Browsing by Author "Nguyen, AP"
Now showing 1 - 7 of 7
Results Per Page
Sort Options
- ItemBioaccumulation kinetics and organ distribution of cadmium and zinc in the freshwater decapod crustacean macrobrachium australiense(ACS Publications, 2014-12-24) Cresswell, T; Simpson, SL; Mazumder, D; Callaghan, PD; Nguyen, APThis study used the radioisotopes 109Cd and 65Zn to explore the uptake, retention and organ distribution of these nonessential and essential metals from solution by the freshwater decapod crustacean Macrobrachium australiense. Three treatments consisting of cadmium alone, zinc alone, and a mixture of cadmium and zinc were used to determine the differences in uptake and efflux rates of each metal individually and in the metal mixture over a three-week period, followed by depuration for 2 weeks in metal-free water using live-animal gamma-spectrometry. Following exposure, prawns were cryosectioned and the spatial distribution of radionuclides visualized using autoradiography. Metal uptake and efflux rates were the same in the individual and mixed-metal exposures, and efflux rates were close to zero. The majority of cadmium uptake was localized within the gills and hepatopancreas, while zinc accumulated in the antennal gland at concentrations orders of magnitude greater than in other organs. This suggested that M. australiense may process zinc much faster than cadmium by internally transporting the accumulated zinc to the antennal gland. The combination of uptake studies and autoradiography greatly increases our understanding of how metal transport kinetics and internal processing may influence the toxicity of essential and nonessential metals in the environment. © 2014 American Chemical Society
- ItemFluorine-18 radiolabelling and in vitro / in vivo metabolism of [18F]D4-PBR111(John Wiley & Sons, Inc, 2019-05-26) Wyatt, NA; Safavi-Naeini, M; Wotherspoon, ATL; Arthur, A; Nguyen, AP; Parmar, A; Hamze, H; Day, CM; Zahra, D; Matesic, L; Davis, E; Rahardjo, GL; Yepuri, NR; Shepherd, R; Murphy, RB; Pham, TQ; Nguyen, VH; Callaghan, PD; Holden, PJ; Grégoire, MC; Darwish, TA; Fraser, BHObjectives The purinergic receptor P2X ligand-gated ion channel type 7 (P2X7R) is an adenosine triphosphate (ATP)-gated ion-channel, and P2X7R is a key player in inflammation. P2X7R is an emerging therapeutic target in central nervous system (CNS) diseases including Alzheimer's disease (AD) and Parkinson's disease (PD), because P2X7R also plays a pivotal role in neuroinflammation. P2X7R represents a potential molecular imaging target for neuroinflammation via biomedical imaging technique positron emission tomography (PET), and several radioligands targeting P2X7R have been developed and evaluated in animals. In our previous work, we have developed and characterized [11C]GSK1482160 as a P2X7R radioligand for neuroinflammation,2 clinical evaluation of [11C]GSK1482160 in healthy controls and patients is currently underway, and the estimation of radiation dosimetry for [11C]GSK1482160 in normal human subjects has been reported.3 Since the half-life (t1/2) of radionuclide carbon-11 is only 20.4 min, it is attractive for us to develop derivatives of [11C]GSK1482160, which can be labeled with the radionuclide fluorine-18 (t1/2, 109.7 min), and a fluorine-18 ligand would be ideal for widespread use.4 To this end, a series of [18F]fluoroalkyl including [18F]fluoromethyl (FM), [18F]fluoroethyl (FE), and [18F]fluoropropyl (FP) derivatives of GSK1482160 have been prepared and examined as new potential P2X7R radioligands. © 2019 The Authors
- ItemInvestigating the kinetics of Cd transport between internal organs of the freshwater decapod Macrobrachium australiense(SETAC, 2014-09-14) Cresswell, T; Simpson, SL; Mazumder, D; Callaghan, PD; Nguyen, AP; Corry, MThe bioaccumulation of metals by aquatic organisms can be studied in great detail using radiotracers, allowing insights into rates of uptake and fate of the metals accumulated in tissues. While there have been numerous studies on the whole-body bioaccumulation of metals by organisms, little is known about the kinetics of organ-specific bioaccumulation. This study used the radioisotope 109Cd to explore the internal uptake kinetics of this non-essential metal following accumulation from solution by the freshwater decapod