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https://www.readbyqxmd.com/read/28930822/five-years-experience-on-3-4-diaminopyridine-phosphate-in-lambert-eaton-syndrome-case-reports
#1
Simona Portaro, Teresa Brizzi, Stefano Sinicropi, Alberto Cacciola, Maria Cristina De Cola, Alessia Bramanti, Demetrio Milardi, Antonino Lupica, Placido Bramanti, Antonio Toscano, Carmelo Rodolico
RATIONALE: To report our experience on 7 patients (4 males and 3 females), affected by nonparaneoplastic Lambert-Eaton myasthenic syndrome, treated with 3,4-diaminopyridine phosphate (3,4-DAPP) either alone or in combination with other immunosuppressants or steroids. PATIENT CONCERNS: Patients have been evaluated at specific timepoints (ie, baseline and last 5 year follow-up), with neurological examination, autoantibodies against presynaptic voltage-gated Cav2.1 (P/Q type) calcium ion channel (VGCC) dosage, neurophysiological evaluation focusing on the increased amplitude of the compound muscle action potential (cMAP) after maximum voluntary effort, quantitative myasthenia gravis (QMG) and activities of daily living scales, and autonomic nervous system involvement evaluation...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28930537/differences-in-ion-channel-phenotype-and-function-between-humans-and-animal-models
#2
Mark R Tanner, Christine Beeton
Ion channels play crucial roles in regulating a broad range of physiological processes. They form a very large family of transmembrane proteins. Their diversity results from not only a large number of different genes encoding for ion channel subunits but also the ability of subunits to assemble into homo- or heteromultimers, the existence of splice variants, and the expression of different regulatory subunits. These characteristics and the existence of very selective modulators make ion channels very attractive targets for therapy in a wide variety of pathologies...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28930428/ion-transport-in-confined-geometries-below-the-nanoscale-access-resistance-dominates-protein-channel-conductance-in-diluted-solutions
#3
Antonio Alcaraz, M Lidón López, María Queralt-Martín, Vicente M Aguilella
Synthetic nanopores and mesoscopic protein channels have common traits like the importance of electrostatic interactions between the permeating ions and the nanochannel. Ion transport at the nanoscale occurs under confinement conditions so that the usual assumptions made in microfluidics are challenged, among others, by interfacial effects such as access resistance (AR). Here we show that a sound interpretation of electrophysiological measurements in terms of channel ion selective properties requires the consideration of interfacial effects, up to the point that they dominate protein channel conductance in diluted solutions...
September 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/28929917/mercurius-solubilis-attenuates-scopolamine-induced-memory-deficits-and-enhances-the-motor-coordination-in-mice
#4
Simranjeet Kaur, Anudeep Kaur, Gurjit Singh, Rajbir Bhatti
The present study was designed to investigate the effect of mercurius solubilis (Merc sol) on scopolamine induced memory deficits and motor coordination in mice. The Three different formulations of merc sol (30X, 200 M, 1 M) were screened for their in vitro antioxidant potential and DPPH (2, 2-diphenyl-1-picrylhydrazyl) and nitric oxide scavenging activity using response surface methodology. The Merc sol 30X formulation was found to be most potent and further subjected for in vivo experiment. The Memory impairment was induced by the administration of scopolamine (1 mg/kg i...
