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Elena K Schneider, Rachel M McQuade, Vincenzo C Carbone, Felisa Reyes-Ortega, John W Wilson, Brenda Button, Ayame Saito, Daniel P Poole, Daniel Hoyer, Jian Li, Tony Velkov
Ivacaftor-lumacaftor and ivacaftor are two new breakthrough cystic fibrosis transmembrane conductance modulators. The interactions of ivacaftor and its two metabolites hydroxymethylivacaftor (iva-M1) and ivacaftorcarboxylate (iva-M6) with neurotransmitter receptors were investigated in radioligand binding assays. Ivacaftor displayed significant affinity to the 5-hydroxytryptamine (5-HT; serotonin) 5-HT2C receptor (p K i =6.06±0.03), β3 -adrenergic receptor (p K i =5.71±0.07), δ-opioid receptor (p K i =5...
January 2018: ERJ Open Research
Erika M Manczak, Bryn Dougherty, Edith Chen
Depressive symptoms in parents and in youths have been found to relate to disease comorbidity processes in children, including greater disease-related impairment and poorer clinical outcomes. The current study sought to assess whether coming from a family characterized by more depressive symptoms on average would potentiate the effects of changes in youths' own negative mood on the expression of two receptor genes relevant to asthma that are the primary targets of asthma medication, such that the combination of low child negative mood in the context of greater parental depressive symptoms would relate to the lowest levels of gene expression...
March 20, 2018: Journal of Abnormal Child Psychology
Marcello Panagia, Howard H Chen, Dominique Croteau, Yin-Ching Iris Chen, Chongzhao Ran, Ivan Luptak, Lee Josephson, Wilson S Colucci, David E Sosnovik
BACKGROUND: Substrate utilization in tissues with high energetic requirements could play an important role in cardiometabolic disease. Current techniques to assess energetics are limited by high cost, low throughput, and the inability to resolve multiple readouts simultaneously. Consequently, we aimed to develop a multiplexed optical imaging platform to simultaneously assess energetics in multiple organs in a high throughput fashion. METHODS AND RESULTS: The detection of 18F-Fluordeoxyglucose uptake via Cerenkov luminescence and free fatty acid uptake with a fluorescent C16 free fatty acid was tested...
March 2018: Circulation. Cardiovascular Imaging
Tamer M Sakr, M H Sanad, Walaa H Abd-Alla, Dina H Salama, Gehan M Saleh
Challenges facing cardiovascular imaging necessitate innovation of better radiopharmaceuticals to augment or replace the existing ones. This research assesses the ability and competency of radioiodinated esmolol as a potential cardio selective imaging agent. Radioiodinated esmolol was synthesized with 97.3 ± 0.3% radiochemical yield and with high stability up to 48 h at room temperature as well as in rat serum. Molecular modeling study was performed to confirm the binding of iodinated esmolol to β1 -adrenergic receptor...
March 9, 2018: Applied Radiation and Isotopes
Chu Shan Tan, Mun Fei Yam
Previous studies have demonstrated that 3'-hydroxy-5,6,7,4'-tetramethoxyflavone (TMF) content in Orthosiphon stamineus fractions correlate with its vasorelaxation activity. Even with the availability of previous studies, there is still very little information on the vasorelaxation effect of TMF, and few scientific studies have been carried out. Therefore, the present study was designed to investigate the vasorelaxation activity and mechanism of action of the TMF. The vasorelaxation activity and the underlying mechanisms of TMF were evaluated on thoracic aortic rings isolated from Sprague Dawley rats...
March 19, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Daniel Ramirez-Gordillo, Ming Ma, Diego Restrepo
Neuromodulators such as noradrenaline appear to play a crucial role in learning and memory. The goal of this study was to determine the role of norepinephrine in representation of odorant identity and value by olfactory bulb oscillations in an olfactory learning task. We wanted to determine whether the different bandwidths of olfactory bulb oscillations encode information involved in associating the odor with the value, and whether norepinephrine is involved in modulating this association. To this end mice expressing halorhodopsin under the dopamine-beta-hydrolase (DBH) promoter received an optetrode implant targeted to the olfactory bulb...
2018: Frontiers in Cellular Neuroscience
Ilona A Kaczmarek, Marek E Prost, Jaromir Wasyluk
PURPOSE: To evaluate the incidence of and factors associated with intraoperative floppy iris syndrome (IFIS) in patients undergoing cataract phacoemulsification. METHODS: In total, 319 eyes of 319 patients who underwent phacoemulsification with implantation of an intraocular lens (IOL) into the posterior chamber were included in this study. Direct injection of epinephrine into the anterior chamber was performed in all cases. The following patient information was collected: gender, age, axial length of the eye, presence of pseudoexfoliation syndrome, glaucoma, diabetes mellitus, hypertension, current use of medications including alpha1 adrenergic receptor antagonists (alpha1-ARAs), finasteride, and benzodiazepines, duration of intake of alpha1-ARAs and finasteride, and duration of the surgery...
