ORCID Profile
0000-0002-4350-6357
Current Organisation
Monash Institute of Pharmaceutical Sciences
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Gastroenterology and Hepatology | Autonomic Nervous System | Clinical Sciences |
ANZSRC Socio-Economic Objective (SEO)
Health Related to Ageing | Expanding Knowledge in the Biological Sciences | Expanding Knowledge in the Medical and Health Sciences
Related Links
Publications
Structural characterization and catalytic evaluation of transition and rare earth metal doped ceria-based solid solutions for elemental mercury oxidation
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C3RA41441H
Cross sensitivity effects of volatile organic compounds on a SAW-based elemental mercury vapor sensor
Publisher: Elsevier BV
Date: 06-2015
Highly efficient nanosized Mn and Fe codoped ceria-based solid solutions for elemental mercury removal at low flue gas temperatures
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5CY00231A
Abstract: Mn and Fe codoped ceria-based solid solutions are effective catalysts for Hg 0 removal at low flue gas temperatures.
Mercury migration and speciation study during monoethylene glycol regeneration processes
Publisher: American Chemical Society (ACS)
Date: 07-05-2015
Positive allosteric modulation of endogenous delta opioid receptor signaling in the enteric nervous system is a potential treatment for gastrointestinal motility disorders.
Publisher: American Physiological Society
Date: 2021
Abstract: This study assesses the use of positive allosteric modulation as a pharmacological approach to enhance opioid receptor signaling in the enteric nervous system. We demonstrate that selective modulation of endogenous delta opioid receptor signaling can suppress colonic motility without causing constipation. We propose that allosteric modulation of opioid receptor signaling may be a therapeutic strategy to normalize gastrointestinal motility in conditions such as irritable bowel syndrome.
Inflammation without pain: Immune‐derived opioids hold the key
Publisher: Wiley
Date: 30-01-2020
DOI: 10.1111/NMO.13787
Abstract: Visceral pain is commonly associated with acute or remitting inflammatory bowel disease (IBD). In marked contrast, chronic IBD is often painless, even in the presence of active inflammation. This suggests that inflammation in itself is insufficient to sustain altered nociceptive signaling and raises the possibility that there is an endogenous analgesic system in effect in chronic disease. A new study by Basso et al. published in this issue of Neurogastroenterology & Motility provides additional support for an immune-mediated mechanism that suppresses visceral hypersensitivity. The authors examined visceral pain in the IL-10-piroxicam model of chronic colitis, which differs from other experimental IBD models in that it involves immune suppression. During active inflammation, responses by these mice to graded increases in colorectal distension were equivalent to healthy controls, consistent with normal afferent signaling. However, treatment with a peripherally restricted opioid receptor antagonist resulted in marked visceral hypersensitivity to the same stimuli. This effect was attributed to the production of endogenous opioids by colitogenic CD4
Electrophysiological and morphological changes in colonic myenteric neurons from chemotherapy-treated patients: a pilot study
Publisher: Wiley
Date: 22-02-2016
DOI: 10.1111/NMO.12795
Human enteric neurons: morphological, electrophysiological, and neurochemical identification
Publisher: Wiley
Date: 08-10-2014
DOI: 10.1111/NMO.12453
Electrocatalytic and SERS activity of Pt rich Pt-Pb nanostructures formed via the utilisation of in-situ underpotential deposition of lead
Publisher: Springer Science and Business Media LLC
Date: 05-09-2014
Mercury Sorption and Desorption on Gold: A Comparative Analysis of Surface Acoustic Wave and Quartz Crystal Microbalance-Based Sensors
Publisher: American Chemical Society (ACS)
Date: 23-07-2015
DOI: 10.1021/ACS.LANGMUIR.5B01858
