Melbourne Veterinary School - Research Publications

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    Seroprevalence of Toxoplasma gondii in burrowing bettongs (Bettongia lesueur): A comparison of cat-free and cat-exposed populations
    McKay, PA ; Hufschmid, J ; Meredith, AL ; Zendejas-Heredia, PA ; Moseby, KE ; Deakin, J (CSIRO Publishing, 2022-01-01)
    Toxoplasma gondii is a ubiquitous protozoan transmitted by felids and infection, morbidity, and mortality occur in numerous marsupial species. This study explores the relationship between cat exposure and Toxoplasma in burrowing bettongs (Bettongia lesueur) in the Arid Recovery Reserve (ARR), South Australia. We estimated seroprevalence, using a modified agglutination test for T. gondii-specific immunoglobulins, in cat-free and cat-exposed bettong populations. Tissue samples collected opportunistically from bettong carcasses and from cats within and around the reserve were screened for T. gondii DNA using multiplex real-time polymerase chain reaction (M-qPCR). Two cats trapped inside the ARR tested positive (50.0%; 95% CI: 15.0-85.0%). All bettongs tested from the cat-free (n = 48) and cat-exposed (n = 19) exclosures were seronegative (95% CI: 0-7.41% and 0-16.82% respectively). We found no evidence of fatal toxoplasmosis, with all bettong carcasses negative on M-qPCR (n = 11). We propose that T. gondii was not detected in bettongs coexisting with cats primarily due to low exposure of bettongs at the time of sampling, possibly due to poor oocyst viability in arid conditions or low shedding by cats. Ongoing screening throughout high and low rainfall years should be conducted to better establish the risk of Toxoplasma to bettongs in the ARR.
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    Intravenous Acetaminophen Does Not Provide Adequate Postoperative Analgesia in Dogs Following Ovariohysterectomy
    Leung, J ; Beths, T ; Carter, JE ; Munn, R ; Whittem, T ; Bauquier, SH (MDPI, 2021-12-01)
    (1) Objective: To investigate the analgesic effects of intravenous acetaminophen after intravenous administration in dogs presenting for ovariohysterectomy. (2) Methods: 14 ASA I client-owned female entire dogs. In this randomized, blinded, clinical study, dogs were given meperidine and acepromazine intramuscularly before induction of anesthesia with intravenous propofol. Anesthesia was maintained with isoflurane in oxygen. Intravenous acetaminophen 20 mg/kg or 0.9% NaCl was administered postoperatively. Pain assessments were conducted using the Glasgow Pain Scale short form before premedication and at 10, 20, 60, 120, and 180 min post-extubation or until rescue analgesia was given. The pain scores, times, and incidences of rescue analgesia between the groups was compared. Blood was collected before and 2, 5, 10, 20, 40, and 80 min after acetaminophen administration. Acetaminophen plasma concentration was quantified by liquid chromatography-mass spectrometry. The acetaminophen plasma concentration at the time of each pain score evaluation was subsequently calculated. (3) Results: There was no significant difference in pain scores at 10 min, highest pain scores, or time of rescue analgesia between groups. In each group, 3 dogs (43%) received rescue analgesia within 20 min. (4) Conclusions: Following ovariohysterectomy in dogs, there was no detectable analgesic effect of a 20 mg/kg dosage of intravenous acetaminophen administered at the end of surgery.
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    A new Hendra virus genotype found in Australian flying foxes.
