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https://www.readbyqxmd.com/read/27900368/whole-exome-sequencing-reveals-an-inherited-r566x-mutation-of-the-epithelial-sodium-channel-%C3%AE-subunit-in-a-case-of-early-onset-phenotype-of-liddle-syndrome
#1
Linda M Polfus, Eric Boerwinkle, Richard A Gibbs, Ginger Metcalf, Donna Muzny, Narayanan Veeraraghavan, Megan Grove, Sanjay Shete, Stephanie Wallace, Dianna Milewicz, Neil Hanchard, James R Lupski, Syed Shahrukh Hashmi, Monesha Gupta-Malhotra
To comprehensively evaluate a European-American child with severe hypertension, whole-exome sequencing (WES) was performed on the child and parents, which identified causal variation of the proband's early-onset disease. The proband's hypertension was resistant to treatment, requiring a multiple drug regimen including amiloride, spironolactone, and hydrochlorothiazide. We suspected a monogenic form of hypertension because of the persistent hypokalemia with low plasma levels of renin and aldosterone. To address this, we focused on rare functional variants and indels, and performed gene-based tests incorporating linkage scores and allele frequency and filtered on deleterious functional mutations...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27865862/impaired-mucus-clearance-exacerbates-allergen-induced-type-2-airway-inflammation-in-juvenile-mice
#2
Benedikt Fritzsching, Matthias Hagner, Lu Dai, Sandra Christochowitz, Raman Agrawal, Charlotte van Bodegom, Simone Schmidt, Jolanthe Schatterny, Stephanie Hirtz, Ryan Brown, Michelle Goritzka, Julia Duerr, Zhe Zhou-Suckow, Marcus A Mall
BACKGROUND: Type 2 airway inflammation plays a central role in the pathogenesis of allergen-induced asthma, but the underlying mechanisms remain poorly understood. We recently demonstrated that reduced mucociliary clearance, a characteristic feature of asthma, produces spontaneous type 2 airway inflammation in juvenile Scnn1b-transgenic (Scnn1b-Tg) mice. OBJECTIVE: To determine the role of impaired mucus clearance in the pathogenesis of allergen-induced type 2 airway inflammation and identify cellular sources of the signature cytokine IL-13...
November 16, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27847440/gintonin-facilitates-catecholamine-secretion-from-the-perfused-adrenal-medulla
#3
Seung-Yeol Na, Ki-Hwan Kim, Mi-Sung Choi, Kang-Su Ha, Dong-Yoon Lim
The present study was designed to investigate the characteristics of gintonin, one of components isolated from Korean Ginseng on secretion of catecholamines (CA) from the isolated perfused model of rat adrenal gland and to clarify its mechanism of action. Gintonin (1 to 30 µg/ml), perfused into an adrenal vein, markedly increased the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. The gintonin-evoked CA secretion was greatly inhibited in the presence of chlorisondamine (1 µM, an autonomic ganglionic bloker), pirenzepine (2 µM, a muscarinic M1 receptor antagonist), Ki14625 (10 µM, an LPA1/3 receptor antagonist), amiloride (1 mM, an inhibitor of Na(+)/Ca(2+) exchanger), a nicardipine (1 µM, a voltage-dependent Ca(2+) channel blocker), TMB-8 (1 µM, an intracellular Ca(2+) antagonist), and perfusion of Ca(2+)-free Krebs solution with 5mM EGTA (a Ca(2+)chelater), while was not affected by sodium nitroprusside (100 µM, a nitrosovasodialtor)...
November 2016: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/27829053/no-evidence-for-ionotropic-pheromone-transduction-in-the-hawkmoth-manduca-sexta
#4
Andreas Nolte, Petra Gawalek, Sarah Koerte, HongYing Wei, Robin Schumann, Achim Werckenthin, Jürgen Krieger, Monika Stengl
Insect odorant receptors (ORs) are 7-transmembrane receptors with inverse membrane topology. They associate with the conserved ion channel Orco. As chaperon, Orco maintains ORs in cilia and, as pacemaker channel, Orco controls spontaneous activity in olfactory receptor neurons. Odorant binding to ORs opens OR-Orco receptor ion channel complexes in heterologous expression systems. It is unknown, whether this also occurs in vivo. As an alternative to this ionotropic transduction, experimental evidence is accumulating for metabotropic odor transduction, implicating that insect ORs couple to G-proteins...
