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https://www.readbyqxmd.com/read/28426886/risk-of-stroke-in-chronic-heart-failure-patients-with-preserved-ejection-fraction-but-without-atrial-fibrillation-analysis-of-the-charm-preserved-and-i-preserve-trials
#1
Azmil H Abdul-Rahim, Ana-Cristina Perez, Rachael L MacIsaac, Pardeep S Jhund, Brian L Claggett, Peter E Carson, Michel Komajda, Robert S McKelvie, Michael R Zile, Karl Swedberg, Salim Yusuf, Marc A Pfeffer, Scott D Solomon, Gregory Y H Lip, Kennedy R Lees, John J V McMurray
Aims: The incidence and predictors of stroke in patients with heart failure and preserved ejection fraction (HF-PEF), but without atrial fibrillation (AF), are unknown. We described the incidence of stroke in HF-PEF patients with and without AF and predictors of stroke in those without AF. Methods and results: We pooled data from the CHARM-Preserved and I-Preserve trials. Using Cox regression, we derived a model for stroke in patients without AF in this cohort and compared its performance with a published model in heart failure patients with reduced ejection fraction (HF-REF)-predictive variables: age, body mass index, New York Heart Association class, history of stroke, and insulin-treated diabetes...
March 7, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28415046/cost-benefit-effectiveness-of-angiotensin-ii-receptor-blockers-in-patients-with-uncomplicated-hypertension-a-comparative-analysis
#2
Alberto Mazza, Antonella Paola Sacco, Danyelle M Townsend, Gianni Bregola, Edgardo Contatto, Isabella Cappello, Laura Schiavon, Emilio Ramazzina, Domenico Rubello
OBJECTIVE: The treatment of hypertensive patients (HTs) requires a long-term commitment of compliance for the patient and resources by the healthcare system. This poses an economic dilemma in countries where universal healthcare is standard. The aim of this study was to evaluate the costs/health benefit and effectiveness of treatment with angiotensin-II receptor blockers (ARBs) in uncomplicated essential hypertension. DESIGN AND METHODS: The daily and annual economic commitment for treating patients with ARBs was estimated using pharmacy dispensing records and the BP-lowering effects of candesartan, irbesartan, losartan, olmesartan, telmisartan and valsartan was evaluated retrospectively...
April 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28405886/pharmacokinetic-variability-of-drugs-used-for-prophylactic-treatment-of-migraine
#3
REVIEW
Peer Tfelt-Hansen, Frederik Nybye Ågesen, Agniezka Pavbro, Jacob Tfelt-Hansen
In this review, we evaluate the variability in the pharmacokinetics of 11 drugs with established prophylactic effects in migraine to facilitate 'personalized medicine' with these drugs. PubMed was searched for 'single-dose' and 'steady-state' pharmacokinetic studies of these 11 drugs. The maximum plasma concentration was reported in 248 single-dose and 115 steady-state pharmacokinetic studies, and the area under the plasma concentration-time curve was reported in 299 single-dose studies and 112 steady-state pharmacokinetic studies...
April 12, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28400916/angiotensin-receptor-blocker-drugs-and-inhibition-of-adrenal-beta-arrestin-1-dependent-aldosterone-production-implications-for-heart-failure-therapy
#4
EDITORIAL
Anastasios Lymperopoulos, Beatrix Aukszi
Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II (AngII). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure (HF), is induced by AngII type 1 receptors (AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1 (βarr1) or -2 (βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 protein-independent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated...
