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Jennifer C Cook, Richard H Tran, J Herbert Patterson, Jo E Rodgers
PURPOSE: The pharmacology, clinical efficacy, and safety profiles of evolving therapies for the management of chronic heart failure (HF) and acute decompensated heart failure (ADHF) are described. SUMMARY: HF confers a significant financial burden despite the widespread use of traditional guideline-directed medical therapies such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone receptor antagonists, and the rates of HF-related mortality and hospitalization have remained unacceptably high...
November 1, 2016: American Journal of Health-system Pharmacy: AJHP
Raktim Kumar Ghosh, Kinjal Banerjee, Ramyashree Tummala, Somedeb Ball, Keyvan Ravakhah, Anjan Gupta
Heart failure continues to be a widely prevalent disease across the world, affecting millions of Americans annually. Acute heart failure (AHF) has a substantial effect on rising health care costs and one of the major causes of morbidity and mortality. The search for new drugs for symptom relief and to improve long term outcomes in heart failure has led to development of serelaxin, a recombinant human relaxin-2 hormone. Relaxin was discovered in pregnancy but eventually found to have a number of other physiological actions, not only in pregnancy, but also in non-pregnant women and men...
October 11, 2016: Cardiovascular Therapeutics
Simon G Royce, Anna M Tominaga, Matthew Shen, Krupesh P Patel, Brooke M Huuskes, Rebecca Lim, Sharon D Ricardo, Chrishan S Samuel
Current asthma therapies primarily target airway inflammation (AI) and suppress episodes of airway hyperresponsiveness (AHR) but fail to treat airway remodelling (AWR), which can develop independently of AI and contribute to irreversible airway obstruction. This study compared the anti-remodelling and therapeutic efficacy of human bone marrow-derived mesenchymal stem cells (MSCs) to that of human amnion epithelial stem cells (AECs) in the setting of chronic allergic airways disease (AAD), in the absence or presence of an anti-fibrotic (serelaxin; RLX)...
September 19, 2016: Clinical Science (1979-)
Jose A Santiago-Font, Lorena M Amaral, Jessica L Faulkner, Tarek Ibrahim, Venkata Ramana Vaka, Mark W Cunningham, Babbette D LaMarca
Preeclampsia is a hypertensive disorder of pregnancy with limited therapeutic options. In healthy pregnancy, relaxin plays an important vasodilatory role to maintain vascular compliance; however, there is currently no preclinical evidence to support the use of relaxin during preeclampsia. Therefore, the goal of this study was to test the hypothesis that recombinant human relaxin-2 (Serelaxin, Novartis, RLX) could reduce mean arterial pressure (MAP) and improve uterine artery resistance index (UARI) and nitric oxide bioavailability and/or decrease prepro-endothelin-1 (PPET-1), soluble fms-like tyrosine kinase-1 (sFlt-1) and tumor necrosis factor (TNF-alpha) in the Reduced Uterine Perfusion Pressure (RUPP) model of preeclampsia...
September 14, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Gerson Weiss, Sam Teichman, Dennis Stewart, David Nader, Susan Wood, Peter Breining, Elaine Unemori
BACKGROUND: Nonclinical studies indicate that the hormone relaxin is a good candidate for a safe cervical ripening agent that does not cause uterine contractions. METHODS: This Phase II study (conducted November 2, 2005-October 20, 2006) was a randomised, double blind, placebo controlled trial testing 24-h intravenous infusion of serelaxin (recombinant human relaxin) or placebo for cervical ripening in 72 healthy, primiparous women. Eligible subjects had a singleton pregnancy ≥40 weeks, were planned for elective induction, had vertex presentation of the fetus, intact membranes and a Bishop score at screening ≤4...
2016: BMC Pregnancy and Childbirth
Barry Greenberg
Despite advances in therapy, patients with heart failure (HF) continue to experience unacceptably high rates of hospitalization and death, as well as poor quality of life. As a consequence, there is an urgent need for new treatments that can improve the clinical course of the growing worldwide population of HF patients. Serelaxin and ularatide, both based on naturally occurring peptides, have potent vasodilatory as well as other effects on the heart and kidneys. For both agents, phase 3 studies that are designed to determine whether they improve outcomes in patients with acute HF have completed enrollment...
August 25, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
Mariana Pintalhao, Paulo Castro-Chaves, Francisco Vasques-Novoa, Francisco Gonçalves, Luís Mendonça, Ricardo Fontes-Carvalho, Patrícia Lourenço, Pedro Almeida, Adelino Leite-Moreira, Paulo Bettencourt
AIMS: Despite the promising results of serelaxin as a new potential acute heart failure (HF) therapy, its clinical use preceded the understanding of the endogenous relaxin system in HF. We aimed to evaluate relaxin circulating levels in a population of acute HF and their association with clinical and echocardiographic parameters. METHODS AND RESULTS: We included 117 patients from a registry of acute HF. Admission serum relaxin was measured using an enzyme-linked immunosorbent assay (ELISA) kit...