2016: PloS One
https://www.readbyqxmd.com/read/27827955/a-novel-role-of-dickkopf-related-protein-3-in-macropinocytosis-in-human-bladder-cancer-t24-cells
#5
Nonoka Tsujimura, Nami O Yamada, Yuki Kuranaga, Minami Kumazaki, Haruka Shinohara, Kohei Taniguchi, Yukihiro Akao
Dickkopf-related protein 3 (Dkk-3) is a potential tumor suppressor reported in various cancer entities. However, we found that Dkk-3 was exceptionally upregulated in bladder cancer T24 cells. To validate the biological role of Dkk-3 other than a tumor suppressor, we examined the function of Dkk-3 in T24 cells. Gene silencing of Dkk-3 inhibited cell growth through inducing G₀/G₁ cell-cycle arrest. Furthermore, Dkk-3 knock-down caused macropinocytosis accompanied by autophagy, which were canceled in part by their inhibitors 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and 3-methyladenine (3-MA)...
November 5, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27820820/asic1a-deficient-mice-show-unaltered-neurodegeneration-in-the-subacute-mptp-model-of-parkinson-disease
#6
Daniel Komnig, Silke Imgrund, Arno Reich, Stefan Gründer, Björn H Falkenburger
Inflammation contributes to the death of dopaminergic neurons in Parkinson disease and can be accompanied by acidification of extracellular pH, which may activate acid-sensing ion channels (ASIC). Accordingly, amiloride, a non-selective inhibitor of ASIC, was protective in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson disease. To complement these findings we determined MPTP toxicity in mice deficient for ASIC1a, the most common ASIC isoform in neurons. MPTP was applied i...
2016: PloS One
https://www.readbyqxmd.com/read/27816051/molecular-features-of-the-cytotoxicity-of-an-nhe-inhibitor-evidence-of-mitochondrial-alterations-ros-overproduction-and-dna-damage
#7
Francesca Aredia, Sebastian Czaplinski, Simone Fulda, A Ivana Scovassi
BACKGROUND: NH exchangers (NHEs) play a crucial role in regulating intra/extracellular pH, which is altered in cancer cells, and are therefore suitable targets to alter cancer cell metabolism in order to inhibit cell survival and proliferation. Among NHE inhibitors, amiloride family members are commonly used in clinical practice as diuretics; we focused on the amiloride HMA, reporting a net cytotoxic effect on a panel of human cancer cell lines; now we aim to provide new insights into the molecular events leading to cell death by HMA...
November 5, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27802150/feeding-through-your-gills-and-turning-a-toxicant-into-a-resource-how-the-dogfish-shark-scavenges-ammonia-from-its-environment
#8
Chris M Wood, Marina Giacomin
Nitrogen (N) appears to be a limiting dietary resource for elasmobranchs, required not only for protein growth but also for urea-based osmoregulation. Building on recent evidence that the toxicant ammonia can be taken up actively at the gills of the shark and made into the valuable osmolyte urea, we demonstrate that the uptake exhibits classic Michaelis-Menten saturation kinetics with an affinity constant (Km) of 379 µmol l(-1), resulting in net N retention at environmentally realistic ammonia concentrations (100-400 µmol l(-1)) and net N loss through stimulated urea-N excretion at higher levels...
October 15, 2016: Journal of Experimental Biology
https://www.readbyqxmd.com/read/27787836/should-all-patients-with-resistant-hypertension-receive-spironolactone
#9
REVIEW
Ján Rosa, Tomáš Zelinka, Ondřej Petrák, Branislav Štrauch, Robert Holaj, Jiří Widimský
PURPOSE OF REVIEW: Resistant hypertension is a common clinical situation. Identification of true resistant hypertension (using 24-h ambulatory blood pressure monitoring to exclude white coat phenomenon, excluding secondary causes and non-adherence to treatment) is important mostly because of the application of a proper therapeutic approach and the higher cardiovascular risk of these patients. This review surveys recent studies, with a focus on mineralocorticoid receptor antagonists, including spironolactone, in the treatment of resistant hypertension...
