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https://www.readbyqxmd.com/read/28611771/tnf-lectin-like-domain-restores-epithelial-sodium-channel-function-in-frameshift-mutants-associated-with-pseudohypoaldosteronism-type-1b
#1
Anita Willam, Mohammed Aufy, Susan Tzotzos, Dina El-Malazi, Franziska Poser, Alina Wagner, Birgit Unterköfler, Didja Gurmani, David Martan, Shahid Muhammad Iqbal, Bernhard Fischer, Hendrik Fischer, Helmut Pietschmann, Istvan Czikora, Rudolf Lucas, Rosa Lemmens-Gruber, Waheed Shabbir
Previous in vitro studies have indicated that tumor necrosis factor (TNF) activates amiloride-sensitive epithelial sodium channel (ENaC) current through its lectin-like (TIP) domain, since cyclic peptides mimicking the TIP domain (e.g., solnatide), showed ENaC-activating properties. In the current study, the effects of TNF and solnatide on individual ENaC subunits or ENaC carrying mutated glycosylation sites in the α-ENaC subunit were compared, revealing a similar mode of action for TNF and solnatide and corroborating the previous assumption that the lectin-like domain of TNF is the relevant molecular structure for ENaC activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28604611/eplerenone-resistant-salt-sensitive-hypertension-in-nedd4-2-c2-ko-mice
#2
Tabito Kino, Tomoaki Ishigami, Tsumugi Murata, Hiroshi Doi, Rie Nakashima-Sasaki, Lin Chen, Michiko Sugiyama, Kengo Azushima, Hiromichi Wakui, Shintaro Minegishi, Kouichi Tamura
The epithelial sodium channel (ENaC) plays critical roles in maintaining fluid and electrolyte homeostasis and is located in the aldosterone-sensitive distal nephron (ASDN). We previously found that Nedd4-2 C2 knockout (KO) mice showed salt-sensitive hypertension with paradoxically enhanced ENaC gene expression in ASDN under high oral salt intake. Eplerenone (EPL), a selective aldosterone blocker, is a promising therapeutic option for resistant or/and salt-sensitive hypertension. We examined the effect of EPL on Nedd4-2 C2 KO mice with respect to blood pressure, metabolic parameters, and molecular level changes in ASDN under high oral salt intake...
June 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28596575/infectious-pancreatic-necrosis-virus-enters-chse-214-cells-via-macropinocytosis
#3
Jorge Levican, Camila Miranda-Cárdenas, Ricardo Soto-Rifo, Francisco Aguayo, Aldo Gaggero, Oscar León
Infectious pancreatic necrosis virus (IPNV) is a non-enveloped virus belonging to the Birnaviridae family. IPNV produces an acute disease in salmon fingerlings, with high mortality rates and persistent infection in survivors. Although there are reports of IPNV binding to various cells, the viral receptor and entry pathways remain unknown. The aim of this study was to determine the endocytic pathway that allows for IPNV entry. We observed that IPNV stimulated fluid uptake and virus particles co-localysed with the uptake marker dextran in intracellular compartments, suggesting a role for macropinocytosis in viral entry...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28590304/antinociceptive-effect-of-epicatechin-in-inflammatory-and-neuropathic-pain-in-rats
#4
Geovanna N Quiñonez-Bastidas, Jorge B Pineda-Farias, Francisco J Flores-Murrieta, Juan Rodríguez-Silverio, Juan G Reyes-García, Beatriz Godínez-Chaparro, Vinicio Granados-Soto, Héctor I Rocha-González
The aim of this study was to investigate the antinociceptive potential of (-)-epicatechin and the possible mechanisms of action involved in its antinociceptive effect. The carrageenan and formalin tests were used as inflammatory pain models. A plethysmometer was used to measure inflammation and L5/L6 spinal nerve ligation as a neuropathic pain model. Oral (-)-epicatechin reduced carrageenan-induced inflammation and nociception by about 59 and 73%, respectively, and reduced formalin- induced and nerve injury-induced nociception by about 86 and 43%, respectively...
June 5, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28586600/liddle-s-syndrome
#5
Danish Abdul Aziz, Fozia Memon, Arshalooz Rahman, Madiha Ali
Hypertension in paediatric age group is commonly secondary to a known cause. It is crucial to identify the cause of hypertension and treat it before development of any associated complications to prevent morbidity and mortality. Paediatric Hypertension is one of the important clinical finding in a child with certain clinical syndrome. We are presenting a case of a 10 month old child presenting with hypertension and hypokalaemia, after excluding all identifiable causes and her positive response to therapy, that is amiloride, along with supportive biochemical data she was diagnosed as a case of monogenic type of hypertension known as Liddle's syndrome...
