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Andrei Tsentsevitsky, Leniz Nurullin, Evgeny Nikolsky, Artem Malomouzh
There is some evidence that glutamate (Glu) acts as a signaling molecule at vertebrate neuromuscular junctions where acetylcholine (ACh) serves as a neurotransmitter. In this study, performed on the cutaneous pectoris muscle of the frog Rana ridibunda, Glu receptor mechanisms that modulate ACh release processes were analyzed. Electrophysiological experiments showed that Glu reduces both spontaneous and evoked quantal secretion of ACh and synchronizes its release in response to electrical stimulation. Quisqualate, an agonist of ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptors and metabotropic Group I mGlu receptors, also exerted Glu-like inhibitory effects on the secretion of ACh but had no effect on the kinetics of quantal release...
October 22, 2016: Journal of Neuroscience Research
Zhen Lei, Abdul Sami Shaikh, Wenshuai Zheng, Xiao Yu, Jingui Yu, Jingxin Li
Itch, the unpleasant sensation that evokes a desire to scratch, accompanies numerous skin and nervous system disorders. However, the molecular mechanisms of itch are unclear. Acid sensing ion channel 3 (ASIC3) is a sensor of acidic and primary inflammatory pain. The whole-cell patch-clamp technique was used to determine the effect of Chloroquine (CQ)on ASICs currents in primary sensory neurons or the Chinese hamster ovary (CHO) cells transfected with rat-ASIC1a or- ASIC3. Site-directed mutagenesis of plasmid was performed...
October 22, 2016: Journal of Neurochemistry
Laszlo Kunos, Zsofia Lazar, Fruzsina Martinovszky, Adam D Tarnoki, David L Tarnoki, Daniel Kovacs, Bianka Forgo, Peter Horvath, Gyorgy Losonczy, Andras Bikov
PURPOSE: Obstructive sleep apnoea (OSA) is a prevalent disorder, characterised by collapse of the upper airways during sleep. The impact of sleep-disordered breathing on pulmonary function indices is however currently not well described. The aim of the study was to evaluate diurnal change in lung function indices in a cohort of patients with OSA and relate pulmonary function changes to disease severity. METHODS: 42 patients with OSA and 73 healthy control subjects participated in the study...
October 21, 2016: Lung
Jennifer C Cook, Richard H Tran, J Herbert Patterson, Jo E Rodgers
PURPOSE: The pharmacology, clinical efficacy, and safety profiles of evolving therapies for the management of chronic heart failure (HF) and acute decompensated heart failure (ADHF) are described. SUMMARY: HF confers a significant financial burden despite the widespread use of traditional guideline-directed medical therapies such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone receptor antagonists, and the rates of HF-related mortality and hospitalization have remained unacceptably high...
November 1, 2016: American Journal of Health-system Pharmacy: AJHP
Toby N Weingarten, Tasha L Welch, Tamara L Moore, Gulshat F Walters, Joni L Whipple, Alexandre Cavalcante, Irina Bancos, William F Young, Lucinda M Gruber, Muhammad Z Shah, Travis J McKenzie, Darrell R Schroeder, Juraj Sprung
OBJECTIVE: To determine whether, despite pharmacologic adrenergic receptor blockade, higher preoperative levels of catecholamines and metanephrines (adrenergic activity) are associated with increased intraoperative complications. METHODS: Records of patients undergoing paraganglioma and pheochromocytoma (PGL-PCC) resection from January 1, 2000, through June 31, 2015, were reviewed for preoperative levels of adrenergic activity, intraoperative variability in blood pressure and heart rate (range), and postoperative outcomes (hypotension requiring treatment)...
October 18, 2016: Urology
Yuzuki Kanda, Miho Okada, Rina Ikarashi, Eri Morioka, Takashi Kondo, Masayuki Ikeda
Clozapine (Clz) and olanzapine (Olz) are second generation (atypical) antipsychotics, used widely for treating schizophrenia and bipolar disorder. These drugs share multiple sites of actions, however their mechanisms remain incompletely understood. Here, we analyzed the effects of these drugs on primary cultures of rat cortical astrocytes and C6 glioma cells using fura-2-based Ca(2+) imaging. C6 cells, but not cortical astrocytes, express the serotonin 2A receptor subtype, which couples to phospholipase C. Clz (1μM) significantly blocked serotonin-induced Ca(2+) transients in C6 cells, consistent with known antagonistic actions of Clz...
