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https://www.readbyqxmd.com/read/29158353/blood-pressure-control-by-a-secreted-fgfbp1-fibroblast-growth-factor-binding-protein
#1
Elena Tassi, En Yin Lai, Lingli Li, Glenn Solis, Yifan Chen, William E Kietzman, Patricio E Ray, Anna T Riegel, William J Welch, Christopher S Wilcox, Anton Wellstein
Fibroblast growth factors (FGFs) participate in organ development and tissue maintenance, as well as the control of vascular function. The paracrine-acting FGFs are stored in the extracellular matrix, and their release is controlled by a secreted FGF-binding protein (FGF-BP, FGFBP1, and BP1) that modulates FGF receptor signaling. A genetic polymorphism in the human FGFBP1 gene was associated with higher gene expression and an increased risk of familial hypertension. Here, we report on the effects of inducible BP1 expression in a transgenic mouse model...
November 20, 2017: Hypertension
https://www.readbyqxmd.com/read/29118031/neurohormonal-blockade-and-circulating-cardiovascular-biomarkers-during-anthracycline-therapy-in-breast-cancer-patients-results-from-the-prada-prevention-of-cardiac-dysfunction-during-adjuvant-breast-cancer-therapy-study
#2
Geeta Gulati, Siri L Heck, Helge Røsjø, Anne H Ree, Pavel Hoffmann, Tor-Arne Hagve, Jon Norseth, Berit Gravdehaug, Kjetil Steine, Jürgen Geisler, Torbjørn Omland
BACKGROUND: Anthracyclines are associated with cardiotoxic effects. Cardiovascular biomarkers may reflect myocardial injury, dysfunction, inflammation, and fibrosis and may precede and predict the development of left ventricular impairment. The aim of this study was to assess: (1) longitudinal change in circulating cardiovascular biomarkers, (2) the effect of metoprolol succinate and candesartan cilexetil on the biomarker response, and (3) the associations between on-treatment changes in biomarker concentrations and subsequent left ventricular dysfunction in patients with early breast cancer receiving anthracyclines...
November 8, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29106497/effect-of-candesartan-and-metoprolol-on-myocardial-tissue-composition-during-anthracycline-treatment-the-prada-trial
#3
Siri Lagethon Heck, Geeta Gulati, Pavel Hoffmann, Florian von Knobelsdorff-Brenkenhoff, Tryggve Holck Storås, Anne Hansen Ree, Berit Gravdehaug, Helge Røsjø, Kjetil Steine, Jürgen Geisler, Jeanette Schulz-Menger, Torbjørn Omland
Aims: Anthracycline treatment may cause myocyte loss and expansion of the myocardial extracellular volume (ECV) fraction by oedema and fibrosis. We tested the hypotheses that adjuvant treatment for early breast cancer with the anthracycline epirubicin is dose dependently associated with increased ECV fraction and total ECV, as well as reduced total myocardial cellular volume, and that these changes could be prevented by concomitant angiotensin or beta-adrenergic blockade. Methods and results: PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA) was a 2 × 2 factorial, placebo-controlled, double-blinded trial of candesartan and metoprolol...
June 29, 2017: European Heart Journal Cardiovascular Imaging
https://www.readbyqxmd.com/read/29105106/angiotensin-receptor-blocker-use-and-gastro-oesophageal-cancer-survival-a-population-based-cohort-study
#4
J Busby, Ú McMenamin, A Spence, B T Johnston, C Hughes, C R Cardwell
BACKGROUND: Angiotensin receptor blockers (ARBs; including candesartan, losartan, olmesartan and valsartan) are widely used to treat hypertension, heart failure and diabetic neuropathy. There is considerable pre-clinical evidence that ARBs can reduce cancer progression, particularly for gastric cancer. Despite this, epidemiological studies have yet to assess the impact of ARB use on gastro-oesophageal cancer survival. AIM: To investigate the association between post-diagnosis ARB use and gastro-oesophageal cancer survival...
