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Calcium Antagonist

Dominik Diamandakis, Elzbieta Zieminska, Marcin Siwiec, Krzysztof Tokarski, Elzbieta Salinska, Jacek Lenart, Grzegorz Hess, Jerzy W Lazarewicz
The brominated flame retardant tetrabromobisphenol A (TBBPA) is toxic to cultured brain neurons, and glutamate receptors partially mediate this effect; consequently, the depolarizing effect of TBBPA on neurons is to be expected, but it is yet to be actually demonstrated. The aim of this study was to detect TBBPA-evoked depolarization and identify the underlying mechanisms. The plasma membrane potential of rat cerebellar granule cells (CGC) in cerebellar slices or in primary cultures was measured using whole-cell current clamp recordings, or the fluorescent probe oxonol VI, respectively...
February 8, 2019: Chemosphere
Subhendu Mukherjee, Wei Sheng, Alexander Michkov, Krishna Sriarm, Rui Sun, Anna Dvorkin-Gheva, Paul A Insel, Luke J Janssen
We have shown that calcium (Ca2+ ) oscillations in human pulmonary fibroblasts (HPFs) contribute to pro-fibrotic effects of TGFβ and that disruption of these oscillations blunts features of pulmonary fibrosis. Prostaglandin E2 (PGE2 ) exerts anti-fibrotic effects in the lung but the mechanisms for this action are not well defined. We thus sought to explore interactions between PGE2 and the pro-fibrotic agent transforming growth factor beta (TGFβ) in pulmonary fibroblasts (PFs) isolated from patients with or without idiopathic pulmonary fibrosis (IPF)...
February 13, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
Jing Zhang, Jia Liu, Dan Li, Canfei Zhang, Ming Liu
BACKGROUND: The sudden loss of blood supply in ischemic stroke is associated with an increase of calcium ions within neurons. Inhibiting this increase could protect neurons and might reduce neurological impairment, disability, and handicap after stroke. OBJECTIVES: To assess the effects of calcium antagonists for reducing the risk of death or dependency after acute ischemic stroke. We investigated the influence of different drugs, dosages, routes of administration, time intervals after stroke, and trial design on the outcomes...
February 13, 2019: Cochrane Database of Systematic Reviews
Dibyadeep Datta, Sheng-Tao Yang, Veronica Galvin, John Solder, Fei Luo, Yury M Morozov, Jon Arellano, Alvaro Duque, Pasko Rakic, Amy Arnsten, Min Wang
Noradrenergic (NE) α1-adrenoceptors (α1-AR) contribute to arousal mechanisms, and play an important role in therapeutic medications, e.g. for treating Post-Traumatic Stress Disorder (PTSD). However, little is known about how α1-AR stimulation influences neuronal firing in the dorsolateral prefrontal cortex (dlPFC), a newly evolved region that is dysfunctional in PTSD and other mental illnesses. The current study examined the effects of α1-AR manipulation on neuronal firing in dlPFC of rhesus monkeys performing a visuospatial working memory task, focusing on the "Delay cells" that maintain spatially-tuned information across the delay period...
February 12, 2019: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Lauren Z Atkinson, Lucy Colbourne, Alexander Smith, Catherine H Harmer, Anna C Nobre, Jennifer Rendell, Helen Jones, Christopher Hinds, Arne Mould, Elizabeth M Tunbridge, Andrea Cipriani, John R Geddes, Kate E A Saunders, Paul J Harrison
BACKGROUND: The discovery that voltage-gated calcium channel genes such as CACNA1C are part of the aetiology of psychiatric disorders has rekindled interest in the therapeutic potential of L-type calcium channel (LTCC) antagonists. These drugs, licensed to treat hypertension and angina, have previously been used in bipolar disorder, but without clear results. Neither is much known about the broader effects of these drugs on the brain and behaviour. METHODS: The Oxford study of Calcium channel Antagonism, Cognition, Mood instability and Sleep (OxCaMS) is a high-intensity randomised, double-blind, placebo-controlled experimental medicine study on the effect of the LTCC antagonist nicardipine in healthy young adults with mood instability...
February 12, 2019: Trials
Hillel Sternlicht, George L Bakris
PURPOSE OF REVIEW: This is an update of data regarding changes in blood pressure using sodium-glucose co-transporter 2 inhibitors (SGLT2i) for the treatment of diabetes. The mechanism of blood pressure lowering by SGLT2i was thought to be due to their osmotic diuretic effects. New data, however, has emerged from meta-analyses and studies of people with impaired kidney function demonstrating similar or greater magnitudes of blood pressure reduction in the absence of significant glycosuria...
February 12, 2019: Current Hypertension Reports
Xiaohua Zhang, Kejing Lao, Zhongyin Qiu, Md Saidur Rahman, Yuelin Zhang, Xingchun Gou
Alzheimer's disease (AD) is the most common cause of dementia and is characterized by the progressive loss of memory and cognition in the aging population. However, the etiology of and therapies for AD remain far from understood. Astrocytes, the most abundant neuroglia in the brain, have recently aroused substantial concern due to their involvement in synaptotoxicity, amyloidosis, neuroinflammation, and oxidative stress. In this review, we summarize the candidate molecules of astrocytes, especially receptors and transporters, that may be involved in AD pathogenesis...