    Wang, J ; Anderson, DE ; Halpin, K ; Hong, X ; Chen, H ; Walker, S ; Valdeter, S ; van der Heide, B ; Neave, MJ ; Bingham, J ; O'Brien, D ; Eagles, D ; Wang, L-F ; Williams, DT (Springer Science and Business Media LLC, 2021-10-13)
    BACKGROUND: Hendra virus (HeV) has caused lethal disease outbreaks in humans and horses in Australia. Flying foxes are the wildlife reservoir from which the virus was first isolated in 1996. Following a heat stress mortality event in Australian flying foxes in 2013, a novel HeV variant was discovered. This study describes the subsequent surveillance of Australian flying foxes for this novel virus over a nine year period using qRT-PCR testing of tissues from flying foxes submitted primarily for Australian bat lyssavirus diagnosis. Genome sequencing and characterisation of the novel HeV variant was also undertaken. METHODS: Spleen and kidney samples harvested from flying fox carcasses were initially screened with two real-time qRT-PCR assays specific for the prototype HeV. Two additional qRT-PCR assays were developed specific for the HeV variant first detected in samples from a flying fox in 2013. Next-generation sequencing and virus isolation was attempted from selected samples to further characterise the new virus. RESULTS: Since 2013, 98 flying foxes were tested and 11 were positive for the new HeV variant. No samples were positive for the original HeV. Ten of the positive samples were from grey-headed flying foxes (GHFF, Pteropus poliocephalus), however this species was over-represented in the opportunistic sampling (83% of bats tested were GHFF). The positive GHFF samples were collected from Victoria and South Australia and one positive Little red flying fox (LRFF, Pteropus scapulatus) was collected from Western Australia. Immunohistochemistry confirmed the presence of henipavirus antigen, associated with an inflammatory lesion in cardiac blood vessels of one GHFF. Positive samples were sequenced and the complete genome was obtained from three samples. When compared to published HeV genomes, there was 84% sequence identity at the nucleotide level. Based on phylogenetic analyses, the newly detected HeV belongs to the HeV species but occupies a distinct lineage. We have therefore designated this virus HeV genotype 2 (HeV-g2). Attempts to isolate virus from PCR positive samples have not been successful. CONCLUSIONS: A novel HeV genotype (HeV-g2) has been identified in two flying fox species submitted from three states in Australia, indicating that the level of genetic diversity for HeV is broader than first recognised. Given its high genetic relatedness to HeV, HeV-g2 is a zoonotic pathogen.
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    The genome sequence of the European golden eagle, Aquila chrysaetos chrysaetos Linnaeus 1758.
    Mead, D ; Ogden, R ; Meredith, A ; Peniche, G ; Smith, M ; Corton, C ; Oliver, K ; Skelton, J ; Betteridge, E ; Doulcan, J ; Holmes, N ; Wright, V ; Loose, M ; Quail, MA ; McCarthy, SA ; Howe, K ; Chow, W ; Torrance, J ; Collins, J ; Challis, R ; Durbin, R ; Blaxter, M (F1000 Research Ltd, 2021)
    We present a genome assembly from an individual female Aquila chrysaetos chrysaetos (the European golden eagle; Chordata; Aves; Accipitridae). The genome sequence is 1.23 gigabases in span. The majority of the assembly is scaffolded into 28 chromosomal pseudomolecules, including the W and Z sex chromosomes.
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    Tetrathiomolybdate Treatment Attenuates Bleomycin-Induced Angiogenesis and Lung Pathology in a Sheep Model of Pulmonary Fibrosis
    Derseh, HB ; Perera, KUE ; Dewage, SNV ; Stent, A ; Koumoundouros, E ; Organ, L ; Pagel, CN ; Snibson, KJ (FRONTIERS MEDIA SA, 2021-10-22)
    Idiopathic pulmonary fibrosis (IPF) is a progressive chronic lung disease characterized by excessive extracellular matrix (ECM) deposition in the parenchyma of the lung. Accompanying the fibrotic remodeling, dysregulated angiogenesis has been observed and implicated in the development and progression of pulmonary fibrosis. Copper is known to be required for key processes involved in fibrosis and angiogenesis. We therefore hypothesized that lowering bioavailable serum copper with tetrathiomolybdate could be of therapeutic value for treating pulmonary fibrosis. This study aimed to investigate the effect of tetrathiomolybdate on angiogenesis and fibrosis induced in sheep lung segments infused with bleomycin. Twenty sheep received two fortnightly infusions of either bleomycin (3U), or saline (control) into two spatially separate lung segments. A week after the final bleomycin/saline infusions, sheep were randomly assigned into two groups (n = 10 per group) and received twice-weekly intravenous administrations of either 50 mg tetrathiomolybdate, or sterile saline (vehicle control), for 6 weeks. Vascular density, expressed as the percentage of capillary area to the total area of parenchyma, was determined in lung tissue sections immuno-stained with antibodies against CD34 and collagen type IV. The degree of fibrosis was assessed by histopathology scoring of H&E stained sections and collagen content using Masson's trichrome staining. Lung compliance was measured via a wedged bronchoscope procedure prior to and 7 weeks following final bleomycin infusion. In this large animal model, we show that copper lowering by tetrathiomolybdate chelation attenuates both bleomycin-induced angiogenesis and pulmonary fibrosis. Moreover, tetrathiomolybdate treatment downregulates vascular endothelial growth factor (VEGF) expression, and improved lung function in bleomycin-induced pulmonary fibrosis. Tetrathiomolybdate also suppressed the accumulation of inflammatory cells in bronchoalveolar lavage fluid 2 weeks after bleomycin injury. The molecular mechanism(s) underpinning copper modulation of fibrotic pathways is an important area for future investigation, and it represents a potential therapeutic target for pulmonary fibrosis.
