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https://www.readbyqxmd.com/read/29233471/resolvin-d1-regulates-epithelial-ion-transport-and-inflammation-in-cystic-fibrosis-airways
#1
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
https://www.readbyqxmd.com/read/29229646/nhe-and-diffusion-dependent-proton-fluxes-across-the-tubular-system-membranes-of-fast-twitch-muscle-fibers-of-the-rat
#2
Bradley S Launikonis, Tanya R Cully, Laszlo Csernoch, D George Stephenson
The complex membrane structure of the tubular system (t-system) in skeletal muscle fibers is open to the extracellular environment, which prevents measurements of H+ movement across its interface with the cytoplasm by conventional methods. Consequently, little is known about the t-system's role in the regulation of cytoplasmic pH, which is different from extracellular pH. Here we describe a novel approach to measure H+-flux measurements across the t-system of fast-twitch fibers under different conditions. The approach involves loading the t-system of intact rat fast-twitch fibers with a strong pH buffer (20 mM HEPES) and pH-sensitive fluorescent probe (10 mM HPTS) before the t-system is sealed off...
December 11, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29227582/role-of-the-sodium-hydrogen-exchanger-in-mediating-the-renal-effects-of-drugs-commonly-used-in-the-treatment-of-type-2-diabetes
#3
REVIEW
Milton Packer
Diabetes is characterized by an increased activity of the sodium-hydrogen exchanger (NHE) in the glomerulus and renal tubules, which contributes importantly to the development of nephropathy. Despite the established role played by the exchanger in experimental studies, it has not been specifically targeted by those seeking to develop novel pharmacological treatments for diabetes. This review demonstrates that many existing drugs that are commonly prescribed to patients with diabetes act on the NHE1 and NHE3 isoforms in the kidney...
December 11, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29227377/effectiveness-of-low-dose-diuretics-for-blood-pressure-reduction-to-optimal-values-in-prehypertension-a-randomized-clinical-trial
#4
Flávio D Fuchs, Sandra C Fuchs, Carlos E Poli-de-Figueiredo, José A Figueiredo Neto, Luiz César N Scala, José F Vilela-Martin, Leila B Moreira, Hilton Chaves, Marco Mota Gomes, Marcos R de Sousa, Ricardo Pereira E Silva, Iran Castro, Evandro José Cesarino, Ana Luiza Lima Sousa, João Guilherme Alves, André Avelino Steffens, Andréa Araujo Brandão, Luiz Aparecido Bortolotto, Abrahão Afiune Neto, Antônio C Nóbrega, Roberto Silva Franco, Dario C Sobral Filho, Fernando Nobre, Rosane Schlatter, Miguel Gus, Caroline Nespolo De David, Leticia Rafaelli, Guilhermo Prates Sesin, Otávio Berwanger, Paul K Whelton
BACKGROUND: To determine the effectiveness of low-dose diuretic therapy to achieve an optimal level of blood pressure (BP) in adults with prehypertension. METHODS: The PREVER-prevention trial was a randomized, parallel, double-blinded, placebo-controlled trial, with 18 months of follow-up, conducted at 21 academic medical centers in Brazil. Of 1772 individuals evaluated for eligibility, 730 volunteers with prehypertension who were aged 30-70 years, and who did not reach optimal blood pressure after 3 months of lifestyle intervention, were randomized to a fixed association of chlorthalidone 12...
December 7, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/29214230/cytotoxicity-of-endocytosis-and-efflux-inhibitors-in-the-bewo-cell-line
#5
Mansi Shah, Luke Bourner, Shariq Ali, Sanaalarab Al-Enazy, Erik Rytting
Aims: The purpose of this study was to determine the cell viability and cytotoxicity of various endocytosis and efflux inhibitors which can be used to determine transport and uptake mechanisms in the BeWo (b30 clone) human placental trophoblast cell line. Ethanol and dimethylsulfoxide (DMSO) were also studied since they are often used as cosolvents for administration of these inhibitors. Methodology: The water-soluble tetrazolium-1 (WST-1) assay was used to quantify cell viability and the lactate dehydrogenase (LDH) assay was used to determine cytotoxicity...
