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Baseline acetylcholine levels

H B Do, T Ohbuchi, M Yokoyama, T Kitamura, T Wakasugi, J-I Ohkubo, H Suzuki
OBJECTIVE: We investigated the difference in ciliary beat responsiveness to acetylcholine in ex vivo and the difference in the expressions of associated molecules (M1/M3 muscarinic receptors, pannexin-1 and P2X7 purinergic receptor) between the nasal polyp and turbinate mucosa. STUDY DESIGN: Laboratorial study. PARTICIPANTS: Nasal polyp and inferior turbinate were collected from patients with hypertrophic rhinitis and/or nasal polyp during endoscopic sinonasal surgery...
February 14, 2019: Clinical Otolaryngology
Daniel Zaldivar, Alexander Rauch, Nikos K Logothetis, Jozien Goense
Cholinergic neuromodulation is involved in all aspects of sensory processing and is crucial for processes such as attention, learning and memory, etc. However, despite the known roles of acetylcholine (ACh), we still do not how to disentangle ACh contributions from sensory or task-evoked changes in functional magnetic resonance imaging (fMRI). Here, we investigated the effects of local injection of ACh on fMRI and neural signals in the primary visual cortex (V1) of anesthetized macaques by combining pharmaco-based MRI (phMRI) with electrophysiological recordings, using single electrodes and electrode arrays...
December 3, 2018: Proceedings of the National Academy of Sciences of the United States of America
Diogo Van Bavel, Roger de Moraes, Eduardo Tibirica
The incidence of cardiovascular diseases in vegetarian individuals is lower than that in the general population. Nevertheless, individuals who adhere to vegan diets have a higher prevalence of hyperhomocysteinemia with eventual adverse effects on vascular reactivity. Creatine supplementation (CrS) reduces plasma homocysteine levels and enhances vascular reactivity in the microcirculation. Thus, we investigated the effects of CrS on systemic microcirculation and homocysteine blood levels in strict vegan subjects...
December 3, 2018: Fundamental & Clinical Pharmacology
Liqin Zhang, Calvin Wu, David T Martel, Michael West, Michael A Sutton, Susan E Shore
Here, we investigate remodeling of hippocampal cholinergic inputs after noise exposure and determine the relevance of these changes to tinnitus. To assess the effects of noise exposure on the hippocampus, guinea pigs were exposed to unilateral noise for 2 hr and 2 weeks later, immunohistochemistry was performed on hippocampal sections to examine vesicular acetylcholine transporter (VAChT) expression. To evaluate whether the changes in VAChT were relevant to tinnitus, another group of animals was exposed to the same noise band twice to induce tinnitus, which was assessed using gap-prepulse Inhibition of the acoustic startle (GPIAS) 12 weeks after the first noise exposure, followed by immunohistochemistry...
November 24, 2018: Hippocampus
Abdallah El Sabbagh, Megha Prasad, Chad J Zack, Robert J Widmer, Brad S Karon, Amir Lerman, Allan S Jaffe
BACKGROUND: Coronary endothelial dysfunction (CED) is associated with recurrent ischemia. The role of high-sensitivity cardiac troponin I (hscTnI) levels in patients with CED has not been established. METHODS: Patients with suspected ischemia, who underwent clinically indicated coronary angiography and were found to have non-obstructive coronary artery disease, were included in the study. CED was defined as ≤50% increase in coronary blood flow from baseline and/or a decrease in epicardial coronary artery diameter >20% in response to maximal dosages of acetylcholine...
November 2018: Journal of Invasive Cardiology
Kwan Woo Kang, Byoung Geol Choi, Seung Woon Rha
PURPOSE: Coronary artery spasm (CAS) and diabetes mellitus (DM) are implicated in endothelial dysfunction, and insulin resistance (IR) is a major etiological cause of type 2 DM. However, the association between CAS and IR in non-diabetic individuals has not been elucidated. The aim of the present study was to evaluate the impact of IR on CAS in patients without DM. MATERIALS AND METHODS: A total of 330 eligible patients without DM and coronary artery disease who underwent acetylcholine (Ach) provocation test were enrolled in this study...
November 2018: Yonsei Medical Journal
Megan B Miller, Rashaun S Wilson, TuKiet T Lam, Angus C Nairn, Marina R Picciotto
Activation of nicotinic acetylcholine receptors containing α4 and β2 subunits (α4/β2* nAChRs) in the mammalian brain is necessary for nicotine reinforcement and addiction. We previously identified interactions between α4/β2* nAChRs and calcium/calmodulin-dependent protein kinase II (CaMKII) in mouse and human brain tissue. Following co-expression of α4/β2 nAChR subunits with CaMKII in HEK cells, mass spectrometry identified 8 phosphorylation sites in the α4 subunit. One of these sites and an additional site were identified when isolated α4/β2* nAChRs were dephosphorylated and subsequently incubated with CaMKII in vitro, while 3 phosphorylation sites were identified following incubation with protein kinase A (PKA) in vitro...