September 20, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/28928655/effects-of-simvastatin-beyond-dyslipidemia-exploring-its-antinociceptive-action-in-an-animal-model-of-complex-regional-pain-syndrome-type-i
#5
Graziela Vieira, Juliana Cavalli, Elaine C D Gonçalves, Tainara R Gonçalves, Larissa R Laurindo, Maíra Cola, Rafael C Dutra
Simvastatin is a lipid-lowering agent that blocks the production of cholesterol through inhibition of 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase. In addition, recent evidence has suggested its anti-inflammatory and antinociceptive actions during inflammatory and pain disorders. Herein, we investigated the effects of simvastatin in an animal model of complex regional pain syndrome-type I, and its underlying mechanisms. Chronic post-ischemia pain (CPIP) was induced by ischemia and reperfusion (IR) injury of the left hind paw...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28928472/a-high-conductance-chemo-optogenetic-system-based-on-the-vertebrate-channel-trpa1b
#6
Pui-Ying Lam, Suresh K Mendu, Robert W Mills, Baohui Zheng, Hugo Padilla, David J Milan, Bimal N Desai, Randall T Peterson
Optogenetics is a powerful research approach that allows localized optical modulation of selected cells within an animal via the expression of genetically encoded photo-excitable ion channels. Commonly used optogenetic techniques rely on the expression of microbial opsin variants, which have many excellent features but suffer from various degrees of blue spectral overlap and limited channel conductance. Here, we expand the optogenetics toolbox in the form of a tunable, high-conductance vertebrate cation channel, zTrpa1b, coupled with photo-activated channel ligands, such as optovin and 4g6...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928238/talk-1-channels-control-%C3%AE-cell-endoplasmic-reticulum-ca-2-homeostasis
#7
Nicholas C Vierra, Prasanna K Dadi, Sarah C Milian, Matthew T Dickerson, Kelli L Jordan, Patrick Gilon, David A Jacobson
Ca(2+) handling by the endoplasmic reticulum (ER) serves critical roles in controlling pancreatic β cell function and becomes perturbed during the pathogenesis of diabetes. ER Ca(2+) homeostasis is determined by ion movements across the ER membrane, including K(+) flux through K(+) channels. We demonstrated that K(+) flux through ER-localized TALK-1 channels facilitated Ca(2+) release from the ER in mouse and human β cells. We found that β cells from mice lacking TALK-1 exhibited reduced basal cytosolic Ca(2+) and increased ER Ca(2+) concentrations, suggesting reduced ER Ca(2+) leak...
September 19, 2017: Science Signaling
https://www.readbyqxmd.com/read/28928236/histone-deacetylase-inhibition-ameliorates-hypertension-and-hyperglycemia-in-a-model-of-cushing-s-syndrome
#8
Hae-Ahm Lee, Seol-Hee Kang, Mina Kim, Eunjo Lee, Hyun-Min Cho, Eun-Kyung Moon, Inkyeom Kim
Cushing's syndrome (CS) caused by hypercortisolism is occasionally accompanied by metabolic disorders such as hypertension, diabetes mellitus (DM), dyslipidemia and central obesity. Thus, morbidity and mortality, observed in cardiovascular disease, are elevated in patients with CS. We hypothesized that HDAC inhibition (HDACi) decreased transcriptional activity of glucocorticoid receptor (GR), which ameliorates hypertension and hyperglycemia in patients with CS. To establish an animal model of hypercortisolism, Sprague-Dawley rats were infused with adrenocorticotropic hormone (ACTH, 40 ng/day) or dexamethasone (Dex, 10 μg/day) via osmotic minipumps for 4 weeks...
September 19, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28928053/development-of-correction-formula-for-field-potential-duration-of-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-sheets
#9
Hiroko Izumi-Nakaseko, Yasunari Kanda, Yuji Nakamura, Mihoko Hagiwara-Nagasawa, Takeshi Wada, Kentaro Ando, Atsuhiko T Naito, Yuko Sekino, Atsushi Sugiyama
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been used in many studies to assess proarrhythmic risks of chemical compounds. In those studies, field potential durations (FPD) of hiPSC-CMs have been corrected by clinically used Fridericia's and/or Bazett's formulae, however, the rationale for the use of these formulae has not been well established. In the present study, we developed a correction formula for experiments using hiPSC-CMs. First, we analyzed the effect of beating rate on FPD in the hiPSC-CMs sheets with electrical stimuli and a HCN channel inhibitor zatebradine...
September 6, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28928044/electrocardiographic-biomarkers-to-confirm-drug-s-electrophysiological-effects-used-for-proarrhythmic-risk-prediction-under-cipa
#10
Jose Vicente, Meisam Hosseini, Lars Johannesen, David G Strauss
The ECG plays a critical role in the thorough QT study. This clinical study is part of the assessment of proarrhythmic potential of drugs under the current regulatory paradigm. While the current paradigm has been successful in preventing drugs with unexpected QT prolongation or torsade risk from reaching the market, the focus on QT prolongation has likely resulted in potentially beneficial compounds with minimal torsade risk being dropped from development. The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is developing and validating a new mechanistic-based paradigm for cardiac safety evaluation of drugs...
