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https://www.readbyqxmd.com/read/28814143/ly3045697-results-from-two-randomized-clinical-trials-of-a-novel-inhibitor-of-aldosterone-synthase
#1
Joanne Sloan-Lancaster, Eyas Raddad, Amy Flynt, Yan Jin, James Voelker, Jeffrey W Miller
INTRODUCTION: LY3045697 is a potent and selective aldosterone synthase (CYP11B2) inhibitor that was developed as a safer alternative to mineralocorticoid receptor antagonists. Effects of LY3045697 on aldosterone and cortisol synthesis, as well as potassium ion homeostasis, were evaluated in two clinical studies in healthy subjects. MATERIALS AND METHODS: Two incomplete, placebo-controlled crossover-design clinical studies examined safety, pharmacodynamics, and pharmacokinetics under single and repeated dose conditions in healthy subjects...
July 2017: Journal of the Renin-angiotensin-aldosterone System: JRAAS
https://www.readbyqxmd.com/read/28811691/association-of-prooxidant-antioxidant-balance-with-clinical-and-laboratory-parameters-and-its-relation-to-different-drug-regimens-in-polycystic-ovary-syndrome-women-with-normal-bmi
#2
Niloofar Heshmati, Shoaleh Shahgheibi, Bahram Nikkhoo, Sabrieh Amini, Mohammad Abdi
Polycystic ovarian syndrome is one of the most common hormonally leading cause infertility disorders. The effect of oxidant-antioxidant imbalance on disease progression has been studied in many disorders. The present study was aimed to evaluate prooxidant-antioxidant balance (PAB) in patients with polycystic ovarian syndrome compared to healthy subjects. We also studied the possible effect of treatment with available drugs on serum PAB. In this case-control study 100 polycystic ovary syndrome (PCOS) patients and 100 healthy individuals were enrolled in the study...
July 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28801620/a-novel-aldosterone-antagonist-limits-renal-injury-in-5-6-nephrectomy
#3
Clarice K Fujihara, M C Kowala, M D Breyer, Claudia R Sena, Mariliza V Rodrigues, Simone C A Arias, Camilla Fanelli, Denise M Malheiros, P K Jadhav, Chahrzad Montrose-Rafizadeh, Jose E Krieger, Roberto Zatz
Aldosterone antagonists slow the progression of chronic kidney disease (CKD), but their use is limited by hyperkalemia, especially when associated with RAS inhibitors. We examined the renoprotective effects of Ly, a novel non-steroidal mineralocorticoid receptor (MR) blocker, through two experimental protocols: In Protocol 1, male Munich-Wistar rats underwent 5/6 renal ablation (Nx), being divided into: Nx+V, receiving vehicle, Nx+Eple, given eplerenone, 150 mg/kg/day, and Nx+Ly, given Ly, 20 mg/kg/day...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28797006/amiloride-is-effective-in-the-management-of-abiraterone-induced-mineralocorticoid-excess-syndrome-without-interfering-with-its-antineoplastic-activity
#4
Francesca Bedussi, Diego Galli, Martina Fragni, Francesca Valcamonico, Elisa Rossini, Alberto Dalla Volta, Sara Vezzoli, Elisa Roca, Vittorio Ferrari, Barbara Lazzari, Maurizio Memo, Sandra Sigala, Alfredo Berruti
BACKGROUND: The administration of abiraterone acetate (abiraterone) leads to an adrenocorticotropic hormone (ACTH)-driven increase in mineralocorticoid hormones, requiring glucocorticoid supplementation that may stimulate the growth of prostate cancer (PCa). Amiloride is a drug that selectively reduces the aldosterone-sensitive Na+/K+ exchange and could be effective in the management of mineralocorticoid excess syndrome (MCES). METHODS: The efficacy of amiloride + hydrochlorothiazide (HCT) in the clinical management of abiraterone-induced MCES was assessed in 5 consecutive patients with castration-resistant PCa (CRPC)...
August 11, 2017: Pharmacology
https://www.readbyqxmd.com/read/28793999/association-of-qt-prolonging-medication-use-in-ckd-with-electrocardiographic-manifestations
#5
Soren Snitker, Rebecca M Doerfler, Elsayed Z Soliman, Rajat Deo, Wendy L St Peter, Susan Kramlik, Michael J Fischer, Sankar Navaneethan, Patrice Delafontaine, Bernard G Jaar, Akinlolu Ojo, Gail K Makos, Anne Slaven, Matthew R Weir, Min Zhan, Jeffrey C Fink
BACKGROUND AND OBJECTIVES: Several drugs used in CKD can prolong electrocardiographic conduction. We examined the use of electrocardiogram QT-prolonging medications in predialysis CKD and their association with QT duration. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 3252 Chronic Renal Insufficiency Cohort participants with at least one study electrocardiogram between 2003 and 2011 were included. QT-prolonging medications used in 100 or more visits (n=16,451 visits) along with diuretics and proton pump inhibitors, given their potential for electrolyte disturbances, were examined for QT interval prolongation...