March 26, 2017: World Journal of Cardiology
https://www.readbyqxmd.com/read/28374982/angiotensin-ii-receptor-blockers-inhibit-the-generation-of-epoxyeicosatrienoic-acid-from-arachidonic-acid-in-recombinant-cyp2c9-cyp2j2-and-human-liver-microsomes
#5
Asuna Senda, Yuji Mukai, Toru Hayakawa, Yuka Kato, Erik Eliasson, Anders Rane, Takaki Toda, Nobuo Inotsume
Cytochrome P450 (CYP) 2C9, CYP2C8 and CYP2J2 enzymes, which metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs), have cardioprotective effects including anti-inflammation and vasodilation. We have recently shown that some angiotensin II receptor blockers (ARBs) may inhibit AA metabolism via CYP2C8. Using recombinant CYP2C9, CYP2J2, and human liver microsomes (HLMs), the aim was now to compare the ability of six different clinically used ARBs to inhibit AA metabolism in vitro. The rank order of the ARBs for the 50% inhibitory concentration (IC50 ) of AA metabolism was losartan < telmisartan < irbesartan < candesartan < olmesartan < valsartan via CYP2C9, and telmisartan < irbesartan < olmesartan < losartan < candesartan and valsartan via CYP2J2...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28290850/-prevention-of-cardiovascular-complications-in-patients-with-arterial-hypertension-while-use-of-angiotensin-ii-receptor-antagonists-possibilities-of-candesartan
#6
N M Savina
The article demonstrates advantages of angiotensin II receptor antagonists in treatment of arterial hypertension (AH). Subjects for consideration are evidences of antihypertensive efficacy of candesartan and possibilities of the product in prevention of cardiovascular complications in patients with AH.
June 2016: Kardiologiia
https://www.readbyqxmd.com/read/28274926/%C3%AE-arrestin-biased-at1r-stimulation-promotes-extracellular-matrix-synthe-sis-in-renal-fibrosis
#7
Yandao Wang, Jieli Huang, Xi Liu, Yangyang Niu, Liqin Zhao, Ying Yu, Li Zhou, Limin Lu, Chen Yu
BACKGROUND: Renin-angiotensin system (RAS) plays a critical role in the progression of renal fibrosis. Angiotensin II type 1 receptor (AT1R) belongs to the B family of G protein coupled receptors (GPCRs) family. β-arrestins are known as negative regula-tors of GPCRs. Recently, β-arrestins have been found to regulate multiple intracellu-lar signaling pathways independent of G proteins. In this study we investigated the role of β-arrestins in regulating extracellular matrix (ECM) synthesis in renal fibrosis...
March 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28239165/antihypertensive-agents-do-not-prevent-blood-brain-barrier-dysfunction-and-cognitive-deficits-in-dietary-induced-obese-mice
#8
J C L Mamo, V Lam, C Giles, S H Coulson, N Fimognari, A Mooranian, H Al-Salami, R Takechi
BACKGROUND: While vascular risk factors including Western-styled diet and obesity are reported to induce cognitive decline and increase dementia risk, recent reports consistently suggest that compromised integrity of cerebrovascular blood-brain barrier (BBB) may have an important role in neurodegeneration and cognitive deficits. A number of studies report that elevated blood pressure increases the permeability of BBB. METHODS: In this study, we investigated the effects of antihypertensive agents, candesartan or ursodeoxycholic acid (UDCA), on BBB dysfunction and cognitive decline in wild-type mice maintained on high fat and fructose (HFF) diet for 24 weeks...
March 21, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28230330/comparing-six-antihypertensive-medication-classes-for-preventing-new-onset-diabetes-mellitus-among-hypertensive-patients-a-network-meta-analysis
#9
Yang Yang, Huilan Xu
Hypertensive patients usually have a higher risk of new-onset diabetes mellitus (NOD) which may trigger cardiovascular diseases. In this study, the effectiveness of six antihypertensive agents with respect to NOD prevention in hypertensive patients was assessed. A network meta-analysis was conducted to compare the efficacy of specific drug classes. PubMed and Embase databases were searched for relevant articles. Results of the pairwised meta-analysis were illustrated by odd ratios (OR) and a corresponding 95% confidence interval (CI)...
February 23, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28220370/the-effect-of-candesartan-on-pentraxin-3-plasma-levels-as-marker-of-endothelial-dysfunction-in-patients-with-essential-arterial-hypertension
#10
V Buda, M Andor, C Cristescu, M Voicu, F Cochera, P Tuduce, L Petrescu, M C Tomescu
BACKGROUND: In the last decades, the studies performed on the field of endothelial dysfunction confirmed the fact that the starting point of this pathology is the inflammation. Several inflammatory biomarkers had been discovered and studied, ones showing systemic inflammation, and others being more specific biomarkers and showing the local inflammation. Pentraxin-3 (PTX3) is a new inflammatory biomarker, from the same family as high-selectivity C-reactive protein (hs-CRP), but it is a more specific biomarker, due to its local production: the endothelial cells and not the liver like in the case of hs-CRP...