August 9, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28927993/voltage-gated-sodium-channel-%C3%AE-subunits-the-power-outside-the-pore-in-brain-development-and-disease
#11
REVIEW
Jacob M Hull, Lori L Isom
Voltage gated sodium channels (VGSCs) were first identified in terms of their role in the upstroke of the action potential. The underlying proteins were later identified as saxitoxin and scorpion toxin receptors consisting of α and β subunits. We now know that VGSCs are heterotrimeric complexes consisting of a single pore forming α subunit joined by two β subunits; a noncovalently linked β1 or β3 and a covalently linked β2 or β4 subunit. VGSC α subunits contain all the machinery necessary for channel cell surface expression, ion conduction, voltage sensing, gating, and inactivation, in one central, polytopic, transmembrane protein...
September 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28927796/development-and-evaluation-of-4-pyrrolidin-3-yl-benzonitrile-derivatives-as-inhibitors-of-lysine-specific-demethylase-1
#12
Daniel P Mould, Ulf Bremberg, Allan M Jordan, Matthis Geitmann, Alison E McGonagle, Tim C P Somervaille, Gary J Spencer, Donald J Ogilvie
As part of our ongoing efforts to develop reversible inhibitors of LSD1, we identified a series of 4-(pyrrolidin-3-yl)benzonitrile derivatives that act as successful scaffold-hops of the literature inhibitor GSK-690. The most active compound, 21g, demonstrated a Kd value of 22nM and a biochemical IC50 of 57nM. In addition, this compound displayed improved selectivity over the hERG ion channel compared to GSK-690, and no activity against the related enzymes MAO-A and B. In human THP-1 acute myeloid leukaemia cells, 21g was found to increase the expression of the surrogate cellular biomarker CD86...
August 24, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28927426/the-acid-sensing-ion-channel-asic2-promotes-invasion-and-metastasis-of-colorectal-cancer-under-acidosis-by-activating-the-calcineurin-nfat1-axis
#13
Zhi-Hang Zhou, Jin-Wen Song, Wen Li, Xue Liu, Liu Cao, Lu-Ming Wan, Ying-Xia Tan, Shou-Ping Ji, Yu-Mei Liang, Feng Gong
BACKGROUND: The tumor acidic microenvironment, a common biochemical event in solid tumors, offers evolutional advantage for tumors cells and even enhances their aggressive phenotype. However, little is known about the molecular mechanism underlying the acidic microenvironment-induced invasion and metastasis. METHODS: We examined the expression of the acid-sending ion channel (ASIC) family members after acidic exposure using RT-PCR and immunofluoresence. Gene manipulation was applied to reveal the potential of ASIC2 on invasion, proliferation, colony formation of colorectal cancer (CRC)...
September 19, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28927342/expert-opinion-biomimetic-functionalized-surfaces-and-the-induction-of-bone-formation
#14
Ugo Ripamonti
Tissue engineering still needs to assign the molecular basis of pattern formation, tissue induction and morphogenesis: What next to morphogens and stem cells? Macroporous biomimetic matrices per se, without the addition of the soluble osteogenic molecular signals of the transforming growth factor-β (TGF-β) supergene family, initiate the induction of bone formation. Carving geometries within different calcium phosphate-based macroporous bioreactors we show that geometric cues imprinted within the macroporous spaces initiate the spontaneous induction of bone...
September 19, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28926221/fourier-transform-ms-and-closed-path-multi-reflection-time-of-flight-ms-using-an-electrostatic-linear-ion-trap
#15
Eric T Dziekonski, Joshua T Johnson, Kenneth W Lee, Scott A McLuckey
An electrostatic linear ion trap (ELIT) has been configured to allow for the simultaneous acquisition of mass spectra via Fourier transform (FT) techniques (frequency measurement) and via time-of-flight (TOF) (time measurement). In the former case, the time-domain image charge derived from a pick-up electrode in the field-free region of the ELIT is converted to frequency-domain data via Fourier transformation (i.e., FT-ELIT MS). In the latter case, the time difference between ion injection into the ELIT and ion detection after release from the ELIT using a micro-channel plate (MCP) enables the acquisition of multi-reflection time-of-flight mass spectra (MR-TOF MS)...