August 9, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28791061/visual-and-anatomical-outcomes-of-spironolactone-therapy-in-patients-with-chronic-central-serous-chorioretinopathy
#6
Khalil Ghasemi Falavarjani, Anahita Amirsardari, Abbas Habibi, Acieh Eshaghi, Shohreh Bakhti, Kaveh Abri Aghdam
PURPOSE: To evaluate the effect of spironolactone on chronic central serous chorioretinopathy (CSC). METHODS: In this prospective interventional case series, patients with chronic CSC were treated with spironolactone (25 mg daily) for at least 6 weeks. If the subretinal fluid (SRF) had not completely resolved by this time, treatment was continued, and the dosage was increased to 25 mg twice daily. Primary outcome measure was the change in maximum SRF height at the final follow-up visit, as detected by optical coherence tomography...
July 2017: Journal of Ophthalmic & Vision Research
https://www.readbyqxmd.com/read/28776539/characteristics-management-and-outcomes-of-acute-heart-failure-in-the-emergency-department-a-multicenter-registry-study-with-1-year-follow-up-in-a-chinese-cohort-in-beijing
#7
Guo-Gan Wang, Si-Jia Wang, Jian Qin, Chun-Sheng Li, Xue-Zhong Yu, Hong Shen, Li-Pei Yang, Yan Fu, Ya-An Zheng, Bin Zhao, Dong-Min Yu, Fu-Jun Qin, De-Gui Zhou, Ying Li, Fu-Jun Liu, Wei Li, Wei Zhao, Xin Gao, Zheng Wang, Ming Jin, Hong Zeng, Yi Li, Guo-Xing Wang, Hong Zhou, Xiao-Lu Sun, Peng-Bo Wang, Kam-Sang Woo
BACKGROUND: The emergency department (ED) has a pivotal influence on the management of acute heart failure (AHF), but data concerning current ED management are scarce. This Beijing AHF Registry Study investigated the characteristics, ED management, and short- and long-term clinical outcomes of AHF. METHODS: This prospective, multicenter, observational study consecutively enrolled 3335 AHF patients who visited 14 EDs in Beijing from January 1, 2011, to September 23, 2012...
August 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28771453/nonsteroidal-mineralocorticoid-antagonists-in-diabetic-kidney-disease
#8
Farheen K Dojki, George Bakris
PURPOSE OF REVIEW: Current data highlight the pathological aspects of excess aldosterone in promoting glomerular hypertrophy, glomerulosclerosis, and proteinuria in diabetic kidney disease (DKD). The role of nonsteroidal mineralocorticoid receptor antagonists (MRAs) in DKD is being evaluated in ongoing clinical trials. RECENT FINDINGS: Recent studies demonstrate beneficial effects of adding MRAs to the treatment regimen of patients with type 2 diabetes with nephropathy...
September 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28768320/effects-of-sodium-glucose-cotransporter-2-inhibitors-for-the-treatment-of-patients-with-heart-failure-proposal-of-a-novel-mechanism-of-action
#9
Milton Packer, Stefan D Anker, Javed Butler, Gerasimos Filippatos, Faiez Zannad
Importance: Only 1 class of glucose-lowering agents-sodium-glucose cotransporter 2 (SGLT2) inhibitors-has been reported to decrease the risk of cardiovascular events primarily by reducing the risk of the development or progression of heart failure. In a landmark trial called Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes [EMPA-REG Outcomes], long-term treatment with empagliflozin prevented fatal and nonfatal heart failure events but did not reduce the risk of myocardial infarction or stroke in diabetic patients...
August 2, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28756533/long-term-spironolactone-treatment-reduces-coronary-trpc-expression-vasoconstriction-and-atherosclerosis-in-metabolic-syndrome-pigs
#10
Wennan Li, Xingjuan Chen, Ashley M Riley, S Christopher Hiett, Constance J Temm, Eleni Beli, Xin Long, Saikat Chakraborty, Mouhamad Alloosh, Fletcher A White, Maria B Grant, Michael Sturek, Alexander G Obukhov
Coronary transient receptor potential canonical (TRPC) channel expression is elevated in metabolic syndrome (MetS). However, differential contribution of TRPCs to coronary pathology in MetS is not fully elucidated. We investigated the roles of TRPC1 and TRPC6 isoforms in coronary arteries of MetS pigs and determined whether long-term treatment with a mineralocorticoid receptor inhibitor, spironolactone, attenuates coronary TRPC expression and associated dysfunctions. MetS coronary arteries exhibited significant atherosclerosis, endothelial dysfunction, and increased histamine-induced contractions...