February 21, 2017: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/28215000/angiotensin-ii-receptor-blockers-attenuate-lipopolysaccharide-induced-memory-impairment-by-modulation-of-nf-%C3%AE%C2%BAb-mediated-bdnf-creb-expression-and-apoptosis-in-spontaneously-hypertensive-rats
#11
Ruby Goel, Shahnawaz Ali Bhat, Kashif Hanif, Chandishwar Nath, Rakesh Shukla
Clinical studies demonstrated a positive correlation between hypertension and cognitive decline. Beneficial effects of angiotensin II receptor blockers on cognitive functions have also been reported earlier; however, its role in chronic neuroinflammation-induced memory impairment in the hypertensive state is not well understood. Therefore, in the present study, we investigated the effect of angiotensin II receptor blockers on memory impairment induced by lipopolysaccharide (LPS) in spontaneously hypertensive rats (SHRs)...
February 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28203527/superoxide-increases-angiotensin-ii-at1-receptor-function-in-human-kidney-2-cells
#12
Mohammad Saleem, Indira Pokkunuri, Mohammad Asghar
The redox-sensitive Sp family transcription factor has been linked to the regulation of angiotensin II type 1 receptor (AT1R). However, the exact mechanism of AT1R regulation in renal cells is poorly understood. We tested the specificity of reactive oxygen species (ROS), superoxide vs. hydrogen peroxide (H2O2), and the specific role of Sp3 transcription factor, if any, in the regulation of AT1R in human kidney cells (HK2 cells). Superoxide dismutase (SOD) inhibitor diethyldithiocarbamate (DETC), but not H2O2 treatment, increased fluorescence levels of superoxide probe dihydroethidium (DHE)...
December 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/28178410/strategies-to-extend-thrombolytic-time-window-for-ischemic-stroke-treatment-an-unmet-clinical-need
#13
REVIEW
Ike Dela Peña, Cesar Borlongan, Guofang Shen, Willie Davis
To date, reperfusion with tissue plasminogen activator (tPA) remains the gold standard treatment for ischemic stroke. However, when tPA is given beyond 4.5 hours of stroke onset, deleterious effects of the drug ensue, especially, hemorrhagic transformation (HT), which causes the most significant morbidity and mortality in stroke patients. An important clinical problem at hand is to develop strategies that will enhance the therapeutic time window for tPA therapy and reduce the adverse effects (especially HT) of delayed tPA treatment...
January 2017: Journal of Stroke
https://www.readbyqxmd.com/read/28178366/the-simultaneous-uplc-ms-ms-determination-of-emerging-drug-combination-candesartan-and-chlorthalidone-in-human-plasma-and-its-application
#14
Bhargav Patel, Arvind G Jangid, B N Suhagia, Nirmal Desai
A novel, precise, sensitive and accurate ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed for the simultaneous determination of novel drug combination, candesartan (CAN) and chlorthalidone (CHL) in human plasma. Chromatographic separation was achieved on Waters Acquity UPLC BEH C18 (50 mm × 2.1 mm, 1.7 µm). Mobile phase consisting of 1 mM Ammonium acetate in water: acetonitrile (20:80 v/v) was used. The total chromatographic runtime was 1...
February 8, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28144709/glucagon-increase-after-chronic-at1-blockade-is-more-likely-related-to-an-indirect-leptin-dependent-than-to-a-pancreatic-%C3%AE-cell-dependent-mechanism
#15
Martin Mildner, Helge Müller-Fielitz, Ines Stölting, Olaf Jöhren, Muscha Steckelings, Walter Raasch
AT1 blockers (ARB) prevent diabetes by improving pancreatic β cell function. Less is known about whether α cells are affected although they express angiotensin II (AngII) receptors. We aimed to investigate glucagon release upon AngII stimulation. We determined glucagon release after AngII stimulation (0.01-100 μM) in α cells (InR1G9) and isolated murine islets. We determined plasma glucagon in rats that were chronically treated with AngII (9 μg/h) or the ARBs telmisartan (8 mg/kg/day) and candesartan (16 mg/kg/day) and correlated glucagon with additional hormones (e...
