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https://www.readbyqxmd.com/read/29329357/mineralocorticoid-receptor-antagonists-treatment-in-resistant-hypertension-and-hfpef-evidence-and-courage
#1
Daniel Duprez, Aigerim Toleuova
No abstract text is available yet for this article.
January 10, 2018: American Journal of Hypertension
https://www.readbyqxmd.com/read/29318439/mind-the-gap-mismatches-between-clinicians-and-patients-in-heart-failure-medication-management
#2
Ken Lee Chin, Marina Skiba, Christopher M Reid, Andrew Tonkin, Ingrid Hopper, Justin A Mariani, Danny Liew
PURPOSE: Previous studies on the 'treatment gap' in patients with heart failure (HF) have focused either on prescribing or patients' adherence to prescribed treatment. This study sought to determine whether or not recent initiatives to close the gap have also minimised any mismatches between physicians' expectation of their patients' medications, medications in the patients' possession and their actual medication use. METHODS: A cross-sectional observational survey was conducted from December 2015 to June 2016 in The Alfred Hospital HF clinic in Melbourne, Australia...
January 9, 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29310346/a-systematic-review-and-meta-analysis-of-the-impact-of-mineralocorticoid-receptor-antagonists-on-glucose-homeostasis
#3
Sandra Korol, Fannie Mottet, Sylvie Perreault, William L Baker, Michel White, Simon de Denus
BACKGROUND: Spironolactone, a nonselective mineralocorticoid receptor antagonist (MRA), may have a deleterious effect on glycemia. The objective of this review was to assess current knowledge on MRAs' influence (spironolactone, eplerenone, and canrenone) on glucose homeostasis and the risk of diabetes. METHOD: A systematic review was conducted using the Medline database on articles published from 1946 to January 2017 that studied the effects of MRAs on any glucose-related endpoints, without any restrictions regarding the participants' characteristics...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29300474/identification-of-morpholino-2h-pyrido-3-2-b-1-4-oxazin-3-4h-ones-as-non-steroidal-mineralocorticoid-antagonists
#4
David W Piotrowski, Kentaro Futatsugi, Agustin Casimiro-Garcia, Liuqing Wei, Matthew Sammons, Michael Herr, Wenhua Jiao, Sophie Y Lavergne, Steven B Coffey, Stephen W Wright, Kun Song, Paula M Loria, Mary Ellen Banker, Donna N Petersen, Jonathan Bauman
A novel series of morpholine-based non-steroidal mineralocorticoid receptor antagonists is reported. Starting from a pyrrolidine HTS hit 9 that possessed modest potency but excellect selectivity versus related nuclear hormone receptors, a series of libraries led to identification of morpholine lead 10. After further optimization, cis disubstituted morpholine 22 was discovered, which showed a 45-fold boost in binding affinity and corresponding functional potency compared to 13. While 22 had high clearance in rat, it provided sufficient exposure at high doses to favorably assess in vivo efficacy (increased urinary Na+/K+ ratio) and safety...
January 4, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29289651/neutrophil-gelatinase-associated-lipocalin-from-immune-cells-is-mandatory-for-aldosterone-induced-cardiac-remodeling-and-inflammation
#5
Mathieu Buonafine, Ernesto Martínez-Martínez, Cristian Amador, Basile Gravez, Jaime Ibarrola, Amaya Fernández-Celis, Soumaya El Moghrabi, Patrick Rossignol, Natalia López-Andrés, Frédéric Jaisser
Immune system activation is involved in cardiovascular (CV) inflammation and fibrosis, following activation of the mineralocorticoid receptor (MR). We previously showed that Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a novel target of MR signaling in CV tissue and plays a critical role in aldosterone/MR-dependent hypertension and fibrosis. We hypothesized that the production of NGAL by immune cells may play an important part in the mediation of these deleterious mineralocorticoid-induced effects. We analyzed the effect of aldosterone on immune cell recruitment and NGAL expression in vivo...