September 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28751810/effectiveness-of-tolvaptan-monotherapy-and-low-dose-furosemide-tolvaptan-combination-therapy-for-hepatoprotection-and-diuresis-in-a-rat-cirrhotic-model
#11
Norikazu Tanabe, Taro Takami, Koichi Fujisawa, Toshihiko Matsumoto, Naoki Yamamoto, Isao Sakaida
Spironolactone and furosemide, which are used to treat ascites associated with decompensated cirrhosis, are ineffective in treating refractory ascites. Hence, combination therapy with tolvaptan, a vasopressin V2 receptor antagonist, has been approved in Japan. Tolvaptan monotherapy and combination therapy with furosemide inhibit fibrosis in cardiac remodeling; hence, we examined these therapies in a rat cirrhotic model, including their usefulness in inhibiting hepatic fibrosis. In the present study, we used a model of hepatic fibrosis induced by a choline-deficient l-amino-acid-defined diet + diethylnitrosamine...
July 2017: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/28749696/the-influence-of-physiological-gastrointestinal-surfactant-ratio-on-the-equilibrium-solubility-of-bcs-class-ii-drugs-investigated-using-a-four-component-mixture-design
#12
Zhou Zhou, Claire Dunn, Ibrahim Khadra, Clive G Wilson, Gavin W Halbert
The absorption of poorly water-soluble drugs is influenced by the luminal gastrointestinal fluid content and composition which controls solubility. Simulated intestinal fluids have been introduced into dissolution testing including endogenous amphiphiles and digested lipids at physiological levels; however, in vivo individual variation exists in the concentrations of these components, which will alter drug absorption through an effect on solubility. The use of a factorial design of experiment and varying media by introducing different levels of bile, lecithin and digested lipids has been previously reported, but here we investigate the solubility variation of poorly-soluble drugs through more complex biorelevant amphiphile interactions...
July 27, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28746811/the-acute-effects-of-different-spironolactone-doses-on-cardiac-function-in-streptozotocin-induced-diabetic-rats
#13
Aleksandra Vranic, Stefan Simovic, Petar Ristic, Tamara R Nikolic, Isidora Stojic, Ivan M Srejovic, Vladimir I Zivkovic, Vladimir Jakovljevic, Dusan Djuric
Currently, cardiovascular diseases are leading cause of global mortality, while diabetes mellitus remains an important cause of cardiovascular morbidity. Findings suggest that obesity and diabetes mellitus are closely interconnected with high aldosterone levels, while mineralocorticoid receptors antagonist therapy has shown positive effects on cardiovascular complications associated with diabetes mellitus. A recent study showed that patients with diabetes mellitus treated with mineralocorticoid receptors antagonist have improved coronary microvascular function, leading to improved diastolic dysfunction...
July 26, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28743784/spironolactone-is-an-antagonist-of-nrg1-erbb4-signaling-and-schizophrenia-relevant-endophenotypes-in-mice
#14
Michael C Wehr, Wilko Hinrichs, Magdalena M Brzózka, Tilmann Unterbarnscheidt, Alexander Herholt, Jan P Wintgens, Sergi Papiol, Maria Clara Soto-Bernardini, Mykola Kravchenko, Mingyue Zhang, Klaus-Armin Nave, Sven P Wichert, Peter Falkai, Weiqi Zhang, Markus H Schwab, Moritz J Rossner
Enhanced NRG1-ERBB4 signaling is a risk pathway in schizophrenia, and corresponding mouse models display several endophenotypes of the disease. Nonetheless, pathway-directed treatment strategies with clinically applicable compounds have not been identified. Here, we applied a cell-based assay using the split TEV technology to screen a library of clinically applicable compounds to identify modulators of NRG1-ERBB4 signaling for repurposing. We recovered spironolactone, known as antagonist of corticosteroids, as an inhibitor of the ERBB4 receptor and tested it in pharmacological and biochemical assays to assess secondary compound actions...
July 25, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28734620/treatment-of-dogs-with-compensated-myxomatous-mitral-valve-disease-with-spironolactone-a-pilot-study
#15
M J Hezzell, A Boswood, J López-Alvarez, N Lötter, J Elliott
OBJECTIVES: Spironolactone improves outcome in dogs with advanced myxomatous mitral valve disease (MMVD). Its efficacy in preclinical MMVD is unknown. The hypothesis was the administration of spironolactone to dogs with compensated MMVD demonstrating risk factors for poorer prognosis will decrease the rate of disease progression. The aim was to provide pilot data to evaluate preliminary effects and sample size calculation for a definitive clinical trial. ANIMALS: Twenty-five client-owned dogs with MMVD with at least one of the following; left atrial to aortic ratio (LA:Ao) ≥ 1...