October 18, 2016: Neuroscience Letters
Benjamin Albright, Roni Dhaher, Helen Wang, Roa Harb, Tih-Shih W Lee, Hitten Zaveri, Tore Eid
Loss of glutamine synthetase (GS) in hippocampal astrocytes has been implicated in the causation of human mesial temporal lobe epilepsy (MTLE).However, the mechanism by which the deficiency in GS leads to epilepsy is incompletely understood. Here we ask how hippocampal GS inhibition affects seizure phenotype and neuronal activation during epilepsy development (epileptogenesis). Epileptogenesis was induced by infusing the irreversible GS blocker methionine sulfoximine (MSO) unilaterally into the hippocampal formation of rats...
October 18, 2016: Experimental Neurology
Alessandro Rubini, Vincenzo Catena, Daniele Del Monte, Gerardo Bosco
CONTEXT: Calcium channel blockers may theoretically exhibit relaxing effects not only on vascular smooth muscle but also on airway smooth muscle. OBJECTIVE: To investigate possible effects of nifedipine on respiratory mechanics in the rat. METHODS: Respiratory system mechanical parameters were measured by the end-inflation occlusion method in the rat in vivo before and after the intraperitoneal administration of nifedipine. RESULTS: We found that nifedipine affects respiratory mechanics, inducing a reduction of airway resistance and of respiratory system elastance, probably because of a relaxing action on airway and parenchimal smooth muscle cells...
October 21, 2016: Journal of Enzyme Inhibition and Medicinal Chemistry
Cosmo Godino, Antonio Colombo, Alberto Margonato
Heart rate is an established prognostic marker for longevity and is an important contributor in the pathophysiology of various cardiovascular diseases, including ischemic heart disease and heart failure. Most ischemic episodes are triggered by an increase in heart rate, which causes an imbalance between myocardial oxygen delivery and consumption. In addition, increased heart rate is a modifiable risk factor for chronic heart failure. Ivabradine, an inhibitor of If ion channels, is an approved second-line anti-ischemic drug for the treatment of angina...
October 21, 2016: Clinical Drug Investigation
Jay S Mishra, Gary D Hankins, Sathish Kumar
INTRODUCTION: Blood pressure is lower in females than males. Angiotensin II type-2 receptor (AT2R) induces vasodilation. This study determined whether sex differences in vascular AT2R expression occur and if androgens exert control on AT2R expression in the vasculature. METHODS: AT2Rs in the aorta of male and female Sprague-Dawley rats were examined following alteration in androgen levels by gonadectomy or hormone supplementation. RESULTS: AT2R mRNA and protein expression levels were lower in the aortas of males than females...
October 2016: Journal of the Renin-angiotensin-aldosterone System: JRAAS
Donal Melanaphy, Christpher D Johnson, Maxim Kustov, Connall Watson, Lyudmyla Borysova, Theodore Burdyga, Alexander V Zholos
Transient receptor potential melastatin 8 (TRPM8) is the principal cold and menthol receptor channel. Characterized primarily for its cold sensing role in sensory neurons, it is expressed and functional in several non-neuronal tissues, including vasculature. We previously demonstrated that menthol causes vasoconstriction and vasodilatation in isolated arteries, depending on vascular tone. Here we investigated calcium's role in responses mediated by TRPM8 ligands in rat tail artery myocytes using patch-clamp electrophysiology and ratiometric Ca(2+) recording...
October 7, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Sheng-Jie Shiue, Chi-Hsu Wang, Tao-Yeuan Wang, Yi-Chun Chen, Jen-Kun Cheng
OBJECTIVE: T-type channel (TCC) CaV3.2 plays a pivotal role in pain transmission. In this study, we examined the effects of intrathecal TCC blockers on CaV3.2 expression in a L5/6 spinal nerve ligation (SNL) pain model. The neurotoxicity of TCC blockers were also evaluated. METHODS: Male Sprague-Dawley rats (200-250 g) were used for right L5/6 SNL to induce neuropathic pain. Intrathecal infusion of saline or TCC blockers [mibefradil (0.7 μg/h) or ethosuximide (60 μg/h)] was started after surgery for 7 days...
October 17, 2016: Acta Anaesthesiologica Taiwanica: Official Journal of the Taiwan Society of Anesthesiologists
Fahima Syeda, Andrew P Holmes, Ting Y Yu, Samantha Tull, Stefan Michael Kuhlmann, Davor Pavlovic, Daniel Betney, Genna Riley, Jan P Kucera, Florian Jousset, Joris R de Groot, Stephan Rohr, Nigel A Brown, Larissa Fabritz, Paulus Kirchhof
BACKGROUND: Antiarrhythmic drugs are widely used to treat patients with atrial fibrillation (AF), but the mechanisms conveying their variable effectiveness are not known. Recent data suggested that paired like homeodomain-2 transcription factor (PITX2) might play an important role in regulating gene expression and electrical function of the adult left atrium (LA). OBJECTIVES: After determining LA PITX2 expression in AF patients requiring rhythm control therapy, the authors assessed the effects of Pitx2c on LA electrophysiology and the effect of antiarrhythmic drugs...