November 3, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29069238/urinary-cytokine-profiles-according-to-the-site-of-blockade-of-the-renin-angiotensin-system-in-nephrectomized-rats
#5
Nilo César do Vale Baracho, Kátia Daniela da Silveira, Natália Pessoa Rocha, Thiago Macedo Cordeiro, Victor Feracin, Regina Maria Pereira, Marconi Augusto Aguiar Dos Reis, Mauro Martins Teixeira, Ana Cristina Simões E Silva
INTRODUCTION: It is still unknown how the pharmacological inhibition of the Renin Angiotensin System (RAS) impacts the levels of inflammation and fibrosis biomarkers. OBJECTIVE: This study sought to evaluate the effect of enalapril, candesartan and aliskiren on urinary levels of cytokines in a model of chronic kidney disease (CKD). METHODS: Male Wistar rats were submitted to surgical removal of ¾ of renal parenchyma to induce CKD (¾ nephrectomy), or subjected to sham surgery (control)...
April 2017: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/29061726/angiotensin-ii-type-1-receptor-mechanoactivation-involves-rgs5-regulator-of-g-protein-signaling-5-in-skeletal-muscle-arteries-impaired-trafficking-of-rgs5-in-hypertension
#6
Kwangseok Hong, Min Li, Zahra Nourian, Gerald A Meininger, Michael A Hill
Studies suggest that arteriolar pressure-induced vasoconstriction can be initiated by GPCRs (G protein-coupled receptors), including the AT1R (angiotensin II type 1 receptor). This raises the question, are such mechanisms regulated by negative feedback? The present studies examined whether RGS (regulators of G protein signaling) proteins in vascular smooth muscle cells are colocalized with the AT1R when activated by mechanical stress or angiotensin II and whether this modulates AT1R-mediated vasoconstriction...
December 2017: Hypertension
https://www.readbyqxmd.com/read/28993503/myh9-e1841k-mutation-augments-proteinuria-and-podocyte-injury-and-migration
#7
Sylvia Cechova, Fan Dong, Fang Chan, Michael J Kelley, Phillip Ruiz, Thu H Le
Intronic variants of the MYH9 gene that encodes the nonmuscle myosin heavy chain IIA are associated with diabetic nephropathy in European Americans and with sickle cell disease-associated nephropathy. However, the causal functional variants of MYH9 have remained elusive. Rare missense mutations in MYH9 cause macrothrombocytopenia and are occasionally associated with development of nephropathy. The E1841K mutation is among the common MYH9 missense mutations and has been associated with nephropathy in some carriers...
October 9, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28974512/impact-of-the-commercialization-of-three-generic-angiotensin-ii-receptor-blockers-on-adverse-events-in-quebec-canada-a-population-based-time-series-analysis
#8
Jacinthe Leclerc, Claudia Blais, Louis Rochette, Denis Hamel, Line Guénette, Paul Poirier
BACKGROUND: Once the patent of a brand-name drug expires, generic drugs are commercialized, and substitution from brand-name to generics may occur. Generic drug equivalence is evaluated through comparative bioavailability studies. Few studies have assessed outcomes after generic drug commercialization at a population level. We evaluated the impact of 3 generic angiotensin II receptor blockers commercialization on adverse events: hospitalizations or emergency room consultations. METHODS AND RESULTS: This is an interrupted time series analysis using the Quebec Integrated Chronic Disease Surveillance System...
October 2017: Circulation. Cardiovascular Quality and Outcomes
https://www.readbyqxmd.com/read/28968380/nano-hydroxyapatite-derived-drug-and-gene-co-delivery-system-for-anti-angiogenesis-therapy-of-breast-cancer
#9
Lina Zhao, Wenhui Zhao, Ye Liu, Xue Chen, Yan Wang
BACKGROUND Breast cancer is among the deadliest cancers across the world and is responsible for countless deaths. There is an urgent need for co-delivery systems which can simultaneously transport both drug and gene into a single cancer cell with low toxicity and high anti-angiogenesis efficiency. MATERIAL AND METHODS In the present study, well-formed amine-functionalized hydroxyapatite nanoparticles based on combined angiogenesis therapy for breast cancer were successfully constructed for the simultaneous delivery of p53 and candesartan (CD) (p53/CD/NHAP)...