2017: Journal of Pharmaceutical Research International
https://www.readbyqxmd.com/read/29210147/drug-exposure-and-the-risk-of-multiple-sclerosis-a-systematic-review
#6
REVIEW
Heather Y Yong, Kyla A McKay, Cole G J Daley, Helen Tremlett
BACKGROUND: Several environmental and lifestyle factors have been associated with multiple sclerosis (MS) risk, including some pharmacological treatments. We systematically reviewed the literature on prescription drug exposure and MS risk. METHODS: Six databases were searched for original observational studies reporting drug exposure and MS risk published before 2017. RESULTS: Thirteen articles fulfilled inclusion criteria. Exposure to neither amiloride nor valproic acid was associated with MS (adjusted hazard ratio (adj...
December 6, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/29172994/amiloride-does-not-protect-retinal-nerve-fibre-layer-thickness-in-optic-neuritis-in-a-phase-2-randomised-controlled-trial
#7
Justin B McKee, Charles L Cottriall, John Elston, Simon Epps, Nikos Evangelou, Stephen Gerry, Christopher Kennard, Yazhuo Kong, Abigail Koelewyn, Wilhelm Kueker, Maria Isabel Leite, Jacqueline Palace, Matthew Craner
BACKGROUND: Recent basic and clinical evidence suggests amiloride may be neuroprotective in multiple sclerosis (MS) through the blockade of the acid sensing ion channel (ASIC). OBJECTIVE: To examine the neuroprotective efficacy of amiloride in acute optic neuritis (ON). METHODS: A total of 48 patients were recruited to a phase 2, double blind, single site, randomised controlled trial. Scanning laser polarimetry (GDx) at 6 months was the primary outcome measure and optical coherence tomography (OCT) and visual and electrophysiological measures were secondary outcome measures...
November 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29169687/understanding-the-inhibitory-mechanism-of-bit225-drug-against-p7-viroporin-using-computational-study
#8
Esmaeil Behmard, Parviz Abdolmaleki, Majid Taghdir
P7 is the only viral channel encoded by the Hepatitis C Virus (HCV) genome. It is a small, highly hydrophobic protein containing 63 amino acids. Structural studies have shown that p7 has two transmembrane (TM) α helices linked by a short dibasic cytoplasmic loop. P7, mostly placed in the endoplasmic reticulum (ER), is a membrane-associated protein. The results obtained from different studies revealed that p7 is a polytopic membrane protein that could oligomerize in membrane bilayer to create ion channels with cation selectivity...
November 16, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/29162216/treatment-regimens-by-pediatric-nephrologists-in-children-with-congenital-nephrogenic-diabetes-insipidus-a-mwpnc-study%C3%A2
#9
Cynthia D'Alessandri-Silva, Melinda Carpenter, John D Mahan
BACKGROUND: Congenital nephrogenic diabetes insipidus (NDI) is a rare genetic disorder affecting urinary concentration. Clinicians have varied medication regimens as well as nutritional plan approaches for these children. MATERIALS AND METHODS: An electronic survey was distributed to member pediatric nephrologists of the Midwest Pediatric Nephrology Consortium via email (n = 179). Questions included types of drugs prescribed, factors contributing to drug choice, common drug combinations given, and dietary/failure to thrive interventions used...
November 22, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/29145481/amiloride-enhanced-gene-transfection-of-octa-arginine-functionalized-calcium-phosphate-nanoparticles
#10
Juan Ramón Vanegas Sáenz, Taichi Tenkumo, Yuya Kamano, Hiroshi Egusa, Keiichi Sasaki
Nanoparticles represent promising gene delivery systems in biomedicine to facilitate prolonged gene expression with low toxicity compared to viral vectors. Specifically, nanoparticles of calcium phosphate (nCaP), the main inorganic component of human bone, exhibit high biocompatibility and good biodegradability and have been reported to have high affinity for protein or DNA, having thus been used as gene transfer vectors. On the other hand, Octa-arginine (R8), which has a high permeability to cell membrane, has been reported to improve intracellular delivery systems...
