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Serelaxin

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https://www.readbyqxmd.com/read/28245243/serelaxin-as-a-potential-treatment-for-renal-dysfunction-in-cirrhosis-preclinical-evaluation-and-results-of-a-randomized-phase-2-trial
#1
Victoria K Snowdon, Neil J Lachlan, Anna M Hoy, Patrick W F Hadoke, Scott I Semple, Dilip Patel, Will Mungall, Timothy J Kendall, Adrian Thomson, Ross J Lennen, Maurits A Jansen, Carmel M Moran, Antonella Pellicoro, Prakash Ramachandran, Isaac Shaw, Rebecca L Aucott, Thomas Severin, Rajnish Saini, Judy Pak, Denise Yates, Neelesh Dongre, Jeremy S Duffield, David J Webb, John P Iredale, Peter C Hayes, Jonathan A Fallowfield
BACKGROUND: Chronic liver scarring from any cause leads to cirrhosis, portal hypertension, and a progressive decline in renal blood flow and renal function. Extreme renal vasoconstriction characterizes hepatorenal syndrome, a functional and potentially reversible form of acute kidney injury in patients with advanced cirrhosis, but current therapy with systemic vasoconstrictors is ineffective in a substantial proportion of patients and is limited by ischemic adverse events. Serelaxin (recombinant human relaxin-2) is a peptide molecule with anti-fibrotic and vasoprotective properties that binds to relaxin family peptide receptor-1 (RXFP1) and has been shown to increase renal perfusion in healthy human volunteers...
February 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28217307/worse-prognosis-of-real-world-patients-with-acute-heart-failure-from-the-czech-ahead-registry-in-comparison-to-patients-from-the-relax-ahf-trial
#2
Jindrich Spinar, Jiri Jarkovsky, Lenka Spinarova, Jiri Vitovec, Ales Linhart, Petr Widimsky, Roman Miklik, Kamil Zeman, Jan Belohlavek, Filip Malek, Cestmir Cihalik, Jiri Spac, Marian Felsoci, Petr Ostadal, Ladislav Dusek, Jiri Kettner, Jan Vaclavik, Simona Littnerova, Zdeněk Monhart, Josef Malek, Jiri Parenica
AIMS: The randomized clinical trial RELAX-AHF demonstrated a positive effect of vasodilator therapy with serelaxin in the treatment of AHF patients. The aim of our study was to compare clinical characteristics and outcomes of patients from the AHEAD registry who met criteria of the RELAX-AHF trial (relax-comparable group) with the same characteristics and outcomes of patients from the AHEAD registry who did not meet those criteria (relax-non-comparable group), and finally with characteristics and outcomes of patients from the RELAX-AHF trial...
February 2017: ESC Heart Failure
https://www.readbyqxmd.com/read/28150186/serelaxin-in-acute-heart-failure-patients-with-and-without-atrial-fibrillation-a-secondary-analysis-of-the-relax-ahf-trial
#3
Gerasimos Filippatos, Dimitrios Farmakis, Marco Metra, Gad Cotter, Beth A Davison, G Michael Felker, Barry H Greenberg, Tsushung A Hua, Peter S Pang, Piotr Ponikowski, Min Qian, Thomas A Severin, Adriaan A Voors, John R Teerlink
BACKGROUND: Atrial fibrillation (AFib) is a common comorbidity in HF and affects patients' outcome. We sought to assess the effects of serelaxin in patients with and without AFib. METHODS: In a post hoc analysis of the RELAX-AHF trial, we compared the effects of serelaxin on efficacy end points, safety end points and biomarkers in 1161 patients with and without AFib on admission electrocardiogram. RESULTS: AFib was present in 41.3% of patients...
