Pharmacology and Therapeutics - Research Publications
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ItemPreclinical Evaluation of Caprylic Acid-Fractionated IgG Antivenom for the Treatment of Taipan (Oxyuranus scutellatus) Envenoming in Papua New Guinea(PUBLIC LIBRARY SCIENCE, 2011-05)BACKGROUND: Snake bite is a common medical emergency in Papua New Guinea (PNG). The taipan, Oxyuranus scutellatus, inflicts a large number of bites that, in the absence of antivenom therapy, result in high mortality. Parenteral administration of antivenoms manufactured in Australia is the current treatment of choice for these envenomings. However, the price of these products is high and has increased over the last 25 years; consequently the country can no longer afford all the antivenom it needs. This situation prompted an international collaborative project aimed at generating a new, low-cost antivenom against O. scutellatus for PNG. METHODOLOGY/PRINCIPAL FINDINGS: A new monospecific equine whole IgG antivenom, obtained by caprylic acid fractionation of plasma, was prepared by immunising horses with the venom of O. scutellatus from PNG. This antivenom was compared with the currently used F(ab')(2) monospecific taipan antivenom manufactured by CSL Limited, Australia. The comparison included physicochemical properties and the preclinical assessment of the neutralisation of lethal neurotoxicity and the myotoxic, coagulant and phospholipase A(2) activities of the venom of O. scutellatus from PNG. The F(ab')(2) antivenom had a higher protein concentration than whole IgG antivenom. Both antivenoms effectively neutralised, and had similar potency, against the lethal neurotoxic effect (both by intraperitoneal and intravenous routes of injection), myotoxicity, and phospholipase A(2) activity of O. scutellatus venom. However, the whole IgG antivenom showed a higher potency than the F(ab')(2) antivenom in the neutralisation of the coagulant activity of O. scutellatus venom from PNG. CONCLUSIONS/SIGNIFICANCE: The new whole IgG taipan antivenom described in this study compares favourably with the currently used F(ab')(2) antivenom, both in terms of physicochemical characteristics and neutralising potency. Therefore, it should be considered as a promising low-cost candidate for the treatment of envenomings by O. scutellatus in PNG, and is ready to be tested in clinical trials.
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ItemRegenerating Indigenous literacy resourcefulness: A middle school intervention(Australian Literacy Educators' Association, 2014)
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ItemSharing Place, Learning Together: Mutual Capacity and Partnership Building(Early Learning Centre, the University of Melbourne, 2015)Sharing Place, Learning Together (SPLT) is a cross-disciplinary education project that aims to develop the English and Science literacy skills of remote Aboriginal students. The project comprises an interdisciplinary team from the University of Melbourne (UoM) partnering with Maningrida College and the Djelk Rangers (Bawaninga Aboriginal Corporation) to support the College’s ‘Learning on Country’ program. Through cross-cultural exchanges and ‘on country’ visits Aboriginal biocultural knowledge is integrated with Western scientific understanding to develop curriculum and literacy resources. This paper details SPLT’s evolvement and discusses activities and learning experiences the partnership has generated. Linked to the project’s development, the paper presents the findings of a research study that investigated mutual capacity and partnership building between the Maningrida College Community and UoM. These findings reveal that relationship-building, coupled with a sustained presence in the community, were critical to strengthening the partnership, and highlighted that establishing trust and credibility must precede research initiatives.
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ItemSharing Place, Learning Together: Perspectives and Reflections on an Educational Partnership Formation With a Remote Indigenous Community School(Cambridge University Press (CUP), 2015)Sustainable partnership formation in a remote Indigenous community involves social, cultural and political considerations. This article reports on the project, ‘Sharing Place, Learning Together: Supporting Sustainable Educational Partnerships to Advance Social Equity’, funded by the Melbourne Social Equity Institute (MSEI) at the University of Melbourne (UoM). The project's aims were to document insights into working with communities and educators in a remote community school in Western Arnhem Land, and to promote and raise Aboriginal students’ aspirations for engagement in further education through knowledge exchanges. Two project deliverables focus this paper: a participatory workshop conducted at UoM by educators and students from the school, and a qualitative research study that investigated the mutual partnership capacity building between the school community and UoM. The workshop provided an environment conducive to the participants sharing their cultural knowledge and perspectives on a two-way Learning on Country program with the wider UoM community. Extensive interview data collected from school and community-based participants identified the enabling and constraining factors impacting the formation of a sustainable partnership. The findings revealed the importance of prioritising relationship-building, the valuing of resource development, and the need for humility and openness to criticism when working with remote communities.
