - 47 ng L{sup -1}). The sample siting GU103-12 (23°41'88.5”S 46°44'67.3”W) was the

  1. Los baroquimiorreceptores carotídeos: órganos blanco de la hipertensión arterial

    Directory of Open Access Journals (Sweden)

    Celeste Carrero

    2007-01-01

    Full Text Available El cuerpo carotídeo (CC es el principal quimiorreceptor arterial periférico, capaz de sensar los cambios en la PaO2, la PaCO2 y de pH y transducirlos en señales nerviosas reguladoras de respuestas ventilatorias, circulatorias y endócrinas, que permiten una adaptación a la hipoxemia, la acidosis y la hipercapnia. El seno carotídeo, ubicado próximo al CC, con función barorreceptora, genera respuestas cardiovasculares que descienden la tensión arterial (TA. Ambas estructuras son inervadas por el nervio del seno carotídeo (NSC, que a su vez se proyecta al núcleo del tracto solitario (NTS, y se relacionan íntimamente entre sí y reciben la denominación de baroquimiorreceptores. Últimamente estos órganos se han considerado claves en la regulación de respuestas cardiorrespiratorias homeostáticas que podrían estar íntimamente relacionadas con el desarrollo y el mantenimiento de la hipertensión arterial (HTA.Existe escasa información sobre los cambios estructurales que ocurren en estos órganos durante la HTA y/o como consecuencia de ella. Nuestro planteo es que los baroquimiorreceptores carotídeos representarían un nuevo “órgano blanco” de la HTA. En diversos estudios realizados en seres humanos y en modelos de hipertensión sistólica en animales observamos un daño severo en el CC que se correlacionó significativamente con la elevación de la TA. A su vez, considerando que el sistema renina-angiotensina-aldosterona (SRAA tendría un papel significativo en la fisiopatología del daño observado, demostramos que el ramipril, versus el atenolol, ejerce un efecto protector sobre el CC más allá de la mera reducción de la TA. Incluso el losartán mostró dicho efecto protector, aun cuando los animales utilizados en los modelos fueron normotensos.Nuestros hallazgos indican que el CC se comporta como un órgano blanco de la HTA y que la activación de un SRAA local sería responsable de los cambios morfológicos y funcionales

  2. Attenuation of trace organic compounds (TOrCs) inbioelectrochemical systems

    KAUST Repository

    Werner, Craig M.

    2015-04-01

    Microbial fuel cells (MFCs) and microbial electrolysis cells (MECs) are two types of microbial bioelectrochemical systems (BESs) that use microorganisms to convert chemical energy in wastewaters into useful energy products such as (bio)electricity (MFC) or hydrogen gas (MEC). These two systems were evaluated for their capacity to attenuate trace organic compounds (TOrCs), commonly found in municipal wastewater, under closed circuit (current generation) and open circuit (no current generation) conditions, using acetate as the carbon source. A biocide was used to evaluate attenuation in terms of biotransformation versus sorption. The difference in attenuation observed before and after addition of the biocide represented biotransformation, while attenuation after addition of a biocide primarily indicated sorption. Attenuation of TOrCs was similar in MFCs and MECs for eight different TOrCs, except for caffeine and trimethoprim where slightly higher attenuation was observed in MECs. Electric current generation did not enhance attenuation of the TOrCs except for caffeine, which showed slightly higher attenuation under closed circuit conditions in both MFCs and MECs. Substantial sorption of the TOrCs occurred to the biofilm-covered electrodes, but no consistent trend could be identified regarding the physico-chemical properties of the TOrCs tested and the extent of sorption. The octanol-water distribution coefficient at pH 7.4 (log DpH 7.4) appeared to be a reasonable predictor for sorption of some of the compounds (carbamazepine, atrazine, tris(2-chloroethyl) phosphate and diphenhydramine) but not for others (N,N-Diethyl-meta-toluamide). Atenolol also showed high levels of sorption despite being the most hydrophilic in the suite of compounds studied (log DpH 7.4=-1.99). Though BESs do not show any inherent advantages over conventional wastewater treatment, with respect to TOrC removal, overall removals in BESs are similar to that reported for conventional wastewater

  3. Removal of organic micropollutants in an artificial recharge system

    Science.gov (United States)

    Valhondo, C.; Nödler, K.; Köck-Schulmeyer, M.; Hernandez, M.; Licha, T.; Ayora, C.; Carrera, J.