February 1, 2019: Journal of Alzheimer's Disease: JAD
Yu-Peng Guo, Yu-Ru Zhi, Ting-Ting Liu, Yun Wang, Ying Zhang
The Ca2+ -binding protein Kv channel interacting protein 3 (KChIP3) or downstream regulatory element antagonist modulator (DREAM), a member of the neuronal calcium sensor (NCS) family, shows remarkable multifunctional properties. It acts as a transcriptional repressor in the nucleus and a modulator of ion channels or receptors, such as Kv4, NMDA receptors and TRPV1 channels on the cytomembrane. Previous studies of Kcnip3 -/- mice have indicated that KChIP3 facilitates pain hypersensitivity by repressing Pdyn expression in the spinal cord...
2019: Frontiers in Molecular Neuroscience
Wei Liu, Hui Qin, Yifan Pan, Fang Luo, Zhou Zhang
Humans are exposed to perfluorooctane sulfonate (PFOS) from sources of both continuing discharges and environmental legacies, and the health effects of low dose exposure remain unknown. We assessed the effects of PFOS at 0.2-200 nmol/L on osteogenic and adipogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). PFOS affected hBMSCs differentiation in a nonmonotonic dose-response relationship, where the effects peaked at 100 nmol/L. PFOS repressed calcium deposition on day 14 of osteogenic differentiation...
February 7, 2019: Toxicology and Applied Pharmacology
Írisz Szabó, Orsolya M Tóth, Zsolt Török, Dániel Péter Varga, Ákos Menyhárt, Rita Frank, Dóra Hantosi, Ákos Hunya, Ferenc Bari, Ibolya Horváth, László Vigh, Eszter Farkas
BACKGROUND AND PURPOSE: A new class of heat shock protein co-inducer dihydropyridine derivatives devoid of calcium channel antagonist and vasodilator effects have been recently developed with the purpose to target neurodegeneration selectively. Here we set out to evaluate the action of one of these novel compounds LA1011 on neurovascular coupling in the ischemic rat cerebral cortex. As a reference, we applied nimodipine, a well-known calcium channel antagonist, vasodilator dihydropyridine compound...
February 9, 2019: British Journal of Pharmacology
Daniel J Conklin, Yiru Guo, Ganapathy Jagatheesan, Matthew A Nystoriak, Detlef Obal, Peter Kilfoil, Luping Guo, Joseph David Hoetker, Roberto Bolli, Aruni Bhatnagar
Myocardial ischemia-reperfusion (I/R) results in generation of free radicals, accumulation of lipid peroxidation-derived unsaturated aldehydes, variable angina (pain) and infarction. Transient receptor potential ankyrin-1 (TRPA1) mediates pain signaling and is activated by unsaturated aldehydes, including acrolein and 4-hydroxynonenal. The contribution of TRPA1 (a calcium permeable channel) to I/R-induced myocardial injury is unknown. We tested the hypothesis that cardiac TRPA1 confers myocyte sensitivity to aldehyde accumulation and promotes I/R injury...
February 8, 2019: American Journal of Physiology. Heart and Circulatory Physiology
Qingbiao Xu, Nisha Singh, Hui Hong, Xianghua Yan, Wenlin Yu, Xu Jiang, Prashen Chelikani, Jianping Wu
Bitter sensation is mediated by various bitter taste receptors (T2Rs), thus T2R antagonists are actively explored. Our objective was to look for novel T2R blockers in hen protein hydrolysate (HPH). We screened the least bitter HPH fractions using electronic tongue, and analyzed their peptide sequences and calcium mobilization in HEK293T cells expressing T2Rs. The results showed that the HPH fractions with higher bitterness intensity had higher hydrophobicity, more hydrophobic amino acids, and more positively charged peptides, but fewer known umami peptides...
June 15, 2019: Food Chemistry
Vincenzo Lariccia, Maria Loredana Macrì, Alessandra Matteucci, Marta Maiolino, Salvatore Amoroso, Simona Magi
Ticagrelor is a direct acting and reversibly binding P2Y12 antagonist approved for the prevention of thromboembolic events. Clinical effects of ticagrelor cannot be simply accounted for by pure platelet inhibition, and off-target mechanisms can potentially play a role. In particular, recent evidence suggests that ticagrelor may also influence heart function and improve the evolution of myocardial ischemic injury by more direct effects on myocytes. The cardiac sodium/calcium exchanger 1 (NCX1) is a critical player in the generation and control of calcium (Ca2+ ) signals, which orchestrate multiple myocyte activities in health and disease...