August 4, 2016: European Journal of Heart Failure
Veronika Wetzl, Elisabeth Schinner, Frieder Kees, Franz Hofmann, Lothar Faerber, Jens Schlossmann
INTRODUCTION: Kidney fibrosis has shown to be ameliorated through the involvement of cyclic guanosine monophosphate (cGMP) and its dependent protein kinase I (cGKI). Serelaxin, the recombinant form of human relaxin-II, increases cGMP levels and has shown beneficial effects on kidney function in acute heart failure patients. Antifibrotic properties of serelaxin are supposed to be mediated via relaxin family peptide receptor 1 and subsequently enhanced nitric oxide/cGMP to inhibit transforming growth factor-β (TGF-β) signaling...
2016: Frontiers in Pharmacology
Javier Díez, Luis M Ruilope
Acute heart failure (AHF) is a complex clinical syndrome characterized by fluid overload and haemodynamic abnormalities (short-term clinical consequences) and the development of end-organ damage (long-term consequences). Current therapies for the treatment of AHF, such as loop diuretics and vasodilators, help to relieve haemodynamic imbalance and congestion, but have not been shown to prevent (and may even contribute to) end-organ damage, or to provide long-term clinical benefit. Serelaxin is the recombinant form of human relaxin-2, a naturally occurring hormone involved in mediating haemodynamic changes during pregnancy...
April 2016: European Heart Journal. Cardiovascular Pharmacotherapy
Sabine J Bischoff, Martin Schmidt, Thomas Lehmann, Andrey Irintchev, Harald Schubert, Christian Jung, Matthias Schwab, Otmar Huber, Georg Matziolis, René Schiffner
Serelaxin, recombinant human relaxin-2, modulates endothelial vasodilatory functionality and is under evaluation for treatment of acute heart failure. Little is known about acute effects on cerebral perfusion. We tested the hypothesis that Serelaxin might also have effects on the cerebral microcirculation in a sheep model, which resembles human brain structure quite well. We used laser Doppler flowmetry and sidestream dark-field (SDF) imaging techniques, which are reliable tools to continuously assess dynamic changes in cerebral perfusion...
September 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Vedat Tiyerili, Thomas Beiert, Hannah Schatten, Bakary Camara, Julian Jehle, Jan W Schrickel, Georg Nickenig, René P Andrié
BACKGROUND AND AIMS: Serelaxin (SLX) is a recombinant form of human relaxin-2, a naturally occurring peptide that regulates maternal cardiovascular adaptations to pregnancy. It is unclear whether SLX has a therapeutic effect on atherosclerosis. Therefore, we investigated direct vascular effects of SLX in a mouse model of atherosclerosis. METHODS: 6-8 week-old female apolipoprotein E-deficient mice were fed a high-fat, cholesterol-rich diet for 6 weeks and additionally received a continuous treatment with vehicle or SLX (0...
August 2016: Atherosclerosis
Mohsin Sarwar, Xiao-Jun Du, Thomas B Dschietzig, Roger J Summers
The insulin-like peptide relaxin, originally identified as a hormone of pregnancy, is now known to exert a range of pleiotropic effects including vasodilatory, anti-fibrotic, angiogenic, anti-apoptotic and anti-inflammatory effects in both males and females. Relaxin produces these effects by binding to a cognate receptor RXFP1 and activating a variety of signalling pathways including cAMP, cGMP and MAPKs as well as by altering gene expression of TGF-β, MMPs, angiogenic growth factors and endothelin receptors...
May 30, 2016: British Journal of Pharmacology
Chen Huei Leo, Maria Jelinic, Hooi Hooi Ng, Marianne Tare, Laura J Parry
Vascular dysfunction is an important hallmark of cardiovascular disease. It is characterized by increased sensitivity to vasoconstrictors, decreases in the endothelium-derived vasodilators nitric oxide (NO) and prostacyclin (PGI2), and endothelium-derived hyperpolarization (EDH). Serelaxin (recombinant human relaxin) has gained considerable attention as a new vasoactive drug, largely through its beneficial therapeutic effects in acute heart failure. In this review we first describe the contribution of endogenous relaxin to vascular homeostasis...
