Sarah Arrowsmith

University of Liverpool

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Susan Wray

University of Liverpool

Markus Muttenthaler

University of Vienna

Christian W. Gruber

Medical University of Vienna

James P Neilson

University of Liverpool

Andrew Sharp

Liverpool Women's Hospital

Leanne Bricker

Abu Dhabi Health Services

Peter Keov

Monash University

Karen Noble

Brain Tumour Research

Theodor Burdyga

University of Liverpool

Siobhan Quenby

University of Warwick

Cooperative Institutions

University of Liverpool

University of Queensland

Harvard University

Johns Hopkins University

University of California, Los Angeles

Johns Hopkins Medicine

University of Rochester

Istituti di Ricovero e Cura a Carattere Scientifico

University of Pennsylvania

Medical University of Vienna

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Cyclotides as templates for peptide GPCR ligand design - discovery of the target receptor of the oxytocic plant peptide kalata B7

Johannes Koehbach Margaret O’Brien Markus Muttenthaler Marion Miazzo Muharrem Akcan

Publication Information Koehbach, J,O'Brien, M,Muttenthaler, M,Miazzo, M,Akcan, M,Elliott, AG,Daly, NL,Harvey, PJ,Arrowsmith, S,Gunasekera, S,Smith, TJ,Wray, S,Goransson, U,Dawson, PE,Craik, DJ,Freissmuth, M,Gruber, CW (2013) 'Oxytocic plant cyclotides as templates for peptide G protein-coupled receptor ligand design'. Proceedings Of The National Academy Of Sciences Of The United States Of America, 110 (52):21183-21188.

Template

10.2210/pdb2m9o/pdb

Cite

Citations (0)

ATP3 Unified Field Study Data

OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (2018)

Edward J. Wolfrum Eric P. Knoshaug Lieve M. L. Laurens Valerie L. Harmon Thomas A. Dempster

10.7799/1400389

Cite

Citations (4)

Drugs acting on the pregnant uterus

Obstetrics Gynaecology & Reproductive Medicine (2010)

Sarah Arrowsmith Annabelle Kendrick Susan Wray

In this review we overview the mechanisms responsible for uterine contractility and relaxation. We then use this as the basis for discussing the two major uterotonins, oxytocin and prostaglandins followed by currently available (although often unlicensed) tocolytics; progesterone, magnesium, calcium channel blockers, oxytocin receptor blockers, β-adrenergic receptor agonists, prostaglandin synthesis inhibitors and nitric oxide donors. In this brief review we have concentrated on the most important mechanisms of action and data obtained on human tissue. By focussing on mechanisms, meta-analyses and Cochrane literature reviews, our aim is to provide insight for clinical usefulness, and highlight where further research is required and where the targets may be.

Oxytocin receptor

Contractility

10.1016/j.ogrm.2010.05.001

Cite

Citations (57)

Gestational and Hormonal Effects on Magnesium Sulfate’s Ability to Inhibit Mouse Uterine Contractility

Reproductive Sciences (2020)

Blessing E. Osaghae Sarah Arrowsmith Susan Wray

Contractility

10.1007/s43032-020-00185-8

Cite

Citations (5)

Poor Spontaneous and Oxytocin-Stimulated Contractility in Human Myometrium from Postdates Pregnancies

PLoS ONE (2012)