Abstract: Microelectromechanical sensors based on surface acoustic wave (SAW) and quartz crystal microbalance (QCM) transducers possess substantial potential as online elemental mercury (Hg(0)) vapor detectors in industrial stack effluents. In this study, a comparison of SAW- and QCM-based sensors is performed for the detection of low concentrations of Hg(0) vapor (ranging from 24 to 365 ppbv). Experimental measurements and finite element method (FEM) simulations allow the comparison of these sensors with regard to their sensitivity, sorption and desorption characteristics, and response time following Hg(0) vapor exposure at various operating temperatures ranging from 35 to 75 °C. Both of the sensors were fabricated on quartz substrates (ST and AT cut quartz for SAW and QCM devices, respectively) and employed thin gold (Au) layers as the electrodes. The SAW-based sensor exhibited up to ∼111 and ∼39 times higher response magnitudes than did the QCM-based sensor at 35 and 55 °C, respectively, when exposed to Hg(0) vapor concentrations ranging from 24 to 365 ppbv. The Hg(0) sorption and desorption calibration curves of both sensors were found to fit well with the Langmuir extension isotherm at different operating temperatures. Furthermore, the Hg(0) sorption and desorption rate demonstrated by the SAW-based sensor was found to decrease as the operating temperature increased, while the opposite trend was observed for the QCM-based sensor. However, the SAW-based sensor reached the maximum Hg(0) sorption rate faster than the QCM-based sensor regardless of operating temperature, whereas both sensors showed similar response times (t90) at various temperatures. Additionally, the sorption rate data was utilized in this study in order to obtain a faster response time from the sensor upon exposure to Hg(0) vapor. Furthermore, comparative analysis of the developed sensors' selectivity showed that the SAW-based sensor had a higher overall selectivity (90%) than did the QCM counterpart (84%) while Hg(0) vapor was measured in the presence of ammonia (NH3), humidity, and a number of volatile organic compounds at the chosen operating temperature of 55 °C.
The transient receptor potential vanilloid 4 (TRPV4) ion channel mediates protease activated receptor 1 (PAR1)-induced vascular hyperpermeability.
Publisher: Elsevier BV
Date: 08-2020
Galvanically replaced Au-Pd nanostructures: Study of their enhanced elemental mercury sorption capacity over gold
Publisher: Royal Society of Chemistry (RSC)
Date: 28-07-2014
DOI: 10.1039/C4CP02233E
Abstract: In this study, the efficiency of bimetallic (Au-Pd) nanostructures over Au and Pd substrates for elemental mercury (Hg(0)) vapor sensing and capturing was investigated. The quartz crystal microbalance (QCM) technique was utilized to determine the sorption kinetics and quantity of Hg(0) captured by the developed Au-Pd surfaces. The Au-Pd nanostructures were synthesized directly on the QCM's Pd electrodes using galvanic replacement (GR) reactions for periods of 0.5 to 48 hours, which enabled the ratio of Au to Pd on the surface to be controlled. It was observed that the mercury affinity of the surface does not increase with increased Au loading, rather the Au : Pd ratio obtained after a GR reaction time of 1 hour was found to have the highest affinity towards Hg(0) vapor under the GR reaction conditions used in this study. Any further increase in Au : Pd ratio at the surface resulted in reduced affinity for Hg(0) with the Au-rich Au-Pd nanostructures behaving similar to an Au-control substrate. However, short reaction periods (i.e. 1 h) produced small Au nanoparticles increasing the surface to volume ratio for better sensitivity and response times. Remarkably, the QCM data showed that GR based Au-Pd nanostructures removed 2.5 μg cm(-2) of Hg(0) from a gas stream containing 9.1 mg m(-3) of Hg(0) vapor within the first 3 minutes of exposure. The control surfaces (Pd and Au based thin-films) on the other hand took a total of 106 and 159 minutes, respectively to reach the same Hg(0) sorption capacity from the same gas stream.