crustacean Macrobrachium australiense. The first stage of the study involved exposing 24 organisms for up to 2 weeks to 0.55 µg Cd/L in synthetic river water with three individuals being removed at pre-defined time points. Following exposure, animals were rinsed in a 0.1 mM EDTA solution to remove any loosely-bound metal, rapidly frozen and the anatomical distribution of the radionuclide visualised from fresh frozen sections (20 um) using autoradiography. The second phase of the study consisted of exposing organisms to the same radiotracer solution for a short period (6 h) and long period (7 d), followed by depuration in metal- and isotope-free water for up to 3 weeks. Organisms were removed from depuration at pre-defined time points, rapidly frozen, the anatomical distribution of the radionuclide determined as above. Preliminary results suggest that the gills appeared to saturate after 7 d exposure, with negligible increase over another 7 d of exposure. However, the ratio of Cd between the hepatopancreas and gills increased over time, suggesting the organism was actively processing accumulated metal. Rates of accumulation into different internal compartments in response to changes in uptake and depuration durations will be discussed. The findings of the study provide new information on the processing of a non-essential metal by M. australiense and could potentially be used to estimate the exposure history of field-caught organisms.
- ItemMetal transfer among organs following short- and long-term exposures using autoradiography: cadmium bioaccumulation by the freshwater prawn macrobrachium australiense(American Chemical Society, 2017-03-16) Cresswell, T; Mazumder, D; Callaghan, PD; Nguyen, AP; Corry, M; Simpson, SLThe uptake, depuration, and organ distribution of the radioisotope 109Cd were used to explore the internal kinetics of this nonessential metal following accumulation from waterborne cadmium by the freshwater decapod crustacean Macrobrachium australiense. Short- (6 h) and long-term (7 to 14 days) exposures to the radioisotope in solutions of 0.56 μg Cd/L were followed by depuration in metal- and isotope-free water for up to 21 days. The anatomical distribution of the radionuclide was visualized using autoradiography at predefined time points. The gills did not become saturated with cadmium after 14 days of exposure and demonstrated a greater rate of cadmium uptake relative to the hepatopancreas. Cadmium concentrations decreased rapidly during depuration from both gills and hepatopancreas after short exposures but slowly following long-term exposures. This suggests that the duration of cadmium exposure influences the depuration rate for this organism. The study demonstrates the complex behavior of cadmium accumulated by M. australiense and improves our understanding of how exposure duration will influence the internal location and potential toxicity of metals. © 2017 American Chemical Society
- ItemPartial genetic deletion of neuregulin 1 and adolescent stress interact to alter NMDA receptor binding in the medial prefrontal cortex(Frontiers, 2014-09-29) Chohan, TW; Nguyen, AP; Todd, SM; Bennett, MR; Callaghan, PD; Arnold, JCSchizophrenia is thought to arise due to a complex interaction between genetic and environmental factors during early neurodevelopment. We have recently shown that partial genetic deletion of the schizophrenia susceptibility gene neuregulin 1 (Nrg1) and adolescent stress interact to disturb sensorimotor gating, neuroendocrine activity and dendritic morphology in mice. Both stress and Nrg1 may have converging effects upon N-methyl-D-aspartate receptors (NMDARs) which are implicated in the pathogenesis of schizophrenia, sensorimotor gating and dendritic spine plasticity. Using an identical repeated restraint stress paradigm to our previous study, here we determined NMDAR binding across various brain regions in adolescent Nrg1 heterozygous (HET) and wild-type (WT) mice using [3H] MK-801 autoradiography. Repeated restraint stress increased NMDAR binding in the ventral part of the lateral septum (LSV) and the dentate gyrus (DG) of the hippocampus irrespective of genotype. Partial genetic deletion of Nrg1 interacted with adolescent stress to promote an altered pattern of NMDAR binding in the infralimbic (IL) subregion of the medial prefrontal cortex. In the IL, whilst stress tended to increase NMDAR binding in WT mice, it decreased binding in Nrg1 HET mice. However, in the DG, stress selectively increased the expression of NMDAR binding in Nrg1 HET mice but not WT mice. These results demonstrate a Nrg1-stress interaction during adolescence on NMDAR binding in the medial prefrontal cortex. © 2014 Chohan, Nguyen, Todd, Bennett, Callaghan and Arnold this is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)
