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https://www.readbyqxmd.com/read/29206314/inhibition-of-spinal-p38-mapk-prevents-articular-neutrophil-infiltration-in-experimental-arthritis-via-sympathetic-activation
#1
Alexandre Kanashiro, Marcelo Franchin, Gabriel Shimizu Bassi, Dênis Augusto Reis-Santana, Thiago Mattar Cunha, Fernando Queiróz Cunha, Luis Ulloa, Gerson Jonathan Rodrigues
The central nervous system controls the innate immunity by modulating efferent neuronal networks. Recently, we have reported that central brain stimulation inhibits inflammatory responses. In the present study, we investigate whether spinal p38 mitogen-activated protein kinase (MAPK) affects joint inflammation in experimental arthritis. Firstly, we observed that intra-articular administration of zymosan in mice induces the phosphorylation of the spinal cord p38 MAPK. In addition, we demonstrated that spinal p38 MAPK inhibition with intrathecal injection of SB203580, a conventional and well-characterized inhibitor, prevents knee joint neutrophil recruitment, edema formation, experimental score and cytokine production...
December 5, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29183838/abediterol-las100977-an-inhaled-long-acting-%C3%AE-2-adrenoceptor-agonist-has-a-fast-association-rate-and-long-residence-time-at-receptor
#2
Israel Ramos, Mònica Aparici, Maria Letosa, Carlos Puig, Amadeu Gavaldà, Josep Maria Huerta, Sonia Espinosa, Dolors Vilella, Montserrat Miralpeix
This study describes the association rate and residence time of abediterol, a novel long-acting β2-adrenoceptor agonist (LABA) in Phase II development for treatment of asthma and COPD, in comparison with indacaterol, olodaterol, vilanterol and salmeterol, for both human β1- and β2-adrenoceptors. Abediterol association and dissociation rates were monitored directly by using its tritiated form. Moreover, association was determined indirectly using experimental Ki and koff obtained from assays performed with unlabelled compound...
November 25, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29155297/divergent-profile-between-hypothalamic-and-plasmatic-aminopeptidase-activities-in-wky-and-shr-influence-of-beta-adrenergic-blockade
#3
Isabel Prieto, Ana B Segarra, Marc de Gasparo, Magdalena Martínez-Cañamero, Manuel Ramírez-Sánchez
AIMS: Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) differ in their renin-angiotensin system function and sympathetic tone. The metabolism of angiotensins and vasopressin depends on the action of certain aminopeptidases whose activity may be influenced by the autonomic nervous system. Their regulation may differ between WKY and SHR in hypothalamus and plasma according to the sympathetic tone. We analyzed aminopeptidases responsible for the hydrolysis of certain angiotensins, vasopressin, cholecystokinin or enkephalins in hypothalamus and plasma of WKY and SHR in untreated controls rats and under beta-adrenoceptor blockade...
November 16, 2017: Life Sciences
https://www.readbyqxmd.com/read/29132172/can-screening-and-confirmatory-testing-in-the-management-of-patients-with-primary-aldosteronism-be-improved
#4
Michael Stowasser, Ashraf Ahmed, Zeng Guo, Martin Wolley, Jacobus Ungerer, Brett McWhinney, Marko Poglitsch, Richard Gordon
Widespread application of the plasma aldosterone/renin ratio (ARR) as a screening test has led to the recognition that primary aldosteronism (PA) is the most common specifically treatable and potentially curable form of hypertension, accounting for 5-10% of patients. Maximal detection requires accurate diagnostic approaches and awareness and control of factors that confound results, including most antihypertensives, posture, time of day, dietary salt, and plasma potassium. Recent studies have revealed potential for false positives in patients on beta-adrenoceptor blockers, and, when direct renin concentration (but not plasma renin activity) is used to measure renin, in women during the luteal phase of the menstrual cycle or receiving estrogen-containing contraceptives or hormonal replacement therapy...
November 13, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28953050/repeated-administration-of-amitriptyline-in-neuropathic-pain-modulation-of-the-noradrenergic-descending-inhibitory-system
#5
Tadanao Hiroki, Takashi Suto, Shigeru Saito, Hideaki Obata
BACKGROUND: The tricyclic antidepressant amitriptyline, the serotonin and noradrenaline reuptake inhibitor duloxetine, and gabapentinoids are first-line drugs for treatment of neuropathic pain. The analgesic effect of these drugs relates to brainstem-spinal descending noradrenergic systems. However, amitriptyline utilizes a variety of mechanisms for analgesia in neuropathic pain, and it is unclear which mechanism is most important. In the present study, we investigated the role of descending noradrenergic systems in the analgesic effect of these drugs for treatment of neuropathic pain...
