- Heart Failure Treatment and Management
- Neuropeptides and Animal Physiology
- Stress Responses and Cortisol
- Receptor Mechanisms and Signaling
- Hormonal Regulation and Hypertension
- Cardiovascular Function and Risk Factors
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Adipose Tissue and Metabolism
- Cardiac electrophysiology and arrhythmias
- Peptidase Inhibition and Analysis
- Heart Rate Variability and Autonomic Control
- Neuroendocrine regulation and behavior
- Microbial Community Ecology and Physiology
- Renin-Angiotensin System Studies
- Electrolyte and hormonal disorders
- Apelin-related biomedical research
- GDF15 and Related Biomarkers
- Cardiac Structural Anomalies and Repair
- Cardiovascular Disease and Adiposity
- MicroRNA in disease regulation
- Extracellular vesicles in disease
- Coronary Interventions and Diagnostics
- Cardiac Imaging and Diagnostics
- Microbial Fuel Cells and Bioremediation
- Cardiac Ischemia and Reperfusion
University of Otago
2014-2024
National University of Singapore
2017-2024
National University Heart Centre Singapore
2019-2024
TRIUMF
2024
National University Health System
2017-2023
University of Huddersfield
2015-2022
New Zealand Brain Research Institute
2013-2019
Fisheries and Oceans Canada
2017
University of Manitoba
2017
NIHR Leeds Musculoskeletal Biomedical Research Unit
2012
Implanted bioelectronic devices can form distributed networks capable of sensing health conditions and delivering therapy throughout the body. Current clinically-used approaches for wireless communication, however, do not support direct networking between implants because signal losses from absorption reflection by As a result, existing examples such rely on an external relay device that needs to be periodically recharged constitutes single point failure. Here, we demonstrate...
Background Adrenomedullin is a recently discovered endogenous peptide with hypotensive and natriuretic actions in normal animals. Circulating ventricular adrenomedullin are elevated congestive heart failure, suggesting possible role the pathophysiology of this disease. No studies have previously examined effects failure. Methods Results Eight sheep pacing-induced failure received human adrenomedullin(1-52) at 10 100 ng · kg −1 min IV for 90 minutes each. Compared vehicle control data,...
Although many studies have examined the effects of administering natriuretic peptide receptor C (NPR-C) ligands and endopeptidase 24.11 (EP 24.11) inhibitors on clearance bioactivity atrial (ANP), none systematically compared their endogenous levels both ANP brain (BNP) under physiological conditions. Accordingly, we hemodynamic, hormonal, renal actions an EP inhibitor, SCH-32615, NPR-C ligand, C-ANP-(4-23), alone in combination eight normal conscious sheep. blockade inhibition induce...
The observations that mesenchymal stem cells (MSCs) exert cardiac protection and repair via their secretome with the active component(s) identified as exosomes underpinned our test of efficacy MSC in a porcine model myocardial infarction (MI) when administered systemically by convenient method intravenous (IV) bolus injection. Results show 7 days IV results clear reduction (30-40%) infarct size measured at both 28 post-MI, despite near identical release hs Troponin T. Together reduced size,...
Metabolism of natriuretic peptides is regulated by two degradative pathways: uptake the clearance receptor (natriuretic peptide C--NPR-C) and hydrolysis neutral endopeptidase (NEP). Affinity studies favour a dominant role NPR-C in hormone degradation several species but do not account for efficacy NEP inhibitors vivo, nor uniquely prolonged half life (t((1/2))) human brain (hBNP). Postulating that (1) delayed metabolism hBNP reflects resistance to (2) interactions between increase enzyme...
Urocortin 2 (Ucn2) has potent cardiovascular actions and may participate in the pathophysiology of heart failure (HF). The integrated hemodynamic, endocrine, renal effects Ucn2 are unknown.Eight sheep received incremental intravenous boluses murine (10, 50, 100 microg at 2-hour intervals) before (normal) during pacing-induced HF. Compared with control data, induced rapid dose-dependent increases cardiac output (peak effects: normal 4.3+/-0.2 versus 6.1+/-0.2 L/min, P<0.001; HF 2.3+/-0.1...
The time course of cardiac sympathetic nerve activity (CSNA) following acute myocardial infarction (MI) is unknown. We therefore undertook serial direct recordings CSNA, arterial blood pressure (MAP) and heart rate (HR) in 11 conscious sheep before after MI, compared them with 10 controls. Conscious CSNA were taken daily from electrodes glued into the thoracic nerves. Infarction was induced under pethidine diazepam analgesia by applying tension to a coronary suture. MI size assessed left...