October 2016: Journal of Ayub Medical College, Abbottabad: JAMC
https://www.readbyqxmd.com/read/28576417/low-concentrations-of-neutrophil-extracellular-traps-induce-proliferation-in-human-keratinocytes-via-nf-kb-activation
#6
Stelvio Tonello, Manuela Rizzi, Mario Migliario, Vincenzo Rocchetti, Filippo Renò
INTRODUCTION: Granulocytes play a pivotal role in innate immune response, as pathogen invasion activates neutrophils, a subclass of granulocytes, inducing the production of neutrophil extracellular traps (NETs). In this study, it has been evaluated how NETs could affect human keratinocytes (HaCaT cells) behaviour. MATERIALS AND METHODS: HaCaT cells were treated with increasing NETs concentrations (0.01-200ng/ml) and the effect on cell proliferation was evaluated by MTT assay...
May 23, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28559392/renal-dysfunction-induced-by-kidney-specific-gene-deletion-of-hsd11b2-as-a-primary-cause-of-salt-dependent-hypertension
#7
Kohei Ueda, Mitsuhiro Nishimoto, Daigoro Hirohama, Nobuhiro Ayuzawa, Wakako Kawarazaki, Atsushi Watanabe, Tatsuo Shimosawa, Johannes Loffing, Ming-Zhi Zhang, Takeshi Marumo, Toshiro Fujita
Genome-wide analysis of renal sodium-transporting system has identified specific variations of Mendelian hypertensive disorders, including HSD11B2 gene variants in apparent mineralocorticoid excess. However, these genetic variations in extrarenal tissue can be involved in developing hypertension, as demonstrated in former studies using global and brain-specific Hsd11b2 knockout rodents. To re-examine the importance of renal dysfunction on developing hypertension, we generated kidney-specific Hsd11b2 knockout mice...
May 30, 2017: Hypertension
https://www.readbyqxmd.com/read/28557567/gene-expression-of-the-concentration-sensitive-sodium-channel-is-suppressed-in-lipopolysaccharide-induced-acute-lung-injury-in-mice
#8
Teruki Hagiwara, Shigeru Yoshida, Yuji Hidaka
PURPOSE: The concentration-sensitive sodium channel (NaC) is expressed in alveolar type II epithelial cells and pulmonary microvascular endothelial cells in mouse lungs. We recently reported that NaC contributes to amiloride-insensitive sodium transport in mouse lungs (Respiratory Physiology & Neurobiology, 2016). However, details regarding its physiological role in the lung remain unknown. To examine whether NaC is involved in alveolar fluid clearance during an acute lung injury (ALI), we analyzed the relationship between NaC gene expression in the lung and the development of pulmonary edema in lipopolysaccharide (LPS)-induced ALI mice...
April 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28526336/activation-of-na-h-exchanger-other-than-formation-of-transmembrane-pore-underlies-the-cytotoxicity-of-nematocyst-venom-from-chrysaora-helvola-brandt-jellyfish
#9
Lanlan Fan, Jun Luo, Xiaoyong Li, Ming Chen, Wei Shu, Xiaosheng Qu
We previously reported unexpected apoptosis-like cell death induced by nematocyst venom (NV) from Chrysaora helvola Brandt (C. helvola) jellyfish. To assess whether the pore formation mechanism underlay the action of NV, the change in cell membrane permeability was studied in both chicken erythrocytes and human CNE-2 cells. Initially, paradoxical results were derived from osmoprotectant protection assays. Polyethylene glycol (PEG)2000, which completely inhibited the NV induced hemolysis, failed to protect CNE-2 cells...
July 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28481660/spx-101-is-a-novel-enac-targeted-therapeutic-for-cystic-fibrosis-that-restores-mucus-transport
#10
David W Scott, Matthew P Walker, Juliana Sesma, Bryant Wu, Timothy J Stuhlmiller, Juan R Sabater, William M Abraham, Timothy M Crowder, Dale J Christensen, Robert Tarran
RATIONALE: Cystic Fibrosis lung disease (CF) is caused by the loss of function of the cystic fibrosis transmembrane conductance regulator (CFTR) combined with hyperactivation of the epithelial sodium channel (ENaC). In the lung, ENaC is responsible for movement of sodium which creates an osmotic gradient that pulls fluid out of the airway. Hyperactivation of ENaC contributes to reduced airway hydration causing mucus dehydration, decreased mucociliary clearance, and chronic bacterial infections...
