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https://www.readbyqxmd.com/read/27936434/mineralocorticoid-receptor-haplotype-estradiol-progesterone-and-emotional-information-processing
#1
Danielle A Hamstra, E Ronald de Kloet, Ina Quataert, Myrthe Jansen, Willem Van der Does
BACKGROUND: Carriers of MR-haplotype 1 and 3 (GA/CG; rs5522 and rs2070951) are more sensitive to the influence of oral contraceptives (OC) and menstrual cycle phase on emotional information processing than MR-haplotype 2 (CA) carriers. We investigated whether this effect is associated with estradiol (E2) and/or progesterone (P4) levels. METHOD: Healthy MR-genotyped premenopausal women were tested twice in a counterbalanced design. Naturally cycling (NC) women were tested in the early-follicular and mid-luteal phase and OC-users during OC-intake and in the pill-free week...
November 30, 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/27934887/aldosterone-induces-rapid-sodium-intake-by-a-nongenomic-mechanism-in-the-nucleus-tractus-solitarius
#2
Hu Qiao, Bo Hu, Hong Zhou, Jianqun Yan, Ru Jia, Bo Lu, Bo Sun, Xiao Luo, Yuanyuan Fan, Nan Wang
The purpose of this study was to determine whether aldosterone has a rapid action in the nucleus tractus solitarius (NTS) that increases sodium intake, and to examine whether this effect of aldosterone, if present, is mediated by G protein-coupled estrogen receptor (GPER). Adult male Sprague-Dawley rats with a stainless-steel cannula in the NTS were used. Aldosterone was injected into the NTS at the doses of 1, 5, 10 and 20 ng 0.1 μl(-1). A rapid dose-related increase of 0.3 M NaCl intake was induced within 30 min and this increase was not suppressed by the mineralocorticoid receptor (MR) antagonist spironolactone (10 ng 0...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27930384/the-endothelial-mineralocorticoid-receptor-mediator-of-the-switch-from-vascular-health-to-disease
#3
Ana P Davel, Imran J Anwar, Iris Z Jaffe
PURPOSE OF REVIEW: Endothelial dysfunction is an early feature of vascular disease induced by cardiovascular risk factors (CRFs). In growing populations with obesity, diabetes, hypertension, and heart failure, mineralocorticoid receptor antagonism improves endothelial function. This review summarizes recent advances in our understanding of the specific role of endothelial cell mineralocorticoid receptor in vascular function in health and disease. RECENT FINDINGS: Using transgenic mice with mineralocorticoid receptor expression specifically modulated in endothelial cells, recent studies support the emerging concept that while endothelial cell mineralocorticoid receptor may be protective in health, in the presence of CRFs, endothelial cell mineralocorticoid receptor activity contributes to endothelial dysfunction and progression of vascular disease...
December 7, 2016: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27929707/systemic-mineralocorticoid-antagonists-in-the-treatment-of-central-serous-chorioretinopathy
#4
Dong Yang, Dean Eliott
Central serous chorioretinopathy (CSCR) is a challenging disease characterized by subretinal serous fluid accumulation. The complex pathogenesis is still not fully understood, but is thought to be multifactorial and involves exogenous and endogenous factors affecting the choroid and retinal pigment epithelium. The involvement of corticosteroids is undisputed, while the contribution of mineralocorticoid pathways is under investigation. This review addresses the proposed pathogenesis models and the evidence for systemic treatment of CSCR with mineralocorticoid antagonists...
December 8, 2016: Seminars in Ophthalmology
https://www.readbyqxmd.com/read/27927713/high-fibre-diet-and-acetate-supplementation-change-the-gut-microbiota-and-prevent-the-development-of-hypertension-and-heart-failure-in-doca-salt-hypertensive-mice
#5
Francine Z Marques, Erin M Nelson, Po-Yin Chu, Duncan Horlock, April Fiedler, Mark Ziemann, Jian K Tan, Sanjaya Kuruppu, Niwanthi W Rajapakse, Assam El-Osta, Charles R Mackay, David M Kaye
BACKGROUND: -Dietary intake of fruit and vegetables is associated with lower incidence of hypertension, but the mechanisms involved have not been elucidated. Here we evaluated the effect of a high fibre diet and supplementation with the short-chain fatty acid (SFCA) acetate on the gut microbiota and the prevention of cardiovascular disease. METHODS: -Gut microbiome, cardiorenal structure/function and blood pressure were examined in sham and mineralocorticoid-excess treated mice with a control diet, high fibre diet or acetate supplementation...