June 2016: Trends in Pharmacological Sciences
Hao A Tran, Felice Lin, Barry H Greenberg
INTRODUCTION: The prevalence of heart failure (HF) has increased globally in recent decades. Advances in our understanding of underlying pathophysiologic mechanisms have given rise to new therapies for treating the growing HF population. Nonetheless, morbidity and mortality associated with HF and its financial implications are daunting. Thus, novel therapies that can improve the natural history of HF patients are urgently needed. AREAS COVERED: This article reviews new investigational drugs being developed for the treatment of both acute decompensated heart failure (ADHF) and chronic heart failure with reduced ejection fraction (HFrEF)...
July 2016: Expert Opinion on Investigational Drugs
K P Patel, A S Giraud, C S Samuel, S G Royce
No abstract text is available yet for this article.
June 2016: British Journal of Pharmacology
Alessandro Pini, Giulia Boccalini, Laura Lucarini, Stefano Catarinicchia, Daniele Guasti, Emanuela Masini, Daniele Bani, Silvia Nistri
Cigarette smoke (CS) is the major etiologic factor of chronic obstructive pulmonary disease (COPD), which is characterized by airway remodeling, lung inflammation and fibrosis, emphysema, and respiratory failure. The current therapies can improve COPD management but cannot arrest its progression and reduce mortality. Hence, there is a major interest in identifying molecules susceptible of development into new drugs to prevent or reduce CS-induced lung injury. Serelaxin (RLX), or recombinant human relaxin-2, is a promising candidate because of its anti-inflammatory and antifibrotic properties highlighted in lung disease models...
June 2016: Journal of Pharmacology and Experimental Therapeutics
Danyaal S Moin, Michelle W Bloom, Lampros Papadimitriou, Javed Butler
Outcomes for patients with acute heart failure remain suboptimal and treatments principally target improvement of symptoms. To date there has been no therapy approved for acute heart failure shown to improve mortality or readmission risk post-discharge. Serelaxin, a recombinant form of the naturally occurring polypeptide hormone relaxin, has demonstrated promise in preclinical and early clinical trials as a potentially novel therapy for acute heart failure. It is postulated through its anti-fibrotic and vasodilatory effects that this agent can improve outcomes in both the short and long term in these patients...
June 2016: Expert Review of Cardiovascular Therapy
Peter S Pang, John R Teerlink, Adriaan A Voors, Piotr Ponikowski, Barry H Greenberg, Gerasimos Filippatos, G Michael Felker, Beth A Davison, Gad Cotter, Joshua Kriger, Margaret F Prescott, Tsushung A Hua, Thomas Severin, Marco Metra
OBJECTIVES: The aim of this study was to determine if a baseline high-sensitivity troponin T (hsTnT) value ≤99th percentile upper reference limit (0.014 μg/l ["low hsTnT"]) identifies patients at low risk for adverse outcomes. BACKGROUND: Approximately 85% of patients who present to emergency departments with acute heart failure are admitted. Identification of patients at low risk might decrease unnecessary admissions. METHODS: A post-hoc analysis was conducted from the RELAX-AHF (Serelaxin, Recombinant Human Relaxin-2, for Treatment of Acute Heart Failure) trial, which randomized patients within 16 h of presentation who had systolic blood pressure >125 mm Hg, mild to moderate renal impairment, and N-terminal pro-brain natriuretic peptide ≥1,600 ng/l to serelaxin versus placebo...
July 2016: JACC. Heart Failure
Licette C Y Liu, Adriaan A Voors, John R Teerlink, Gad Cotter, Beth A Davison, G Michael Felker, Gerasimos Filippatos, Yakuan Chen, Barry H Greenberg, Piotr Ponikowski, Peter S Pang, Margaret F Prescott, Tsushung A Hua, Thomas M Severin, Marco Metra
BACKGROUND: Serelaxin showed beneficial effects on clinical outcome and trajectories of renal markers in patients with acute heart failure. We aimed to study the interaction between renal function and the treatment effect of serelaxin. METHODS: In the current post hoc analysis of the RELAX-AHF trial, we included all patients with available estimated glomerular filtration rate (eGFR) at baseline (n = 1132). Renal impairment was defined as an eGFR <60 ml/min/1...
September 2016: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
Chrishan S Samuel, Roger J Summers, Tim D Hewitson
Fibrosis represents a failed wound healing response to tissue injury. It is characterized by the accumulation of excess connective tissue and is a significant cause of organ failure, morbidity, and mortality. Fibrotic disorders accompany a wide spectrum of conditions including both systemic and organ-specific diseases, for which there is currently no effective cure. Serelaxin, the recombinant form of the major stored and circulating form of human relaxin, has emerged as a pleiotropic drug with rapidly occurring antifibrotic actions...
June 2016: Trends in Pharmacological Sciences
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