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https://www.readbyqxmd.com/read/29146563/characterization-of-the-ipec-j2-mdr1-ip-gp-cell-line-as-a-tool-for-identification-of-p-gp-substrates
#1
Burak Ozgür, Lasse Saaby, Kristine Langthaler, Birger Brodin
Recently, we transfected the porcine intestinal cell line IPEC-J2, with human P-glycoprotein (P-gp, ABCB1). The resulting cell line, iP-gp, has a high expression of functional human P-gp in the apical membrane, and a low expression of nonhuman ATP-binding cassette (ABC) transporters. The aim of the present work was to investigate the usability of iP-gp cell line for determining transepithelial transport kinetics of the prototypical P-gp substrates digoxin and rhodamine 123. The cell line generated tight monolayers after 16days of culture, reflected by high transepithelial electrical resistance values (TEER>15,000Ω·cm(2)), immunocytochemistry and low fluxes of the paracellular flux marker [(14)C]-mannitol...
November 13, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29142156/outcomes-of-rate-control-treatment-in-patients-with-atrial-fibrillation-and-heart-failure%C3%A3-a-nationwide-cohort-study
#2
Hee Tae Yu, Pil-Sung Yang, Hancheol Lee, Seng Chan You, Tae-Hoon Kim, Jae-Sun Uhm, Jong-Youn Kim, Hui-Nam Pak, Moon-Hyoung Lee, Boyoung Joung
BACKGROUND: Rate control is now a front-line therapy in the management of atrial fibrillation (AF). However, the survival benefits of different rate-control medications remain controversial, so we assessed the efficacy of rate-control medications in AF patients with concomitant heart failure (HF).Methods and Results:From January 2002 to December 2008, a total of 7,034 AF patients with a single type of rate-control drug or without rate-control treatment were enrolled from the Korea National Health Insurance Service database...
November 14, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/29130514/involvement-of-src-signaling-in-the-synergistic-effect-between-cisplatin-and-digoxin-on-cancer-cell-viability
#3
Duane Gischewski Pereira, Mariana Alves Resende Salgado, Sayonarah Carvalho Rocha, Hérica L Santos, José Augusto Fp Villar, Ruben G Contreras, Carlos Frederico Leite Fontes, Leandro Augusto Barbosa, Vanessa Faria Cortes
Cisplatin and other platinum-containing drugs have played a crucial role in anticancer treatments for over 30 years. However, treatment with cisplatin may cause serious side effects, such as myelosuppression, nausea, ototoxicity, nephrotoxicity and cell resistance processes. In addition, cardiotonic steroids, particularly digoxin, have recently been suggested to exert potent anticancer effects. Therefore, it is possible that the combined treatment of HeLa cells with cisplatin and digoxin can ameliorate the cytotoxic effects and decrease the side effects of cisplatin...
November 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29129792/the-hypoxia-mimetic-protocatechuic-acid-ethyl-ester-inhibits-synaptic-signaling-and-plasticity-in-the-rat-hippocampus
#4
Sinead M Lanigan, John J O'Connor
During hypoxia a number of physiological changes occur within neurons including the stabilization of hypoxia-inducible factors (HIFs). The activity of these proteins is regulated by O2, Fe(2+), 2-OG and ascorbate-dependant hydroxylases which contain prolyl-4-hydroxylase domains (PHDs). PHD inhibitors have been widely used and have been shown to have a preconditioning and protective effect against a later and more severe hypoxic insult. In this study we have investigated the neuroprotective effects of the PHD inhibitor, protocatechuic acid ethyl ester (ethyl 3,4, dihydroxybenzoate: EDHB) as well as its effects on synaptic transmission and plasticity in the rat hippocampus using electrophysiological techniques...
November 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/29129562/preoperative-use-of-oral-beta-adrenergic-blocking-agents-and-the-incidence-of-new-onset-atrial-fibrillation-after-cardiac-surgery-a-systematic-review-and-meta-analysis
#5
REVIEW
Paul Min Thein, Kyle White, Khyati Banker, Carole Lunny, Sam Mirzaee, Arthur Nasis
BACKGROUND: Current epidemiological data suggests that postoperative atrial fibrillation or atrial flutter (POAF) causes significant morbidity and mortality after cardiac surgery. The literature for prophylactic management of POAF is limited, resulting in the lack of clear guidelines on management recommendations. AIM: To examine the efficacy of prophylactic rate control agents in reducing the incidence of new-onset POAF in patients undergoing elective cardiac surgery...