December 7, 2016: Circulation
https://www.readbyqxmd.com/read/27919009/successful-percutaneous-ct-guided-microwave-ablation-of-adrenal-gland-for-ectopic-cushing-syndrome
#6
Rebecca Zener, Andrew Zaleski, Stan H Van Uum, Daryl K Gray, Amol Mujoomdar
Adrenocorticotropic hormone production by pancreatic neuroendocrine tumor (PNET) is rare and results in hyperstimulation of the adrenal gland to produce ectopic Cushing syndrome. Our case showcases the safety and effectiveness of percutaneous CT-guided microwave ablation of the adrenal gland in a 49-year-old female with PNET and hepatic metastases who presented with ectopic Cushing syndrome despite surgical resection of the primary pancreatic tumor and left adrenal gland. Prior to ablation, the right adrenal gland measured 4...
November 29, 2016: Clinical Imaging
https://www.readbyqxmd.com/read/27915044/a-novel-aldosterone-synthase-inhibitor-ameliorates-mortality-in-pressure-overload-mice-with-heart-failure
#7
Shinji Furuzono, Masaki Meguro, Satoru Miyauchi, Shinichi Inoue, Tsuyoshi Homma, Keisuke Yamada, Yoh-Ichi Tagawa, Futoshi Nara, Takahiro Nagayama
It has been elucidated that mineralocorticoid receptor antagonists reduce mortality in patients with congestive heart failure and post-acute myocardial infarction. A direct inhibition of aldosterone synthase (CYP11B2) is also expected to have therapeutic benefits equal in quality to mineralocorticoid receptor antagonists in terms of reducing mineralocorticoid receptor signaling. Therefore, we have screened our chemical libraries and identified a novel and potent aldosterone synthase inhibitor, 2,2,2-trifluoro-1-{4-[(4-fluorophenyl)amino]pyrimidin-5-y}-1-[1-(methylsulfonyl)piperidin-4-yl]ethanol (compound 1), by lead optimization...
November 30, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27912890/persistence-of-123-i-mibg-prognostic-capability-in-relation-to-medical-therapy-in-heart-failure-from-the-admire-hf-trial
#8
Ileana L Piña, Peter Carson, JoAnn Lindenfeld, W Tad Archambault, Arnold F Jacobson
(123)I-mIBG imaging has been evaluated to assess sympathetic function and prognosis in heart failure (HF). However, the effect of combined HF medical therapies on (123)I-mIBG uptake and its prognostic significance has not been previously examined. This analysis examined the relation between the intensity of guideline-directed HF medical therapy and global (123)I-mIBG cardiac uptake in the AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) database. A second objective was to investigate whether this guideline-based therapy, measured by total medication doses, had the expected effect on outcome, that is, that patients with higher (123)I-mIBG cardiac uptake and more intensive medical therapy had the fewest outcome events...
October 31, 2016: American Journal of Cardiology
https://www.readbyqxmd.com/read/27905877/mineralocorticoid-receptor-antagonists-for-heart-failure-systematic-review-and-meta-analysis
#9
Nicolas M Berbenetz, Marko Mrkobrada
BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) have been associated with improved patient outcomes in patients with heart failure with reduced ejection fraction (HFrEF) but not preserved ejection fraction (HFpEF). We conducted a systematic review and meta-analysis of selective and nonselective MRAs in HFrEF and HFpEF. METHODS: We searched Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE. We included randomized controlled trials (RCT) of MRAs in adults with HFpEF or HFrEF if they reported data on major adverse cardiac events or drug safety...
December 1, 2016: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/27905124/assessment-of-early-atherosclerosis-and-left-ventricular-dysfunction-in-children-with-21-hydroxylase-deficiency
#10
Rahmi Özdemir, Hüseyin Anil Korkmaz, Mehmet Küçük, Cem Karadeniz, Timur Meşe, Behzat Özkan
AIM: We analysed 25 children with 21-hydroxylase deficiency who received glucocorticoid and/or mineralocorticoid treatment for at least 12 months to determine the effects of the disease and its treatment on vascular structures and ventricular function. METHODS: Twenty-five patients with 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH) and 25 control subjects were enrolled into this observational, cross-sectional study. The patients were investigated in terms of fasting blood glucose and insulin; fasting serum lipid profile; serum 17-hydroxyprogesterone; dehydroepiandrosterone sulphate; androstenedione; and adrenocorticotropic hormone...