October 15, 2018: Proteomes
Magdalena König, Beata Berlin, Karima Schwab, Silke Frahm, Franz Theuring, Claude M Wischik, Charles R Harrington, Gernot Riedel, Jochen Klein
Pathological accumulation of misfolded α-synuclein (α-syn) in the brain plays a key role in the pathogenesis of Parkinson's disease, leading to neuronal dysfunction and motor disorders. The underlying mechanisms linking α-syn aggregations with neurotransmitter disturbance in Parkinson's brains are not well characterized. In the present study, we investigated transgenic mice expressing an aggregation-prone form of full-length human α-syn (h-α-synL62) linked to a signal sequence. These mice display dopamine depletion and progressive motor deficits...
September 28, 2018: ACS Chemical Neuroscience
Richard L Verrier, Alexandre L Bortolotto, Bruna A Silva, Alexandre A Marum, Fernando G Stocco, Ederson Evaristo, Victor Z de Antonio, Anderson C Silva, Luiz Belardinelli
BACKGROUND: Pulmonary delivery of antiarrhythmic agents has the potential to increase rapidly targeted drug concentrations in pulmonary veins and left atrium to terminate atrial fibrillation (AF). OBJECTIVE: We evaluated the efficacy of flecainide administered via intratracheal instillation in terminating AF in a reliable preclinical model. METHODS: In 11 closed-chest anesthetized Yorkshire pigs, AF was induced by intrapericardial administration of acetylcholine (1 mL of 102...
June 26, 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Syeda Mehpara Farhat, Touqeer Ahmed
BACKGROUND: Aluminum (Al) causes neurodegeneration and its toxic effects on cholinergic system in the brain is well documented. However, it is unknown whether and how Al changes oscillation patterns, driven by the cholinergic system, in the hippocampus. OBJECTIVE: We studied acute effects of Al on nicotinic acetylcholine receptors (nAChRs)-mediated modulation of persistent gamma oscillations in the hippocampus. METHOD: The field potential recording was done in CA3 area of acute hippocampal slices...
2018: CNS & Neurological Disorders Drug Targets
Ashley A Martin, Janet E Richmond
Nicotinic acetylcholine receptors (nAChR) are present in many excitable tissues and are found both pre and post-synaptically. Through their non-specific cationic permeability, these nAChRs have excitatory roles in neurotransmission, neuromodulation, synaptic plasticity, and neuroprotection. Thus, nAChR mislocalization or functional deficits are associated with many neurological disease states. Therefore identifying the mechanisms that regulate nAChR expression and function will inform our understanding of normal as well as pathological physiological conditions and offer avenues for potential therapeutic advances...
June 2018: Cell Calcium
Ba H Do, Toyoaki Ohbuchi, Tetsuro Wakasugi, Hiroki Koizumi, Mitsuru Yokoyama, Nobusuke Hohchi, Hideaki Suzuki
Background Airway mucociliary transport is an important function for the clearance of inhaled foreign particulates in the respiratory tract. The present study aimed at investigating the regulatory mechanism of acetylcholine (Ach)-induced ciliary beat of the human nasal mucosa in ex vivo. Methods The inferior turbinate mucosa was collected from patients with chronic hypertrophic rhinitis during endoscopic surgery. The mucosa was cut into thin strips, and ciliary movement was observed under a phase-contrast light microscope with a high-speed digital video camera...
July 2018: American Journal of Rhinology & Allergy
Karen Hewett, Donald B Sanders, Richard A Grove, Christine L Broderick, Todd J Rudo, Ashlyn Bassiri, Marina Zvartau-Hind, Vera Bril
OBJECTIVE: To investigate the efficacy and safety of belimumab, a fully human immunoglobulin G1λ monoclonal antibody against B-lymphocyte stimulator, in participants with generalized myasthenia gravis (MG) who remained symptomatic despite standard of care (SoC) therapy. METHODS: Eligible participants with MG were randomized 1:1 to receive IV belimumab 10 mg/kg or placebo in this phase II, placebo-controlled, multicenter, double-blind study (NCT01480596; BEL115123)...
April 17, 2018: Neurology
Y S Qian, Q Y Zhao, S J Zhang, Y J Zhang, Y C Wang, H Y Zhao, Z X Dai, Y H Tang, X Wang, T Wang, C X Huang
Objective: To investigate the effect of α7nAChR mediated cholinergic anti-inflammatory pathway on inhibition of atrial fibrillation by low-level vagus nerve stimulation(LL-VNS). Methods: Eighteen beagles were randomized into control group ( n =6), LL-VNS group ( n =6) and methyllycaconitine (MLA) + LL-VNS group ( n =6). All the beagles were subjected to rapid atrial pacing at 800 beats/min for 6 hours.And the effective refractory period (ERP) of atriums and pulmonary veins and induced atrial fibrillation (AF) were measured hourly during non-pacing...