October 19, 2017: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/29122813/american-heart-association-principles-on-the-accessibility-and-affordability-of-drugs-and-biologics-a-presidential-advisory-from-the-american-heart-association
#6
REVIEW
Elliott M Antman, Mark A Creager, Steven R Houser, John J Warner, Madeleine Konig
Net US spending on pharmaceuticals reached $309.5 billion in 2015, an 8.5% increase from the year before, and is expected to reach between $370 and $400 billion by 2020. These current and projected levels have raised serious concerns by policy makers, providers, payers, and patient groups that they are unsustainable and threaten the affordability of and accessibility to much-needed therapies for patients. Two trends related to drugs/biologics and generic drugs/biosimilars underlie this overall increase in spending...
November 9, 2017: Circulation
https://www.readbyqxmd.com/read/29115894/selectivity-analyses-of-%C3%AE-benzylidene-digoxin-derivatives-to-different-na-k-atpase-%C3%AE-isoforms-a-molecular-docking-approach
#7
Marco T C Pessôa, Silmara L G Alves, Alex G Taranto, José A F P Villar, Gustavo Blanco, Leandro A Barbosa
Digoxin and other cardiotonic steroids (CTS) exert their effect by inhibiting Na,K-ATPase (NKA) activity. CTS bind to the various NKA isoforms that are expressed in different cell types, which gives CTS their narrow therapeutic index. We have synthesised a series of digoxin derivatives (γ-Benzylidene digoxin derivatives) with substitutions in the lactone ring (including non-oxygen and ether groups), to obtain CTS with better NKA isoform specificity. Some of these derivatives show some NKA isoform selective effects, with BD-3, BD-8, and BD-13 increasing NKA α2 activity, BD-5 inhibiting NKA α1 and NKA α3, BD-10 reducing NKA α1, but stimulating NKA α2 and α3; and BD-14, BD-15, and BD-16 enhancing NKA α3 activity...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29110132/novel-mesenchymal-stem-cell-strategy-in-alleviating-toll-like-receptor-4-p53-and-nrf2-signaling-in-isoproterenol-induced-myocardial-infarction-in-rat-model
#8
Mai O Kadry, Rehab M Abdel-Megeed
Mesenchymal stem cells (MSCs) are multipotent stromal cells that merit the differentiation into various cell types. The present study was designed to test the hypothesis that the cardioprotective effect of MSCs transplantation and digoxin treatment is mediated via the regulation of messenger RNA gene expression of pro-inflammatory cytokines and apoptotic markers. Myocardial infarction was induced in Wistar rats via isoproterenol injection in a dose of (85 mg/kg, subcutaneously, twice at an interval of 24 h)...
November 6, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29109583/should-digoxin-continue-to-be-used-for-the-management-of-atrial-fibrillation
#9
(no author information available yet)
No abstract text is available yet for this article.
September 2017: Canadian Journal of Hospital Pharmacy
https://www.readbyqxmd.com/read/29100486/an-ecv304-monoculture-model-for-permeability-assessment-of-blood-brain-barrier
#10
Shu Yang, Hong Jin, Zhigang Zhao
OBJECTIVE: ECV304/C6 co-culture model is a widely used tool for BBB studies. However, cell source may influence the establishment of co-culture model and some C6 cells could damage the barrier integrity. Here, we established an ECV304 monoculture model and evaluated it in the respect of tightness, tight junction proteins and discriminative brain penetration. METHODS: The tightness of ECV304 cell layers was evaluated by the measurement of permeability to hydrophilic marker Lucifer yellow...