2017: PloS One
https://www.readbyqxmd.com/read/29144530/liddle-s-syndrome-in-an-african-male-due-to-a-novel-frameshift-mutation-in-the-beta-subunit-of-the-epithelial-sodium-channel-gene
#11
Robert Freercks, Surita Meldau, Erika Jones, Jason Ensor, Clarise Weimers-Willard, Brian Rayner
Resistant hypertension is a common clinical problem in South Africa and is frequently associated with low renin and aldosterone levels, especially in black Africans. In South Africa, novel variants in the epithelial sodium channel (ENaC) have been described to be associated with varying degrees of hypokalaemia and hypertension due to primary sodium retention. We report here a case of Liddle's syndrome due to a novel c.1709del11 (p.Ser570Tyrfs*20) deletion in the beta-subunit of the ENaC in a young black African male...
September 23, 2017: Cardiovascular Journal of Africa
https://www.readbyqxmd.com/read/29143861/migraine-with-prolonged-aura-phenotype-and-treatment
#12
REVIEW
Michele Viana, Shazia Afridi
We review the published literature on migraine with prolonged aura (PA), specifically with regards to the phenotype and treatment options. PA is not uncommon. A recent study found that about 17% of migraine auras are prolonged and that 26% of patients with migraine with aura have experienced at least one PA. The characteristics of PA are similar to most typical auras with the exception of a higher number of aura symptoms (in particular sensory and/or dysphasic). There are no well-established treatments at present which target the aura component of migraine...
November 16, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29134442/endothelial-tnf-%C3%AE-induction-by-hsp60-secreted-from-thp-1-monocytes-exposed-to-hyperglycaemic-conditions
#13
Ryan Dennis Martinus, Julie Goldsbury
A non-resolving inflammation of the endothelium is recognised to be an important process leading to atherosclerosis. In diabetes, this process is thought to account for a significant number of cardiovascular disease-associated death and disability. However, the molecular mechanisms by which diabetes contributes to endothelial inflammation remain to be established. Whilst there is some evidence linking hyperglycaemia-induced reactive oxygen species (ROS) formation by the mitochondrial electron-transport chain to oxidative stress, cellular injury and apoptosis in the endothelium, a clear link to endothelium inflammation has not yet been established...
November 13, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/29131643/electrophysiology-of-epithelial-sodium-channel-enac-embedded-in-supported-lipid-bilayer-using-a-single-nanopore-chip
#14
Muhammad Shuja Khan, Noura Sayed Dosoky, Ghulam Mustafa, Darayas Patel, Bakhrom K Berdiev, John Dalton Williams
Nanopore-based technologies are highly adaptable supports for developing label-free sensor chips to characterize lipid bilayers, membrane proteins and nucleotides. We utilized a single nanopore chip to study electrophysiology of epithelial Na+ channel (ENaC) incorporated in supported lipid membrane (SLM). An isolated nanopore was developed inside the silicon cavity followed by fusing large unilamellar vesicles (LUVs) of DPPS (1,2-dipalmitoyl-sn-glycero-3-phosphoserine) and DPPE (1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine) to produce a solvent-free SLM with giga-ohm (GΩ) sealed impedance...
November 13, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29131139/capsaicin-used-on-skin-influences-ion-transport-pathways-an-in-vitro-study
#15
Iga Hołyńska-Iwan, Inga Dziembowska, Paulina Smyk, Magdalena Lampka, Dorota Olszewska-Słonina
Acute, adverse skin effects to capsaicin can be activated by inhibition of sodium transport not only in nociceptive neurons, but also in keratinocytes. The aim of the current study was to describe and compare immediate (15 s) and prolonged (30 min) effects of capsaicin on epidermal (not neural) sodium transport using a rabbit skin model. Skin fragments (n = 169) were incubated in 4 conditions: undisturbed ion transport (U; n = 48); inhibited sodium transport (INa; n = 34) with amiloride used as sodium transport blocker; long-term irritation by capsaicin with undisturbed ion transport (CAPSA-U; n = 43) and with inhibited sodium transport (CAPSA-INa; n = 35)...
