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https://www.readbyqxmd.com/read/28528375/hypothalamic-signaling-in-body-fluid-homeostasis-and-hypertension
#1
REVIEW
Brian J Kinsman, Haley N Nation, Sean D Stocker
PURPOSE OF REVIEW: The central nervous system plays a pivotal role in the regulation of extracellular fluid volume and consequently arterial blood pressure. Key hypothalamic regions sense and integrate neurohumoral signals to subsequently alter intake (thirst and salt appetite) and output (renal excretion via neuroendocrine and autonomic function). Here, we review recent findings that provide new insight into such mechanisms that may represent new therapeutic targets. RECENT FINDINGS: Implementation of cutting edge neuroscience approaches such as opto- and chemogenetics highlight pivotal roles of circumventricular organs to impact body fluid homeostasis...
June 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/28528235/mapping-natural-radioactivity-of-soil-samples-in-different-regions-of-punjab-india
#2
Komal Saini, B S Bajwa
Thallium activated sodium iodide (NaI(Tl)) detector and multi channel analyzer has been utilized to measure gamma rays emitted by radio nuclides found in soil samples of south-west (SW) region of Punjab state, India where elevated level of uranium of around value of 700µg/l in groundwater has been reported. For comparative study, soil samples were also collected and analyzed from west (W) and north east (NE) regions of the state. Uranium and potassium has been found to be comparatively higher in SW region whereas thorium level is higher in W and NE part of Punjab state...
May 13, 2017: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/28526152/pharmacologic-properties-of-novel-local-anesthetic-agents-in-anesthesia-practice
#3
REVIEW
Chih H King, Sascha S Beutler, Alan D Kaye, Richard D Urman
Therapeutic duration of traditional local anesthetics when used in peripheral nerve blocks is normally limited. This article describes novel approaches to extend the duration of peripheral nerve blocks currently available or in development. Three newer approaches on extending the duration of peripheral nerve blocks include site-1 sodium channel blockers, novel local anesthetics delivery systems, and novel adjuvants of local anesthetics. Compared with plain amide-based and ester-based local anesthetics, alternative approaches show significant promise in decreasing postoperative pain, rescue opioid requirement, hospital length-of-stay, and overall health care cost, without compromising the established safety profile of traditional local anesthetics...
June 2017: Anesthesiology Clinics
https://www.readbyqxmd.com/read/28523600/sodium-channel-blockers-in-the-treatment-of-epilepsy
#4
Martin J Brodie
Sodium channel blockers have been the mainstay of the pharmacological management of focal and generalised tonic-clonic seizures for more than 70 years. The focus of this paper will be on phenytoin, carbamazepine, lamotrigine, oxcarbazepine, rufinamide, lacosamide and eslicarbazepine acetate. All these antiepileptic drugs have similar efficacy and share similar dose-dependent, adverse effect profiles, although phenytoin, carbamazepine and oxcarbazepine are more likely to cause idiosyncratic reactions than the others...
May 18, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28523441/progress-in-the-presence-of-failure-updates-in-chronic-systolic-heart-failure-management
#5
REVIEW
Katie M Murphy, Julie L Rosenthal
The therapeutic heart failure armamentarium has evolved from drugs to transplantation to devices through further understanding of its complex pathophysiology and pathogenesis. Current medications capitalize on our evolving understanding of the sympathetic and renin-angiotensin-aldosterone systems that subsequently promote both beneficial and maladaptive responses that ultimately yield a decrease in cardiac function. Despite these advancements, the prevalence of heart failure continues to rise and carries a significant burden on our patients and health care system...