October 2, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28962137/tumor-targeting-templated-silica-nanoparticles-as-a-dual-drug-delivery-system-for-anti-angiogenic-ovarian-cancer-therapy
#10
Tianying Zheng, Aijun Wang, Dongyan Hu, Yonggang Wang
The present study indicated the successful construction of a silica nanoparticle (SLN)-based drug delivery system (DDS) for the tumor-targeted co-delivery of two anti-angiogenic drugs, candesartan (CD) and trastuzumab (Tra), for ovarian cancer therapy via different anti-angiogenic mechanisms using hyaluronic acid (HA)/Tra/CD/SLNs. In vitro and in vivo anti-angiogenic assays indicated that CD and Tra exert beneficial functions on suppressing cancer angiogenesis, and exhibited significantly enhanced effects compared with the angiotensin stimulated group (P<0...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28954968/renin-angiotensin-system-inhibitors-can-prevent-intravenous-lipid-infusion-induced-myocardial-microvascular-dysfunction-and-leukocyte-activation
#11
Takanori Yasu, Akiko Mutoh, Hiroshi Wada, Mayumi Kobayashi, Yuji Kikuchi, Shinichi Momomura, Shinichiro Ueda
BACKGROUND: Levels of triglycerides and free fatty acids (FFAs) are elevated in patients with diabetes and may contribute to endothelial dysfunction through renin-angiotensin system (RAS) activation and oxidative stress. The present study investigated how systemic FFA loading affected myocardial microcirculation during hyperemia via RAS.Methods and Results:Eight healthy men received candesartan, perindopril, or a placebo for 2 days in a double-blind crossover design, and then myocardial microcirculation during hyperemia induced by a 2-h infusion of lipid/heparin was assessed using dipyridamole stress-myocardial contrast echocardiography (MCE)...
September 26, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28953991/candesartan-rather-than-losartan-improves-motor-dysfunction-in-thioacetamide-induced-chronic-liver-failure-in-rats
#12
H A Murad, Z J Gazzaz, S S Ali, M S Ibraheem
Minimal hepatic encephalopathy is more common than the acute syndrome. Losartan, the first angiotensin-II receptor blocker (ARB), and candesartan, another widely-used ARB, have protected against developing fibrogenesis, but there is no clear data about their curative antifibrotic effects. The current study was designed to examine their effects in an already-established model of hepatic fibrosis and also their effects on the associated motor dysfunction. Low-grade chronic liver failure (CLF) was induced in 3-month old Sprague-Dawley male rats using thioacetamide (TAA, 50 mg·kg-1·day-1) intraperitoneally for 2 weeks...
September 21, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28948575/comparative-pharmaceutical-evaluation-of-candesartan-and-candesartan-cilexetil-physicochemical-properties-in-vitro-dissolution-and-ex-vivo-in-vivo-studies
#13
Ahmed M Amer, Ahmed N Allam, Ossama Y Abdallah
The aim of the present work is to answer the question is it possible to replace the ester prodrug candesartan cilexetil (CC) by its active metabolite candesartan (C) to bypass the in vivo variable effect of esterase enzymes. A comparative physicochemical evaluation was conducted through solubility, dissolution, and stability studies; additionally, ex vivo permeation and in vivo studies were assessed. C demonstrated higher solubility over CC at alkaline pH. Moreover, dissolution testing using the pharmacopeial method showed better release profile of C even in the absence of surfactant in the testing medium...
September 25, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28948430/prevalence-of-prediabetes-and-undiagnosed-diabetes-in-patients-with-hfpef-and-hfref-and-associated-clinical-outcomes
#14
Søren L Kristensen, Pardeep S Jhund, Matthew M Y Lee, Lars Køber, Scott D Solomon, Christopher B Granger, Salim Yusuf, Marc A Pfeffer, Karl Swedberg, John J V McMurray
PURPOSE: The prevalence and consequences of prediabetic dysglycemia and undiagnosed diabetes is unknown in patients with heart failure (HF) and preserved ejection fraction (HFpEF) and has not been compared to heart failure and reduced ejection fraction (HFrEF). METHODS: We examined the prevalence and outcomes associated with normoglycemia, prediabetic dysglycemia and diabetes (diagnosed and undiagnosed) among individuals with a baseline glycated hemoglobin (hemoglobin A1c, HbA1c) measurement stratified by HFrEF or HFpEF in the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity programme (CHARM)...
September 25, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28919108/the-renin-angiotensin-system-regulates-neurodegeneration-in-a-mouse-model-of-optic-neuritis
#15
Xiaoli Guo, Kazuhiko Namekata, Atsuko Kimura, Chikako Harada, Takayuki Harada
The major role of the renin-angiotensin system (RAS), including that of angiotensin II (Ang II), the principal effector molecule, in the cardiovascular system is well known. Increasing evidence suggests that the RAS also plays a role in the development of autoimmune diseases. Optic neuritis (ie, inflammation of the optic nerve, with retinal ganglion cell loss) is strongly associated with multiple sclerosis. We investigated the effects of candesartan, an Ang II receptor antagonist, on optic neuritis in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis...