November 8, 2017: Skin Pharmacology and Physiology
https://www.readbyqxmd.com/read/29129584/high-salt-loading-induces-urinary-storage-dysfunction-via-upregulation-of-epithelial-sodium-channel-alpha-in-the-bladder-epithelium-in-dahl-salt-sensitive-rats
#16
Seiji Yamamoto, Yuji Hotta, Kotomi Maeda, Tomoya Kataoka, Yasuhiro Maeda, Takashi Hamakawa, Yasuhiro Shibata, Shoichi Sasaki, Shinya Ugawa, Takahiro Yasui, Kazunori Kimura
We aimed to investigate whether high salt intake affects bladder function via epithelial sodium channel (ENaC) by using Dahl salt-resistant (DR) and salt-sensitive (DS) rats. Bladder weight of DR + high-salt diet (HS, 8% NaCl) and DS + HS groups were significantly higher than those of DR + normal-salt diet (NS, 0.3% NaCl) and DS + NS groups after one week treatment. We thereafter used only DR + HS and DS + HS group. Systolic and diastolic blood pressures were significantly higher in DS + HS group than in DR + HS group after the treatment period...
October 10, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29128789/diuretic-and-natriuretic-effect-of-luteolin-in-normotensive-and-hypertensive-rats-role-of-muscarinic-acetylcholine-receptors
#17
Thaise Boeing, Luísa Mota da Silva, Marihá Mariott, Sérgio Faloni de Andrade, Priscila de Souza
BACKGROUND: Luteolin is a very common phenolic compound found in a wide variety of natural products. Although several biological properties have already been described regarding the beneficial effect of luteolin in the cardiovascular and renal system, no scientific research explored its potential effect as a diuretic agent in experimental trials. METHODS: Groups of male normotensive (NTR) and spontaneously hypertensive rats (SHR) were orally treated with vehicle, hydrochlorothiazide or luteolin...
May 24, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29111855/neuroprotective-effects-of-inhibitors-of-acid-sensing-ion-channels-asics-in-optic-nerve-crush-model-in-rodents
#18
Dorota L Stankowska, Brett H Mueller, Hidehiro Oku, Tsunehiko Ikeda, Adnan Dibas
PURPOSE: The purpose of the current study was to assess the potential involvement of acid-sensing ion channel 1 (ASIC1) in retinal ganglion cell (RGC) death and investigate the neuroprotective effects of inhibitors of ASICs in promoting RGC survival following optic nerve crush (ONC). RESULTS: ASIC1 protein was significantly increased in optic nerve extracts at day 7 following ONC in rats. Activated calpain-1 increased at 2 and 7 days following ONC as evidenced by increased degradation of α-fodrin, known substrate of calpain...
November 7, 2017: Current Eye Research
https://www.readbyqxmd.com/read/29075112/effect-of-inhibitors-of-endocytosis-and-nf-kb-signal-pathway-on-folate-conjugated-nanoparticle-endocytosis-by-rat-kupffer-cells
#19
Hongbo Tang, Hongli Chen, Yajing Jia, Xiaoyan Liu, Zhaohong Han, Aihua Wang, Qi Liu, Xinlei Li, Xin Feng
The regular accumulation of nanoparticles in the liver makes them hepatotoxic and decreases the circulation time, thus reducing their therapeutic effect. Resolving this problem will be significant in improving bioavailability and reducing side effects. In this study, we reduced the phagocytosis of epirubicin (EPI)-loaded folic acid-conjugated pullulan acetate (FPA/EPI) nanoparticles by Kupffer cells (KCs) through internalization and nuclear factor kappa B (NF-kB) signal pathway inhibitors, thus allowing development of FPA/EPI nanoparticles as a nanodrug delivery system (NDDS) based on our previous study...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29072388/-the-cellular-mechanisms-of-lung-edema-clearance-does-the-alveolar-epithelium-play-a-role
#20
REVIEW
Gidon Berger, Geula Klorin, Reem Ismael-Badarneh, Julia Guetta, Zaher S Azzam
Pulmonary edema develops as a result of either alteration in the hydrostatic and oncotic pressure gradients across the pulmonary circulation and the lung interstitium or due to increased lung permeability. Alveolar fluid clearance is important in keeping the airspaces free of edema. This process is carried out via the alveolar epithelial active transport of Na+ across the alveolo-capillary barrier mostly by apical Na+ channels and basolateral Na,K-ATPases. Several pharmacologic agents such as catecholamines, vasopressin and gene therapy interventions have currently been found to stimulate the active Na+ transport and lung edema clearance...
October 2017: Harefuah
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