October 25, 2016: Journal of the American College of Cardiology
Antonin Levy, Christophe Massard, Jean-Charles Soria, Eric Deutsch
PURPOSE: To assess preliminary safety and efficacy results of the anti-programmed cell death ligand-1 (anti-PD-L1) durvalumab in combination with radiotherapy (RT) in an expansion cohort of patients included in a phase 1/2 trial at our institution. PATIENTS AND METHODS: Data from patients who received concurrent palliative RT with durvalumab (10 mg/kg every 2 weeks via intravenous infusion) were analysed in terms of safety (CTCAE v4.0) and efficacy (RECIST v1.1 and tumour growth rate [TGR])...
October 17, 2016: European Journal of Cancer
Naoto Fujii, Maya Sarah Singh, Lyra Halili, Jeffrey C Louie, Glen P Kenny
During exercise, cutaneous vasodilation and sweating responses occur, whereas these responses rapidly decrease during postexercise recovery. We hypothesized that the activation of endothelin A (ETA) receptors, but not endothelin B (ETB) receptors, attenuate cutaneous vasodilation during high-intensity exercise and contribute to the subsequent postexercise suppression of cutaneous vasodilation. We also hypothesized that both receptors increase sweating during and following high-intensity exercise. Eleven males (24 ± 4 years) performed an intermittent cycling protocol consisting of two 30-min bouts of moderate- (40% VO2peak) and high- (75% VO2peak) intensity exercise in the heat (35°C), each separated by a 20- and 40-min recovery period, respectively...
October 7, 2016: Journal of Applied Physiology
Mark Wigginton, Laura Lehrian
We compare airway management and lung isolation methods in two pediatric cases of congenital central hypoventilation syndrome undergoing bilateral throacoscopic phrenic-nerve-stimulator surgery. One child received lung isolation using a 7Fr bronchial blocker in conjunction with a 6.0 cuffed endotracheal tube; and the second received a technique of endobronchial intubation using a 3.5 microcuffed tube via the tracheostomy stoma in conjunction with 5.0 cuffed endotracheal intubation; a technique previously undescribed in pediatric patients...
October 20, 2016: Paediatric Anaesthesia
Min Shi, Liang Ma, Li Zhou, Ping Fu
Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by a Chinese herb containing aristolochic acid. Excessive death of renal tubular epithelial cells (RTECs) characterized the acute phase of AAN. Therapies for acute AAN were limited, such as steroids and angiotensin-receptor blockers (ARBs)/angiotensin-converting enzyme inhibitors (ACEIs). It was interesting that, in acute AAN, female patients showed relative slower progression to renal failure than males. In a previous study, female hormone 17β-estradiol (E2) was found to attenuate renal ischemia-reperfusion injury...
October 18, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Ronald L Dalman, Haojun Xuan, Wei Wang, Hiroki Tanaka, Naoki Fujimura, Baohui Xu
No abstract text is available yet for this article.
August 2016: Journal of Vascular Surgery
A Muruganathan, Mangesh Tiwaskar
While the incidence and prevalence of stroke is gradually decreasing in the western world, a parallel increase is seen in the developing world. It is a matter of special concern to us as approximately 20-30% of stroke occur in people younger than 45 years in India. Indians are prone to higher stroke risk because of urbanization, diabetes, cigarette smoking and high incidence of hypertension. Unfortunately, there is an inadequate awareness about the risk of stroke with hypertension among general public. Hypertension is considered to be the most important risk factor for stroke, and all forms of hypertension are associated with an increased risk of both ischemic and haemorrhagic stroke...
September 2016: Journal of the Association of Physicians of India
M Nagai, K Dote, M Kato, S Sasaki, N Oda, E Kagawa, Y Nakano, A Yamane, Y Kubo, T Higashihara, S Miyauchi, W Harada, H Masuda
In a cross-sectional study, visit-to-visit blood pressure (BP) variability was shown to be associated with artery remodelling. Here, we investigated the impact of visit-to-visit BP variability and average BP on the carotid artery remodelling progression in high-risk elderly according to different classes of antihypertension medication use/non-use. BP measurements and carotid ultrasound were performed in the common carotid artery in 164 subjects (mean age 79.7 years at baseline, 74.7% females) with one or more cardiovascular risk factors...
October 20, 2016: Journal of Human Hypertension
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