    2012-04-01

    . Water from the Infiltration pond, the unsaturated zone and groundwater have been sampled and analyzed in order to elucidate the effect of the reactive layer. First results of micropollutants under natural conditions show significant removal rates of atenolol and Ibuprofen as well as the recalcitrant behaviour of carbamazepine. Once the layer was installed, carbamazepine concentration in groundwater samples was lower than the concentration in the infiltration water. These preliminary results are promising but, however, they need to be confirmed by further analysis, which will be conducted during the next weeks.

  4. Synthesis and physical-chemical properties of functional derivatives of 3-benzyl-8-propylxanthinyl-7-acetic acid

    Directory of Open Access Journals (Sweden)

    E. K. Mikhal’chenko

    2017-08-01

    Full Text Available Introduction. Synthetic research of new biologically active compounds occupies an important place in modern pharmaceutical science.Thus it is important to develop techniques for the biologically active substances functionalization. Esters and amides take special place among the variety of functional derivatives of organic acids,. These fragments are well-known pharmacophores and could be found in a wide range of drugs. Thus, the nootropic agent pyracetam is 2-oxo-1-pyrolidineacetamide, and is the selective antagonist of β-adrenoreceptores; atenolol is a derivative of benzeneacetamide. Substituted acetamide and ester fragments are also present in the structures of aprofen, spasmolitin, acetylidine and β-lactam cephalosporins and penicillins antibiotics.Aim of our research was the synthetic method development for functional derivatives of 3-benzyl-8-propylxanthinyl-7-acetic acid and the study of their physical-chemical properties. Materials and methods. Melting points were determined using capillary method on DMP (M. 1Н NMR-spectra were recorded by Varian Mercury VX-200 device (company «Varian» – USA solvent – (DMSO-d6, internal standard – ТМS. Elemental analysis of obtained compounds was produced on device Elementar Vario L cube. Chemical shifts were reported in ppm (parts per million values. Infrared (IR spectra were measured on a Bruker Alpha instrument using a potassium bromide (KBr disk, scanning from 400 to 4000 cm-1. Results and discussion. We selected 3-benzyl-8-propylxanthinyl-7-acetic acid as initial compound for our study. For synthesis of hexyl, heptyl, octyl, nonyl, decyl and benzyl esters of 3-benzyl-8-propylxanthinyl-7-acetic acid we used alternative method, that included alkylation of sodium salts of acids with alkyl halogens. Reaction was made at DMF medium by reflux of reagents. Next stage of our research was the synthesis of amides of 3-beznyl-8-propylxanthinyl-7-acetic acid by the reaction of ethyl or propyl esters

  5. β1 -Adrenoceptor, but not β2 -adrenoceptor, subtype regulates heart rate in type 2 diabetic rats in vivo.

    Science.gov (United States)

    Cook, Rosalind F; Bussey, Carol T; Mellor, Kimberley M; Cragg, Patricia A; Lamberts, Regis R

    2017-08-01

    What is the central question of the study? The sympathetic system regulates heart rate via β-adrenoceptors; this is impaired during diabetes. However, the specific β-adrenoceptor subtype contributions in heart rate regulation in diabetes in vivo are unknown. What is the main finding and its importance? Telemetric recordings in conscious non-diabetic and type 2 diabetic rats demonstrated that the β1 -adrenoceptor subtype, and not the β2 -adrenoceptor, regulated the lower resting heart rate and increased β-adrenoceptor responsiveness in diabetes in vivo. This provides new physiological insight into the dysregulation of heart rate in type 2 diabetes, which is important for improving therapeutic strategies targeting the diabetic chronotropic incompetence. β-Adrenoceptor blockers are widely used to reduce heart rate, the strongest predictor of mortality in cardiac patients, but are less effective in diabetic patients. This study aimed to determine the specific contributions of β1 - and β2 -adrenoceptor subtypes to chronotropic responses in type 2 diabetes in vivo, which are currently unknown. Type 2 diabetic and non-diabetic rats were implanted with radiotelemeters to measure arterial blood pressure and derive heart rate in conscious conditions. Vascular access ports were implanted to inject isoprenaline (β1 - and β2 -adrenoceptor agonist, 0.1-300 μg kg(-1) ) in the presence of atenolol (β1 -adrenoceptor antagonist, 2000 μg kg(-1) ) or nadolol (β1 - and β2 -adrenoceptor agonist, 4000 μg kg(-1) ) to determine the chronotropic contributions of the β-adrenoceptor subtypes. Resting heart rate was reduced in diabetic rats (388 ± 62 versus 290 ± 37 beats min(-1) non-diabetic versus diabetic, P heart rate at highest dose of isoprenaline: 135 ± 66 versus 205 ± 28 beats min(-1) , non-diabetic versus diabetic, P heart rate at highest dose of isoprenaline: 205 ± 37 versus 195 ± 22 beats min(-1) , non-diabetic versus diabetic, P