- ItemRadioisotope techniques and aquatic ecotoxicology: importance of understanding kinetics and internal location of metals(University of New South Wales and Australian Nuclear Science and Technology Organisation, 2015-07-08) Cresswell, T; Mazumder, D; Callaghan, PD; Nguyen, AP; Corry, M; Simpson, SLAquatic ecotoxicology is primarily concerned with the bioaccumulation and effects of anthropogenic contaminants to a range of biota. Traditional methods of assessing the bioaccumulation of contaminants by an organism have typically relied on destructive techniques, generally involving the dissection of internal organs, followed by acid digestion and analysis. To understand how organisms accumulate contaminants over time using these traditional methods, a large number of organisms was required to be sacrificed. Gamma-emitting metal radioisotopes are valuable tools for studying metal bioaccumulation in aquatic invertebrates, allowing the influx and efflux of multiple metals to be analysed rapidly, at multiple intervals in live organisms during an exposure period (Hervé-Fernández et al., 2010, Cresswell et al., 2015). Furthermore, autoradiography of sacrificed and cryosectioned organisms enables the organ distribution of accumulated metals to be visualised and quantified. To cryosection, organisms are snap-frozen to limit the mobilisation of chemical species, preserve the integrity of the organs and allow much higher resolution of organ-specific metal analysis compared to tradition dissection-digestion techniques. This paper describes two studies on a freshwater decapod crustacean that examined the kinetics of non-essential (cadmium) and essential (zinc) metal accumulation in a mixture, and the kinetics of internal partitioning of cadmium among major organs using radioisotope techniques to model environmental conditions.
- ItemWhere do the metals go? Investigating uptake, retention and spatial distribution of cadmium and zinc using radiotracers within a freshwater decapod crustacean(SETAC Australasia, 2013-10-01) Cresswell, T; Simpson, SL; Mazumder, D; Callaghan, PD; Nguyen, APThe bioaccumulation of metals by aquatic organisms can be studied in great depth using radiotracers, allowing insights into rates of uptake and fate of the metals once bioaccumulated. This study used the radioisotopes 109Cd and 65Zn to explore the uptake, retention and internal distribution of these non-essential and essential metals in solution by the freshwater decapod crustacean Macrobrachium australiense. Three treatments consisting of cadmium alone, zinc alone and a combination of cadmium and zinc were used to determine the differences in uptake rate of each metal individually and in a mixture over a three week period. The prawns were then allowed to depurate in metal-free water for two weeks to determine rates of efflux. The effects of moulting on the uptake and loss of each metal radionuclide were also identified during the study. Following exposure, prawns were cryosectioned and the spatial distribution of radionuclides visualised using autoradiography for the 3 experimental cohorts. Results showed that a mixture of the two metals did not affect the uptake or efflux rate of each individual metal. Moulting appeared to result in a short-term loss in zinc but an increased cadmium uptake rate. However, metal isotope concentration remained stable within the body during the depuration period. Autoradiography demonstrated that the majority of cadmium uptake was localised within the hepatopancreas, while zinc uptake was distributed between the hepatopancreas and the exoskeleton. The implications of the study are such that M. australiense readily accumulates both cadmium and zinc from solution but does not effectively eliminate either metal while in metal-free water. © 2013, ANSTO and CSIRO.