November 2016: Current Hypertension Reports
https://www.readbyqxmd.com/read/27787523/fever-range-hyperthermia-improves-the-anti-apoptotic-effect-induced-by-low-ph-on-human-neutrophils-promoting-a-proangiogenic-profile
#10
Fernando Erra Díaz, Ezequiel Dantas, Maia Cabrera, Constanza A Benítez, María V Delpino, Gabriel Duette, Julia Rubione, Norberto Sanjuan, Analía S Trevani, Jorge Geffner
Neutrophils have the shortest lifespan among leukocytes and usually die via apoptosis, limiting their deleterious potential. However, this tightly regulated cell death program can be modulated by pathogen-associated molecular patterns (PAMPs), danger-associated molecular pattern (DAMPs), and inflammatory cytokines. We have previously reported that low pH, a hallmark of inflammatory processes and solid tumors, moderately delays neutrophil apoptosis. Here we show that fever-range hyperthermia accelerates the rate of neutrophil apoptosis at neutral pH but markedly increases neutrophil survival induced by low pH...
October 27, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27784066/trpv2-channels-contribute-to-stretch-activated-cation-currents-and-myogenic-constriction-in-retinal-arterioles
#11
Mary K McGahon, José A Fernández, Durga P Dash, Jon McKee, David A Simpson, Alex V Zholos, J Graham McGeown, Tim M Curtis
Purpose: Activation of the transient receptor potential channels, TRPC6, TRPM4, and TRPP1 (PKD2), has been shown to contribute to the myogenic constriction of cerebral arteries. In the present study we sought to determine the potential role of various mechanosensitive TRP channels to myogenic signaling in arterioles of the rat retina. Methods: Rat retinal arterioles were isolated for RT-PCR, Fura-2 Ca2+ microfluorimetry, patch-clamp electrophysiology, and pressure myography studies...
October 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27776319/medium-dependent-dual-turn-on-turn-off-fluorescence-sensing-for-cu-2-ions-using-ami-sds-assemblies
#12
Varsha B Gujar, Divya Ottoor
Behavior of Amiloride (AMI) as a metal ion sensor in anionic surfactant assemblies of varying concentrations at different pH is depicted in this work. From a non-sensor fluorophore, AMI has been transformed in to a tunable fluorosensor for Cu(2+) ions in various SDS concentrations. At premicellar concentration of SDS, ion-pair complex is expected to be formed between AMI and SDS due to electrostatic interactions between them. However at CMC concentrations of SDS, fluorescence intensity of AMI is greatly enhanced with red shift in emission, due to the incorporation of AMI molecule in the hydrophobic micellar interface...
October 18, 2016: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/27770439/non-proton-ligand-sensing-domain-of-acid-sensing-ion-channel-3-is-required-for-itch-sensation
#13
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
https://www.readbyqxmd.com/read/27762337/formaldehyde-impairs-transepithelial-sodium-transport
#14
Yong Cui, Huiming Li, Sihui Wu, Runzhen Zhao, Deyi Du, Yan Ding, Hongguang Nie, Hong-Long Ji
Unsaturated oxidative formaldehyde is a noxious aldehyde in cigarette smoke that causes edematous acute lung injury. However, the mechanistic effects of formaldehyde on lung fluid transport are still poorly understood. We examined how formaldehyde regulates human epithelial sodium channels (ENaC) in H441 and expressed in Xenopus oocytes and exposed mice in vivo. Our results showed that formaldehyde reduced mouse transalveolar fluid clearance in vivo. Formaldehyde caused a dose-dependent inhibition of amiloride-sensitive short-circuit Na(+) currents in H441 monolayers and of αβγ-ENaC channel activity in oocytes...