February 2, 2019: European Journal of Pharmacology
Xuhui Li, Takanori Matsuura, Ren-Hao Liu, Man Xue, Min Zhuo
The neuropeptide of calcitonin gene-related peptide (CGRP) plays critical roles in chronic pain, especially in migraine. Immunohistochemistry and in situ hybridization studies have shown that CGRP and its receptors are expressed in cortical areas including pain perception related prefrontal anterior cingulate cortex (ACC). However, less information is available for the functional roles of CGRP in cortical regions such as the ACC. Recent studies have consistently demonstrated that long-term potentiation (LTP) is a key cellular mechanism for chronic pain in the ACC...
February 5, 2019: Molecular Pain
Sarah E Webb, Andrew L Miller
We have visualized many of the Ca2+ signaling events that occur during the early stages of zebrafish development using complementary luminescent and fluorescent imaging techniques. We initially microinject embryos with the luminescent Ca2+ reporter, f-holo-aequorin, and using a custom-designed luminescent imaging system, we can obtain pan-embryonic visual information continually for up to the first ~24 h postfertilization (hpf). Once we know approximately when and where to look for these Ca2+ signaling events within a complex developing embryo, we then repeat the experiment using a fluorescent Ca2+ reporter such as calcium green-1 dextran and use confocal laser scanning microscopy to provide time-lapse series of higher-resolution images...
2019: Methods in Molecular Biology
E M Elfimova, A Yu Litvin, I E Chazova
AIM: To study the effectiveness of a fixed combination of perindopril and amlodipine, with the subsequent addition of indapamide-retard in male patients with arterial hypertension (AH), obesity and severe sleep apnea (OSAS). MATERIALS AND METHODS: The study included 43 male patients in whom antihypertensive therapy titration was performed to achieve target blood pressure values with a fixed combination of calcium antagonist amlodipine (10 mg) and an angiotensin-converting inhibitor perindopril (5-10 mg) and indapamide-retard...
December 30, 2018: Terapevticheskiĭ Arkhiv
R V Gostishchev, G N Soboleva, A N Samko, A N Rogoza, A A Minasyan
AIM: The purpose of the study is to prove the effectiveness of pharmacological preconditioning caused by nicorandil in patients with stable coronary heart disease (CHD) during the elective percutaneous coronary intervention (PCI). MATERIALS AND METHODS: We included 88 patients with a stable form of CHD, who were going to pass the elective PCI, in the study. As the method of blind randomization envelope method was used. There were formed two groups or patients: the first group involved 45 patients - were treated with nicorandil (Cordinic, PIQ-FHARMA LLC) (the main group) the other group included 43 patients who were treated by the standard therapy (the comparison group)...
September 20, 2018: Terapevticheskiĭ Arkhiv
Xiaowei Yan, Yong Li, Yugang Dong, Yanhua Wu, Jihu Li, Rui Bian, Dayi Hu
ᅟ: The present study comprised 17,096 Chinese hypertensive dyslipidemia patients who received lipid-lowering treatment for > 3 months in order to investigate blood pressure (BP) as well as low-density lipoprotein cholesterol (LDL-C) goal attainment rates in Chinese hypertensive dyslipidemia patients on antidyslipidemia drugs. The factors that interfered with BP, or BP and LDL-C goal attainment rates and antihypertensive treatment patterns, were analyzed. In total, 89.9% of the 17,096 hypertensive dyslipidemia patients received antihypertensive medications mainly consisting of a calcium channel blocker (CCB) (48...
January 29, 2019: Lipids in Health and Disease
Gokhan Arslan, Bahattin Avci, Süleyman Emre Kocacan, Emil Rzayev, Mustafa Ayyildiz, Erdal Agar
Limited information exists on the link between purinergic class P2X7 receptors (P2X7Rs) and calcium ion channels in epilepsy; no data has been reported regarding the interaction between P2X7Rs and T-type calcium ion channels in epilepsy. Thus, this study is an evaluation of the role that T-type calcium ion channels play in the effect of P2X7Rs on penicillin-induced epileptiform activity. In the first set of experiments, P2X7R agonist BzATP (at 25-, 50-, 100- and 200-μg doses), P2X7R antagonist A-438079 (at 5-, 10-, 20- and 40-μg doses) and T-type calcium ion channel antagonist NNC-550396, were administered for electrophysiological analyses 30 min after penicillin injection (2...
January 26, 2019: Neuropharmacology
Felicity Gallop, Tangunu Fosi, Ponnudas Prabhakar, Sarah Elizabeth Aylett
BACKGROUND: Children with Sturge-Weber syndrome can experience severe headache with or without transient hemiparesis. Flunarizine, a calcium antagonist, has been used for migraine. The experience with flunarizine for headache in a cohort of children at a national center for Sturge-Weber syndrome is reviewed, reporting its efficacy and adverse effect in this population. METHODS: This retrospective review collected data from health care professionals' documentation on headache (severity, frequency, duration) before and on flunarizine in 20 children with Sturge-Weber syndrome...
November 28, 2018: Pediatric Neurology
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