December 28, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29277469/the-seisicat-study-a-pilot-study-assessing-efficacy-and-safety-of-spironolactone-in-cats-with-congestive-heart-failure-secondary-to-cardiomyopathy
#6
Rachel James, Emilie Guillot, Catherine Garelli-Paar, Jacqueline Huxley, Vanessa Grassi, Malcolm Cobb
INTRODUCTION: The pathophysiology of heart failure involves activation of several neurohormonal systems including the renin-angiotensin-aldosterone system. The mineralocorticoid receptor antagonist spironolactone has been shown to be beneficial in humans and dogs with heart failure. The objective of this pilot study was to investigate the efficacy and safety of spironolactone in cats with heart failure secondary to cardiomyopathy already treated with furosemide and an angiotensin-converting enzyme inhibitor...
December 22, 2017: Journal of Veterinary Cardiology: the Official Journal of the European Society of Veterinary Cardiology
https://www.readbyqxmd.com/read/29276898/-clinical-and-demographic-characteristics-of-an-outpatient-russian-population-with-chronic-heart-failure-at-the-time-of-enrollment-in-the-qualify-registry-for-evaluating-consistency-with-clinical-guidelines-on-drug-therapy
#7
S N Tereshchenko, I V Zhirov, A A Petrukhina
BACKGROUND: Chronic heart failure is the most common condition in patients with cardiovascular diseases. Therefore, evaluating consistency of doctor's recommendations with guidelines on drug therapy is a relevant issue. AIM: To evaluate consistency of doctor's recommendations with guidelines on drug therapy for CHF. MATERIALS AND METHODS: The study presents enrollment visit data for the Russian part of the international prospective registry, QUALIFY...
2017: Kardiologiia
https://www.readbyqxmd.com/read/29275377/mineralocorticoid-receptor-antagonists-in-high-risk-heart-failure-patients-with-diabetes-mellitus-and-or-chronic-kidney-disease
#8
EDITORIAL
Bertram Pitt, Patrick Rossignol
No abstract text is available yet for this article.
December 23, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29275368/use-of-mineralocorticoid-receptor-antagonists-in-patients-with-heart-failure-and-comorbid-diabetes-mellitus-or-chronic-kidney-disease
#9
Lauren B Cooper, Steven J Lippmann, Melissa A Greiner, Abhinav Sharma, Jacob P Kelly, Gregg C Fonarow, Clyde W Yancy, Paul A Heidenreich, Adrian F Hernandez
BACKGROUND: Perceived risks of hyperkalemia and acute renal insufficiency may limit use of mineralocorticoid receptor antagonist (MRA) therapy in patients with heart failure, especially those with diabetes mellitus or chronic kidney disease. METHODS AND RESULTS: Using clinical registry data linked to Medicare claims, we analyzed patients hospitalized with heart failure between 2005 and 2013 with a history of diabetes mellitus or chronic kidney disease. We stratified patients by MRA use at discharge...
December 23, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29274772/evidence-for-the-use-of-mineralocorticoid-receptor-antagonists-in-the-treatment-of-coronary-artery-disease-and-post-angioplasty-restenosis
#10
REVIEW
Jochen Dutzmann, Johann Bauersachs, Daniel G Sedding
Mineralocorticoid receptor antagonists (MRAs), such as spironolactone, eplerenone and finerenone, have an established role in the treatment of heart failure. However, many experimental and clinical studies have shown that aldosterone also plays a pivotal role in a variety of other pathophysiological conditions within the cardiovascular system. Aldosterone has been suggested to promote inflammation, endothelial dysfunction and smooth muscle cell hyperplasia during the development of atherosclerosis, thereby promoting the development of coronary artery disease (CAD)...
December 21, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/29251811/impact-of-adolescent-stress-on-the-expression-of-stress-related-receptors-in-the-hippocampus-of-animals-exposed-to-alcohol-prenatally
#11
Charlis Raineki, Linda Ellis, Joanne Weinberg
Many functions of the hippocampus are affected by prenatal alcohol exposure (PAE). In particular, dysregulation of the stress response is especially important because individuals with PAE carry increased risks for exposure to stressful environments throughout life. Little is known, though, about how adolescent stress in the context of PAE-related stress system dysregulation may further alter hippocampal development. Here we investigate the short- and long-term effects of adolescent chronic mild stress (CMS) on mRNA expression of stress-related mineralocorticoid (MR), glucocorticoid (GR), and type 1 CRH (CRHR1) receptors in the dorsal and ventral hippocampal formation of PAE and control rats...
