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https://www.readbyqxmd.com/read/29443544/taste-sensitivity-to-a-mixture-of-monosodium-glutamate-and-inosine-5-monophosphate-by-mice-lacking-both-subunits-of-the-t1r1-t1r3-amino-acid-receptor
#1
Ginger D Blonde, Susan P Travers, Alan Craig Spector
The taste of L-glutamate and its synergism with 5'-ribonucleotides is thought to be primarily mediated through the T1R1+T1R3 heterodimer in some mammals including rodents and humans. While knockout (KO) mice lacking either receptor subunit show impaired sensitivity to a range of monosodium glutamate (MSG) concentrations mixed with 2.5mM inosine 5'-monophosphate (IMP) in amiloride, wild-type (WT) controls can detect this IMP concentration, hindering direct comparison between genotypes. Moreover, some residual sensitivity persists in the KO group, suggesting that the remaining subunit could maintain a limited degree of function...
February 14, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29433578/resistant-hypertension-on-treatment-reshypot-sequential-nephron-blockade-compared-to-dual-blockade-of-the-renin-angiotensin-aldosterone-system-plus-bisoprolol-in-the-treatment-of-resistant-arterial-hypertension-study-protocol-for-a-randomized-controlled-trial
#2
Elizabeth do Espirito Santo Cestário, Letícia Aparecida Barufi Fernandes, Luiz Tadeu Giollo-Júnior, Jéssica Rodrigues Roma Uyemura, Camila Suemi Sato Matarucco, Manoel Idelfonso Paz Landim, Luciana Neves Cosenso-Martin, Lúcia Helena Bonalume Tácito, Heitor Moreno, José Fernando Vilela-Martin, Juan Carlos Yugar-Toledo
BACKGROUND: Resistant hypertension is characterized when the blood pressure (BP) remains above the recommended goal after taking three antihypertensive drugs with synergistic actions at their maximum recommended tolerated doses, preferably including a diuretic. Identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether acting on the control of intravascular volume or sodium balance, or acting on the effects of the renin-angiotensin-aldosterone system (RAAS) on the kidney...
February 12, 2018: Trials
https://www.readbyqxmd.com/read/29422286/visit-to-visit-lipid-variability-clinical-significance-effects-of-lipid-lowering-treatment-and-pharmaco-genetics
#3
REVIEW
Roelof A J Smit, Johan Wouter Jukema, Iris Postmus, Ian Ford, Pieternella Eline Slagboom, Bastiaan T Heijmans, Saskia Le Cessie, Stella Trompet
In recent years, visit-to-visit variability of serum lipids has been linked to both clinical outcomes and surrogate markers for vascular disease. In this article, we present an overview of the current evidence connecting this intraindividual variability to these outcome measures, discuss its interplay with lipid-lowering treatment, and describe the literature regarding genetic factors of possible interest. In addition, we undertook an explorative genome-wide association analysis on visit-to-visit variability of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, examining additive effects in 2530 participants from the placebo arm of the PROspective Study of Pravastatin in the Elderly at Risk trial...
January 11, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29413762/the-epithelial-sodium-channel-%C3%AE-enac-is-a-downstream-therapeutic-target-of-ascl1-in-pulmonary-neuroendocrine-tumors
#4
Min He, Shanshan Liu, Sachith Gallolu Kankanamalage, Mark D Borromeo, Luc Girard, Adi F Gazdar, John D Minna, Jane E Johnson, Melanie H Cobb
Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma, designated as a recalcitrant cancer by the National Cancer Institute, in urgent need of new rational therapeutic targets. Previous studies have determined that the basic helix-loop-helix transcription factor achaete-scute homolog 1 (ASCL1) is essential for the survival and progression of a fraction of pulmonary neuroendocrine cancer cells, which include both SCLC and a subset of non-SCLC. Previously, to understand how ASCL1 initiates tumorigenesis in pulmonary neuroendocrine cancer and identify the transcriptional targets of ASCL1, whole-genome RNA-sequencing analysis combined with chromatin immunoprecipitation-sequencing was performed with a series of lung cancer cell lines...
February 1, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29404051/simultaneous-quantification-of-amiloride-and-hydrochlorothiazide-in-human-plasma-by-liquid-chromatography-tandem-mass-spectrometry
#5
Jaivik V Shah, Priyanka A Shah, Mallika Sanyal, Pranav S Shrivastav
A selective, sensitive and precise assay based on solid phase extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the simultaneous determination of amiloride (AMI) and hydrochlorothiazide (HCTZ) in human plasma. Sample clean-up with 250 µL of plasma was done on Phenomenex Strata™-X extraction cartridges using their labeled internal standards (AMI-15N3 and HCTZ-13C,d2). Chromatography was performed on Hypersil Gold C18 (50 mm×3.0 mm, 5 µm) column using acetonitrile with 4...