  6. A simple HPLC-fluorescence method for the measurement of R,S-sotalol in the plasma of patients with life-threatening cardiac arrhythmias

    Directory of Open Access Journals (Sweden)

    S.R. Santos

    2000-02-01

    Full Text Available R,S-sotalol, a ß-blocker drug with class III antiarrhythmic properties, is prescribed to patients with ventricular, atrial and supraventricular arrhythmias. A simple and sensitive method based on HPLC-fluorescence is described for the quantification of R,S-sotalol racemate in 500 µl of plasma. R,S-sotalol and its internal standard (atenolol were eluted after 5.9 and 8.5 min, respectively, from a 4-micron C18 reverse-phase column using a mobile phase consisting of 80 mM KH2PO4, pH 4.6, and acetonitrile (95:5, v/v at a flow rate of 0.5 ml/min with detection at lex = 235 nm and lem = 310 nm, respectively. This method, validated on the basis of R,S-sotalol measurements in spiked blank plasma, presented 20 ng/ml sensitivity, 20-10,000 ng/ml linearity, and 2.9 and 4.8% intra- and interassay precision, respectively. Plasma sotalol concentrations were determined by applying this method to investigate five high-risk patients with atrial fibrillation admitted to the Emergency Service of the Medical School Hospital, who received sotalol, 160 mg po, as loading dose. Blood samples were collected from a peripheral vein at zero, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0 and 24.0 h after drug administration. A two-compartment open model was applied. Data obtained, expressed as mean, were: CMAX = 1230 ng/ml, TMAX = 1.8 h, AUCT = 10645 ng h-1 ml-1, Kab = 1.23 h-1, a = 0.95 h-1, ß = 0.09 h-1, t(1/2ß = 7.8 h, ClT/F = 3.94 ml min-1 kg-1, and Vd/F = 2.53 l/kg. A good systemic availability and a fast absorption were obtained. Drug distribution was reduced to the same extent in terms of total body clearance when patients and healthy volunteers were compared, and consequently elimination half-life remained unchanged. Thus, the method described in the present study is useful for therapeutic drug monitoring purposes, pharmacokinetic investigation and pharmacokinetic-pharmacodynamic sotalol studies in patients with tachyarrhythmias.

  7. Aortic Stiffness, Ambulatory Blood Pressure, and Predictors of Response to Antihypertensive Therapy in Hemodialysis.

    Science.gov (United States)

    Georgianos, Panagiotis I; Agarwal, Rajiv

    2015-08-01

    Arterial stiffness is associated with elevated blood pressure (BP), but it is unclear whether it also makes hypertension more resistant to treatment. Among hypertensive dialysis patients, this study investigated whether aortic stiffness determines ambulatory BP and predicts its improvement with therapy. Post hoc analysis of the Hypertension in Hemodialysis Patients Treated With Atenolol or Lisinopril (HDPAL) trial. 179 hypertensive hemodialysis patients with echocardiographic left ventricular hypertrophy. Baseline aortic pulse wave velocity (PWV). Baseline and treatment-induced change in 44-hour ambulatory BP at 3, 6, and 12 months. Aortic PWV was assessed with an echocardiographic-Doppler technique (ACUSON Cypress, Siemens Medical), and 44-hour interdialytic ambulatory BP monitoring was performed with a Spacelabs 90207 monitor. Mean baseline aortic PWV was 7.6±2.7 (SD) m/s. Overall treatment-induced changes in ambulatory systolic BP (SBP) were -15.6±20.4, -18.9±22.5, and -20.0±19.7 mmHg at 3, 6, and 12 months. Changes in SBP were no different among tertiles of baseline PWV. Aortic PWV was associated directly with baseline ambulatory SBP and pulse pressure (PP) and inversely with diastolic BP (DBP). After adjustment for several cardiovascular risk factors, each 1-m/s higher PWV was associated with 1.34-mm Hg higher baseline SBP (β=1.34±0.46; P=0.004) and 1.02-mm Hg higher PP (β=1.02±0.33; P=0.002), whereas the association with DBP was no longer significant. Baseline PWV did not predict treatment-induced changes in SBP (Wald test, P=0.3) and DBP (Wald test, P=0.7), but was a predictor of an overall improvement in PP during follow-up (Wald test, P=0.03). Observational design; predominantly black patients were studied. Because aortic PWV is not a predictor of treatment-induced change in ambulatory BP among hypertensive dialysis patients, it indicates that among these patients, hypertension can be controlled successfully regardless of aortic stiffness