December 18, 2017: Hippocampus
https://www.readbyqxmd.com/read/29248852/determination-of-endocrine-disrupting-potencies-of-agricultural-soils-in-china-via-a-battery-of-steroid-receptor-bioassays
#12
Jianyun Zhang, Rui Liu, Lili Niu, Siyu Zhu, Quan Zhang, Meirong Zhao, Weiping Liu, Jing Liu
Pollution of agricultural soils by pesticides, such as organochlorine pesticides (OCPs), can be a significant issue since high detection rates of these compounds were reported in our previous studies. However, more uncertain kinds, quantities and density of pollutants remained in soil samples were unidentified. In this study, the total hormonal activities of complex mixtures of both known and unknown contaminants in agricultural soils in mainland China were measured by applying highly sensitive reporter gene assays for detecting agonists/antagonists for estrogen receptor (ER), androgen receptor (AR), progesterone receptor (PR), glucocorticoid receptor (GR) and mineralocorticoid receptor (MR)...
December 14, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29248456/endothelin-2-injures-the-blood-retinal-barrier-and-macroglial-m%C3%A3-ller-cells-interactions-with-angiotensin-ii-aldosterone-and-nadph-oxidase
#13
Saeed Fadal Alrashdi, Devy Deliyanti, Dean Michael Talia, Jennifer Louise Wilkinson-Berka
Although increasing evidence indicates that endothelin-2 (Edn2) has distinct roles in tissue pathology including inflammation, glial cell dysfunction, and angiogenesis, its role in the retina and the factors that regulate its actions are not fully understood. We hypothesized that Edn2 damages the blood-retinal barrier (BRB) and this is mediated by interactions with the renin-angiotensin aldosterone system and reactive oxygen species derived from NADPH oxidase (Nox). C57BL/6J mice received an intravitreal injection of Edn2 or control vehicle to examine the blood pressure-independent effects of Edn2...
December 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29237722/pannexin-1-channels-as-an-unexpected-new-target-of-the-anti-hypertensive-drug-spironolactone
#14
Miranda E Good, Yu-Hsin Chiu, Ivan K Poon, Christopher B Medina, Joshua T Butcher, Suresh K Mendu, Leon J DeLalio, Alexander W Lohman, Norbert Leitinger, Eugene J Barrett, Ulrike M Lorenz, Bimal N Desai, Iris Z Jaffe, Douglas Bayliss, Brant E Isakson, Kodi S Ravichandran
Rationale: Resistant hypertension is a major health concern with unknown etiology. Spironolactone is an effective anti-hypertensive drug, especially for patients with resistant hypertension, and is considered by the World Health Organization (WHO) as an "essential" medication. Although spironolactone can act at the mineralocorticoid receptor (NR3C2), there is increasing evidence of mineralocorticoid receptor (MR)-independent effects of spironolactone. Objective: Here, we detail the unexpected discovery that pannexin 1 (Panx1) channels could be a relevant in vivo target of spironolactone...
December 13, 2017: Circulation Research
https://www.readbyqxmd.com/read/29231924/the-mineralocorticoid-receptor-knockout-in-medaka-is-further-validated-by-glucocorticoid-receptor-compensation
#15
Tatsuya Sakamoto, Madoka Yoshiki, Hirotaka Sakamoto
To study the critical role of mineralocorticoid signalling, we generated a constitutive mineralocorticoid receptor (MR)-knockout (KO) medaka as the first adult-viable MR-KO animal. This KO medaka displayed abnormal behaviours affected by visual stimuli. In contrast, the loss of MR did not result in overt phenotypic changes in osmoregulation, despite the well-known osmoregulatory functions of MR in mammals. Since glucocorticoid receptor (GR) has been suggested to compensate for loss of MR, we examined expression of duplicated GRs with markedly different ligand sensitivities, in various tissues...
