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The insulin-like peptide relaxin (RLX), an endogenous peptide hormone produced in human for pregnancy and reproduction, is also known to exert a range of physiological and pathological effects. Its use is banned in human sports, horseracing, and equestrian competitions due to its potential performance enhancing effect through vasodilation resulting in the increase of blood and oxygen supplies to muscles. Little is known about the biotransformation and elimination of RLX in horses. This paper describes an administration study of rhRLX-2 and its elimination in horses, and the development of sensitive methods for the detection and confirmation of rhRLX-2 in both horse plasma and urine by nano-liquid chromatography/high resolution mass spectrometry (nano-LC/HRMS) after immunoaffinity extraction with the objective of controlling the abuse of rhRLX-2 in horses. The limits of detection in plasma and urine are 2 pg/mL and 5 pg/mL, respectively. Two thoroughbred geldings were each administered one dose of 10 mg rhRLX-2 subcutaneously daily for 3 consecutive days. The rhRLX-2 could be detected and confirmed in the plasma and urine samples collected 105 h and 80 h, respectively, after the last dose of administration. For doping control purposes, rhRLX-2 ELISA could be used as a screening test to identify potential positive samples for further investigation using the nano-LC/HRMS methods.

The availability of highly purified recombinant human relaxin, serelaxin, has allowed clinical trials to be conducted in several indications and the elucidation of its pharmacology in human subjects. These studies have demonstrated that serelaxin has unique haemodynamic properties that are likely to 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. Linked Articles This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc

Background: Serelaxin, recombinant human relaxin-2, is a hormone with vasodilatory and end-organ protective effects. Recently, it has been licensed to treat acute decompensated heart failure. Here, a systematic review and meta-analysis on randomized controlled trials (RCTs) was performed to assess the effect of serelaxin on mortality and dyspnea improvement in patients with heart failure. Methods: RCTs comparing serelaxin treatment to other heart failure treatments were searched in PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. The main endpoints were mortality and dyspnea improvement. Pooled data were assessed by using a random effects model. Results: A total of 451 studies were identified, of which 8 studies (8477 participants) were eligible and included in our analysis. Compared with other heart failure treatment group, serelaxin group had no effect on 30-day, 60-day, and 180-day mortality (OR, 0.79; 95% CI, 0.65–0.96). Compared with control group, there was no effect on dyspnea improvement. Conclusion: Serelaxin treatment is irrelevant with the mortality, and it cannot improve dyspnea of heart failure patients.

The peptide hormone relaxin is recognized for its connective tissue remodeling actions in the reproductive tract during pregnancy and parturition, but it also has vascular remodeling actions independent of pregnancy. Recombinant human relaxin (serelaxin) treatment in male and non-pregnant female rodents enhances passive arterial compliance in the renal vasculature. This review focuses on serelaxin's actions on passive mechanical wall properties in small arteries and highlights the diversity of responses to serelaxin treatment in rodents. Different experimental approaches (duration of serelaxin treatment, rat strain, age) and animal models of disease (obesity, hypertension) will be considered. Most studies in young rodents demonstrate that serelaxin treatment fails to alter passive compliance in resistance-size arteries (mesenteric and femoral arteries and cerebral parenchymal arterioles), suggesting that serelaxin's beneficial effects are minimal in healthy animals. Short-term serelaxin treatment (5d) in aged, obese, and spontaneously hypertensive rats (SHRs) is largely without effect on passive mechanical wall properties. However, a longer duration of serelaxin treatment in SHRs (14d) enhances passive compliance in large muscular arteries as well as resistance-size arteries. In conclusion, serelaxin is capable of vascular remodeling. Its actions are vascular bed-dependent, more prominent in disease, and likely requires a longer duration of treatment to be effective.

Relaxin (RLX) is a peptide hormone belonging to the relaxin-like peptide family. Relaxin-2 (RLX-2), a heteromeric polypeptide consisting of an A-chain (24 amino acids) and a B-chain (29 amino acids) linked together by two inter-chain disulfide bonds, is the main circulating RLX hormone in human. Due to its ability to dilate blood vessels surrounding the smooth muscles via induction of nitric oxide resulting in the increase of blood and oxygen supplies to the muscles, it may enhance athletic performance and is therefore banned in horseracing, equestrian competitions, and human sports. In order to control the abuse of rhRLX-2, a definitive method is required to detect and confirm the presence of rhRLX-2 in biological samples. This paper describes, for the first time, the detection and confirmation of rhRLX-2 in equine plasma by liquid chromatography-high resolution mass spectrometry (LC-HRMS) after immunoaffinity extraction. rhRLX-2 could be detected at less than 0.1 ng/ml, and confirmed at less than 0.2 ng/ml in plasma samples. Copyright © 2012 John Wiley & Sons, Ltd.