  8. Access to and use of high blood pressure medications in Brazil.

    Science.gov (United States)

    Mengue, Sotero Serrate; Bertoldi, Andréa Dâmaso; Ramos, Luiz Roberto; Farias, Mareni Rocha; Oliveira, Maria Auxiliadora; Tavares, Noemia Urruth Leão; Arrais, Paulo Sergio Dourado; Luiza, Vera Lucia; Pizzol, Tatiane da Silva Dal

    2016-12-01

    To analyze the access to and use of medicines for high blood pressure among the Brazilian population according to social and demographic conditions. Analysis of data from Pesquisa Nacional Sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM - National Survey on Access, Use and Promotion of Rational Use of Medicines), a nationwide cross-sectional, population-based study, with probability sampling, carried out between September 2013 and February 2014 in urban households in the five Brazilian regions. The study evaluated the access and use of medicines to treat people with high blood pressure. The independent variables were gender, age, socioeconomic status and Brazilian region. The study also described the most commonly used drugs and the percentage of people treated with one, two, three or more drugs. Point estimations and confidence intervals were calculated considering the sample weights and sample complex plan. Prevalence of high blood pressure was 23.7% (95%CI 22.8-24.6). Regarding people with this condition, 93.8% (95%CI 92.8-94.8) had indication for drug therapy and, of those, 94.6% (95%CI 93.5-95.5) were using the medication at the time of interview. Full access to medicines was 97.9% (95%CI 97.3-98.4); partial access, 1.9% (95%CI 1.4-2.4); and no access, 0.2% (95%CI 0.1-0.4). The medication used to treat high blood pressure, 56.0% (95%CI 52.6-59.2) were obtained from SUS (Brazilian Unified Health System), 16.0% (95%CI 14.3-17.9) from Popular Pharmacy Program, 25.7% (95%CI 23.4-28.2) were paid for by the patients themselves and 2.3% (95%CI 1.8-2.9) were obtained from other locations. The five most commonly used drugs were, in descending order, hydrochlorothiazide, losartan, captopril, enalapril and atenolol. Of the total number of patients on treatment, 36.1% (95%CI 34.1-37.1) were using two medicines and 13.5% (95%CI 12.3-14.9) used three or more. Access to medicines for the treatment of high blood pressure may be considered high

  9. Prevalence and control of hypertension in a Niger Delta semi urban community, Nigeria

    Directory of Open Access Journals (Sweden)

    Suleiman IA

    2013-03-01

    taking their drugs during the survey and only 12.7% (07/55 had regular adherence to medication and adequate BP control was achieved in 7.3% (04/55. Majority of the patients on drugs (21.8% (12/55 were either taking methydopa as monotherapy or in combination with amiloride and hydrochlorothiazide. Other drugs being taken by patients include lisinopril, propranolol, amlodipine, atenolol, nifedipine and low dose aspirin. Conclusion: The prevalence of hypertension in the semi urban community is 15.0% with a pre-hypertension in another 23.5%. There was poor control of blood pressure among previously hypertensive patients.

  10. Combination of UV absorbance and electron donating capacity to assess degradation of micropollutants and formation of bromate during ozonation of wastewater effluents.

    Science.gov (United States)