February 1, 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/28108636/serelaxin-treatment-promotes-adaptive-hypertrophy-but-does-not-prevent-heart-failure-in-experimental-peripartum-cardiomyopathy
#4
Justus Nonhoff, Melanie Ricke-Hoch, Mirco Mueller, Britta Stapel, Tobias Pfeffer, Martina Kasten, Michaela Scherr, Constantin von Kaisenberg, Johann Bauersachs, Arash Haghikia, Denise Hilfiker-Kleiner
AIMS: Peripartum cardiomyopathy (PPCM) is a systolic left ventricular dysfunction developing in the peripartum phase in previously healthy women. Relaxin-2 is a pregnancy hormone with potential beneficial effects in heart failure patients. We evaluated Relaxin-2 as a potential diagnostic marker and/or a therapeutic agent in PPCM. METHODS AND RESULTS: In healthy peripartum women, serum Relaxin-2 levels (measured by ELISA in the second half of pregnancy) were elevated showing a decreasing trend in the first postpartum week and returned to non-pregnant levels thereafter...
January 20, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28073832/reperfusion-therapy-with-recombinant-human-relaxin-2-serelaxin-attenuates-myocardial-infarct-size-and-nlrp3-inflammasome-following-ischemia-reperfusion-injury-via-enos-dependent-mechanism
#5
Juan Valle Raleigh, Adolfo G Mauro, Teja Devarakonda, Carlo Marchetti, Jun He, Erica Kim, Scott Filippone, Anindita Das, Stefano Toldo, Antonio Abbate, Fadi N Salloum
AIMS: The preconditioning-like infarct-sparing and anti-inflammatory effects of the peptide hormone relaxin following ischemic injury have been studied in the heart. Whether reperfusion therapy with recombinant human relaxin-2, serelaxin, reduces myocardial infarct size and attenuates the subsequent NLRP3 inflammasome activation leading to further loss of functional myocardium following ischemia/reperfusion (I/R) injury is unknown. METHODS AND RESULTS: After baseline echocardiography, adult male wild-type C57BL or eNOS knockout mice underwent myocardial infarction (MI) by coronary artery ligation for 30 min followed by 24 h reperfusion...
January 10, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28067255/serelaxin-treatment-reverses-vascular-dysfunction-and-left-ventricular-hypertrophy-in-a-mouse-model-of-type-1-diabetes
#6
Hooi Hooi Ng, Chen Huei Leo, Darnel Prakoso, Chengxue Qin, Rebecca H Ritchie, Laura J Parry
Serelaxin prevents endothelial dysfunction in the mouse aorta ex vivo and inhibits apoptosis in cardiomyocytes under acute hyperglycaemia. Less is known about the effects of serelaxin in an in vivo mouse model of diabetes. Therefore, we tested the hypothesis in streptozotocin (STZ)-treated mice that serelaxin is able to reverse diabetes-induced vascular dysfunction and cardiac remodelling. Mice were divided into citrate buffer + placebo, STZ + placebo and STZ + serelaxin (0.5 mg/kg/d, 2 weeks) groups...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28009437/serelaxin-in-clinical-development-past-present-and-future
#7
REVIEW
Elaine Unemori
The availability of highly purified recombinant human relaxin, serelaxin, has enabled the conduct of clinical trials in several indications and the elucidation of its pharmacology in human subjects. These studies have demonstrated that serelaxin has unique hemodynamic properties that likely contribute to organ protection and long-term outcome benefits in acute heart failure. Clinical observations support its consideration for therapeutic use in other patient populations, including those with chronic heart failure, coronary artery disease, portal hypertension and acute renal failure...