October 2017: Journal of Pharmaceutical Analysis
https://www.readbyqxmd.com/read/29397423/the-phosphorylation-site-t613-in-the-%C3%AE-subunit-of-rat-epithelial-na-channel-enac-modulates-channel-inhibition-by-nedd4-2
#6
Bettina Krueger, Limin Yang, Christoph Korbmacher, Robert Rauh
The epithelial Na+ channel (ENaC) is a heteromeric channel composed of three subunits (α, β, γ). At the C-terminus of each subunit, a PY-motif allows binding of the ubiquitin ligase Nedd4-2 which plays a key role in promoting ENaC retrieval from the plasma membrane. Phosphorylation of Nedd4-2 by the serum and glucocorticoid-inducible kinase 1 (Sgk1) reduces Nedd4-2 binding to the PY-motifs. In β and γENaC, threonine residues (βT613, γT623) belong to an extracellular signal-regulated kinase (ERK) motif and directly precede the PY-motifs...
February 3, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29373035/epithelial-na-channel-enac-differentially-contributes-to-shear-stress-mediated-vascular-responsiveness-in-carotid-and-mesenteric-arteries-from-mice
#7
Zoe Ashley, Sama Mugloo, Fiona J McDonald, Martin Fronius
A potential "new player" in arteries for mediating shear stress responses is the Epithelial Sodium Channel (ENaC). ENaC's contribution as shear sensor in intact arteries, and particularly different types of arteries (conduit and resistance) is unknown. We investigated the role of ENaC in both conduit (carotid) and resistance (3rd order mesenteric) arteries isolated from C57Bl/6J mice. Vessel characteristics were determined at baseline (60 mmHg, no-flow), in response to increased intraluminal pressure and shear stress using a pressure myograph...
January 26, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29371419/plasma-potassium-determines-ncc-abundance-in-adult-kidney-specific-%C3%AE-enac-knockout
#8
Emilie Boscardin, Romain Perrier, Chloé Sergi, Marc P Maillard, Johannes Loffing, Dominique Loffing-Cueni, Robert Koesters, Bernard C Rossier, Edith Hummler
The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the αENaC subunit leads to a perinatal lethal phenotype characterized by sodium loss and hyperkalemia resembling the human syndrome pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific deletion of αENaC in mice mimics the lethal phenotype observed in neonates, and as in humans, this phenotype is prevented by a high sodium (HNa+)/low potassium (LK+) rescue diet...
January 25, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29371098/distribution-of-fos-immunoreactive-neurons-in-the-gustatory-cortex-elicited-by-intra-oral-infusion-of-taste-solutions-in-conscious-rats
#9
Michael S King
The location of neurons in the gustatory cortex (GC) activated by intra-oral infusion of solutions in conscious rats was mapped using Fos immunohistochemistry. Groups of adult male Wistar rats (N's=5) received an infusion of one of the following: dH2O, 0.1 or 1.0M NaCl, 0.1 or 1.0M sucrose, 0.32M MSG (with 100µM amiloride and 2.5M inosine 5'-monophosphate), 0.03M HCl, or 0.003M QHCl delivered via an intra-oral cannula (0.233ml/min for 5 min). Unstimulated control rats received no infusion. Taste reactivity (TR) behaviors were videotaped and scored...
January 22, 2018: Brain Research
https://www.readbyqxmd.com/read/29363322/albuminuria-in-kidney-transplant-recipients-is-associated-with-increased-urinary-serine-proteases-and-activation-of-the-epithelial-sodium-channel
#10
Gitte Rye Hinrichs, Jannie Solmunde Michelsen, Rikke Zachar, Ulla Glenert Friis, Per Svenningsen, Henrik Birn, Claus Bistrup, Boye L Jensen
Albuminuria predicts adverse renal outcome in kidney transplant recipients. The present study addressed the hypothesis that albuminuria is associated with increased urine serine proteases with the ability to activate the epithelial sodium channel (ENaC) and with greater extracellular volume and higher blood pressure. In a cross-sectional design, kidney transplant recipients with (n=18) and without (n=19) albuminuria were included for office blood pressure measurements, estimation of volume status by bioimpedance, and collection of spot urine and plasma samples...