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    One Health in Indigenous Communities: A Critical Review of the Evidence
    Riley, T ; Anderson, NE ; Lovett, R ; Meredith, A ; Cumming, B ; Thandrayen, J (MDPI, 2021-11-01)
    Indigenous populations around the world face disproportionately high rates of disease related to the environment and animals. One Health is a concept that has been used effectively to understand and address these health risks. One Health refers to the relationships and interdependencies between animal, human, and environmental health and is an emerging research field that aligns with indigenous views of health. To understand the applicability of One Health in indigenous communities, a critical review was undertaken to investigate evidence of One Health research in indigenous communities internationally, assess the strength of evidence, and understand what gaps are present. This review included the appraisal of twenty-four studies based in five regions: Canada, Africa, Australia, South America, and Central America. The review found that there is a need for studies of high strength, with rigorous methods, local leadership, and active involvement of indigenous viewpoints, to be undertaken in indigenous communities internationally that focus on One Health. It highlights the need to further consider indigenous viewpoints in research to reduce limitations, increase effectiveness of findings, consider appropriateness of recommendations, and benefit communities.
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    Evaluation of microRNA expression in a sheep model for lung fibrosis
    Perera, UE ; Derseh, HB ; Dewage, SN ; Stent, A ; Wijayarathna, R ; Snibson, KJ (BMC, 2021-11-17)
    BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibroproliferative disorder that has one of the poorest prognoses amongst interstitial lung diseases. Recently, the finding of aberrant expression levels of miRNAs in IPF patients has drawn significant attention to the involvement of these molecules in the pathogenesis of this disease. Clarification of the differential expression of miRNAs in health and disease may identify novel therapeutic strategies that can be employed in the future to combat IPF. This study evaluates the miRNA expression profiles in a sheep model for lung fibrosis and compares them to the miRNA profiles of both IPF patients and the mouse bleomycin model for pulmonary fibrosis. Pathway enrichment analyses were performed on differentially expressed miRNAs to illustrate which biological mechanisms were associated with lung fibrosis. RESULTS: We discovered 49 differentially expressed miRNAs in the sheep fibrosis model, in which 32 miRNAs were significantly down regulated, while 17 miRNAs were significantly upregulated due to bleomycin-induced lung injury. Moreover, the miRNA families miR-29, miR-26, miR-30, let-7, miR-21, miR-19, miR-17 and miR-199 were aberrantly expressed in both sheep and mouse models, with similar differential miRNAs expression observed in IPF cases. Importantly, 18 miRNAs were aberrantly expressed in both the sheep model and IPF patients, but not in mice. CONCLUSION: Together with pathway enrichment analyses, these results show that the sheep model can potentially be used to characterize previously unrecognized biological pathways associated with lung fibrosis.