BackgroundSerelaxin 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.MethodsIn 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

Objective.We sought to retrospectively review a single-center experience using intravenous immunoglobulin (IVIG) for the treatment of refractory, active diffuse cutaneous systemic sclerosis (dcSSc).Methods.The mean modified Rodnan Skin score (mRSS) at baseline was compared to the mRSS at 6, 12, 18, and 24 months post-IVIG initiation by the paired Student t test. Changes in mRSS at 6 and 12 months were also compared to data from historical controls of 3 large, negative, multicenter, randomized clinical trials of other medications [D-penicillamine (D-pen), recombinant human relaxin (relaxin), and oral bovine type I collagen (collagen)] and to patients treated with mycophenolate mofetil (MMF) alone using the Student t test.Results.Thirty patients were treated with adjunctive IVIG (2 g/kg/mo) for refractory, active dcSSc. The mean baseline mRSS of our cohort was 29.6 ± 7.2, and this significantly decreased to 24.1 ± 9.6 (n = 29, p = 0.0011) at 6 months, 22.5 ± 10.0 (n = 25, p = 0.0001) at 12 months, 20.6 ± 11.8 (n = 23, p = 0.0001) at 18 months, and 15.3 ± 6.4 (n = 15, p < 0.0001) at 24 months. The mean change in mRSS at 6 months was not significantly different in the IVIG group (−5.3 ± 7.9) compared to the relaxin trial (−4.8 ± 6.99, p = 0.74) or MMF group (−3.4 ± 7.4, p = 0.26); however, at 12 months, the mean change in mRSS was significantly better in the IVIG group (−8 ± 8.3) than in the D-pen (−2.47 ± 8.6, p = 0.005) and collagen (−3.4 ± 7.12, p = 0.005) groups, and was comparable to the group of primary MMF responders (−7.1 ± 9, p = 0.67).Conclusion.Our observational study suggests that IVIG may be an effective adjunctive therapy for active dcSSc in patients failing other therapies.

• Relaxin is a 56-amino acid polypeptide that produces relaxation of the pubic ligament. Ten young male pigs were implanted with tissue expanders and osmotic pumps. The pumps in five animals contained recombinant human relaxin to produce a serum relaxin level of 1 ng/mL. The other five pumps contained saline. Repeated measurements of the pressure-volume expansion curves showed a significant decrease in the pressure needed to fill the expanders in the relaxin group compared with the control group. Dermal thickness in the control group and epidermal thickness in both control and experimental groups were increased on histomorphometric measurement. No adverse effects were seen in the relaxin group. Relaxin facilitates tissue expansion in pigs without affecting dermal thickness. ( Arch Otolaryngol Head Neck Surg . 1992;118:153-156)

In the United States, both medical and nonmedical factors have driven the cesarean section rate to over 26% of all deliveries. In addition to questions of increased cost associated with operative delivery, some have questioned the ethics of performing cesarean section for nonmedical reasons. Reduction of both the duration and the pain associated with vaginal delivery would likely bring about a decline in the rate of both medical and nonmedical cesarean sections. This chapter summarizes recent findings that support the premise that through its growth-promoting and softening effects on the cervix, short-term subcutaneous administration of pharmacologic amounts of relaxin to women at term holds promise as a means of reducing the duration and discomfort associated with delivery. Two recent studies conducted in pregnant rats demonstrated that the cervix is highly responsive to relaxin during the antepartum period and that short-term subcutaneous administration of the hormone to relaxin-deficient animals not only promotes growth and softening of the cervix, but also reduces the duration of labor and delivery. Moreover, recent human clinical trials examining the influence of 24 weeks of continuous subcutaneous administration of recombinant human relaxin for the treatment of scleroderma provided evidence not only that the human reproductive tract is responsive to relaxin, but also that the administration of the hormone does not cause serious adverse side effects. It is concluded that recent findings provide an impetus for an investigation into relaxin's potential for cervical remodeling and facilitating birth in women.

Relaxin was discovered more than 50 years ago. However, only with the advent of recombinant DNA technology have sufficient amounts of human relaxin been produced and made available for in-depth biochemical characterization and pharmacological studies. These investigations have characterized the solution and stability behavior of this hormone. In particular, degradation routes and conditions for formulation as a liquid for systemic administration or gel-based formulations for local application have been established. Pharmacological studies of human relaxin have identified the involvement of relaxin in many physiological processes, ranging from collagenolysis, inhibition of myometrial contraction, enhancement of sperm motility, to its effect of the cardiovascular system leading to lowering of blood pressure. However, the differences in relaxin activities among the different animal models have led to some contradictory observations. Thus, the full elucidation of the biology of this important human hormone lags behind the understanding of its biochemical and stability behavior. Human parturition involves a temporal sequence of events and interplay between different hormones and effector molecules (Porter, 1983; Sortino et al., 1989). It is very likely that a successful clinical application of this protein will require additional knowledge of when in the parturition cycle rhR1x should be given, how often, and in what combination with other molecules that are normally produced during labor and delivery. Not until the biology of rhR1x in humans is thoroughly understood, will it be possible to design proper human clinical trials that will demonstrate the therapeutic value of this protein.

Intriguing findings from the RELAX-AHF trial of serelaxin (recombinant human relaxin 2; RLX030, Novartis, Basel, Switzerland) in patients with acute heart failure were presented by John Teerlink at the 2012 AHA Scientific Sessions and published in the Lancet. Patients hospitalized with acute heart failure commonly have a dismal prognosis. Despite decades of clinical trials, no clearly safe and beneficial treatment options have emerged. The aetiology of acute heart failure can be multifactorial, and patient presentation is highly variable. Management of this diverse syndrome in patients admitted to hospital is an ongoing clinical challenge.

Erratum to ‘‘Recombinant human relaxin reduces hypoxic pulmonary hypertension in the rat’’ [Pulmonary Pharmacology & Therapeutics 18 (2005) 346–353] Carol A. Tozzi, George J. Poiani, Nansie A. McHugh, Michael P. Shakarjian, Beverly H. Grove, Chrishan S. Samuel, Elaine N. Unemori, David J. Riley Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854-5635, USA Connetics Corporation, 3400 West Bayshore Road, Palo Alto, CA 94303, USA The Howard Florey Institute of Experimental Physiology and Medicine, The University of Melbourne, Royal Parade and Grattan Street, Parkville, Vic. 3010, Australia