January 24, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29357433/mccdcl1-cells-show-plasticity-consistent-with-the-ability-to-transition-between-principal-and-intercalated-cells
#11
Adrienne M Assmus, Morag K Mansley, Linda J Mullins, Audrey Peter, John J Mullins
The cortical collecting duct of the mammalian kidney plays a critical role in the regulation of body volume, sodium pH and osmolarity and is composed of two distinct cells types, principal cells and intercalated cells. Each cell type is detectable in the kidney by the localization of specific transport proteins such as Aqp2 and ENaC in principal cells and V-ATPase B1 and Cx30 in intercalated cells. mCCDcl1 cells have been widely used as a mouse principal cell line on the basis of their physiological characteristics...
December 20, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29351436/therapeutic-attenuation-of-the-epithelial-sodium-channel-with-a-splunc1-derived-peptide-in-airway-diseases
#12
James F Collawn, Rafal Bartoszewski, Ahmad Lazrak, Sadis Matalon
The airway surface liquid (ASL) coats the lining of the airways and allows for efficient cilial movement and therefore effective mucociliary transport. Cell surface channels regulate the hydration status of the ASL and the two critical channels in the process are the cystic fibrosis transmembrane conductance regulator (CFTR) and the amiloride-sensitive epithelial sodium channel (ENaC). In cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) there is loss of CFTR function or compromised CFTR function in chronic bronchitis, respectively...
January 4, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29350674/takotsubo-cardiomyopathy-in-an-ultra-centenarian-woman
#13
Laura Bonfanti, Silvia Buratti, Luigi Vignali, Giuseppe Lippi, Franco Masini, Michele Bianconcini, Gianfranco Cervellin
A 101 years-old woman was admitted to our Emergency Department (ED) for acute dyspnea which onset nearly two hours before presentation. She had been on hydrochlorothyazyde-amiloride therapy due to mild hypertension. No other relevant features were present in the clinical history. The old lady had never been admitted to the hospital, and she was still living alone. A few days before hospital admission, one of the daughters became ill, so that a caregiver was paid for assisting her 12/24. This new circumstance was reluctantly accepted by the old lady...
January 16, 2018: Acta Bio-medica: Atenei Parmensis
https://www.readbyqxmd.com/read/29329001/improved-antibacterial-activity-of-a-marine-peptide-n2-against-intracellular-salmonella-typhimurium-by-conjugating-with-cell-penetrating-peptides-blfcin6-tat11
#14
Zhanzhan Li, Xiao Wang, Da Teng, Ruoyu Mao, Ya Hao, Na Yang, Huixian Chen, Xiumin Wang, Jianhua Wang
Salmonellae, gram-negative bacteria, are facultative intracellular pathogens that cause a number of diseases in animals and humans. The poor penetration ability of antimicrobial agents limits their use in the treatment of intracellular bacterial infections. In this study, the cell-penetrating peptides (CPPs) bLFcin6 and Tat11 were separately conjugated to the antimicrobial peptide N2, and the antibacterial activity and pharmacodynamics of the CPPs-N2 conjugates were first evaluated against Salmonellae typhimurium in vitro and in macrophage cells...
December 29, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29328476/effect-of-a-synthetic-inhibitor-of-urokinase-plasminogen-activator-on-the-migration-and-invasion-of-human-cervical-cancer-cells-in-vitro
#15
Xuechun Wang, Zhongqing Jiang, Jian An, Xiaodan Mao, Fen Lin, Pengming Sun
As a notable feature of malignant tumors, invasion and metastasis are important events in the process of tumor progression. Amiloride, a synthetic inhibitor of urokinase plasminogen activator (uPA), is involved in these events. To evaluate the therapeutic value of amiloride in cervical cancer, HeLa cells were used as in vitro cellular models. The migration and invasion abilities of HeLa cells, in addition to the mRNA expression of matriptase, uPA, uPA receptor and 72 kDa type IV collagenase (MMP‑2), were detected using scratch assays, Transwell chamber assays and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR)...