Nanosphere monolayer on a transducer for enhanced detection of gaseous heavy metal
Publisher: American Chemical Society (ACS)
Date: 16-01-2015
DOI: 10.1021/AM507069Z
Abstract: This study reports for the first time that polystyrene monodispersed nanosphere monolayer (PS-MNM) based Au (Au-MNM) and Ag (Ag-MNM) nanostructures deposited on quartz crystal microbalance (QCM) transducers can be used for nonoptical based chemical sensing with extremely high sensitivity and selectivity. This was demonstrated by exposing the Au-MNM and Ag-MNM based QCMs to low concentrations of Hg(0) vapor in the presence interferent gas species (i.e., H2O, NH3, volatile organics, etc.) at operating temperatures of 30 and 75 °C. At 30 °C, the Au-MNM and Ag-MNM based QCMs showed ∼16 and ∼20 times higher response magnitude toward Hg(0) vapor concentration of 3.26 mg/m(3) (364 parts per billion by volume (ppbv)) relative to their unmodified control counterparts, respectively. The results indicated that the extremely high sensitivity was not due to the increased surface area (only 4.62 times increase) but due to their long-range interspatial order and high number of surface defect formation which are selectively active toward Hg(0) vapor sorption. The Au-MNM and Ag-MNM also had more than an order of magnitude lower detection limits ( 30 ppbv). When the operating temperature was increased from 30 to 75 °C, it was found that the sensors exhibited lower drift, better accuracy, and better selectivity toward Hg(0) vapor but at the compromise of higher detection limits. The high repeatability (84%), accuracy (97%), and stability of Au-MNM in particular make it practical to potentially be used as nonspectroscopic based Hg(0) vapor sensor in many industries either as mercury emission monitoring or as part of a mercury control feedback system.
Damage from dissection is associated with reduced neuro-musclar transmission and gap junction coupling between circular muscle cells of guinea pig ileum, in vitro
Publisher: Frontiers Media SA
Date: 22-08-2014
Mesenchymal stem cells and conditioned medium avert enteric neuropathy and colon dysfunction in guinea pig TNBS-induced colitis
Publisher: American Physiological Society
Date: 12-2014
Abstract: Damage to the enteric nervous system (ENS) associated with intestinal inflammation may underlie persistent alterations to gut functions, suggesting that enteric neurons are viable targets for novel therapies. Mesenchymal stem cells (MSCs) offer therapeutic benefits for attenuation of neurodegenerative diseases by homing to areas of inflammation and exhibiting neuroprotective, anti-inflammatory, and immunomodulatory properties. In culture, MSCs release soluble bioactive factors promoting neuronal survival and suppressing inflammation suggesting that MSC-conditioned medium (CM) provides essential factors to repair damaged tissues. We investigated whether MSC and CM treatments administered by enema attenuate 2,4,6-trinitrobenzene-sulfonic acid (TNBS)-induced enteric neuropathy and motility dysfunction in the guinea pig colon. Guinea pigs were randomly assigned to experimental groups and received a single application of TNBS (30 mg/kg) followed by 1 × 10 6 human bone marrow-derived MSCs, 300 μl CM, or 300 μl unconditioned medium 3 h later. After 7 days, the effect of these treatments on enteric neurons was assessed by histological, immunohistochemical, and motility analyses. MSC and CM treatments prevented inflammation-associated weight loss and gross morphological damage in the colon decreased the quantity of immune infiltrate in the colonic wall ( P 0.01) and at the level of the myenteric ganglia ( P 0.001) prevented loss of myenteric neurons ( P 0.05) and damage to nerve processes, changes in ChAT, and nNOS immunoreactivity ( P 0.05) and alleviated inflammation-induced colonic dysmotility (contraction speed P 0.001, contractions/min P 0.05). These results provide strong evidence that both MSC and CM treatments can effectively prevent damage to the ENS and alleviate gut dysfunction caused by TNBS-induced colitis.
Endosomal signaling of delta opioid receptors is an endogenous mechanism and therapeutic target for relief from inflammatory pain
Publisher: Proceedings of the National Academy of Sciences
Date: 16-06-2020
Abstract: G protein-coupled receptors are considered to function principally at the cell surface. We present evidence that the δ-opioid receptor (DOPr) signals from endosomes to cause a sustained inhibition of pain. Opioids from the inflamed human and mouse colon, along with selective agonists that evoked DOPr internalization, inhibited the excitability of nociceptors by a mechanism requiring DOPr endocytosis. DOPr in endosomes generated a subset of signals in subcellular compartments that inhibited neuronal excitability. A DOPr agonist that was encapsulated into nanoparticles designed to selectively activate DOPr in endosomes of nociceptors caused a long-lasting inhibition of neuronal excitability and pain. Our results support the hypothesis that endosomal signaling of DOPr is an endogenous mechanism and therapeutic target for relief from inflammatory pain.