July 19, 2017: Journal of Veterinary Cardiology: the Official Journal of the European Society of Veterinary Cardiology
https://www.readbyqxmd.com/read/28734243/caveolin-1-related-autophagy-initiated-by-aldosterone-induced-oxidation-promotes-liver-sinusoidal-endothelial-cells-defenestration
#16
Xiaoying Luo, Dan Wang, Xuan Luo, Xintao Zhu, Guozhen Wang, Zuowei Ning, Yang Li, Xiaoxin Ma, Renqiang Yang, Siyi Jin, Yun Huang, Ying Meng, Xu Li
Aldosterone, with pro-oxidation and pro-autophagy capabilities, plays a key role in liver fibrosis. However, the mechanisms underlying aldosterone-promoted liver sinusoidal endothelial cells (LSECs) defenestration remain unknown. Caveolin 1 (Cav1) displays close links with autophagy and fenestration. Hence, we aim to investigate the role of Cav1-related autophagy in LSECs defenestration. We found the increase of aldosterone/MR (mineralocorticoid receptor) level, oxidation, autophagy, and defenestration in LSECs in the human fibrotic liver, BDL or hyperaldosteronism models; while antagonizing aldosterone or inhibiting autophagy relieved LSECs defenestration in BDL-induced fibrosis or hyperaldosteronism models...
July 13, 2017: Redox Biology
https://www.readbyqxmd.com/read/28733447/mineralocorticoid-receptor-antagonists-attenuate-exaggerated-exercise-pressor-reflex-responses-in-hypertensive-rats
#17
Ryan M Downey, Masaki Mizuno, Jere Holloway Mitchell, Wanpen Vongpatanasin, Scott A Smith
Exaggerated heart rate (HR) and blood pressure responses to exercise in hypertension are mediated, in part, by overactivity of the exercise pressor reflex (EPR). The mechanisms underlying this EPR dysfunction have not been fully elucidated. Previous studies have shown that stimulation of mineralocorticoid receptors (MR) with exogenous administration of aldosterone in normal, healthy rats reproduces the EPR overactivity characteristic of hypertensive animals. Conversely, the purpose of this study was to examine whether antagonizing MR with spironolactone (SPIR) or eplerenone (EPL) in decerebrated hypertensive rats ameliorates abnormal EPR function...
July 21, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28724838/csk-regulates-blood-pressure-by-controlling-the-synthetic-pathways-of-aldosterone
#18
Sung-Moon Kim, Ji-One Kang, Ji Eun Lim, Sue-Yun Hwang, Bermseok Oh
BACKGROUND: Blood pressure is regulated by a network of diverse physiological pathways. The C-terminal Src kinase (CSK) locus (15q24) is associated with blood pressure in various ethnic groups. It was recently reported thatCskinsufficiency increases blood pressure through Src. The mechanisms of hypertension inCsk(+/-)mice are examined further in this study.Methods and Results:To identify a causal component responsible for hypertension inCsk(+/-), the heart rate was measured by electrocardiogram and plasma volume by Evans blue dilution...
July 20, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28719376/stability-of-spironolactone-oral-suspension-in-pcca-base-suspendit
#19
Richard Graves, Kelly V Phan, Levon A Bostanian, Tarun K Mandal, Yashoda V Pramar
Spironolactone (Aldactone) is a potassium-sparing diuretic used to treat hypertension and heart failure and may also be used to treat edema resulting from kidney disease, low potassium levels, or excess aldosterone. No commercial liquid dosage form of spironolactone exists. An extemporaneously compounded suspension from pure drug powder or commercial tablets would provide an alternative option to meet unique patient needs. The purpose of this study was to determine the physicochemical stability of spironolactone in the PCCA base SuspendIt...
July 2017: International Journal of Pharmaceutical Compounding
https://www.readbyqxmd.com/read/28712591/normalizing-ovulation-rate-by-preferential-reduction-of-hepato-visceral-fat-in-adolescent-girls-with-polycystic-ovary-syndrome
#20
Lourdes Ibáñez, Luis Del Río, Marta Díaz, Giorgia Sebastiani, Óscar J Pozo, Abel López-Bermejo, Francis de Zegher
PURPOSE: Polycystic ovary syndrome (PCOS) is an increasingly prevalent disorder in adolescent girls, commonly presenting with hirsutism/oligomenorrhea, commonly treated with an oral contraceptive (OC), and commonly followed by oligoanovulatory subfertility. We tested whether an intervention targeting the reduction of hepato-visceral adiposity is followed by a higher ovulation rate than OC treatment. METHODS: This randomized, open-label, single-center, pilot proof-of-concept study (12 months on treatment, then 12 months off) was performed in adolescent girls with hirsutism and oligomenorrhea (PCOS by National Institutes of Health; no sexual activity; N = 36; mean age 16 years, body mass index 23...
July 13, 2017: Journal of Adolescent Health: Official Publication of the Society for Adolescent Medicine
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