August 4, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28906080/persistence-and-adherence-with-mirabegron-vs-antimuscarinics-in-overactive-bladder-retrospective-analysis-of-a-uk-general-practice-prescription-database
#6
Adrian S Wagg, Steve Foley, John Peters, Jameel Nazir, Leanne Kool-Houweling, Ludmila Scrine
INTRODUCTION AND OBJECTIVES: Persistence with antimuscarinic (AM) drugs prescribed for overactive bladder (OAB) is poor. This study aimed to compare persistence and adherence with the beta-3-adrenoceptor agonist mirabegron (MIR) vs AMs over 12 months. PATIENTS AND METHODS: This retrospective cohort analysis included patients aged ≥18 years who were prescribed MIR, or any AM. A 12-month look-back was used to assess inclusion eligibility. The primary end-point was persistence, defined as time to first discontinuation of index drug, during 1 year follow-up...
October 2017: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/28868931/emerging-inhaled-long-acting-beta-2-adrenoceptor-agonists-for-the-treatment-of-copd
#7
REVIEW
Thomas J Monaco, Nicola A Hanania
Chronic obstructive pulmonary disease (COPD), characterized by persistent and partially reversible airflow obstruction, is a leading cause of morbidity and mortality worldwide. Long-acting inhaled bronchodilators form the backbone for the maintenance therapy for this disease. The ultra-long-acting β2-agonists (ultra-LABAs) represent novel pharmacologic agents with interesting potential benefits as stand-alone therapy or in combination with other therapies for the treatment of COPD. Areas covered: In this review, we will focus newly developed ultra-LABAs, describing currently available evidence of their clinical effect and safety, their comparison relative to older long-acting β2-agonists, and their potential niche in the maintenance treatment of COPD...
September 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28865782/signal-transduction-and-chronopharmacology-of-regulation-of-circadian-cardiovascular-rhythms-in-animal-models-of-human-hypertension
#8
REVIEW
Björn Lemmer
Inbred strains of rats can be used as models of human hypertension to evaluate mechanisms of regulation of the circadian rhythms underlying hypertension. Blood pressure and heart rate rhythms in rodents are endogenous (circadian). Studies have been performed in rats on the turnover of norepinephrine, on processes of signal transduction in the beta-adrenoceptor-adenylate cyclase-cyclic AMP-phosphodiesterase system and in the renin-angiotensin-aldosterone system, and on circadian rhythms in blood pressure and heart rate using radiotelemetry...
October 2017: Heart Failure Clinics
https://www.readbyqxmd.com/read/28622599/adrenergic-regulation-of-cytoplasmic-structures-related-to-secretory-processes-in-pig-pinealocytes-an-ultrastructural-quantitative-study
#9
Barbara Przybylska-Gornowicz, Bogdan Lewczuk, Natalia Ziółkowska, Magdalena Prusik
Two structures, considered as secretory in nature, are present in the pinealocytes in of the domestic pig show the presence of two structures, which are considered as secretory in nature - the dense core vesicles (DCV) and the membrane bounded (dense) bodies (MBB). The latter are extremely numerous in pig pinealocytes (they occupy 6-20% of the cytoplasm), and the number of MBB changes under different physiological and experimental conditions. Norepinephrine is the main neurotransmitter that regulates the secretion of pineal melatonin...