    Chon, Kangmin; Salhi, Elisabeth; von Gunten, Urs

    2015-09-15

    In this study, the changes in UV absorbance at 254 nm (UVA254) and electron donating capacity (EDC) were investigated as surrogate indicators for assessing removal of micropollutants and bromate formation during ozonation of wastewater effluents. To measure the EDC, a novel method based on size exclusion chromatography followed by a post-column reaction was developed and calibrated against an existing electrochemical method. Low specific ozone doses led to a more efficient abatement of EDC than of UVA254. This was attributed to the abatement of phenolic moieties in the dissolved organic matter (DOM), which lose their EDC upon oxidation, but are partially transformed into quinones, which still absorb in the measured UV range. For higher specific ozone doses, the relative EDC abatement was lower than the relative UVA abatement, which can be explained by the oxidation of UV absorbing moieties (e.g. non-activated aromatic compounds), which contribute less to EDC. The abatement of the selected micropollutants (i.e., 17α-ethinylestradiol (EE2), carbamazepine (CBZ), atenolol (ATE), bezafibrate (BZF), ibuprofen (IBU), and p-chlorobenzoic acid (pCBA)) varied significantly depending on their reactivity with ozone in the examined specific ozone dose range of 0-1.45 mgO3/mgDOC. The decrease of EE2 and CBZ with high ozone reactivity was linearly proportional to the reduction of the relative residuals of UVA254 and EDC. The abatement of ATE, BZF, IBU, and pCBA with intermediate to low ozone reactivities was not significant in a first phase (UVA254/UVA254,0 = 1.00-0.70; EDC/EDC0 = 1.00-0.56) while their abatement was more efficient than the degradation of the relative residual UVA254 and much more noticeable than the degradation of the relative residual EDC in a second phase (UVA254/UVA254,0 = 0.70-0.25; EDC/EDC0 = 0.56-0.25) because the partially destroyed UV absorbing and electron donating DOM moieties become recalcitrant to ozone attack. Bromate formation was

  11. Daily dynamics of emerging pollutants in a sewer network (région Centre, France)

    Science.gov (United States)

    Thiebault, Thomas; Réty, Maxime; Jacob, Jérémy; Destandau, Emilie; Fougère, Laetitia; Morio, Cédric

    2017-04-01

    , ratios of co-consumed antibiotics such as sulfamethoxazole and trimethoprim are constant over the study and afford similar estimates for their consumption. For evident reasons, this comparison between theoretical and calculated consumption could not be achieved for illicit drugs. (3) Distinction can clearly be made on the temporal pattern of consumptions. Some compounds (e.g. acetaminophen, atenolol) do not exhibit clear week/week-end pattern whereas it is clearly expressed for cocaine and ecstasy. For the first time, some week/week-end patterns were also found for some pharmaceuticals such as metoprolol. Lower values noticed during week-end days could result from the mobility of the population in the catchment. Our study reveals that monitoring of pharmaceuticals and illicit drugs in wastewaters can bring significant information on the evolution of consumption practices in urban areas. Additional work in engaged to evaluate temporal trends on shorter (hour, minute) and longer (season, year) timescales. Applying this approach to a larger set of cities could reveal useful for developing decision tools for stakeholders and health agencies.

  12. [AII antagonists in the treatment of hypertension and prevention of CVA].

    Science.gov (United States)

    Spinar, J; Vitovec, J

    2013-01-01

    All antagonists (sartans) are considered to be a group of pharmaceuticals with comparable indications and comparable effects as ACE inhibitors, while almost lacking the side effect ofa dry cough. Large clinical trials showed that All antagonists had a comparable (statistically insignificantly smaller) effect on so called "hard targets", i.e. mortality and morbidity, in patients with ischemic heart diseases and/or heart failure. The study of their effect in the treatment of hypertension was first limited to diabetics and patients with microalbuminuria and showed that they had a significant renoprotective effect in said cases. Large clinical trials followed, focusing on hypertension in primary as well as secondary prevention of cardiovascular diseases. Five large clinical trials focusing on All antagonists addressed cerebrovascular accidents and cognitive functions: LIFE, SCOPE, OSCAR, MOSES and POWER. The LIFE study (Losartan Intervention For Endpoint) confirmed that in 9,193 patients with proven left ventricular hypertrophy, losartan led to a lower incidence of cerebrovascular accidents or new development of diabetes mellitus than atenolol, which in turn led to statistically significant lower primary endpoint (fatality, myocardial infarction and cerebrovascular accident) (p = 0.021), while blood pressure dropped at the same rate. The SCOPE study (Study on COgnition and Prognosis in Elderly hypertensives) compared candesartan with another antihypertensive treatment in 4,937 hypertonic patients older than 70. The primary endpoint was a decrease in massive cardiovascular accidents (fatality, MI, CVA). The decrease rate reached 10.9%, which was not considered statistically significant (p = 0.19). However, statistically significant was the decrease in cerebrovascular accidents (p = 0.04). The MOSES study (Morbidity and mortality after stroke) compared eprosartan and nitrendipine in secondary prevention of cerebrovascular diseases in 1,405 patients. Blood pressure was

  13. A pilot study on the assessment of trace organic contaminants including pharmaceuticals and personal care products from on-site wastewater treatment systems along Skaneateles Lake in New York State, USA.