January 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29283974/the-role-of-distal-tubule-and-collecting-duct-sodium-reabsorption-in-sunitinib-induced-hypertension
#16
Jeannine Witte, Josephine Lampe, Anna Koenen, Ines Urbaneck, Antje Steinbach, Rainer Rettig, Olaf Grisk
OBJECTIVE: Antiangiogenic receptor tyrosine kinase inhibitors (RTKI) induce arterial hypertension which may limit their use. Renal fractional sodium excretion (FENa) is reduced in early RTKI-induced hypertension, whereas fractional lithium excretion is unaltered. Therefore, we tested the hypothesis that activated distal tubule and collecting duct sodium reabsorption contributes to RTKI-induced hypertension. METHODS: Amiloride-sensitive and hydrochlorothiazide (HCTZ)-sensitive fractional sodium reabsorption (FRNa) and renal epithelial sodium channel (ENaC) as well as sodium chloride cotransporter (NCC) abundances were determined in sunitinib-treated and control rats...
December 27, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/29280022/molecular-characterization-and-expression-analysis-of-the-na-h-exchanger-gene-family-in-medicago-truncatula
#17
Devinder Sandhu, Manju V Pudussery, Rakesh Kaundal, Donald L Suarez, Amita Kaundal, Rajandeep S Sekhon
One important mechanism plants use to cope with salinity is keeping the cytosolic Na+ concentration low by sequestering Na+ in vacuoles, a process facilitated by Na+/H+ exchangers (NHX). There are eight NHX genes (NHX1 through NHX8) identified and characterized in Arabidopsis thaliana. Bioinformatics analyses of the known Arabidopsis genes enabled us to identify six Medicago truncatula NHX genes (MtNHX1, MtNHX2, MtNHX3, MtNHX4, MtNHX6, and MtNHX7). Twelve transmembrane domains and an amiloride binding site were conserved in five out of six MtNHX proteins...
December 26, 2017: Functional & Integrative Genomics
https://www.readbyqxmd.com/read/29251736/pge2-ep1-receptor-inhibits-vasopressin-dependent-water-reabsorption-and-sodium-transport-in-mouse-collecting-duct
#18
Rania Nasrallah, Joseph Zimpelmann, David Eckert, Jamie Ghossein, Sean Geddes, Jean-Claude Beique, Jean-Francois Thibodeau, Chris R J Kennedy, Kevin D Burns, Richard L Hébert
PGE2 regulates glomerular hemodynamics, renin secretion, and tubular transport. This study examined the contribution of PGE2 EP1 receptors to sodium and water homeostasis. Male EP1-/- mice were bred with hypertensive TTRhRen mice (Htn) to evaluate blood pressure and kidney function at 8 weeks of age in four groups: wildtype (WT), EP1-/-, Htn, HtnEP1-/-. Blood pressure and water balance were unaffected by EP1 deletion. COX1 and mPGE2 synthase were increased and COX2 was decreased in mice lacking EP1, with increases in EP3 and reductions in EP2 and EP4 mRNA throughout the nephron...
December 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29247010/cell-penetrating-peptides-derived-from-clostridium-difficile-tcdb2-and-a-related-large-clostridial-toxin
#19
Jason L Larabee, Garrett D Hauck, Jimmy D Ballard
Clostridium difficile TcdB (2366 amino acid residues) is an intracellular bacterial toxin that binds to cells and enters the cytosol where it glucosylates small GTPases. In the current study, we examined a putative cell entry region of TcdB (amino acid residues 1753-1851) for short sequences that function as cell penetrating peptides (CPPs). To screen for TcdB-derived CPPs, a panel of synthetic peptides were tested for the ability to enhance transferrin (Tf) association with cells. Four candidate CPPs were discovered and further study on one peptide (PepB2) pinpointed an asparagine residue necessary for CPP activity...
December 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29233471/resolvin-d1-regulates-epithelial-ion-transport-and-inflammation-in-cystic-fibrosis-airways
#20
Fiona C Ringholz, Gerard Higgins, Aurélie Hatton, Ali Sassi, Ahmad Moukachar, Coral Fustero-Torre, Monika Hollenhorst, Isabelle Sermet-Gaudelus, Brian J Harvey, Paul McNally, Valerie Urbach
BACKGROUND: Cystic Fibrosis (CF) lung disease is characterised by dysregulated ion transport that promotes chronic bacterial infection and inflammation. The impact of the specialised pro-resolution mediator resolvin D1 (RvD1) on airway surface liquid (ASL) dynamics and innate defence had not yet been investigated in CF airways. METHODS: Ex vivo studies were performed on primary cultures of alveolar macrophages and bronchial epithelial cells from children with CF and in human bronchial epithelial cell lines; in vivo studies were performed in homozygous F508del-CFTR mice treated with vehicle control or RvD1 (1-100nM)...
December 7, 2017: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
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