November 3, 2017: Neurological Research
https://www.readbyqxmd.com/read/29092973/landiolol-is-effective-for-the-treatment-of-tachycardia-induced-cardiogenic-shock-in-patients-during-septic-shock-therapy
#11
Yoh Arita, Takatsugu Segawa, Shohei Yamamoto, Shinji Hasegawa
Septic shock is a life-threatening condition that occurs when the blood pressure drops to a low level after an infection. Atrial fibrillation (AF) is the most common arrhythmia to complicate its course. Beta (β)-blockers are often administrated to manage supraventricular tachyarrhythmias observed in patients presenting with sepsis. A 74-year-old woman presenting with sepsis demonstrated AF tachycardia characterised by severe hypotension. She was refractory to conventional therapy including verapamil and digoxin; therefore, treatment using landiolol (an ultrashort-acting β-blocker) was initiated...
November 1, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29075124/chronic-digitalis-therapy-in-patients-before-heart-transplantation-is-an-independent-risk-factor-for-increased-posttransplant-mortality
#12
Rasmus Rivinius, Matthias Helmschrott, Arjang Ruhparwar, Ann-Kathrin Rahm, Fabrice F Darche, Dierk Thomas, Tom Bruckner, Philipp Ehlermann, Hugo A Katus, Andreas O Doesch
OBJECTIVES: Digitalis therapy (digoxin or digitoxin) in patients with heart failure is subject to an ongoing debate. Recent data suggest an increased mortality in patients receiving digitalis. This study investigated the effects of chronic digitalis therapy prior to heart transplantation (HTX) on posttransplant outcomes. PATIENTS AND METHODS: This was a retrospective, observational, single-center study. It comprised 530 adult patients who were heart-transplanted at Heidelberg University Hospital between 1989 and 2012...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29072445/integrated-graphene-oxide-purification-lateral-flow-test-strips-igop-lfts-for-direct-detection-of-pcr-products-with-enhanced-sensitivity-and-specificity
#13
Shanglin Li, Yin Gu, Yi Lyu, Yan Jiang, Peng Liu
An integrated graphene oxide purification-lateral flow test strip (iGOP-LFTS) was developed for on-strip purifying and visually detecting polymerase chain reaction (PCR) products with an improved sensitivity as well as a more stringent specificity. PCR products amplified with a pair of biotin- and digoxin-labeled primers were directly pipetted onto GO pads, on which graphene oxide selectively adsorbed residual primers and primer-dimers with the aid of a running buffer containing MgCl2 and Tween 20. By stacking up three GO pads to increase the surface area for adsorption, 83...
November 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29071859/-validation-of-in-situ-single-pass-perfusion-model-based-on-p-gp
#14
Yue-Liu Dong, Yang Liu, Xiu-Wen Yin, Meng Pan, Xue-Lian Li, Zi-Yu Wang, Ling Dong
To validate in situ rats intestinal single pass perfusion model based on P-glycoprotein (P-gp). Firstly, phenol red perfusion was carried out to verify the close connection structure of intestinal epithelial cells, and the integrity of the intestinal epithelium, with a gravimetric method for correcting water flux. The level of phenol red was determined by high performance liquid chromatography (HPLC) both before and after perfusion. Secondly, the positive drug digoxin specified by FDA was used to validate the model...
April 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29070518/digoxin-enhances-radiation-response-in-radioresistant-a549-cells-by-reducing-protein-phosphatase-2a-pp2a
#15
Ji Young Lee, Mi-Sook Kim, Mi So Lee, Jae Eun Ju, Namhyun Chung, Youn Kyoung Jeong
Protein phosphatase 2A (PP2A) is a ubiquitous multifunctional enzyme usually known as a tumor suppressor. Recent studies have reported that although inhibition of PP2A leads to acceleration of cell growth, it also induces damaged cells to pass through the cell cycle and renders them sensitive to radiotherapy. Here, we investigated the radiosensitizing effects of digoxin as a PP2A inhibitor in two non-small cell lung cancer cell types (H460 and A549) with differential sensitivity to radiation. Digoxin inhibited the proliferation of H460 and A549 cells in a dose-dependent fashion and was especially effective on radioresistant A549 cells...