December 12, 2017: Scientific Data
https://www.readbyqxmd.com/read/29228101/spironolactone-and-resistant-hypertension-in-heart-failure-with-preserved-ejection-fraction
#16
P Rossignol, B Claggett, J Liu, O Vardeny, B Pitt, F Zannad, S Solomon
Background: Recent evidence suggests that the mineralocorticoid receptor antagonist spironolactone should be the preferred fourth line antihypertensive treatment in resistant hypertension (RHTN). Whether spironolactone improves blood pressure (BP) control in heart failure with preserved ejection fraction (HFpEF) and RHTN is unknown. Methods: We identified patients with RHTN, defined as baseline systolic blood pressure (SBP) between 140 and 160 mmHg on 3 or more medications, in the Americas cohort of the TOPCAT trial, in which patients with HFpEF were randomized to spironolactone vs...
December 7, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/29226122/does-mineralocorticoid-receptor-antagonism-prevent-calcineurin-inhibitor-induced-nephrotoxicity
#17
REVIEW
Line Aas Mortensen, Claus Bistrup, Helle Charlotte Thiesson
Calcineurin inhibitors have markedly reduced acute rejection rates in renal transplantation, thus significantly improved short-term outcome. The beneficial effects are, however, tampered by acute and chronic nephrotoxicity leading to interstitial fibrosis and tubular atrophy, which impairs long-term allograft survival. The mineralocorticoid hormone aldosterone induces fibrosis in numerous organs, including the kidney. Evidence from animal models suggests a beneficial effect of aldosterone antagonism in reducing calcineurin inhibitor-induced nephrotoxicity...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29224647/mineralocorticoid-receptor-antagonists-in-patients-with-acute-myocardial-infarction-a-systematic-review-and-meta-analysis-of-randomized-trials
#18
REVIEW
Matthias Bossard, Yasser Binbraik, Farzin Beygui, Bertram Pitt, Faiez Zannad, Gilles Montalescot, Sanjit S Jolly
BACKGROUND: Although mineralocorticoid antagonists (MRAs) reduce mortality in patients with heart failure complicating myocardial infarction (MI), it is unclear if they could be beneficial to all patients with MI. To evaluate the utility of MRAs in MI patients, we performed a systematic review and meta-analysis. METHODS: MEDLINE, EMBASE, and Cochrane CENTRAL were searched from 1965 to June 2016. Conference abstracts were searched from 2000 to June 2016. Randomized trials evaluating the effect of MRA after MIs were included...
January 2018: American Heart Journal
https://www.readbyqxmd.com/read/29223280/circadian-and-ultradian-patterns-of-hpa-axis-activity-in-rodents-significance-for-brain-functionality
#19
REVIEW
Femke S den Boon, R Angela Sarabdjitsingh
The hypothalamo-pituitary-adrenal (HPA) axis comprises interactions between the hypothalamus, the pituitary and the adrenal glands and its activation results in the release of corticosteroid hormones. Corticosteroids are secreted from the adrenal gland in a distinct 24-h circadian rhythm overarching an ultradian rhythm, which consists of hourly corticosteroid pulses exposing target tissues to rapidly changing steroid levels. On top of these rhythms surges can take place after stress. HPA-axis rhythms promote adaptation to predictable (i...
October 2017: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29212952/dysregulated-aldosterone-secretion-in-persons-of-african-descent-with-endothelin-1-gene-variants
#20
Jia W Tan, Tina Gupta, Worapaka Manosroi, Tham M Yao, Paul N Hopkins, Jonathan S Williams, Gail K Adler, Jose R Romero, Gordon H Williams
Compared with persons of European descent (ED), persons of African descent (AD) have lower aldosterone (ALDO) levels, with the assumption being that the increased cardiovascular disease (CVD) risk associated with AD is not related to ALDO. However, the appropriateness of the ALDO levels for the volume status in AD is unclear. We hypothesized that, even though ALDO levels are lower in AD, they are inappropriately increased, and therefore, ALDO could mediate the increased CVD in AD. To test this hypothesis, we analyzed data from HyperPATH - 1,788 individuals from the total cohort and 765 restricted to ED-to-AD in a 2:1 match and genotyped for the endothelin-1 gene (EDN1)...
December 7, 2017: JCI Insight
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