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ItemFatal presumed tiger snake (Notechis scutatus) envenomation in a cat with measurement of venom and antivenom concentration(PERGAMON-ELSEVIER SCIENCE LTD, 2016-04)A fatal outcome of a presumed tiger snake (Notechis scutatus) envenomation in a cat is described. Detectable venom components and antivenom concentrations in serum from clotted and centrifuged whole blood and urine were measured using a sensitive and specific ELISA. The cat presented in a paralysed state with a markedly elevated serum CK but with normal clotting times. The cat was treated with intravenous fluids and received two vials of equine whole IgG bivalent (tiger and brown snake) antivenom. Despite treatment the cat's condition did not improve and it died 36 h post-presentation. Serum concentration of detectable tiger snake venom components at initial presentation was 311 ng/mL and urine 832 ng/mL, this declined to non-detectable levels in serum 15-min after intravenous antivenom. Urine concentration of detectable tiger snake venom components declined to 22 ng/mL at post-mortem. Measurement of equine anti-tiger snake venom specific antibody demonstrated a concentration of 7.2 Units/mL in serum at post-mortem which had declined from an initial high of 13 Units/mL at 15-min post-antivenom. The ELISA data demonstrated the complete clearance of detectable venom components from serum with no recurrence in the post-mortem samples. Antivenom concentrations in serum at initial presentation were at least 100-fold higher than theoretically required to neutralise the circulating concentrations of venom. Despite the fatal outcome in this case it was concluded that this was unlikely that is was due to insufficient antivenom.
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ItemProspective assessment of the false positive rate of the Australian snake venom detection kit in healthy human samples(PERGAMON-ELSEVIER SCIENCE LTD, 2016-03-01)The Snake Venom Detection Kit (SVDK; bioCSL Pty Ltd, Australia) distinguishes venom from the five most medically significant snake immunotypes found in Australia. This study assesses the rate of false positives that, by definition, refers to a positive assay finding in a sample from someone who has not been bitten by a venomous snake. Control unbroken skin swabs, simulated bite swabs and urine specimens were collected from 61 healthy adult volunteers [33 males and 28 females] for assessment. In all controls, simulated bite site and urine samples [a total of 183 tests], the positive control well reacted strongly within one minute and no test wells reacted during the ten minute incubation period. However, in two urine tests, the negative control well gave a positive reaction (indicating an uninterpretable test). A 95% confidence interval for the false positive rate, on a per-patient rate, derived from the findings of this study, would extend from 0% to 6% and, on a per-test basis, it would be 0-2%. It appears to be a very low incidence (0-6%) of intrinsic true false positives for the SVDK. The clinical impresssion of a high SVDK false positive rate may be mostly related to operator error.
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ItemMembrane interactions and biological activity of antimicrobial peptides from Australian scorpion(ELSEVIER SCIENCE BV, 2014-09)UyCT peptides are antimicrobial peptides isolated from the venom of the Australian scorpion. The activity of the UyCT peptides against Gram positive and Gram negative bacteria and red blood cells was determined. The membrane interactions of these peptides were evaluated by dye release (DR) of the fluorophore calcein from liposomes and isothermal titration calorimetry (ITC); and their secondary structure was determined by circular dichroism (CD). Three different lipid systems were used to mimic red blood cells, Escherichia coli and Staphylococcus aureus membranes. UyCT peptides exhibited broad spectrum antimicrobial activity with low MIC for S. aureus and multi-drug resistant Gram negative strains. Peptide combinations showed some synergy enhancing their potency but not hemolytic activity. The UyCT peptides adopted a helical structure in lipid environments and DR results confirmed that the mechanism of action is by disrupting the membrane. ITC data indicated that UyCT peptides preferred prokaryotic rather than eukaryotic membranes. The overall results suggest that UyCT peptides could be pharmaceutical leads for the treatment of Gram negative multiresistant bacterial infections, especially against Acinetobacter baumanni, and candidates for peptidomimetics to enhance their potency and minimize hemolysis. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.
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ItemInsect envenomation(Wolters Kluwer, 2012)