Sarah Arrowsmith Siobhan Quenby Andrew Weeks Theodor Burdyga Susan Wray

Prolongation of pregnancy i.e. going more than 10 days over the estimated due date, complicates up to 10% of all pregnancies and is associated with increased risk to both mother and fetus. Despite the obvious need for contractions of the uterus to end pregnancy, there have been no studies directly examining the role of uterine smooth muscle, myometrium, in the aetiology of prolonged pregnancy. This study tested the hypothesis that the intrinsic contractile characteristics of myometrium taken from women with prolonged pregnancy (>41 weeks and 3 days) was reduced compared to those delivering at term (39–41 weeks). We recruited women undergoing Caesarean Section (CS) delivery either pre-labour (n = 27) or in labour (n = 66) at term or postdates. The contractile ability of the postdates myometrium, whether spontaneous or elicited by oxytocin or high-K solution, was significantly reduced compared to term myometrium. These differences remained when adjusted for parity and other maternal characteristics. The findings remained significant when expressed per cross sectional area. Histological examination revealed no differences between the two groups. The contractile differences were however related to intracellular Ca transients suggesting an effect of [Ca] on reduced force production in the postdates group. In summary, myometrium from prolonged pregnancies contracts poorly in vitro even when stimulated with oxytocin and in active labour. Responses to high K+ and measurements of Ca suggest that alterations in excitation contraction coupling, rather than any histological changes of the myometrium, may underlie the differences between term and postdates myometrium. We show that postdates pregnancy is associated with poor myometrial activity and suggest that this may contribute to increased myometrial quiescence and hence, prolonged gestation.

Myometrium

Contractility

Uterine contraction

10.1371/journal.pone.0036787

Cite

Citations (37)

Progress in understanding electro-mechanical signalling in the myometrium

Acta Physiologica (2014)

Susan Wray Theodor Burdyga D Noble Karen Noble Lyudmyla Borysova

In this review, we give a state-of-the-art account of uterine contractility, focussing on excitation–contraction (electro-mechanical) coupling (ECC). This will show how electrophysiological data and intracellular calcium measurements can be related to more modern techniques such as confocal microscopy and molecular biology, to advance our understanding of mechanical output and its modulation in the smooth muscle of the uterus, the myometrium. This new knowledge and understanding, for example concerning the role of the sarcoplasmic reticulum (SR), or stretch-activated K channels, when linked to biochemical and molecular pathways, provides a clearer and better informed basis for the development of new drugs and targets. These are urgently needed to combat dysfunctions in excitation–contraction coupling that are clinically challenging, such as preterm labour, slow to progress labours and post-partum haemorrhage. It remains the case that scientific progress still needs to be made in areas such as pacemaking and understanding interactions between the uterine environment and ion channel activity.

Myometrium

Contractility

Uterine contraction

10.1111/apha.12431

Cite

Citations (63)

Biodegradation of petroleum hydrocarbons in a weathered, unsaturated soil is inhibited by peroxide oxidants

Journal of Hazardous Materials (2022)

Onur G. Apul Sarah Arrowsmith Caitlyn Hall Evelyn M. Miranda Fabiha Alam

Field-weathered crude oil-containing soils have a residual concentration of hydrocarbons with complex chemical structure, low solubility, and high viscosity, often poorly amenable to microbial degradation. Hydrogen peroxide (H2O2)-based oxidation can generate oxygenated compounds that are smaller and/or more soluble and thus increase petroleum hydrocarbon biodegradability. In this study, we assessed the efficacy of H2O2-based oxidation under unsaturated soil conditions to promote biodegradation in a field-contaminated and weathered soil containing high concentrations of total petroleum hydrocarbons (25200 mg TPH kg-1) and total organic carbon (80900 mg TOC kg-1). Microcosms amended with three doses of 48 g H2O2 kg-1 soil (unactivated or Fe2+-activated) or 24 g sodium percarbonate kg-1 soil and nutrients did not show substantial TPH changes during the experiment. However, 7.6-41.8% of the TOC concentration was removed. Furthermore, production of DOC was enhanced and highest in the microcosms with oxidants, with approximately 20-40-fold DOC increase by the end of incubation. In the absence of oxidants, biostimulation led to > 50% TPH removal in 42 days. Oxidants limited TPH biodegradation by diminishing the viable concentration of microorganisms, altering the composition of the soil microbial communities, and/or creating inhibitory conditions in soil. Study's findings underscore the importance of soil characteristics and petroleum hydrocarbon properties and inform on potential limitations of combined H2O2 oxidation and biodegradation in weathered soils.