July 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28523371/impact-of-electrocardiogram-screening-during-drug-challenge-test-for-the-prediction-of-t-wave-oversensing-by-a-subcutaneous-implantable-cardioverter-defibrillator-in-patients-with-brugada-syndrome
#6
Tsukasa Kamakura, Mitsuru Wada, Kohei Ishibashi, Yuko Y Inoue, Koji Miyamoto, Hideo Okamura, Satoshi Nagase, Takashi Noda, Takeshi Aiba, Satoshi Yasuda, Kengo Kusano
Screening tests conducted at rest may be inadequate for the prediction of the T-wave oversensing (TWOS) in subcutaneous implantable cardioverter defibrillator (S-ICD) candidates with Brugada syndrome (BrS) because of the dynamic nature of electrocardiogram (ECG) morphology. We evaluated the utility of ECG screening during drug challenge (DC) for prediction of TWOS in BrS patients implanted with an S-ICD. The study enrolled 6 consecutive BrS patients implanted with an S-ICD. In addition to baseline ECG screening, pre-implant screening during DC using a sodium channel blocker was performed in all patients...
May 18, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28522439/interpreting-the-functional-role-of-a-novel-interaction-motif-in-prokaryotic-sodium-channels
#7
REVIEW
Altin Sula, B A Wallace
Voltage-gated sodium channels enable the translocation of sodium ions across cell membranes and play crucial roles in electrical signaling by initiating the action potential. In humans, mutations in sodium channels give rise to several neurological and cardiovascular diseases, and hence they are targets for pharmaceutical drug developments. Prokaryotic sodium channel crystal structures have provided detailed views of sodium channels, which by homology have suggested potentially important functionally related structural features in human sodium channels...
May 18, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28522215/blocking-voltage-gated-sodium-channels-as-a-strategy-to-suppress-pathological-cough
#8
REVIEW
Hui Sun, Marian Kollarik, Bradley J Undem
Pathological cough is thought to be secondary to inappropriate activation of vagal sensory nerves. Sensory nerves can be activated by a large number of disparate stimuli. The most relevant stimuli to block for effective anti-tussive therapy likely depend on the specific underlying pathology that is leading to the coughing. Blocking voltage-gated sodium channels (NaV) will prevent action potential initiation and conduction and therefore prevent sensory communication between the airways and brainstem. In so doing, they would be expected to inhibit evoked cough independently of the nature of the stimulus and underlying pathology...
May 15, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28521022/management-of-untreatable-ventricular-arrhythmias-during-pharmacologic-challenges-with-sodium-channel-blockers-for-suspected-brugada-syndrome
#9
Stefano Poli, Mauro Toniolo, Massimo Maiani, Davide Zanuttini, Luca Rebellato, Igor Vendramin, Ermanno Dametto, Guglielmo Bernardi, Flavio Bassi, Carlo Napolitano, Ugolino Livi, Alessandro Proclemer
Pharmacologic challenge with sodium channel blockers is part of the diagnostic workout in patients with suspected Brugada syndrome. The test is overall considered safe but both ajmaline and flecainide detain well known pro-arrhythmic properties. Moreover, the treatment of patients with life-threatening arrhythmias during these diagnostic procedures is not well defined. Current consensus guidelines suggest to adopt cautious protocols interrupting the sodium channel blockers as soon as any ECG alteration appears...
May 17, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28518218/comparison-and-optimization-of-in-silico-algorithms-for-predicting-the-pathogenicity-of-sodium-channel-variants-in-epilepsy
#10
Katherine D Holland, Thomas M Bouley, Paul S Horn
OBJECTIVE: Variants in neuronal voltage-gated sodium channel α-subunits genes SCN1A, SCN2A, and SCN8A are common in early onset epileptic encephalopathies and other autosomal dominant childhood epilepsy syndromes. However, in clinical practice, missense variants are often classified as variants of uncertain significance when missense variants are identified but heritability cannot be determined. Genetic testing reports often include results of computational tests to estimate pathogenicity and the frequency of that variant in population-based databases...