May 8, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28473934/in-acute-iga-nephropathy-proteinuria-and-creatinine-are-in-the-spot-but-podocyturia-operates-in-silence-any-place-for-amiloride
#11
H Trimarchi, M Paulero, R Canzonieri, A Schiel, A Iotti, C Costales-Collaguazo, A Stern, M Forrester, F Lombi, V Pomeranz, R Iriarte, T Rengel, I Gonzalez-Hoyos, A Muryan, E Zotta
IgA nephropathy is the most frequent cause of primary glomerulonephritis, portends erratic patterns of clinical presentation, and lacks specific treatment. In general, it slowly progresses to end-stage renal disease. The clinical course and the response to therapy are usually assessed with proteinuria and serum creatinine. Validated biomarkers have not been identified yet. In this report, we present a case of acute renal injury with proteinuria and microscopic hematuria in a young male. A kidney biopsy disclosed IgA nephropathy...
2017: Case Reports in Nephrology
https://www.readbyqxmd.com/read/28472315/physiological-phenotyping-for-personalized-therapy-of-uncontrolled-hypertension-in-africa
#12
Adeseye Akintunde, Justus Nondi, Kennedy Gogo, Erika S W Jones, Brian L Rayner, Daniel G Hackam, J David Spence
OBJECTIVES: African and African American hypertensives tend to retain salt and water, with lower levels of plasma renin and more resistant hypertension. We tested the hypothesis that physiological phenotyping with plasma renin and aldosterone would improve blood pressure control in uncontrolled hypertensives in Africa. METHODS: Patients at hypertension clinics in Nigeria, Kenya, and South Africa with a systolic blood pressure >140 mm Hg or diastolic pressure > 90 mm Hg despite treatment were allocated to usual care (UC) vs...
May 2, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28449833/rational-medical-therapy-is-the-key-to-effective-cardiovascular-disease-prevention
#13
REVIEW
J David Spence
In an era in which medicine personalized on the basis of genotyping is being proposed, it is timely to recognize that existing therapies could be markedly improved if they were on the basis of more effective application of principles on the basis of available phenotyping. Blood pressure control, which is poor on a worldwide basis, is a major opportunity to reduce cardiovascular risk. There are many genetic variants that have a small effect on blood pressure, but specific therapies are not available for most of them...
May 2017: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/28430823/modulation-the-alternative-splicing-of-gla-ivs4-919g-a-in-fabry-disease
#14
Wen-Hsin Chang, Dau-Ming Niu, Chi-Yu Lu, Shyr-Yi Lin, Ta-Chih Liu, Jan-Gowth Chang
While a base substitution in intron 4 of GLA (IVS4+919G>A) that causes aberrant alternative splicing resulting in Fabry disease has been reported, its molecular mechanism remains unclear. Here we reported that upon IVS4+919G>A transversion, H3K36me3 was enriched across the alternatively spliced region. PSIP1, an adapter of H3K36me3, together with Hsp70 and NONO were recruited and formed a complex with SF2/ASF and SRp20, which further promoted GLA splicing. Amiloride, a splicing regulator in cancer cells, could reverse aberrant histone modification patterns and disrupt the association of splicing complex with GLA...
2017: PloS One
https://www.readbyqxmd.com/read/28411035/altered-ion-transport-in-normal-human-bronchial-epithelial-cells-following-exposure-to-chemically-distinct-metal-welding-fume-particles
#15
Jeffrey S Fedan, Janet A Thompson, Terence G Meighan, Patti C Zeidler-Erdely, James M Antonini
Welding fume inhalation causes pulmonary toxicity, including susceptibility to infection. We hypothesized that airway epithelial ion transport is a target of fume toxicity, and investigated the effects of fume particulates from manual metal arc-stainless steel (MMA-SS) and gas metal arc-mild steel (GMA-MS) on ion transport in normal human bronchial epithelium (NHBE) cultured in air-interface. MMA-SS particles, more soluble than GMA-MS particles, contain Cr, Ni, Fe and Mn; GMA-MS particles contain Fe and Mn...