October 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27760555/a-modulatory-role-of-asics-on-gabaergic-synapses-in-rat-hippocampal-cell-cultures
#15
Maksim Storozhuk, Elena Kondratskaya, Lyudmila Nikolaenko, Oleg Krishtal
Rapid acidification occurring during synaptic vesicle release can activate acid-sensing ion channels (ASICs) both on pre- and postsynaptic neurons. In the latter case, a fraction of postsynaptic current would be mediated by cation-selective acid-sensing ion channels. Additionally, in both cases, activation of acid-sensing ion channels could modulate synaptic strength by affecting transmitter release and/or sensitivity of postsynaptic receptors. To address potential involvement of acid-sensing ion channels in mediation/modulation of synaptic transmission at hippocampal GABAergic synapses, we studied effects of three structurally different blockers of acid-sensing ion channels on evoked postsynaptic currents using the patch-clamp technique...
October 19, 2016: Molecular Brain
https://www.readbyqxmd.com/read/27754303/lbos-02-04-blood-pressure-associated-polymorphisms-in-slc4a7%C3%A2-sodium-bicarbonate-co-transporter-nbcn1-are-linked-to-gene-expression-and-intracellular-ph-regulation
#16
Fu Liang Ng, Ebbe Boedtkjer, Shu Ye, Mark Caulfield
OBJECTIVE: Chromosome 3p24.1 containing the SLC4A7 gene has been identified by genome-wide association studies as one of the genomic loci that influence blood pressure. SLC4A7 encodes electroneutral Na/HCO3 co-transporter (NBCn1) which regulates intracellular pH (pHi) in various tissues including vascular smooth muscle and endothelium, with knockout models demonstrating an altered blood pressure phenotype. We conducted a functional study of blood pressure-associated single nucleotide polymorphisms at the SLC4A7 locus in primary cultures of human vascular smooth muscle and endothelial cells...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27754008/js-ish-esh-4-what-do-clinical-trials-teach-us-about-selection-of-antihypertensive-drugs
#17
William C Cushman
Beginning with the Veterans Administration (VA) Cooperative Hypertension Study of the 1960 s, blood pressure (BP) lowering with antihypertensive medications has been shown to reduce major cardiovascular (CV) outcomes, including coronary heart disease, stroke, heart failure (HF) and CV and all-cause mortality in randomized controlled CV outcome trials. Multiple drugs were usually required in these trials to lower BP in treated participants. Medication regimens in the early trials, including the VA trial, included a thiazide-type diuretic (TTD) as initial therapy...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27753817/ssa-05-4-differences-in-management-of-hypertension-between-ethnic-groups
#18
Brian Rayner
Although the consequences of hypertension are universal, Blacks (African Americans or Indigenous Africans) have been the subject of a differential approach to causation, outcome and treatment. Blacks have a greater propensity to salt sensitivity and suppressed plasma renin suggesting a predisposition to Na retention by the kidney. As a result blood pressure (BP) response to diuretics and amlodipine is better than inhibitors of the renin-angiotensin-system in monotherapy. Target organ damage is more frequent and blood pressure (BP) is more difficult to control despite more intensive therapy...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27727333/corrigendum-to-spinal-antinociceptive-action-of-amiloride-and-its-interaction-with-tizanidine-in-the-rat-formalin-test
#19
Handong Ouyang, Peizong Wang, Wan Huang, Qian Li, Bilin Nie, Weian Zeng
[This corrects the article DOI: 10.1155/2015/902914.].
2016: Pain Research & Management: the Journal of the Canadian Pain Society
https://www.readbyqxmd.com/read/27717709/cns-sites-activated-by-renal-pelvic-epithelial-sodium-channels-enacs-in-response-to-hypertonic-saline-in-awake-rats
#20
Vanessa S Goodwill, Christopher Terrill, Ian Hopewood, Arthur D Loewy, Mark M Knuepfer
In some patients, renal nerve denervation has been reported to be an effective treatment for essential hypertension. Considerable evidence suggests that afferent renal nerves (ARN) and sodium balance play important roles in the development and maintenance of high blood pressure. ARN are sensitive to sodium concentrations in the renal pelvis. To better understand the role of ARN, we infused isotonic or hypertonic NaCl (308 or 500mOsm) into the left renal pelvis of conscious rats for two 2hours while recording arterial pressure and heart rate...
September 22, 2016: Autonomic Neuroscience: Basic & Clinical
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