    Science.gov (United States)

    Subedi, Bikram; Codru, Neculai; Dziewulski, David M; Wilson, Lloyd R; Xue, Jingchuan; Yun, Sehun; Braun-Howland, Ellen; Minihane, Christine; Kannan, Kurunthachalam

    2015-04-01

    (caffeine) whereas that for PFASs ranged from 7.0 (perfluorobutanesulfonate) to 833 μg/m(2)/day (perfluorooctanoic acid). Based on the ratio of measured concentrations and method detection limit, triclocarban, perfluorooctanoic acid, and perfluorooctanesulfonate have the potential to be used as chemical tracers of septic water contamination in Skaneateles Lake. The median concentrations of atenolol, a beta-blocker drug, in septic water were significantly (ρ = 0.86, p = 0.01) correlated with enterococci counts. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Occurrence and fate of pharmaceutically active compounds in the environment, a case study: Höje River in Sweden.

    Science.gov (United States)

    Bendz, David; Paxéus, Nicklas A; Ginn, Timothy R; Loge, Frank J

    2005-07-15

    boron (B) were used as natural inert tracers to estimate the relative extent of dilution of PhACs measured in the effluent of the STP on concentrations measured further downstream. Based on spatial trends of concentrations (recalculated to reflect a hypothetical scenario with no dilution), ibuprofen, ketoprofen, naproxen and dicofenac were shown to be subject to significant abiotic or biotic transformations or physical sequestration in the river. The beta-blockers atenolol, metoprolol and propanolol, the antibiotics trimetoprim and sulfametoxazole, and carbamazepine demonstrated a high degree of persistence. Fluctuations in the concentration of carbamazepine and gemfibrozil were observed along the series of reservoirs and within the river and are hypothesized to be due to release of parent compound from glucuronides. Several of the investigated substances (metaprolol, propanolol and carbamazepin) that exhibit low excretion rates as parent compounds demonstrate a surprising persistence in the aquatic environment. It is concluded that pharmaceutical substances with a high metabolic rate in humans (low excretion rate) do not necessarily induce a short lifetime in aquatic environments. Results from this study emphasize the need for a broader view on the concept of persistence that accounts for loading rates, in addition to removal mechanisms (e.g., transformation, volatility and physical sequestration by solids), under a variety of spatial and temporal scales.

  15. Removal of a wide range of emerging pollutants from wastewater treatment plant discharges by micro-grain activated carbon in fluidized bed as tertiary treatment at large pilot scale

    Energy Technology Data Exchange (ETDEWEB)

    Mailler, R., E-mail: romain.mailler@siaap.fr [LEESU (UMR MA 102, Université Paris-Est, AgroParisTech), Université Paris-Est Créteil, 61 avenue du Général de Gaulle, 94010 Créteil Cedex (France); Gasperi, J., E-mail: gasperi@u-pec.fr [LEESU (UMR MA 102, Université Paris-Est, AgroParisTech), Université Paris-Est Créteil, 61 avenue du Général de Gaulle, 94010 Créteil Cedex (France); Coquet, Y. [SAUR, Direction de la Recherche et du Développement, 1 rue Antoine Lavoisier, 78064 Guyancourt (France); Buleté, A.; Vulliet, E. [Université de Lyon, Institut des Sciences Analytiques, UMR5280 CNRS, Université Lyon 1, ENS-Lyon, 5 rue de la Doua, 69100 Villeurbanne (France); Deshayes, S. [LEESU (UMR MA 102, Université Paris-Est, AgroParisTech), Université Paris-Est Créteil, 61 avenue du Général de Gaulle, 94010 Créteil Cedex (France); LCPP (Laboratoire Central de la Préfecture de Police), 39 bis rue de Dantzig, 75015 Paris (France); Zedek, S. [LEESU (UMR MA 102, Université Paris-Est, AgroParisTech), Université Paris-Est Créteil, 61 avenue du Général de Gaulle, 94010 Créteil Cedex (France); and others

    2016-01-15

    /32), i.e. atenolol (92–97%), carbamazepine (80–94%), ciprofloxacin (75–95%), diclofenac (71–97%), oxazepam (74–91%) or sulfamethoxazole (56–83%). In addition, alkylphenols, artificial sweeteners, benzotriazole, bisphenol A, personal care products (triclocarban and parabens) and pesticides have removals lying in the 50 −> 90% range. Overall, the fluidized bed of μGAC allows obtaining performances comparable to PAC at the same activated carbon dose. Indeed, the average removal of the 13 PPHs found at a high occurrence (> 75%) in WWTP discharges is similar at 20 g/m{sup 3} of μGAC (78–89%) and PAC (85–93%). In addition, this recycled μGAC operation leads to several operational advantages (no FeCl{sub 3}, reactivable, higher SRT, higher treated flow) and has a stronger impact on the overall wastewater quality compared to PAC. - Highlights: • Pharmaceuticals and hormones are well removed (50 to > 90%) by micro-grain activated carbon (μGAC). • 50 to > 90% removals are also achieved for alkylphenols, bisphenol A, parabens, pesticides and sweeteners. • UV absorbance at 254 nm, dissolved organic carbon and micropollutant removals are well correlated. • Elimination of NH{sub 4}{sup +}, NO{sub 2}{sup −} and total suspended solids occurs with μGAC. • Performances obtained with μGAC are similar to those with powdered activated carbon.