Role of oxidative stress in oxaliplatin-induced enteric neuropathy and colonic dysmotility in mice
Publisher: Wiley
Date: 16-11-2016
DOI: 10.1111/BPH.13646
Studying mercury partition in monoethylene glycol (MEG) used in gas facilities
Publisher: Elsevier BV
Date: 11-2015
Effect of MnOx Loading on Structural, Surface, and Catalytic Properties of CeO2‐MnOx Mixed Oxides Prepared by Sol‐Gel Method
Publisher: Wiley
Date: 07-04-2015
Ascending excitatory neural pathways modulate slow phasic myogenic contractions in the isolated human colon
Publisher: Wiley
Date: 05-2013
DOI: 10.1111/NMO.12129
Abstract: In animal models, enteric reflex pathways have potent effects on motor activity their roles have been much less extensively studied in human gut. The aim of this study was to determine if ascending excitatory interneuronal pathways can modulate spontaneous phasic contractions in isolated preparations of human colonic circular muscle. Human colonic preparations were cut into T shapes, with vertical bar of the 'T' pharmacologically isolated. Electrical stimulation and the nicotinic agonist, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), were applied to the isolated region and circular muscle contractile activity was measured from the cross-bar of the T, more than 10 mm orally from the region of stimulation. The predominant form of spontaneous muscle activity consisted of tetrodotoxin-resistant, large litude, slow phasic contractions (SPCs), occurring at average intervals of 124 ± 68 s. Addition of a high concentration of hexamethonium (1 mmol L(-1)) to the superfusing solution significantly increased the interval between SPCs to 278.1 ± 138.3 s (P < 0.005). Focal electrical stimulation more than 10 mm aboral to the muscle recording site advanced the onset of the next SPC, and this effect persisted in hexamethonium. However, the effect of electrical stimulation was blocked by tetrodotoxin (TTX, 1 μmol L(-1)). Application of the nicotinic agonist DMPP (1 mmol L(-1)) to the aboral chamber often stimulated a premature SPC (n = 4). The major form of spontaneous contractility in preparations of human colonic circular muscle is SPCs, which are myogenic in origin. Activation of ascending excitatory neural pathways, which involve nicotinic receptors, can modulate the timing of SPCs and thus influence human colonic motility.
Alterations of colonic function in the Winnie mouse model of spontaneous chronic colitis
Publisher: American Physiological Society
Date: 2017
Abstract: The Winnie mouse, carrying a missense mutation in Muc2, is a model for chronic intestinal inflammation demonstrating symptoms closely resembling inflammatory bowel disease (IBD). Alterations to the immune environment, morphological structure, and innervation of Winnie mouse colon have been identified however, analyses of intestinal transit and colonic functions have not been conducted. In this study, we investigated in vivo intestinal transit in radiographic studies and in vitro motility of the isolated colon in organ bath experiments. We compared neuromuscular transmission using conventional intracellular recording between distal colon of Winnie and C57BL/6 mice and smooth muscle contractions using force displacement transducers. Chronic inflammation in Winnie mice was confirmed by detection of lipocalin-2 in fecal s les over 4 wk and gross morphological damage to the colon. Colonic transit was faster in Winnie mice. Motility was altered including decreased frequency and increased speed of colonic migrating motor complexes and increased occurrence of short and fragmented contractions. The mechanisms underlying colon dysfunctions in Winnie mice included inhibition of excitatory and fast inhibitory junction potentials, diminished smooth muscle responses to cholinergic and nitrergic stimulation, and increased number of α-smooth muscle actin-immunoreactive cells. We conclude that diminished excitatory responses occur both prejunctionally and postjunctionally and reduced inhibitory purinergic responses are potentially a prejunctional event, while diminished nitrergic inhibitory responses are probably due to a postjunction mechanism in the Winnie mouse colon. Many of these changes are similar to disturbed motor functions in IBD patients indicating that the Winnie mouse is a model highly representative of human IBD. NEW & NOTEWORTHY This is the first study to provide analyses of intestinal transit and whole colon motility in an animal model of spontaneous chronic colitis. We found that cholinergic and purinergic neuromuscular transmission, as well as the smooth muscle cell responses to cholinergic and nitrergic stimulation, is altered in the chronically inflamed Winnie mouse colon. The changes to intestinal transit and colonic function we identified in the Winnie mouse are similar to those seen in inflammatory bowel disease patients.