March 20, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Tiziana Cappello, Alessia Giannetto, Vincenzo Parrino, Maria Maisano, Sabrina Oliva, Giuseppe De Marco, Giulia Guerriero, Angela Mauceri, Salvatore Fasulo
The Mediterranean mussel Mytilus galloprovincialis (Lamarck 1819) is a popular shellfish commonly included in human diet and is routinely used as bioindicator in environmental monitoring programmes worldwide. Recently, metabolomics has emerged as a powerful tool both in food research and ecotoxicology for monitoring mussels' freshness and assessing the effects of environmental changes. However, there is still a paucity of data on complete metabolic baseline of mussel tissues. To mitigate this knowledge gap, similarities and differences in metabolite profile of digestive gland (DG), gills (G), and posterior adductor muscle (PAM) of aquaculture-farmed M...
June 2018: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
Carl Johan Molin, Liis Sabre, Cleo-Aron Weis, Tanel Punga, Anna Rostedt Punga
Objective: The aim of the study was to analyze the effect of thymectomy on the proposed disease-specific microRNA (miRNA) biomarkers miR-150-5p and miR-21-5p in patients from the prospective randomized trial of thymectomy in myasthenia gravis (MGTX trial) and to evaluate the longitudinal changes in clinical patterns compared with these miRNA levels. Methods: Serum samples were obtained from 80 patients with MG who were included in the MGTX trial. Thirty-eight patients were randomized to thymectomy plus prednisone treatment, and 42 patients were randomized to prednisone treatment...
May 2018: Neurology® Neuroimmunology & Neuroinflammation
Brice Ongali, Nektaria Nicolakakis, Xin-Kang Tong, Clotilde Lecrux, Hans Imboden, Edith Hamel
Transgenic mice constitutively overexpressing the cytokine transforming growth factor-β1 (TGF-β1) (TGF mice) display cerebrovascular alterations as seen in Alzheimer's disease (AD) and vascular cognitive impairment and dementia (VCID), but no or only subtle cognitive deficits. TGF-β1 may exert part of its deleterious effects through interactions with angiotensin II (AngII) type 1 receptor (AT1R) signaling pathways. We test such interactions in the brain and cerebral vessels of TGF mice by measuring cerebrovascular reactivity, levels of protein markers of vascular fibrosis, nitric oxide synthase activity, astrogliosis, and mnemonic performance in mice treated (6 months) with the AT1R blocker losartan (10 mg/kg per day) or the angiotensin converting enzyme inhibitor enalapril (3 mg/kg per day)...
May 2018: Canadian Journal of Physiology and Pharmacology
Nobuaki Egashira, Yuki Akiyoshi, Hikari Iba, Takashi Arai, Izzettin Hatip-Al-Khatib, Kenichi Mishima, Katsunori Iwasaki
Previously, we reported that ovariectomy (OVX) combined with β-amyloid peptide (Aβ) impaired spatial memory by decreasing extracellular acetylcholine (ACh) levels in the dorsal hippocampus. Here, we investigated the effect of tokishakuyakusan (TSS), a Kampo medicine, on the impairment of spatial memory induced by OVX combined with Aβ in rats. Repeated administration of TSS (300 mg/kg, p.o.) significantly decreased the number of errors in the eight-arm radial maze test. Though TSS had no effect on extracellular ACh levels at baseline, TSS significantly increased extracellular ACh levels in the dorsal hippocampus...
March 2018: Journal of Pharmacological Sciences
Hilary S McCarren, Julia A Arbutus, Cherish Ardinger, Emily N Dunn, Cecelia E Jackson, John H McDonough
Nerve agents are highly toxic chemicals that pose an imminent threat to soldiers and civilians alike. Nerve agent exposure leads to an increase in acetylcholine within the central nervous system, resulting in development of protracted seizures known as status epilepticus (SE). Currently, benzodiazepines are the standard of care for nerve agent-induced SE, but their efficacy quickly wanes as the time to treatment increases. Here, we examine the role of the α2-adrenoceptor in termination of nerve agent-induced SE using the highly specific agonist dexmedetomidine (DEX)...
March 2018: Epilepsy Research
Walter Roberts, Sherry A McKee
Varenicline reduces drinking in people with alcohol use disorder, but little is known about the mechanisms underlying this effect. Varenicline targets α4β2 and α7 nicotinic acetylcholine receptors, which are associated with several cognitive functions such as working memory. Varenicline may improve drinking outcomes by enhancing cognitive functioning. The current manuscript reports on cognitive outcomes from a placebo-controlled, double-blind human laboratory experiment examining the effects of varenicline on drinking behavior (Verplaetse et al...
February 2018: Experimental and Clinical Psychopharmacology
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