December 23, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27972086/budget-impact-analysis-of-standard-care-with-serelaxin-in-treatment-of-patients-with-acute-decompensated-heart-failure
#8
G Tolordava, E Arinina, R Yagudina, A Kulikov
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27972082/cost-effectiveness-analysis-of-serelaxin-in-treatment-of-patients-with-acute-decompensated-heart-failure
#9
G Tolordava, E Arinina, R Yagudina, A Kulikov
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27833558/serelaxin-elicits-bronchodilation-and-enhances-%C3%AE-adrenoceptor-mediated-airway-relaxation
#10
Maggie Lam, Simon G Royce, Chantal Donovan, Maria Jelinic, Laura J Parry, Chrishan S Samuel, Jane E Bourke
Treatment with β-adrenoceptor agonists does not fully overcome the symptoms associated with severe asthma. Serelaxin elicits potent uterine and vascular relaxation via its cognate receptor, RXFP1, and nitric oxide (NO) signaling, and is being clinically evaluated for the treatment of acute heart failure. However, its direct bronchodilator efficacy has yet to be explored. Tracheal rings were prepared from male Sprague-Dawley rats (250-350 g) and tricolor guinea pigs, and precision cut lung slices (PCLSs) containing intrapulmonary airways were prepared from rats only...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27825893/evaluating-the-efficacy-safety-and-tolerability-of-serelaxin-when-added-to-standard-therapy-in-asian-patients-with-acute-heart-failure-design-and-rationale-of-relax-ahf-asia-trial
#11
Naoki Sato, Carolyn S P Lam, John R Teerlink, Barry H Greenberg, Hiroyuki Tsutsui, Byung-Hee Oh, Jian Zhang, Martin Lefkowitz, Tsushung A Hua, Thomas Holbro, Miriam Marshood, Xing Li Wang, Junbo Ge
BACKGROUND: Acute heart failure (AHF), a common and growing health concern worldwide, is associated with high risk of post-discharge rehospitalization and mortality. Existing evidence indicates potential therapeutic benefits of serelaxin in Caucasian AHF patients, but corresponding data in Asians remain scarce. RELAX-AHF-ASIA, a multinational, randomized, double-blind, placebo-controlled, phase III trial, will evaluate the effects of serelaxin on symptom relief and clinical outcomes in Asian AHF patients, with the use of novel assessments...
January 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/27769970/evolving-therapies-for-the-management-of-chronic-and-acute-decompensated-heart-failure
#12
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
https://www.readbyqxmd.com/read/27727514/serelaxin-in-acute-heart-failure-most-recent-update-on-clinical-and-preclinical-evidence
#13
REVIEW
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 healthcare costs and is 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 nonpregnant women and men...
February 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/27647937/serelaxin-improves-the-therapeutic-efficacy-of-rxfp1-expressing-human-amnion-epithelial-cells-in-experimental-allergic-airways-disease
#14
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-)
https://www.readbyqxmd.com/read/27629886/serelaxin-improves-the-pathophysiology-of-placental-ischemia-in-the-reduced-uterine-perfusion-pressure-rat-model-of-preeclampsia
#15
Jose A Santiago-Font, Lorena M Amaral, Jessica Faulkner, Tarek Ibrahim, Venkata Ramana Vaka, Mark W Cunningham, Babbette LaMarca
Preeclampsia is a hypertensive disorder of pregnancy that has limited therapeutic options. In healthy pregnancy, relaxin plays an important vasodilatory role to maintain vascular compliance; however, currently, there is 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 TNF-α) in the reduced uterine perfusion pressure (RUPP) model of preeclampsia...
December 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/27596360/recombinant-human-relaxin-versus-placebo-for-cervical-ripening-a-double-blind-randomised-trial-in-pregnant-women-scheduled-for-induction-of-labour
#16
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...
September 5, 2016: BMC Pregnancy and Childbirth
https://www.readbyqxmd.com/read/27545139/novel-therapies-for-heart-failure%C3%A3-where-do-they-stand
#17
REVIEW
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
https://www.readbyqxmd.com/read/27488261/relaxin-serum-levels-in-acute-heart-failure-are-associated-with-pulmonary-hypertension-and-right-heart-overload
#18
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
https://www.readbyqxmd.com/read/27462268/involvement-of-cyclic-guanosine-monophosphate-dependent-protein-kinase-i-in-renal-antifibrotic-effects-of-serelaxin
#19
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
https://www.readbyqxmd.com/read/27418970/serelaxin-for-the-treatment-of-acute-heart-failure-a-review-with-a-focus-on-end-organ-protection
#20
REVIEW
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
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