January 31, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28104076/comparison-of-propensity-score-methods-and-covariate-adjustment-evaluation-in-4-cardiovascular-studies
#16
REVIEW
Markus C Elze, John Gregson, Usman Baber, Elizabeth Williamson, Samantha Sartori, Roxana Mehran, Melissa Nichols, Gregg W Stone, Stuart J Pocock
Propensity scores (PS) are an increasingly popular method to adjust for confounding in observational studies. Propensity score methods have theoretical advantages over conventional covariate adjustment, but their relative performance in real-word scenarios is poorly characterized. We used datasets from 4 large-scale cardiovascular observational studies (PROMETHEUS, ADAPT-DES [the Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents], THIN [The Health Improvement Network], and CHARM [Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity]) to compare the performance of conventional covariate adjustment with 4 common PS methods: matching, stratification, inverse probability weighting, and use of PS as a covariate...
January 24, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28088883/candesartan-cilexetil-loaded-nanodelivery-systems-for-improved-oral-bioavailability
#17
Narendar Dudhipala, Kishan Veerabrahma
Candesartan cilexetil (CC), an antihypertensive drug, has low oral bioavailability due to poor solubility and hepatic first-pass metabolism. These are major limitations in oral delivery of CC. Several approaches are known to reduce the problems of solubility and improve the bioavailability of CC. Among various approaches, nanotechnology-based delivery of CC has potential to overcome the challenges associated with the oral administration. This review focuses on various nano-based delivery systems available and tried for improving the aqueous solubility, dissolution and consequently bioavailability of CC upon oral administration...
February 2017: Therapeutic Delivery
https://www.readbyqxmd.com/read/28079517/pharmacokinetic-and-bioequivalence-study-comparing-a-candesartan-cilexetil-rosuvastatin-calcium-fixed-dose-combination-with-the-concomitant-administration-of-candesartan-cilexetil-and-rosuvastatin-calcium-in-healthy-korean-subjects%C3%A2
#18
Dan-Bee Park, Kyungho Jang, Jae-Won Lee, Cheol-Won Park, Back-Hwan Lee, Min-Gul Kim, Ji-Young Jeon
CONTEXT: A fixed-dose combination (FDC) of candesartan and rosuvastatin was recently developed for the treatment of cardiovascular disease and expected to enhance patient compliance. OBJECTIVE: This study was performed to compare the single-dose pharmacokinetic properties and tolerability of DP-R208 (candesartan and rosuvastatin FDC) to those of each component administered alone in healthy Korean male volunteers. MATERIALS AND METHODS: A total of 40 healthy Korean volunteers were enrolled in this randomized, open-label, single-dose, two-treatment, two-way crossover study...
March 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28045910/comparative-efficacy-and-safety-of-antihypertensive-agents-for-adult-diabetic-patients-with-microalbuminuric-kidney-disease-a-network-meta-analysis
#19
Rongzhong Huang, Yuxing Feng, Ying Wang, Xiaoxia Qin, Narayan Dhruvaraj Melgiri, Yang Sun, Xingsheng Li
BACKGROUND: Antihypertensive treatment mitigates the progression of chronic kidney disease. Here, we comparatively assessed the effects of antihypertensive agents in normotensive and hypertensive diabetic patients with microalbuminuric kidney disease. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) comparing oral antihypertensive agents in adult diabetic patients with microalbuminuria...
2017: PloS One
https://www.readbyqxmd.com/read/28034361/formulation-and-optimization-of-candesartan-cilexetil-nano-lipid-carrier-in-vitro-and-in-vivo-evaluation
#20
Anjan Paudel, EmptyYN Y Ameeduzzafar, Syed Sarim Imam, Abdul Hafeez, Mohd Fazil, Shahroz Khan, Farhan Jalees Ahmad, Asgar Ali
PURPOSE: The objective of this study was to formulate and optimize Candesartan Cilexetil (CC) loaded nanostructured lipid carriers (NLCs) for enhanced oral bioavailability. METHOD: Glycerol monostearate (GMS), Oleic acid, Tween 80 and Span 40 were selected as a solid lipid, liquid lipid, surfactant and co- surfactant, respectively. The CC-NLCs were prepared by hot emulsion probe sonication technique and optimized using experimental design approach. The formulated CC-NLCs were evaluated for various physicochemical parameters and further optimized formulation (CC-NLC-Opt) was assessed for in-vivo pharmacokinetic and pharmacodynamic activity...
December 30, 2016: Current Drug Delivery
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