September 15, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28889028/development-and-in-vitro-in-vivo-performance-of-self-nanoemulsifying-drug-delivery-systems-loaded-with-candesartan-cilexetil
#16
Khaled AboulFotouh, Ayat A Allam, Mahmoud El-Badry, Ahmed M El-Sayed
Candesartan cilexetil is widely used in the management of hypertension and heart failure. The drug delivery encounters obstacles of poor aqueous solubility, efflux by intestinal P-glycoprotein and vulnerability to enzymatic degradation in small intestine. Self-nanoemulsifying drug delivery systems (SNEDDS) loaded with candesartan cilexetil were successfully developed to overcome such obstacles. Preliminary screening was carried out to select proper surfactant, co-surfactant and oil combination for successful SNEDDS formulation...
September 6, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28884281/angiotensin-receptor-blockade-by-inhibiting-glial-activation-promotes-hippocampal-neurogenesis-via-activation-of-wnt-%C3%AE-catenin-signaling-in-hypertension
#17
Shahnawaz Ali Bhat, Ruby Goel, Shubha Shukla, Rakesh Shukla, Kashif Hanif
Hypertension is one of the major risk factors for central nervous system (CNS) disorders like stroke and Alzheimer's disease (AD). On the other hand, CNS diseases like AD have been associated with gliosis and impaired neurogenesis. Further, renin angiotensin system (RAS) is intricately associated with hypertension; however, the accumulating evidences suggest that over-activity of RAS may perpetuate the brain inflammation related with AD. Therefore, in the present study, we examined the effect of hypertension and RAS on glial (astrocytes and microglia) activation and hippocampal neurogenesis in a rat model of chronic hypertension...
September 7, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28882562/candesartan-prevents-resiniferatoxin-induced-sensory-small-fiber-neuropathy-in-mice-by-promoting-angiotensin-ii-mediated-at2-receptor-stimulation
#18
Flavien Bessaguet, Aurore Danigo, Laurent Magy, Franck Sturtz, Alexis Desmoulière, Claire Demiot
Sensory defects associated with small-fiber neuropathy (SFN) can lead to profound disabilities. The relationship between the sensory nervous system and modulation of the renin-angiotensin system (RAS) has been described and focused on pain and neurodegeneration in several animal models. We have recently developed an experimental model of functional sensory neuropathy showing thermal hypoalgesia and neuropeptide depletion without nerve fiber degeneration. Here, we aimed to determine whether the modulation of angiotensin II (Ang II) activity could prevent sensory neuropathy induced by RTX...
September 5, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28877878/angiotensin-ii-type-1a-receptor-deficient-mice-develop-angiotensin-ii-induced-oxidative-stress-and-dna-damage-without-blood-pressure-increase
#19
Anna Zimnol, Kerstin Amann, Philipp Mandel, Christina Hartmann, Nicole Schupp
Hypertensive patients have an increased risk to develop kidney cancer. We have shown in vivo, that besides elevating blood pressure, angiotensin II causes DNA damage dose-dependently. Here, the role of blood pressure in the formation of DNA damage is studied. Mice lacking one of the two murine angiotensin II type 1 receptor (AT1R) subtypes, AT1aR, were equipped with osmotic minipumps, delivering angiotensin II during 28 days. Parameters of oxidative stress and DNA damage of kidneys and hearts of AT1aR-knockout mice were compared to wildtype (C57BL/6) mice receiving angiotensin II, and additionally, to wildtype (WT) mice treated with candesartan, an antagonist of both AT1R-subtypes...
September 6, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28872259/prevalence-and-prognostic-importance-of-precipitating-factors-leading-to-heart-failure-hospitalization-recurrent-hospitalizations-and-mortality
#20
Elke Platz, Pardeep S Jhund, Brian L Claggett, Marc A Pfeffer, Karl Swedberg, Christopher B Granger, Salim Yusuf, Scott D Solomon, John J McMurray
AIMS: Hospitalizations for heart failure (HF) are common and are associated with significant morbidity, mortality and cost. However, precipitating factors leading to HF hospitalization and their importance with respect to subsequent outcomes are not well understood. METHODS AND RESULTS: The symptoms and signs present at admission and investigator-identified factors thought to have contributed to the first adjudicated HF hospitalization in the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) programme were prospectively collected and stratified by ejection fraction (EF)...
September 4, 2017: European Journal of Heart Failure
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