November 7, 2016: Clinical Endocrinology
https://www.readbyqxmd.com/read/27900561/mineralocorticoid-antagonists-as-adjuncts-in-neovascular-age-related-macular-degeneration
#11
Kapil G Kapoor, Niket Todi, Alan L Wagner
INTRODUCTION: The purpose of this project was to evaluate the role of MR antagonists as an adjunct in patients with neovascular age-related macular degeneration (AMD) who have chronic subretinal fluid. METHODS: Inclusion criteria were patients with a diagnosis of neovascular AMD, who had completed at least six anti-VEGF injections, and had persistent subretinal fluid (SRF) on optical coherence tomography (OCT). Treatment with oral eplerenone was initiated and dose titrated according to protocol...
November 29, 2016: Ophthalmology and Therapy
https://www.readbyqxmd.com/read/27899856/effect-of-spironolactone-on-plasma-apelin-12-levels-in-patients-with-chronic-systolic-heart-failure
#12
Mustafa Topuz, Mehmet Cosgun, Oğuz Akkuş, Atilla Bulut, Omer Sen, Ayşe Nur Topuz, Murat Caylı
BACKGROUND: The aim of this study was to determine whether spironolactone therapy has an effect on serum apelin-12 levels in heart failure with reduced ejection fraction (HFrEF) patients. METHODS: Eighty outpatients previously diagnosed with HFrEF were enrolled in the current study. Included patients were taking only standard heart failure therapy (ST) (angiotensin converting enzyme or angiotensin receptor blocker, beta-blockers, loop diuretics and anticoagulant or antiagregan agents) without a mineralocorticoid receptor antagonists (MRA) because of its side effects, and were designated the non-MRA group; those patients taking 25 mg/daily spironolactone in addition to the ST were deemed the MRA group...
November 2016: Acta Cardiologica Sinica
https://www.readbyqxmd.com/read/27897427/structure-based-drug-design-of-mineralocorticoid-receptor-antagonists-to-explore-oxosteroid-receptor-selectivity
#13
Anneli Nordqvist, Gavin O'Mahony, Maria Fridén-Saxin, Marlene Fredenwall, Anders Hogner, Kenneth L Granberg, Anna Aagaard, Stefan Bäckström, Anders Gunnarsson, Tim Kaminski, Yafeng Xue, Anita Dellsén, Eva Hansson, Pia Hansson, Ida Ivarsson, Ulla Karlsson, Krister Bamberg, Majlis Hermansson, Jennie Georgsson, Bo Lindmark, Karl Edman
The mineralocorticoid receptor (MR) is a nuclear hormone receptor involved in regulation of body fluid and electrolyte homeostasis. In this study we explore selectivity triggers for a series of non-steroidal MR antagonists to improve selectivity over other members of the oxosteroid receptor family. A biaryl sulfonamide compound was identified in a high-throughput screening (HTS) campaign. The compound bound to MR with a pKi=6.6, but displayed poor selectivity over the glucocorticoid receptor (GR) and the progesterone receptor (PR)...
November 29, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27897263/principal-function-of-mineralocorticoid-signaling-suggested-by-constitutive-knockout-of-the-mineralocorticoid-receptor-in-medaka-fish
#14
Tatsuya Sakamoto, Madoka Yoshiki, Hideya Takahashi, Masayuki Yoshida, Yukiko Ogino, Toshitaka Ikeuchi, Tomoya Nakamachi, Norifumi Konno, Kouhei Matsuda, Hirotaka Sakamoto
As in osmoregulation, mineralocorticoid signaling is implicated in the control of brain-behavior actions. Nevertheless, the understanding of this role is limited, partly due to the mortality of mineralocorticoid receptor (MR)-knockout (KO) mice due to impaired Na(+) reabsorption. In teleost fish, a distinct mineralocorticoid system has only been identified recently. Here, we generated a constitutive MR-KO medaka as the first adult-viable MR-KO animal, since MR expression is modest in osmoregulatory organs but high in the brain of adult medaka as for most teleosts...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895136/recognition-and-management-of-resistant-hypertension
#15
REVIEW
Branko Braam, Sandra J Taler, Mahboob Rahman, Jennifer A Fillaus, Barbara A Greco, John P Forman, Efrain Reisin, Debbie L Cohen, Mohammad G Saklayen, S Susan Hedayati
Despite improvements in hypertension awareness and treatment, 30%-60% of hypertensive patients do not achieve BP targets and subsequently remain at risk for target organ damage. This therapeutic gap is particularly important to nephrologists, who frequently encounter treatment-resistant hypertension in patients with CKD. Data are limited on how best to treat patients with CKD and resistant hypertension, because patients with CKD have historically been excluded from hypertension treatment trials. First, we propose a consistent definition of resistant hypertension as BP levels confirmed by both in-office and out-of-office measurements that exceed appropriate targets while the patient is receiving treatment with at least three antihypertensive medications, including a diuretic, at dosages optimized to provide maximum benefit in the absence of intolerable side effects...