Simultaneous multi-mode analysis of surface acoustic wave device temperature stability utilizing time-frequency methods
Publisher: IEEE
Date: 10-2015
Contributions of bile acids to gastrointestinal physiology as receptor agonists and modifiers of ion channels
Publisher: American Physiological Society
Date: 02-2022
Abstract: Bile acids (BAs) are known to be important regulators of intestinal motility and epithelial fluid and electrolyte transport. Over the past two decades, significant advances in identifying and characterizing the receptors, transporters, and ion channels targeted by BAs have led to exciting new insights into the molecular mechanisms involved in these processes. Our appreciation of BAs, their receptors, and BA-modulated ion channels as potential targets for the development of new approaches to treat intestinal motility and transport disorders is increasing. In the current review, we aim to summarize recent advances in our knowledge of the different BA receptors and BA-modulated ion channels present in the gastrointestinal system. We discuss how they regulate motility and epithelial transport, their roles in pathogenesis, and their therapeutic potential in a range of gastrointestinal diseases.
Distribution and trafficking of the μ-opioid receptor in enteric neurons of the guinea pig.
Publisher: American Physiological Society
Date: 08-2016
Abstract: The μ-opioid receptor (MOR) is a major regulator of gastrointestinal motility and secretion and mediates opiate-induced bowel dysfunction. Although MOR is of physiological and therapeutic importance to gut function, the cellular and subcellular distribution and regulation of MOR within the enteric nervous system are largely undefined. Herein, we defined the neurochemical coding of MOR-expressing neurons in the guinea pig gut and examined the effects of opioids on MOR trafficking and regulation. MOR expression was restricted to subsets of enteric neurons. In the stomach MOR was mainly localized to nitrergic neurons (∼88%), with some overlap with neuropeptide Y (NPY) and no expression by cholinergic neurons. These neurons are likely to have inhibitory motor and secretomotor functions. MOR was restricted to noncholinergic secretomotor neurons (VIP-positive) of the ileum and distal colon submucosal plexus. MOR was mainly detected in nitrergic neurons of the colon (nitric oxide synthase positive, 87%), with some overlap with choline acetyltransferase (ChAT). No expression of MOR by intrinsic sensory neurons was detected. [d-Ala 2 , MePhe 4 , Gly(ol) 5 ]enkephalin (DAMGO), morphiceptin, and loperamide induced MOR endocytosis in myenteric neurons. After stimulation with DAMGO and morphiceptin, MOR recycled, whereas MOR was retained within endosomes following loperamide treatment. Herkinorin or the δ-opioid receptor agonist [d-Ala 2 , d-Leu 5 ]enkephalin (DADLE) did not evoke MOR endocytosis. In summary, we have identified the neurochemical coding of MOR-positive enteric neurons and have demonstrated differential trafficking of MOR in these neurons in response to established and putative MOR agonists.
Determining the optimum exposure and recovery periods for efficient operation of a QCM based elemental mercury vapor sensor
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/727432
Abstract: In recent years, mass based transducers such as quartz crystal microbalance (QCM) have gained huge interest as potential sensors for online detection of elemental mercury (Hg 0 ) vapor from anthropogenic sources due to their high portability and robust nature enabling them to withstand harsh industrial environments. In this study, we determined the optimal Hg 0 exposure and recovery times of a QCM based sensor for ensuring its efficient operation while monitoring low concentrations of Hg 0 vapor ( p p b v ). The developed sensor was based on an AT-cut quartz substrate and utilized two gold (Au) films on either side of the substrate which functions as the electrodes and selective layer simultaneously. Given the temporal response mechanisms associated with mass based mercury sensors, the experiments involved the variation of Hg 0 vapor exposure periods while keeping the recovery time constant following each exposure and vice versa. The results indicated that an optimum exposure and recovery periods of 30 and 90 minutes, respectively, can be utilized to acquire the highest response magnitudes and recovery rate towards a certain concentration of Hg 0 vapor whilst keeping the time it takes to report an accurate reading by the sensor to a minimum level as required in real-world applications.