June 9, 2017: Micron: the International Research and Review Journal for Microscopy
https://www.readbyqxmd.com/read/28597249/differential-regulation-of-protein-phosphatase-1-pp1-isoforms-in-human-heart-failure-and-atrial-fibrillation
#10
Stefanie Meyer-Roxlau, Simon Lämmle, Annett Opitz, Stephan Künzel, Julius P Joos, Stefan Neef, Karolina Sekeres, Samuel Sossalla, Friedrich Schöndube, Konstantin Alexiou, Lars S Maier, Dobromir Dobrev, Kaomei Guan, Silvio Weber, Ali El-Armouche
Protein phosphatase 1 (PP1) is a key regulator of important cardiac signaling pathways. Dysregulation of PP1 has been heavily implicated in cardiac dysfunctions. Accordingly, pharmacological targeting of PP1 activity is considered for therapeutic intervention in human cardiomyopathies. Recent evidence from animal models implicated previously unrecognized, isoform-specific activities of PP1 in the healthy and diseased heart. Therefore, this study examined the expression of the distinct PP1 isoforms PP1α, β, and γ in human heart failure (HF) and atrial fibrillation (AF) and addressed the consequences of β-adrenoceptor blocker (beta-blocker) therapy for HF patients with reduced ejection fraction on PP1 isoform expression...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28539361/synthesis-of-the-ca-2-mobilizing-messengers-naadp-and-cadpr-by-intracellular-cd38-enzyme-in-the-mouse-heart-role-in-%C3%AE-adrenoceptor-signaling
#11
Wee K Lin, Emma L Bolton, Wilian A Cortopassi, Yanwen Wang, Fiona O'Brien, Matylda Maciejewska, Matthew P Jacobson, Clive Garnham, Margarida Ruas, John Parrington, Ming Lei, Rebecca Sitsapesan, Antony Galione, Derek A Terrar
Nicotinic acid adenine dinucleotide phosphate (NAADP) and cyclic ADP-ribose (cADPR) are Ca(2+)-mobilizing messengers important for modulating cardiac excitation-contraction coupling and pathophysiology. CD38, which belongs to the ADP-ribosyl cyclase family, catalyzes synthesis of both NAADP and cADPR in vitro However, it remains unclear whether this is the main enzyme for their production under physiological conditions. Here we show that membrane fractions from WT but not CD38(-/-) mouse hearts supported NAADP and cADPR synthesis...
August 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28522796/effects-of-%C3%AE-adrenoceptor-and-catechol-o-methyl-transferase-comt-polymorphism-on-postoperative-outcome-in-cardiac-surgery-patients
#12
Stefan Dhein, Pascal M Dohmen, Matthias Sauer, Julia Tews, Johannes Weickmann, Anne-Kathrin Funkat, Martin Misfeld, Michael A Borger, Friedrich W Mohr
BACKGROUND There is a long-standing debate about the role of beta-adrenoceptor polymorphisms in the cardiovascular system. We wanted to elucidate whether β1-adrenoceptor-polymorphisms affects the postoperative catecholamine consumption and the length of intermediate care unit stay in patients undergoing cardiac surgery, and whether this might be enhanced or attenuated by catechol-O-methyl-transferase (COMT) polymorphism. MATERIAL AND METHODS We included 116 patients (63±1.2 years; 34% females; 81±1 kg) undergoing cardiac surgery...
May 19, 2017: Medical Science Monitor Basic Research
https://www.readbyqxmd.com/read/28486910/clinical-significance-of-the-sympathetic-nervous-system-in-the-development-and-progression-of-pulmonary-arterial-hypertension
#13
Ru-Xia Liu, Qian Luo, Hui Qiao, Juan Yu, Qian-Long Zhang, Peng Wang, Yong-Gang Cao, Chang-Lin Jiang, Li-Hui Qu
Pulmonary arterial hypertension (PAH) is defined as a complex disease of clinically characterized by elevated pulmonary pressure eventually resulting in right heart failure and premature death. To date, PAH still remains a life-threatening disease. Published evidence suggests that patients with PAH present profound sympathetic nervous system abnormalities and sympathetic activity has been shown to be increased. The mechanism of PAH is still complex and poorly understood. <p> Results: Some data have showed that adrenoceptors are involved in the process of the pathology and have different functions in the progression of PAH followed by heart failure...
January 12, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28459660/beta-adrenoceptor-polymorphism-and-clinical-response-to-sertraline-in-major-depressive-patients
#14
Negar Firouzabadi, Roshanak Raeesi, Kamiar Zomorrodian, Ehsan Bahramali, Ilnaz Yavarian
PURPOSE: The adrenoceptor family, as one of the main contributors in regulating the noradrenergic system, has been studied in involvement of depression and its treatment. A functional polymorphism of G1165C on beta adrenoceptor (βAR) enhances post receptor signalling and is assumed to be involved in pharmacotherapy of depression. The aim of the present study was to discern the influence of G1165C polymorphism in the β1AR gene on individual differences in response to sertraline. METHODS: One hundred newly diagnosed patients completed 6 weeks of sertraline treatment...