May 18, 2017: Epilepsia
https://www.readbyqxmd.com/read/28514017/isopimaric-acid-a-multi-targeting-ion-channel-modulator-reducing-excitability-and-arrhythmicity-in-a-spontaneously-beating-mouse-atrial-cell-line
#11
Sajjad Salari, Malin Silverå Ejneby, Johan Brask, Fredrik Elinder
AIM: Atrial fibrillation is the most common persistent cardiac arrhythmia, and it is not well controlled by present drugs. Because some resin acids open voltage-gated potassium channels and reduce neuronal excitability, we explored the effects of the resin acid isopimaric acid (IPA) on action potentials and ion currents in cardiomyocytes. METHODS: Spontaneously beating mouse atrial HL-1 cells were investigated with the whole-cell patch-clamp technique. RESULTS: 1-25 μmol L(-1) IPA reduced the action potential frequency by up to 50%...
May 17, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28512574/crystallographic-and-saxs-studies-of-s-adenosyl-l-homocysteine-hydrolase-from-bradyrhizobium-elkanii
#12
Tomasz Manszewski, Kamil Szpotkowski, Mariusz Jaskolski
S-Adenosyl-l-homocysteine hydrolase (SAHase) from the symbiotic bacterium Bradyrhizobium elkanii (BeSAHase) was crystallized in four ligand complexes with (i) mixed adenosine (Ado) and cordycepin (Cord; 3'-deoxyadenosine), (ii) adenine (Ade), (iii) Ado and (iv) mixed 2'-deoxyadenosine (2'-dAdo) and Ade. The crystal structures were solved at resolutions of 1.84, 1.95, 1.95 and 1.54 Å, respectively. Only the Ade complex crystallized with a dimer in the asymmetric unit, while all of the other complexes formed a crystallographically independent tetrameric assembly...
May 1, 2017: IUCrJ
https://www.readbyqxmd.com/read/28510137/possible-mechanism-of-bursting-suppression-in-nociceptive-neurons
#13
O E Dick, B V Krylov, A D Nozdrachev
The use of the mathematical model of rat nociceptive neuron membrane allowed us to predict a new mechanism of suppression of ectopic bursting discharges, which arise in neurons of dorsal root ganglia and are one of the causes of neuropathic pain. The treatment with comenic acid leads to switching off the ectopic bursting discharges due to a decrease in the effective charge transferring via the activation gating structure of the slow sodium channels (Na V1.8a). Comenic acid is a drug substance of a new non-opioid analgesic [1] Thus, this analgesic not only reduces the frequency of rhythmic discharges of nociceptive neuron membrane [2] but also it suppresses its ectopic bursting discharges...
March 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28507035/long-term-sensitization-training-in-aplysia-decreases-the-excitability-of-a-decision-making-neuron-through-a-sodium-dependent-mechanism
#14
John S Hernandez, Marcy L Wainwright, Riccardo Mozzachiodi
In Aplysia, long-term sensitization (LTS) occurs concurrently with a suppression of feeding. At the cellular level, the suppression of feeding is accompanied by decreased excitability of decision-making neuron B51. We examined the contribution of voltage-gated Na(+) and K(+) channels to B51 decreased excitability. In a pharmacologically isolated Na(+) channels environment, LTS training significantly increased B51 firing threshold, compared with untrained controls. Conversely, in a pharmacologically isolated K(+) channels environment, no differences were observed between trained and untrained animals in either amplitude or area of B51 K(+)-dependent depolarizations...
June 2017: Learning & Memory
https://www.readbyqxmd.com/read/28506097/a-computational-model-of-the-ca-2-transients-and-influence-of-buffering-in-guinea-pig-urinary-bladder-smooth-muscle-cells
#15
Vijay Dave, Rohit Manchanda
Many cellular events including electrical activity and muscle contraction are regulated and coordinated by intracellular [Formula: see text] concentration ([[Formula: see text]][Formula: see text]. In detrusor smooth muscle (DSM) cells, [[Formula: see text]]i is normally maintained at very low levels and rises transiently during signalling processes as a result of (i) influx from the extracellular space (mainly via L-type and T-type [Formula: see text] channels) and (ii) [Formula: see text] release from sarcoplasmic reticulum (SR) into the cytoplasm...