Therapeutic potential of allosteric modulators for the treatment of gastrointestinal motility disorders
Publisher: Wiley
Date: 18-01-2023
DOI: 10.1111/BPH.16023
Abstract: Gastrointestinal motility is tightly regulated by the enteric nervous system (ENS). Disruption of coordinated enteric nervous system activity can result in dysmotility. Pharmacological treatment options for dysmotility include targeting of G protein‐coupled receptors (GPCRs) expressed by neurons of the enteric nervous system. Current GPCR‐targeting drugs for motility disorders bind to the highly conserved endogenous ligand‐binding site and promote indiscriminate activation or inhibition of the target receptor throughout the body. This can be associated with significant side‐effect liability and a loss of physiological tone. Allosteric modulators of GPCRs bind to a distinct site from the endogenous ligand, which is typically less conserved across multiple receptor subtypes and can modulate endogenous ligand signalling. Allosteric modulation of GPCRs that are important for enteric nervous system function may provide effective relief from motility disorders while limiting side‐effects. This review will focus on how allosteric modulators of GPCRs may influence gastrointestinal motility, using 5‐hydroxytryptamine (5‐HT), acetylcholine (ACh) and opioid receptors as ex les.
Regional variation in the neurochemical coding of the myenteric plexus of the human colon and changes in patients with slow transit constipation
Publisher: Wiley
Date: 12-2008
DOI: 10.1111/J.1365-2982.2008.01165.X
Abstract: There are differences in the structure and function between regions of the colon. In patients with slow transit constipation the activity of all regions is markedly slowed. Counts of colonic neurones in slow transit constipation have been semiquantitative and led to varying results. We have applied new methods of quantification of markers in whole mounts of the colonic myenteric plexus to compare density of innervation between regions and between normal patients and those undergoing resection for severe constipation. Whole mounts of colonic myenteric plexus were made from specimens removed for cancer treatment (controls) and cases of severe constipation. All neurones were labelled by anti-human neuronal protein antibodies. Neurones synthesizing acetyl choline were labelled for choline acetyltransferase (ChAT) and those for nitric oxide by antisera to nitric oxide synthase (NOS). Four populations of neurones were distinguished and quantified according to the two selective markers, ChAT and NOS. In the normal major populations were NOS alone (51% of ascending colon neurones and 44% of descending colon neurones) and ChAT alone (41% ascending colon, 48% descending colon). Nitric oxide synthase/ChAT and NOS-/ChAT-comprised only small populations. In all regions in severe constipation, the percentage of NOS-only colonic myenteric neurones was raised (54% ascending colon, 49% descending colon) and ChAT only was reduced (36% ascending colon, 42% descending colon). The other populations were not changed. Accurate quantification of neuronal populations in whole mounts of human colon reveals inter-regional differences in innervation and marked changes in innervation in cases of very severe constipation.
Selective detection of elemental mercury vapor using a surface acoustic wave (SAW) sensor
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5AN00360A
Abstract: Theoretical and experimental demonstration that the developed SAW based sensor is highly sensitive and selective toward mercury vapor.
Serotonin-induced vascular permeability is mediated by transient receptor potential vanilloid 4 in the airways and upper gastrointestinal tract of mice
Publisher: Elsevier BV
Date: 07-2021
Related Organisations
Related Funding Activities
Discovery Early Career Researcher Award - Grant ID: DE200100825
Start Date: 05-2020
End Date: 10-2024
Amount: $422,955.00
Funder: Australian Research Council
View Funded Activity