Objective The expression of FcγRIIIa/CD16 may render monocytes targets for activation by IgG-containing immune complexes (IC). We investigated whether was upregulated in rheumatoid arthritis (RA), associated with TNF production response to IC-stimulation, and if this predicted methotrexate therapy. Methods on CD14low CD14++ measured flow cytometry healthy controls RA patients (early long-standing disease). Intracellular TNF-staining carried out after vitro LPS or heat-aggregated...
Abstract Aims A significant proportion of heart failure (HF) patients have HF preserved ejection fraction (HFpEF). The lack effective treatments for HFpEF remains a critical unmet need. key obstacle to therapeutic innovation in is the paucity pre‐clinical models. Although several large animal models been reported, few demonstrate progression decompensated HF. We established model by enhancing porcine progressive left ventricular (LV) pressure overload and characterized this including...
Adrenomedullin is a recently discovered peptide that has been shown to reduce arterial pressure and induce natriuresis. However, few studies have examined the biological actions of adrenomedullin in conscious animals an integrative manner. Accordingly, we hemodynamic, renal, endocrine infused intravenously at 10 100 ng.kg-1.min-1 (each 90 min) vehicle-controlled study eight normal sheep. reduced right atrial (P < 0.05) diastolic (15 mmHg, P 0.01) mean (10 increased cardiac output (3 l/min,...
1. Atrial and brain natriuretic peptide are both circulating hormones subject to degradation by neutral endopeptidase 24.11. Whereas endogenous levels of atrial increased inhibition in most pathophysiological states, the effect on influence cardiac status is less clear. To further evaluate role 24.11, we directly compared responses peptide, together with effects other vasoactive hormones, haemodynamics renal indices, a inhibitor, SCH32615, vehicle control eight conscious sheep before during...
Whilst the tissue distribution and range of biological actions reported for apelin suggest a role peptide in pressure/volume homeostasis, conflicting reports make precise unclear. Furthermore, few integrated studies have been performed there are no bioactivity large animal model. Accordingly, we examined haemodynamic, hormonal renal effects ten normal conscious sheep. Apelin (1 mg i.v. bolus) induced biphasic haemo-dynamic response characterised by an acute fall arterial pressure rise heart...
ABSTRACT The survival of microorganisms within a cementitious geological disposal facility for radioactive wastes heavily depends on their ability to survive the calcium-dominated, hyperalkaline conditions resulting from dissolution materials. results this study show that formation flocs, composed complex mixture extracellular polymeric substances (EPS), provides protection against alkaline pH values up 13.0. flocs were dominated by Alishewanella and Dietzia spp., producing mannose-rich...
Abstract Osteocrin (OSTN) is an endogenous protein sharing structural similarities with the natriuretic peptides [NPs; atrial (ANP), B‐type (BNP) and C‐type (CNP) NP], which are hormones known for their crucial role in maintaining pressure/volume homeostasis. competes NPs binding to receptor involved clearance (NPR‐C). In present study, having identified, first time, major circulating form of OSTN human ovine plasma, we examined integrated haemodynamic, endocrine renal effects...
We examined for the first time specific roles of angiotensin II and natriuretic peptides during inhibition angiotensin-converting enzyme (captopril, 25 mg bolus + 6 mg/3 h infusion) endopeptidase 24.11 (SCH32615, 5 mg/kg 3 mg/kg/3 infusion), both separately in combination, eight sheep with pacing-induced heart failure. Plasma atrial brain peptide levels were similarly increased by SCH32615 to a lesser extent combined but decreased captopril. Captopril induced identical increases plasma renin...
Although atrial natriuretic peptide (ANP) and brain (BNP) appear to share functional homology, there is doubt concerning a possible endocrine function for C-type (CNP) the relative potency of species-specific forms these hormones. Accordingly, we have examined biological effects, interactions, pharmacokinetics equimolar doses (0.5 followed by 2.5 pmol.kg-1.min-1, each 2 h) ANP, BNP-26, CNP-22 in vehicle-controlled studies normal conscious sheep. (metabolic clearance rates 5.7 +/- 1.17, 7.5...
Aims To investigate the subacute effects of a sustained intravenous infusion urocortin-I (Ucn-I) in experimental heart failure (HF).
Although acute administration of urocortin 2 has beneficial actions in heart failure, the integrated hemodynamic, hormonal, and renal effects sustained treatment this disease have not been investigated. In current study, we administered a 4-day infusion vehicle control (0.9% saline; n=6) or (0.75 μg/kg per hour; to sheep with pacing-induced failure. Compared time-matched controls, produced rapid (30-minute) persistent (4-day) improvements cardiac contractility (day 4: 905±73 versus 1424±158...