  16. Removal of a wide range of emerging pollutants from wastewater treatment plant discharges by micro-grain activated carbon in fluidized bed as tertiary treatment at large pilot scale.

    Science.gov (United States)

    Mailler, R; Gasperi, J; Coquet, Y; Buleté, A; Vulliet, E; Deshayes, S; Zedek, S; Mirande-Bret, C; Eudes, V; Bressy, A; Caupos, E; Moilleron, R; Chebbo, G; Rocher, V

    2016-01-15

    Among the solutions to reduce micropollutant discharges into the aquatic environment, activated carbon adsorption is a promising technique and a large scale pilot has been tested at the Seine Centre (240,000 m(3)/d - Paris, France) wastewater treatment plant (WWTP). While most of available works studied fixed bed or contact reactors with a separated separation step, this study assesses a new type of tertiary treatment based on a fluidized bed containing a high mass of activated carbon, continuously renewed. For the first time in the literature, micro-grain activated carbon (μGAC) was studied. The aims were (1) to determine the performances of fluidized bed operating with μCAG on both emerging micropollutants and conventional wastewater quality parameters, and (2) to compare its efficiency and applicability to wastewater to former results obtained with PAC. Thus, conventional wastewater quality parameters (n=11), pharmaceuticals and hormones (PPHs; n=62) and other emerging pollutants (n=57) have been monitored in μGAC configuration during 13 campaigns. A significant correlation has been established between dissolved organic carbon (DOC), PPHs and UV absorbance at 254 nm (UV-254) removals. This confirms that UV-254 could be used as a tertiary treatment performance indicator to monitor the process. This parameter allowed identifying that the removals of UV-254 and DOC reach a plateau from a μGAC retention time (SRT) of 90-100 days. The μGAC configuration substantially improves the overall quality of the WWTP discharges by reducing biological (38-45%) and chemical oxygen demands (21-48%), DOC (13-44%) and UV-254 (22-48%). In addition, total suspended solids (TSS) are retained by the μGAC bed and a biological activity (nitratation) leads to a total elimination of NO2(-). For micropollutants, PPHs have a good affinity for μGAC and high (>60%) or very high (>80%) removals are observed for most of the quantified compounds (n=22/32), i.e. atenolol (92

  17. Gestational Pityriasis Rosea: Suggestions for Approaching Affected Pregnant Women.

    Science.gov (United States)

    Monastirli, Alexandra; Pasmatzi, Efstathia; Badavanis, George; Tsambaos, Dionysios

    2016-12-01

    pityriasis rosea, for intrauterine fetal death. All miscarrying women reportedly revealed an aggressive course of widespread eruption and severe constitutional symptoms; all of them had HHV-6 DNA in the plasma, placenta, skin lesions, and fetal tissues, whereas HHV-7 DNA was detected in the plasma and skin lesions in 3 out of 8 (37.5%) miscarrying women. HHV-6 DNA was found only in the plasma of 2 out of 31 women (6.45%) with normal pregnancy, whereas HHV-7 DNA was detected in the plasma of 3 (9.45%) and in the skin lesions of 2 women (6.45%) with normal pregnancy. The total abortion rate in women who developed pityriasis rosea during their pregnancy (13%) does not differ from that observed in the general population. Nevertheless, it is markedly higher in cases affected during the first 15 gestational weeks (57%) (4,5). Surprisingly, this devastating impact of pityriasis rosea on the outcome of pregnancy is almost completely unknown not only to the public but also to many members of the medical community. It is also largely unknown that, particularly during the first 15 gestational weeks, all pregnant women should avoid any contact with patients known to have pityriasis rosea. Since we have received a considerable number of requests for consultation with pregnant women with pityriasis rosea over the last few years, our group has compiled suggestions approaching the affected patients: 1. If an eruption suggestive for pityriasis rosea occurs in a pregnant woman, the following factors should be excluded: a. Exposure to drugs prior to the development of the rash (biologic agents, captopril, clonidine, hydrochlorothiazide, atenolol, lamotrigine, nortriptyline, barbiturates, metronidazole, terbinafine, omeprazole, non-steroidal anti-inflammatory drugs, and isotretinoin), which are capable of inducing a pityriasis rosea-like eruption (6) and b. Disorders included in the differential diagnosis (syphilis and infections due to parvovirus, herpes virus, cytomegalovirus, and Epstein