March 17, 2018: International Ophthalmology
Milton Packer
BACKGROUND: Current guidelines for the treatment of heart failure strongly recommend the use of inhibitors of the renin-angiotensin system and sympathetic nervous system in all patients with a reduced ejection fraction who can tolerate these drugs. Yet, there is no consensus about the efficacy of low doses of these drugs or the likely shape of the dose-response relationship for these agents. METHODS: Inferences were made by examining the effects of drugs in placebo-controlled trials before the protocol-specified opportunity for uptitration and by reassessing the results of large-scale trials with active comparators that inadvertently produced different intensities of neurohormonal blockade...
March 11, 2018: International Journal of Cardiology
Ken Matsui, Makoto Ozawa, Maki Kiso, Makoto Yamashita, Toshihiko Maekawa, Minoru Kubota, Sumio Sugano, Yoshihiro Kawaoka
Influenza A viruses cause seasonal epidemics and occasional pandemics. The emergence of viruses resistant to neuraminidase (NA) inhibitors and M2 ion channel inhibitors underlines the need for alternate anti-influenza drugs with novel mechanisms of action. Here, we report the discovery of a host factor as a potential target of anti-influenza drugs. By using cell-based virus replication screening of a chemical library and several additional assays, we identified clonidine as a new anti-influenza agent in vitro...
March 15, 2018: Scientific Reports
Guang-Zhe Huang, Mutsuo Taniguchi, Ye-Bo Zhou, Jing-Ji Zhang, Fumino Okutani, Yoshihiro Murata, Masahiro Yamaguchi, Hideto Kaba
The formation of mate recognition memory in mice is associated with neural changes at the reciprocal dendrodendritic synapses between glutamatergic mitral cell (MC) projection neurons and GABAergic granule cell (GC) interneurons in the accessory olfactory bulb (AOB). Although noradrenaline (NA) plays a critical role in the formation of the memory, the mechanism by which it exerts this effect remains unclear. Here we used extracellular field potential and whole-cell patch-clamp recordings to assess the actions of bath-applied NA (10 µM) on the glutamatergic transmission and its plasticity at the MC-to-GC synapse in the AOB...
April 2018: Learning & Memory
A Sicras-Mainar, S Traseira-Lugilde, T Fernández-Sánchez, R Navarro-Artieda
OBJECTIVE: To determine the persistence, exacerbations, and use of resources in patients who use inhaler treatment with fluticasone propionate/formoterol (PF/Form) in relation with other combinations of inhaled corticosteroid/long-acting β-adrenergic (ICS/LABA) at fixed doses, for the treatment of asthma in real-life practice. MATERIAL AND METHODS: Observational study conducted by reviewing medical records. The study included subjects ≥18 years of age who started treatment with ICS/LABA and who met certain inclusion/exclusion criteria...
March 12, 2018: Semergen
Nourdine Chakouri, Cyril Reboul, Doria Boulghobra, Adrien Kleindienst, Stéphane Nottin, Sandrine Gayrard, François Roubille, Stefan Matecki, Alain Lacampagne, Olivier Cazorla
BACKGROUND: The interplay between oxidative stress and other signaling pathways in the contractile machinery regulation during cardiac stress and its consequences on cardiac function remains poorly understood. We evaluated the effect of the crosstalk between β-adrenergic and redox signaling on post-translational modifications of sarcomeric regulatory proteins, Myosin Binding Protein-C (MyBP-C) and Troponin I (TnI). METHODS AND RESULTS: We mimicked in vitro high level of physiological cardiac stress by forcing rat hearts to produce high levels of oxidized glutathione...
May 1, 2018: International Journal of Cardiology
Carmen Scheibenbogen, Madlen Loebel, Helma Freitag, Anne Krueger, Sandra Bauer, Michaela Antelmann, Wolfram Doehner, Nadja Scherbakov, Harald Heidecke, Petra Reinke, Hans-Dieter Volk, Patricia Grabowski
INTRODUCTION: Infection-triggered disease onset, chronic immune activation and autonomic dysregulation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) point to an autoimmune disease directed against neurotransmitter receptors. We had observed elevated autoantibodies against ß2 adrenergic receptors, and muscarinic 3 and 4 acetylcholine receptors in a subset of patients. Immunoadsorption (IA) was shown to be effective in removing autoantibodies and improve outcome in various autoimmune diseases...