Peroxide

Organic peroxide

10.1016/j.jhazmat.2022.128770

Cite

Citations (21)

Uterine Smooth Muscle

Elsevier eBooks (2012)

Susan Wray Sarah Arrowsmith

Myometrium

Uterine contraction

10.1016/b978-0-12-381510-1.00090-9

Cite

Citations (5)

Maternal obesity and labour complications following induction of labour in prolonged pregnancy

BJOG An International Journal of Obstetrics & Gynaecology (2011)

Sarah Arrowsmith Susan Wray Siobhan Quenby

To investigate the effect of maternal obesity on mode of delivery following induction of labour (IOL) for prolonged pregnancy and subsequent intrapartum and neonatal complications.Retrospective (historical) cohort study.Liverpool Women's Hospital NHS Foundation Trust, UK.A total of 29, 224 women with singleton pregnancies between 2004 and 2008 of whom 3076 had a prolonged pregnancy (defined as ≥290 days or 41(+3) weeks of gestation) and received IOL.Kruskal-Wallis test, chi-square test and multivariable logistic regression.Mode of delivery and risk of delivery and neonatal complications in obese verses non-obese women following IOL.Obese women had a significantly higher rate of IOL ending in caesarean section compared with women of normal weight following IOL (38.7% versus 23.8% primiparous; 9.9% versus 7.9% multiparous women, respectively); however, length of labour, incidence of postpartum haemorrhage and third-degree tear, rate of low cord blood pH, low Apgar scores and shoulder dystocia were similar in all body mass index categories. Complications included a higher incidence of fetal macrosomia and second-degree, but not third-degree, tear in primiparous women.Higher maternal body mass index at booking is associated with an increased risk of prolonged pregnancy and increased rate of IOL. Despite this, more than 60% of obese primiparous and 90% of multiparous women with prolonged pregnancies who were induced achieved vaginal delivery and labour complications in the obese women with prolonged pregnancies were largely comparable to those of normal weight women with prolonged pregnancies. Our data suggest that IOL for prolonged pregnancy in obese women is a reasonable and safe management option.

Apgar score

10.1111/j.1471-0528.2010.02889.x

Cite

Citations (242)

Development of a human vasopressin V1a-receptor antagonist from an evolutionary-related insect neuropeptide

Scientific Reports (2017)

Maria Giulia Di Giglio Markus Muttenthaler Kasper Harpsøe Zita Liutkevičiūtė Peter Keov

Abstract Characterisation of G protein-coupled receptors (GPCR) relies on the availability of a toolbox of ligands that selectively modulate different functional states of the receptors. To uncover such molecules, we explored a unique strategy for ligand discovery that takes advantage of the evolutionary conservation of the 600-million-year-old oxytocin/vasopressin signalling system. We isolated the insect oxytocin/vasopressin orthologue inotocin from the black garden ant ( Lasius niger ), identified and cloned its cognate receptor and determined its pharmacological properties on the insect and human oxytocin/vasopressin receptors. Subsequently, we identified a functional dichotomy: inotocin activated the insect inotocin and the human vasopressin V 1b receptors, but inhibited the human V 1a R. Replacement of Arg8 of inotocin by D-Arg8 led to a potent, stable and competitive V 1a R-antagonist ([D-Arg8]-inotocin) with a 3,000-fold binding selectivity for the human V 1a R over the other three subtypes, OTR, V 1b R and V 2 R. The Arg8/D-Arg8 ligand-pair was further investigated to gain novel insights into the oxytocin/vasopressin peptide-receptor interaction, which led to the identification of key residues of the receptors that are important for ligand functionality and selectivity. These observations could play an important role for development of oxytocin/vasopressin receptor modulators that would enable clear distinction of the physiological and pathological responses of the individual receptor subtypes.

10.1038/srep41002

Cite

Citations (40)