  18. Occurrence and fate of pharmaceutically active compounds in the environment, a case study: Hoeje River in Sweden

    Energy Technology Data Exchange (ETDEWEB)

    Bendz, David [Swedish Geotechnical Institute, Department of Environmental Technology, Hospitalsgatan 16A, S-211 33 Malmoe (Sweden)]. E-mail: David.Bendz@swedgeo.se; Paxeus, Nicklas A. [Gryaab, Karl IX:s vaeg, S-418 34 Gothenburg (Sweden); Ginn, Timothy R. [University of California, Department of Civil and Environmental Engineering, 1 Shields Avenue, 2001 Engineering III, Davis, CA 95616 (United States); Loge, Frank J. [University of California, Department of Civil and Environmental Engineering, 1 Shields Avenue, 2001 Engineering III, Davis, CA 95616 (United States)

    2005-07-15

    {sup -}) and boron (B) were used as natural inert tracers to estimate the relative extent of dilution of PhACs measured in the effluent of the STP on concentrations measured further downstream. Based on spatial trends of concentrations (recalculated to reflect a hypothetical scenario with no dilution), ibuprofen, ketoprofen, naproxen and dicofenac were shown to be subject to significant abiotic or biotic transformations or physical sequestration in the river. The {beta}-blockers atenolol, metoprolol and propanolol, the antibiotics trimetoprim and sulfametoxazole, and carbamazepine demonstrated a high degree of persistence. Fluctuations in the concentration of carbamazepine and gemfibrozil were observed along the series of reservoirs and within the river and are hypothesized to be due to release of parent compound from glucuronides. Several of the investigated substances (metaprolol, propanolol and carbamazepin) that exhibit low excretion rates as parent compounds demonstrate a surprising persistence in the aquatic environment. It is concluded that pharmaceutical substances with a high metabolic rate in humans (low excretion rate) do not necessarily induce a short lifetime in aquatic environments. Results from this study emphasize the need for a broader view on the concept of persistence that accounts for loading rates, in addition to removal mechanisms (e.g., transformation, volatility and physical sequestration by solids), under a variety of spatial and temporal scales.

  19. [Neurobiology and pharmacotherapy of social phobia].

    Science.gov (United States)

    Aouizerate, B; Martin-Guehl, C; Tignol, J

    2004-01-01

    now clearly examined the efficacy of major classes of psychotropic agents including monoamine oxidase inhibitors, beta-blockers, selective serotonin reuptake inhibitors and benzodiazepines in social phobia. Until recently, irreversible non-selective monoamine oxidase inhibitors, of which phenelzine was the most extensively evaluated, were considered as the most efficacious treatment in reducing the symptomatology associated with social phobia in 50-70% of cases after 4 to 6 weeks. However, side effects and dietary restrictions limit their use. This led to the development of reversible inhibitors of monoamine oxidase A, for which careful dietary monitoring is not required. Moclobemide has been the most widely studied but produced unconvincingly therapeutic effects on social phobic symptoms. To date, selective serotonin reuptake inhibitors may be considered as a reasonable first-line pharmacotherapy for social phobia. There is growing evidence for the efficacy of the selective serotonin reuptake inhibitors fluvoxamine, fluoxetine, citalopram, paroxetine and sertraline. They have beneficial effects with response rates ranging from 50 to 80% in social phobia. It has been recommended that the treatment period should be extended at least 6 months beyond the early improvement achieved within the first 4 to 6 weeks. The overall advantages include tolerability with a low risk of adverse events. The benzodiazepines clonazepam and alprazolam have also been proposed for the treatment of social phobia. Symptomatic relief occurred in 40 to 80% of the cases with a relatively rapid onset of action within the first two weeks. Untoward effects, discontinuation-related withdrawal symptoms and abuse or dependence liability constitute major concerns about the use of benzodiazepines, so they should be reserved for cases unresponsive to the safer medications cited above. Beta-blockers such as atenolol and propanolol have commonly been employed in performance anxiety, decreasing autonomic