October 25, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29064846/pre-and-post-conditioning-by-cardiac-glycosides-in-the-mouse-heart
#16
Qiming Duan, Yunhui Xu, Pauline Marck, Jennifer Kalisz, Eric E Morgan, Sandrine V Pierre
Ouabain preconditioning (OPC) initiated by low concentrations of the cardiac glycoside (CG) ouabain binding to Na/K-ATPase is relayed by a unique intracellular signaling and protects cardiac myocytes against ischemia/reperfusion (IR) injury. To explore more clinically applicable protocols based on CG properties, we tested whether the FDA-approved CG digoxin could trigger cardioprotective effects comparable to those of ouabain using PC and PostC protocols in the Langendorff-perfused mouse heart subjected to global ischemia and reperfusion...
October 23, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29061976/ontology-based-systematical-representation-and-drug-class-effect-analysis-of-package-insert-reported-adverse-events-associated-with-cardiovascular-drugs-used-in-china
#17
Liwei Wang, Mei Li, Jiangan Xie, Yuying Cao, Hongfang Liu, Yongqun He
With increased usage of cardiovascular drugs (CVDs) for treating cardiovascular diseases, it is important to analyze CVD-associated adverse events (AEs). In this study, we systematically collected package insert-reported AEs associated with CVDs used in China, and developed and analyzed an Ontology of Cardiovascular Drug AEs (OCVDAE). Extending the Ontology of AEs (OAE) and NDF-RT, OCVDAE includes 194 CVDs, CVD ingredients, mechanisms of actions (MoAs), and CVD-associated 736 AEs. An AE-specific drug class effect is defined to exist when all the drugs (drug chemical ingredients or drug products) in a drug class are associated with an AE, which is formulated as a new proportional class level ratio ("PCR") = 1...
October 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29059256/identification-of-two-immortalized-cell-lines-ecv304-and-bend3-for-in-vitro-permeability-studies-of-blood-brain-barrier
#18
Shu Yang, Shenghui Mei, Hong Jin, Bin Zhu, Yue Tian, Jiping Huo, Xu Cui, Anchen Guo, Zhigang Zhao
To identify suitable cell lines for a mimetic system of in vivo blood-brain barrier (BBB) for drug permeability assessment, we characterized two immortalized cell lines, ECV304 and bEnd3 in the respect of the tightness, tight junction proteins, P-glycoprotein (P-gp) function and discriminative brain penetration. The ECV304 monoculture achieved higher transendothelial electrical resistance (TEER) and lower permeability to Lucifer yellow than bEnd3. However, co-culture with rat glioma C6 cells impaired the integrity of ECV304 and bEnd3 cell layers perhaps due to the heterogeneity among C6 cells in inducing BBB characteristics...
2017: PloS One
https://www.readbyqxmd.com/read/29057503/reply-to-correspondence-topical-ionic-contra-viral-therapy-comprised-of-digoxin-and-furosemide-as-a-potential-novel-treatment-approach-for-common-warts
#19
T van der Kolk, R Rissmann
We appreciate Dr Abdelmaksoud's thorough review of our manuscript (1) and would like to reply to the comments that were raised with this letter. First, it appears that the understanding is that the study describes the 'clinical response of common warts to a topical application of a fixed dose of 980 mg of the ICVT gel on the patients' lower back. It should be clarified that the main objective of this first-in-man study was evaluate the systemic exposure, safety and tolerability of ionic-contra-viral therapy (ICVT) (2)...
October 23, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29055937/reaching-consensus-on-communication-of-critical-laboratory-results-using-a-collective-intelligence-method
#20
Maria Isabel Llovet, Carmen Biosca, Alicia Martínez-Iribarren, Aurora Blanco, Glòria Busquets, María José Castro, Maria Antonia Llopis, Mercè Montesinos, Joana Minchinela, Carme Perich, Judith Prieto, Rosa Ruiz, Núria Serrat, Margarita Simón, Alex Trejo, Josep Maria Monguet, Carlos López-Pablo, Mercè Ibarz
BACKGROUND: There is no consensus in the literature about what analytes or values should be informed as critical results and how they should be communicated. The main aim of this project is to establish consensual standards of critical results for the laboratories participating in the study. Among the project's secondary objectives, establishing consensual procedures for communication can be highlighted. METHODS: Consensus was reached among all participating laboratories establishing the basis for the construction of the initial model put forward for consensus in conjunction with the clinicians...
October 23, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
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