2018: PloS One
LaDonya Jackson, Wael Eldahshan, Susan C Fagan, Adviye Ergul
For many years, modulators of the renin angiotensin system (RAS) have been trusted by clinicians for the control of essential hypertension. It was recently demonstrated that these modulators have other pleiotropic properties independent of their hypotensive effects, such as enhancement of cognition. Within the brain, different components of the RAS have been extensively studied in the context of neuroprotection and cognition. Interestingly, a crosstalk between the RAS and other systems such as cholinergic, dopaminergic and adrenergic systems have been demonstrated...
March 15, 2018: International Journal of Molecular Sciences
Gian Marco Rosa, Danilo Baccino, Alberto Valbusa, Carolina Scala, Fabio Barra, Claudio Brunelli, Simone Ferrero
Overactive bladder (OAB) syndrome is common in the general population, particularly in elderly patients. Antimuscarinic drugs (AMs) are considered the mainstay pharmaceutical treatment of OAB whereas β3-adrenoceptor agonists, such as mirabegron, represent a good alternative. Owing to the important role of muscarinic and β3 receptors in cardiovascular (CV) tissue and to the fact that OAB patients often have CV comorbidities, the safety-profile of these drugs constitute an important challenge. Area covered: The aim of this review is to evaluate the CV effects of AMs and mirabegron in OAB...
March 15, 2018: Expert Opinion on Drug Safety
Marion Griton, Jan Pieter Konsman
Although the immune and nervous systems have long been considered independent biological systems, they turn out to mingle and interact extensively. The present review summarizes recent insights into the neural pathways activated by and involved in infection-induced inflammation and discusses potential clinical applications. The simplest activation concerns a reflex action within C-fibers leading to neurogenic inflammation. Low concentrations of pro-inflammatory cytokines or bacterial fragments may also act on these afferent nerve fibers to signal the central nervous system and bring about early fever, hyperalgesia and sickness behavior...
March 14, 2018: Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society
Syed Rizwan A Bokhari, Faisal Akhtar, Qurrat-Ul-Ain Abid, Uzma Jahanzaib, Maria R Bokhari, Sana Hasan, Khurshid Khan
Postural hypotension, as a manifestation of autonomic neuropathy is a very sinister long-term debilitating complication of diabetes, is usually irreversible and tough to manage with medications. The treatment of this condition following the standard treatment protocols can be contraindicated in the patients with underlying heart conditions. We report the case of a patient at our hospital who presented with full-blown symptomatic dysautonomia secondary to long-standing diabetes, with bedside testing positive for autonomic dysfunction...
January 8, 2018: Curēus
Li Wang, Yang Li, Na Ning, Jin Wang, Zi Yan, Suli Zhang, Xiangying Jiao, Xiaohui Wang, Huirong Liu
It has been recognized that myocardial apoptosis is one major factor in the development of heart dysfunction and autophagy has been shown to influence the apoptosis. In previous studies, we reported that anti-β1 -adrenergic receptor autoantibodies (β1 -AABs) decreased myocardial autophagy, but the role of decreased autophagy in cardiomyocyte apoptosis remains unclear. In the present study, we used a β1 -AAB-immunized rat model to investigate the role of decreased autophagy in cardiomyocyte apoptosis. We reported that the level of autophagic flux increased early and then decreased in an actively β1 -AAB-immunized rat model...
March 14, 2018: Cell Death & Disease
Jessica N R Peoples, Timmi Maxmillian, Quynh Le, Sergiy M Nadtochiy, Paul S Brookes, George A Porter, Victor L Davidson, Steven N Ebert
Cardiac energy demands during early embryonic periods are sufficiently met through glycolysis, but as development proceeds, oxidative phosphorylation in mitochondria becomes increasingly vital. Adrenergic hormones are known to stimulate metabolism in adult mammals and are essential for embryonic development, but relatively little is known about their effects on metabolism in the embryonic heart.  Here, we show that embryos lacking adrenergic stimulation have approximately 10-fold less cardiac ATP compared to littermate controls...
March 14, 2018: Journal of Biological Chemistry
Gerd Wallukat, Harald Prüss, Johannes Müller, Ingolf Schimke
Dementia in general and Alzheimer's disease in particular is increasingly seen in association with autoimmunity being causatively or supportively involved in the pathogenesis. Besides classic autoantibodies (AABs) present in dementia patients, there is the new autoantibody class called functional autoantibodies, which is directed against G-protein coupled receptors (GPCRs; GPCR-AABs) and are seen as pathogenic players. However, less is known about dementia patients' burden with functional autoantibodies. We present here for the first time a study analyzing the prevalence of GPCR-AABs in patients with different dementia forms such as unclassified, Lewy body, vascular and Alzheimer's dementia...
2018: PloS One
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