April 20, 2017: Journal of Bioinformatics and Computational Biology
https://www.readbyqxmd.com/read/28504831/from-discrete-molecular-cage-to-networked-cage-exhibiting-enhanced-co2-adsorption-capacity
#16
Lei Zhang, Long Xiang, Cheng Hang, Wenlong Liu, Wei Huang, YiChang Pan
The synthetic strategy from cage to framework has been successfully achieved in the case of a rigid imine-linked [3+6] NC1 and a corresponding sodium-directed coordination networked cage Na-NC1. It is found that Na-NC1 exhibits hierarchical porosity (inherent permanent voids and interconnected channel) and gas sorption measurements reveal a significantly enhanced CO2 uptake (1093 cm3 g-1 at 23 bar and 273 K) than that of NC1 (162 cm3 g-1 under the same condition). In addition, Na-NC1 exhibits very low CO2 adsorption enthalpy making it a good candidate for porous materials with high CO2 storage and low adsorption enthalpy simultaneously...
May 15, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28503166/inhibition-of-ectopic-arginine-vasopressin-production-by-phenytoin-in-the-small-cell-lung-cancer-cell-line-lu-165
#17
Takahiro Ohta, Mitsuo Mita, Shigeru Hishinuma, Reiko Ishii-Nozawa, Kazuhisa Takahashi, Masaru Shoji
Phenytoin, a voltage-gated sodium channel (NaV channel) antagonist, reportedly inhibits arginine vasopressin (AVP) release from an isolated rat neurohypophysis. So far, it is uncertain whether phenytoin has a direct action on ectopic AVP-producing neuroendocrine tumors. We studied the effect of phenytoin on the release of copeptin, the C-terminal fragment of pro-AVP, and expression of AVP gene in the human small cell lung cancer cell line Lu-165. Cells were maintained in RPMI1640 medium with 10% fetal bovine serum and were used within the fifth passage...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28501647/application-of-optical-action-potentials-in-human-induced-pluripotent-stem-cells-derived-cardiomyocytes-to-predict-drug-induced-cardiac-arrhythmias
#18
H R Lu, M P Hortigon-Vinagre, V Zamora, I Kopljar, A De Bondt, D J Gallacher, G Smith
INTRODUCTION: Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are emerging as new and human-relevant source in vitro model for cardiac safety assessment that allow us to investigate a set of 20 reference drugs for predicting cardiac arrhythmogenic liability using optical action potential (oAP) assay. METHODS: Here, we describe our examination of the oAP measurement using a voltage sensitive dye (Di-4-ANEPPS) to predict adverse compound effects using hiPS-CMs and 20 cardioactive reference compounds...
May 10, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28498103/a-selectivity-filter-at-the-intracellular-end-of-the-acid-sensing-ion-channel-pore
#19
Timothy Lynagh, Emelie Flood, Céline Boiteux, Matthias Wulf, Vitaly V Komnatnyy, Janne M Colding, Toby W Allen, Stephan A Pless
Increased extracellular proton concentrations during neurotransmission are converted to excitatory sodium influx by acid-sensing ion channels (ASICs). 10-fold sodium/potassium selectivity in ASICs has long been attributed to a central constriction in the channel pore, but experimental verification is lacking due to the sensitivity of this structure to conventional manipulations. Here, we explored the basis for ion selectivity by incorporating unnatural amino acids into the channel, engineering channel stoichiometry and performing free energy simulations...
May 12, 2017: ELife
https://www.readbyqxmd.com/read/28497312/phenytoin-neuroprotection-or-neurotoxicity
#20
REVIEW
Jan M Keppel Hesselink, David J Kopsky
Phenytoin is an 80-year young molecule and new indications are still emerging. The neuroprotective potential of phenytoin has been evaluated for decades. Recently, a positive phase II trial supported its further development in the treatment of optic neuritis in multiple sclerosis. In 1942, however, peripheral neuritis was first reported to be an adverse event of phenytoin, and since then a small but steady stream of publications discussed peripheral polyneuropathy as being a possible adverse event of phenytoin...
May 11, 2017: Neurological Sciences
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