July 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28409833/dietary-salt-blunts-vasodilation-by-stimulating-epithelial-sodium-channels-in-endothelial-cells-from-salt-sensitive-rats
#16
Zi-Rui Wang, Hui-Bin Liu, Ying-Ying Sun, Qing-Qing Hu, Yu-Xia Li, Wei-Wan Zheng, Chang-Jiang Yu, Xin-Yuan Li, Ming-Ming Wu, Bin-Lin Song, Jian-Jun Mu, Zu-Yi Yuan, Zhi-Ren Zhang, He-Ping Ma
BACKGROUND AND PURPOSE: Our recent studies show that the reduced activity of epithelial sodium channels (ENaC) in endothelial cells accounts for the adaptation of vasculature to salt in Sprague-Dawley (SD) rats. The present study examines a hypothesis that enhanced ENaC activity mediates the loss of vasorelaxation in Dahl salt-sensitive (SS) rats. EXPERIMENTAL APPROACH: We used the cell-attached patch-clamp technique to record ENaC activity in split-open mesenteric arteries...
April 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28401046/functional-neuroanatomy-in-panic-disorder-status-quo-of-the-research
#17
Thomas Sobanski, Gerd Wagner
AIM: To provide an overview of the current research in the functional neuroanatomy of panic disorder. METHODS: Panic disorder (PD) is a frequent psychiatric disease. Gorman et al (1989; 2000) proposed a comprehensive neuroanatomical model of PD, which suggested that fear- and anxiety-related responses are mediated by a so-called "fear network" which is centered in the amygdala and includes the hippocampus, thalamus, hypothalamus, periaqueductal gray region, locus coeruleus and other brainstem sites...
March 22, 2017: World Journal of Psychiatry
https://www.readbyqxmd.com/read/28396810/management-of-liddle-syndrome-in-pregnancy-a-case-report-and-literature-review
#18
Michael Awadalla, Manasi Patwardhan, Adham Alsamsam, Nashat Imran
Liddle syndrome is an autosomal dominant genetic condition that causes hypertension and hypokalemia due to a gain-of-function mutation in the SCNN1B or SCNN1G genes which code for the epithelial sodium channel in the kidney. This leads to increased sodium and water reabsorption causing hypertension. We report a case of a 27-year-old pregnant woman who was admitted for hypertension and hypokalemia and later diagnosed and treated for Liddle syndrome using amiloride. Maintaining a high suspicion of Liddle syndrome in pregnancy is essential in such cases to be able to adequately and effectively treat the hypertension...
2017: Case Reports in Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28383056/involvement-of-epithelial-na-channel-in-the-elevated-myogenic-response-in-posterior-cerebral-arteries-from-spontaneously-hypertensive-rats
#19
Soo-Kyoung Choi, Soo-In Yeon, Youngin Kwon, Seonhee Byeon, Young-Ho Lee
Hypertension is characterized by increased peripheral vascular resistance which is related with elevated myogenic response. Recent findings have indicated that epithelial sodium channel (ENaC) is involved in mechanotransduction of the myogenic response. The purpose of this study was to investigate the involvement of ENaC in the elevated myogenic response of posterior cerebral arteries (PCAs) from spontaneously hypertensive rats (SHRs). Sixteen to eighteen weeks old male wistar kyoto rats (WKYs) and SHRs were used in this study...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28381704/efficacy-of-precordial-percussion-pacing-assessed-in-a-cardiac-standstill-microminipig-model
#20
Takeshi Wada, Hiroshi Ohara, Yuji Nakamura, Xin Cao, Hiroko Izumi-Nakaseko, Kentaro Ando, Mitsuru Honda, Katsunori Yoshihara, Yuji Nakazato, Keith G Lurie, Atsushi Sugiyama
BACKGROUND: Potential cardiovascular benefits of precordial percussion pacing (PPP) during cardiac standstill are unknown.Methods and Results:A cardiac standstill model in amicrominipigwas created by inducing complete atrioventricular block with a catheter ablation technique (n=7). Next, the efficacy of cardiopulmonary resuscitation by standard chest compressions (S-CPR), PPP and ventricular electrical pacing in this model were analyzed in series (n=4). To assess the mechanism of PPP, a non-selective, stretch-activated channel blocker, amiloride, was administered during PPP (n=3)...
April 4, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
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