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https://www.readbyqxmd.com/read/28713285/amiloride-improves-endothelial-function-and-reduces-vascular-stiffness-in-female-mice-fed-a-western-diet
#1
Luis A Martinez-Lemus, Annayya R Aroor, Francisco I Ramirez-Perez, Guanghong Jia, Javad Habibi, Vincent G DeMarco, Brady Barron, Adam Whaley-Connell, Ravi Nistala, James R Sowers
Obese premenopausal women lose their sex related cardiovascular disease protection and develop greater arterial stiffening than age matched men. In female mice, we have shown that consumption of a Western diet (WD), high in fat and refined sugars, is associated with endothelial dysfunction and vascular stiffening, which occur via activation of mineralocorticoid receptors and associated increases in epithelial Na(+) channel (ENaC) activity on endothelial cells (EnNaC). Herein our aim was to determine the effect that reducing EnNaC activity with a very-low-dose of amiloride would have on decreasing endothelial and arterial stiffness in young female mice consuming a WD...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28710092/a-missense-mutation-in-the-extracellular-domain-of-%C3%AE-enac-causes-liddle-syndrome
#2
Mahdi Salih, Ivan Gautschi, Miguel X van Bemmelen, Michael Di Benedetto, Alice S Brooks, Dorien Lugtenberg, Laurent Schild, Ewout J Hoorn
Liddle syndrome is an autosomal dominant form of hypokalemic hypertension due to mutations in the β- or γ-subunit of the epithelial sodium channel (ENaC). Here, we describe a family with Liddle syndrome due to a mutation in αENaC. The proband was referred because of resistant hypokalemic hypertension, suppressed renin and aldosterone, and no mutations in the genes encoding β- or γENaC. Exome sequencing revealed a heterozygous, nonconservative T>C single-nucleotide mutation in αENaC that substituted Cys479 with Arg (C479R)...
July 14, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28692350/the-muscular-dystrophic-chicken-is-hypernatremic
#3
N Saito, H Hirayama, K Yoshimura, Y Atsumi, M Mizutani, K Kinoshita, A Fujiwara, T Namikawa
1. The WWP1 gene, the mutation of which causes muscular dystrophy in chickens, is expressed not only in the pectoral muscle, but also in a number of tissues such as the kidney. Therefore, this study examined some parameters related to kidney function in muscular dystrophic (MD) chickens. 2. Plasma osmolality, Na(+) and K(+) concentrations, aldosterone levels, and the expression of aquaporin (AQP) 2, AQP3, and α subunits of the amiloride-sensitive epithelial sodium channel (αENaC) were analysed in the kidneys of 5-week-old MD chickens and White Leghorn (WL) chickens under physiological conditions or after one day of water deprivation...
July 10, 2017: British Poultry Science
https://www.readbyqxmd.com/read/28678485/an-ursolic-acid-derived-small-molecule-triggers-cancer-cell-death-through-hyperstimulation-of-macropinocytosis
#4
Lin Sun, Bin Li, Xiaohui Su, Ge Chen, Yaqin Li, Linqian Yu, Li Li, Wanguo Wei
Macropinocytosis is a transient endocytosis that internalizes extracellular fluid and particles into vacuoles. Recent studies suggest that hyperstimulation of macropinocytosis can induce a novel nonapoptotic cell death, methuosis. In this report, we describe the identification of an ursolic acid derived small molecule (compound 17), which induces cancer cell death through hyperstimulation of macropinocytosis. 17 causes the accumulation of vacuoles derived from macropinosomes based on transmission electron microscopy, time-lapse microscopy, and labeling with extracellular fluid phase tracers...
July 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28667127/effect-of-urokinase-type-plasminogen-activator-on-in-vitro-bovine-oocyte-maturation
#5
Mariela Roldán-Olarte, Veronica Maillo, Maria-Jesús Sánchez Calabuig, Paula Beltran-Breña, Dimitrios Rizos, Alfonso Gutierrez-Adan
This study examines the impacts of the urokinase type plasminogen activator (uPA) on the in vitro maturation (IVM) of bovine oocytes. Cumulus-oocyte complexes in IVM medium were treated with uPA, amiloride (an uPA inhibitor), DMSO or left untreated (control group). After 24 h of IVM, oocytes were recovered for testing or were in vitro fertilized and cultured to the blastocyst stage. The factors examined in all groups were: i) oocyte nuclear maturation (Hoëscht staining), ii) oocyte cytoplasmic maturation (cortical granules, CG, distribution assessed by LCA-FITC), iii) oocyte and cumulus cell (CC) gene expression (RT-qPCR), and iv) embryo development (cleavage rate and blastocyst yield)...
June 30, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28658531/assessment-of-acquired-mucociliary-clearance-defects-using-micro-optical-coherence-tomography
#6
Kiranya E Tipirneni, Jessica W Grayson, Shaoyan Zhang, Do-Yeon Cho, Daniel F Skinner, Dong-Jin Lim, Calvin Mackey, Guillermo J Tearney, Steven M Rowe, Bradford A Woodworth
BACKGROUND: Dehydration of airway surface liquid (ASL) disrupts normal mucociliary clearance (MCC) in sinonasal epithelium, which may lead to chronic rhinosinusitis (CRS). Abnormal chloride (Cl(-) ) transport is one such mechanism that contributes to this disorder and can be acquired secondary to environmental perturbations, such as hypoxia at the tissue surface. The objective of this study was to assess the technological feasibility of the novel micro-optical coherence tomography (μOCT) imaging technique for investigating acquired MCC defects in cultured human sinonasal epithelial (HSNE) cells...
June 28, 2017: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/28656379/physiology-and-pathophysiology-of-the-plasminogen-system-in-the-kidney
#7
REVIEW
Per Svenningsen, Gitte Rye Hinrichs, Rikke Zachar, Rikke Ydegaard, Boye L Jensen
The plasminogen system is important for fibrinolysis in addition to tissue remodeling and inflammation with significance for kidney disease. The system consists of the circulating zymogen plasminogen (Plg) and the tissue- and urokinase-type plasminogen activators, tPA and uPA, expressed in the glomeruli, endothelium and tubular epithelium, respectively, and the inhibitors α2-antiplasmin and plasminogen activator inhibitor-type1, PAI-1. Plasminogen is activated by surface receptors, some with renal expression: urokinase-type plasminogen activator receptor (uPAR), plasminogen receptor KT (Plg-RKT), and tPA, most evident in the endothelium...
June 27, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28655784/inhibition-of-megakaryocyte-differentiation-by-antibody-drug-conjugates-adcs-is-mediated-by-macropinocytosis-implications-for-adc-induced-thrombocytopenia
#8
Hui Zhao, Sara Gulesserian, Sathish Kumar Ganesan, Jimmy Ou, Karen Morrison, Zhilan Zeng, Veronica Robles, Josh Snyder, Lisa Do, Hector Aviña, Sher Karki, David R Stover, Fernando Doñate
Thrombocytopenia is a common adverse event in cancer patients treated with antibody-drug conjugates (ADCs), including AGS-16C3F, an ADC targeting ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase-3) and Trastuzumab emtansine (T-DM1). This study aims to elucidate the mechanism of action of ADC-induced thrombocytopenia. ENPP3 expression in platelets and megakaryocytes (MKs) was investigated and shown to be negative. The direct effect of AGS-16C3F on platelets was evaluated using platelet rich plasma following the expression of platelet activation markers...
June 27, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28611771/tnf-lectin-like-domain-restores-epithelial-sodium-channel-function-in-frameshift-mutants-associated-with-pseudohypoaldosteronism-type-1b
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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