2017: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28437032/autonomic-receptor-mediated-regulation-of-production-and-release-of-nitric-oxide-in-normal-and-malignant-human-urothelial-cells
#15
Michael Winder, Renata Vesela, Patrik Aronsson, Bhavik Patel, Thomas Carlsson
In the urinary bladder, the main source of NO seems to be the urothelium and the underlying suburothelium. In this study, we aimed to characterize how receptors in the human urothelium regulate the production and release of NO. For this, we cultured two human urothelial cell lines - the normal immortalized cell line UROtsa and the malignant cell line T24. These were treated with an array of agonists and antagonists with affinity for adrenergic, muscarinic and purinergic receptors. The production of NO and expression of nitric oxide synthase (NOS) was studied by immunocytochemistry and Western blotting...
April 24, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28434969/translational-science-approach-for-assessment-of-cardiovascular-effects-and-proarrhythmogenic-potential-of-the-beta-3-adrenergic-agonist-mirabegron
#16
Cees Korstanje, Masanori Suzuki, Koichiro Yuno, Shuichi Sato, Masashi Ukai, Marlowe J Schneidkraut, Gan X Yan
INTRODUCTION: Translational assessment of cardiac safety parameters is a challenge in clinical development of beta-3 adrenoceptor agonists. The preclinical tools are presented that were used for assessing human safety for mirabegron. METHODS: Studies were performed on electrical conductance at ion channels responsible for cardiac repolarization (IKr, IKs, Ito, INa, and ICa,L), on QT-interval, subendocardial APD90, Tpeak-end interval, and arrhythmia's in ventricular dog wedge tissue in vitro and on cardiovascular function (BP, HR, and QTc) in conscious dogs...
April 21, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28410967/involvement-of-alpha-and-beta-adrenoceptors-in-the-automaticity-of-the-isolated-guinea-pig-pulmonary-vein-myocardium
#17
Masahiko Irie, Yayoi Tsuneoka, Mariko Shimobayashi, Nao Hasegawa, Yusuke Tanaka, Soh Mochizuki, Sho Ichige, Shogo Hamaguchi, Iyuki Namekata, Hikaru Tanaka
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...
April 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28389717/sex-difference-in-expression-and-function-of-beta-adrenoceptors-in-macrovessels-role-of-the-endothelium
#18
Suzan Al-Gburi, Andreas Deussen, Birgit Zatschler, Silvio Weber, Stephan Künzel, Ali El-Armouche, Kristina Lorenz, Maria Cybularz, Henning Morawietz, Irakli Kopaliani
Estrogen modulates adrenergic reactivity of macrovessels, resulting in weaker α-adrenergic vasoconstriction in females than males. However, the mechanisms governing this important sex-specific difference are not well understood. We hypothesized that vessels of females express more dilatory β-adrenoceptors, which counteract constrictive effects of α-adrenoceptors. This hypothesis was tested using aortas of normotensive (WKY) and hypertensive rats (SHR), along with human mammary artery. Selective blockade of β1 (CGP20712) or β3 (SR59230A), but not β2 (ICI118,551) adrenoceptors, greatly increased α-adrenergic constriction (norepinephrine) of aorta in female SHRs, but not in male SHRs at 12 weeks of age...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28387384/nebivolol-valsartan-fixed-dose-combination-for-treatment-of-hypertension
#19
REVIEW
D M Paton
Clinical trials demonstrated that a fixed-dose combination (FDC) of the beta-blocker nebivolol (5 mg) and the angiotensin II antagonist valsartan (80 mg) produced a significant reduction of both diastolic and systolic blood pressure in patients with hypertension. Both nebivolol and valsartan contributed to this effect, partial additivity of 86.6% and 82.2% being observed for diastolic and systolic blood pressure, respectively. These values are very similar to the additivity ratios of other recently approved FDCs for hypertension...
January 2017: Drugs of Today
https://www.readbyqxmd.com/read/28279368/imaging-guided-cardioprotective-treatment-in-a-community-elderly-population-of-stage-b-heart-failure
#20
RANDOMIZED CONTROLLED TRIAL
Hong Yang, Kazuaki Negishi, Ying Wang, Mark Nolan, Thomas H Marwick
OBJECTIVES: The purpose of the study was to evaluate the benefit of care guided by the detection of stage B heart failure (SBHF) using advanced echocardiography for the reduction of new HF in the community. BACKGROUND: The detection of nonischemic SBHF has been facilitated by advanced echocardiographic imaging modalities. However, improved outcomes have not been proven as they are predicated on benefit of treatment. METHODS: Between September 13, 2013 and November 6, 2015, 618 asymptomatic community-based patients with HF risks (age 71 ± 5 years) were randomized to care guided by advanced echocardiography (myocardial deformation and detailed diastolic function) versus usual care...
March 2017: JACC. Cardiovascular Imaging
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