September 19, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28925884/prevention-and-treatment-for-chemotherapy-induced-peripheral-neuropathy-therapies-based-on-cipn-mechanisms
#16
Lang-Yue Hu, Wen-Li Mi, Gen-Cheng Wu, Yan-Qing Wang, Qi-Liang Mao-Ying
BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a progressive, enduring, and often irreversible adverse effect of many antineoplastic agents, among which sensory abnormities are common and the most suffering issues. The pathogenesis of CIPN has not been completely understood, and strategies for CIPN prevention and treatment are still open problems for medicine. OBJECTIVES: The objective of this paper is to review the mechanism-based therapies against sensory abnormities in CIPN...
September 15, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28925723/expression-patterns-of-members-of-the-isocitrate-dehydrogenase-gene-family-in-murine-inner-ear
#17
Y-R Kim, K-H Kim, S Lee, S-K Oh, J-W Park, K-Y Lee, J-I Baek, U-K Kim
Age-related hearing loss (ARHL) is characterized by an age-dependent decline of auditory function characterized by with loss of sensory hair cells, spiral ganglion neurons, and stria vascularis (SV) cells in the cochlea of the inner ear. Aging and age-related diseases result from accumulated oxidative damage caused by reactive oxygen species (ROS) generated by mitochondria. The isocitrate dehydrogenase (IDH) family includes three enzymes in human cells: IDH1, IDH2, and IDH3. Although all three enzymes catalyze the same enzymatic reaction, that is, oxidative decarboxylation of isocitrate to produce α-ketoglutarate, each IDH enzyme has unique features...
September 19, 2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/28925721/the-more-effective-treatment-of-atrial-fibrillation-applying-the-natural-compounds-as-nadph-oxidase-and-ion-channel-inhibitors
#18
Samira Barangi, A Wallace Hayes, Gholamreza Karimi
Atrial fibrillation (AF) is the most common cardiac arrhythmia that occurs because of several different risk factors, e.g., valvular heart disease, coronary artery disease, age ≥75 years, hypertension and diabetes mellitus. One key risk factor that results in AF, is oxidative stress. Evidence suggests that there is a correlation between oxidative processes and the genesis of AF. Oxidative stress occurs when the generation of reactive oxygen species (ROS) increase due to excessive activity of enzymes including NADPH oxidase (NOX) and xanthine oxidase; or its degradation decrease by dysfunctional antioxidant enzyme systems, such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx)...
September 19, 2017: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/28924161/molecular-mechanisms-involved-in-the-non-monotonic-effect-of-bisphenol-a-on-ca2-entry-in-mouse-pancreatic-%C3%AE-cells
#19
Sabrina Villar-Pazos, Juan Martinez-Pinna, Manuel Castellano-Muñoz, Paloma Alonso-Magdalena, Laura Marroqui, Ivan Quesada, Jan-Ake Gustafsson, Angel Nadal
In regulatory toxicology, the dose-response relationship is a key element towards fulfilling safety assessments and satisfying regulatory authorities. Conventionally, the larger the dose, the greater the response, following the dogma "the dose makes the poison". Many endocrine disrupting chemicals, including bisphenol-A (BPA), induce non-monotonic dose response (NMDR) relationships, which are unconventional and have tremendous implications in risk assessment. Although several molecular mechanisms have been proposed to explain NMDR relationships, they are largely undemonstrated...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923947/tpc2-polymorphisms-associated-with-a-hair-pigmentation-phenotype-in-humans-result-in-gain-of-channel-function-by-independent-mechanisms
#20
Yu-Kai Chao, Verena Schludi, Cheng-Chang Chen, Elisabeth Butz, O N Phuong Nguyen, Martin Müller, Jens Krüger, Claudia Kammerbauer, Manu Ben-Johny, Angelika M Vollmar, Carola Berking, Martin Biel, Christian A Wahl-Schott, Christian Grimm
Two-pore channels (TPCs) are endolysosomal cation channels. Two members exist in humans, TPC1 and TPC2. Functional roles associated with the ubiquitously expressed TPCs include VEGF-induced neoangiogenesis, LDL-cholesterol trafficking and degradation, physical endurance under fasting conditions, autophagy regulation, the acrosome reaction in sperm, cancer cell migration, and intracellular trafficking of pathogens such as Ebola virus or bacterial toxins (e.g., cholera toxin). In a genome-wide association study for variants associated with human pigmentation characteristics two coding variants of TPC2, rs35264875 (encoding M484L) and rs3829241 (encoding G734E), have been found to be associated with a shift from brown to blond hair color...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
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