November 28, 2016: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/27895120/ankyrin-g-expression-regulates-apical-delivery-of-the-epithelial-sodium-channel-enac
#16
Christine A Klemens, Robert S Edinger, Lindsay Kightlinger, Xiaoning Liu, Michael B Butterworth
The epithelial sodium channel (ENaC) is the limiting entry point for Na(+) reabsorption in the distal kidney nephron and is regulated by numerous hormones, including the mineralocorticoid hormone aldosterone. Previously we identified ankyrin G (AnkG), a cytoskeletal protein involved in vesicular transport, as a novel aldosterone-induced protein that can alter Na(+) transport in mouse cortical collecting duct (mCCD) cells. However, the mechanisms underlying AnkG's regulation of Na(+) transport were unknown. Here we report that AnkG expression directly regulates Na(+) transport by altering ENaC activity in the apical membrane...
November 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27893293/prevelence-of-primary-aldosteronism-in-an-urban-hypertensive-population
#17
Sandi-Jo Galati, Khadeen C Cheesman, Ryan Springer-Miller, Sarah M Hopkins, Lawrence Krakoff, Emilia Bagiella, Rachel A Zhuk, Tiffany K Ying, Chelsey Amer, Michael K Boyajian, W B Inabnet, Alice C Levine
OBJECTIVE: To determine the prevalence of primary aldosteronism (PA) in hypertensive patients presenting to the primary care clinic at The Mount Sinai Hospital, regardless of the degree of hypertension and to identify clinical criteria that should prompt screening for PA. METHODS: An aldosterone:renin ratio (ARR, cutoff ≥20, with plasma aldosterone concentration [PAC] ≥10 and suppressed renin) was used to prospectively screen 296 hypertensive patients (blood pressure [BP] ≥140/90) over the age of 18 from August 2012 through May 2013...
November 2016: Endocrine Practice
https://www.readbyqxmd.com/read/27892684/angiotensin-receptor-neprilysin-inhibitor-lcz696-pharmacology-pharmacokinetics-and-clinical-development
#18
Yue Hua, Ian Wang, Bin Liu, Darren J Kelly, Christopher Reid, Danny Liew, Yingchun Zhou, Bing H Wang
Heart failure still has a significant disease burden with poor outcomes worldwide despite advances in therapy. The standard therapies have been focused on blockade of renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and mineralocorticoid antagonists and the sympathetic nervous system with β-blockers. The natriuretic peptide system is a potential counter-regulatory system that promotes vasodilatation and natriuresis. Angiotensin receptor neprilysin inhibitors are a new class drug capable of blocking the renin-angiotensin-aldosterone system and enhancing the natriuretic peptide system to improve neurohormonal balance...
November 28, 2016: Future Cardiology
https://www.readbyqxmd.com/read/27889894/glucocorticoid-induced-leucine-zipper-in-central-nervous-system-health-and-disease
#19
REVIEW
Mythily Srinivasan, Debomoy K Lahiri
The central nervous system (CNS) is a large network of intercommunicating cells that function to maintain tissue health and homeostasis. Considerable evidence suggests that glucocorticoids exert both neuroprotective and neurodegenerative effects on the CNS. Glucocorticoids act by binding two related receptors in the cytoplasm, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). The glucocorticoid receptor complex mediates cellular responses by transactivating target genes and by protein: protein interactions...
November 26, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27884222/a-reassessment-of-the-pathophysiology-of-progressive-cardiorenal-disorders
#20
REVIEW
Richard N Re
Heart failure and chronic renal diseases are usually progressive and only partially amenable to therapy. These disorders can be the sequelae of hypertension or worsened by hypertension. They are associated with the tissue up-regulation of multiple peptides, many of which are capable of acting within the cell interior. This article proposes that these peptides, intracrines, can form self-sustaining regulatory loops that can spread through heart or kidney, producing progressive disease. Moreover, mineralocorticoid activation seems capable of amplifying some of these peptide networks...
January 2017: Medical Clinics of North America
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