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    The efficacy and safety of pinocembrin in a sheep model of bleomycin-induced pulmonary fibrosis
    Derseh, HB ; Goodger, JQD ; Scheerlinck, J-PY ; Samuel, CS ; Woodrow, IE ; Palombo, EA ; Cumming, A ; Snibson, K ; Freeman, CM (PUBLIC LIBRARY SCIENCE, 2021-12-02)
    The primary flavonoid, pinocembrin, is thought to have a variety of medical uses which relate to its reported anti-oxidant, anti-inflammatory, anti-microbial and anti-cancer properties. Some studies have reported that this flavonoid has anti-fibrotic activities. In this study, we investigated whether pinocembrin would impede fibrosis, dampen inflammation and improve lung function in a large animal model of pulmonary fibrosis. Fibrosis was induced in two localized lung segments in each of the 10 sheep participating in the study. This was achieved via two infusions of bleomycin delivered bronchoscopically at a two-week interval. Another lung segment in the same sheep was left untreated, and was used as a healthy control. The animals were kept for a little over 5 weeks after the final infusion of bleomycin. Pinocembrin, isolated from Eucalyptus leaves, was administered to one of the two bleomycin damaged lung segments at a dose of 7 mg. This dose was given once-weekly over 4-weeks, starting one week after the final bleomycin infusion. Lung compliance (as a measure of stiffness) was significantly improved after four weekly administrations of pinocembrin to bleomycin-damaged lung segments. There were significantly lower numbers of neutrophils and inflammatory cells in the bronchoalveolar lavage of bleomycin-infused lung segments that were treated with pinocembrin. Compared to bleomycin damaged lung segments without drug treatment, pinocembrin administration was associated with significantly lower numbers of immuno-positive CD8+ and CD4+ T cells in the lung parenchyma. Histopathology scoring data showed that pinocembrin treatment was associated with significant improvement in inflammation and overall pathology scores. Hydroxy proline analysis showed that the administration of pinocembrin did not reduce the increased collagen content that was induced by bleomycin in this model. Analyses of Masson's Trichrome stained sections showed that pinocembrin treatment significantly reduced the connective tissue content in lung segments exposed to bleomycin when compared to bleomycin-infused lungs that did not receive pinocembrin. The striking anti-inflammatory and modest anti-fibrotic remodelling effects of pinocembrin administration were likely linked to the compound's ability to improve lung pathology and functional compliance in this animal model of pulmonary fibrosis.
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    Mathematical modeling and simulation in animal health. Part III: Using nonlinear mixed-effects to characterize and quantify variability in drug pharmacokinetics
    Bon, C ; Toutain, PL ; Concordet, D ; Gehring, R ; Martin-Jimenez, T ; Smith, J ; Pelligand, L ; Martinez, M ; Whittem, T ; Riviere, JE ; Mochel, JP (WILEY, 2018-04-01)
    A common feature of human and veterinary pharmacokinetics is the importance of identifying and quantifying the key determinants of between-patient variability in drug disposition and effects. Some of these attributes are already well known to the field of human pharmacology such as bodyweight, age, or sex, while others are more specific to veterinary medicine, such as species, breed, and social behavior. Identification of these attributes has the potential to allow a better and more tailored use of therapeutic drugs both in companion and food-producing animals. Nonlinear mixed effects (NLME) have been purposely designed to characterize the sources of variability in drug disposition and response. The NLME approach can be used to explore the impact of population-associated variables on the relationship between drug administration, systemic exposure, and the levels of drug residues in tissues. The latter, while different from the method used by the US Food and Drug Administration for setting official withdrawal times (WT) can also be beneficial for estimating WT of approved animal drug products when used in an extralabel manner. Finally, NLME can also prove useful to optimize dosing schedules, or to analyze sparse data collected in situations where intensive blood collection is technically challenging, as in small animal species presenting limited blood volume such as poultry and fish.
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    Effect of distal ulnar ostectomy on carpal joint stability during weight bearing in the dog
    Amsellem, PM ; Young, AN ; Muirhead, TL ; Pack, L ; Moak, P ; Matthews, AR ; Marcellin-Little, DJ (WILEY, 2017-11-01)
    OBJECTIVE: To assess the influence of a 50% distal ulnectomy on mediolateral carpal stability in the dog. STUDY DESIGN: Canine cadaveric study. SAMPLE POPULATION: Seven canine thoracic limbs METHODS: Thoracic limbs were placed in a jig to mimic weight bearing with a load representing 30% of body weight. Carpal extension angle was standardized at 190° ± 5°. Frontal plane carpal angles were measured with the limb loaded on craniocaudal radiographs before and after ulnectomy. Valgus and varus stress radiographs with the limb loaded were acquired before and after ulnectomy. The limbs were palpated and were subjectively graded for valgus or varus instability by 2 investigators before and after ulnectomy. RESULTS: Mean (±SD) valgus angulation increased after ulnectomy (2.1° ± 1.7°; P = .017; CI95  = 0.5°-3.7°) when the limb was loaded without valgus or varus stress applied. Mean valgus angulation increased after ulnectomy (2.7° ± 2.8°; P = .032; CI95  = -0.2°-5.5°) when valgus stress was applied to the loaded limb. Varus angulation was unchanged after ulnectomy (0.6° ± 4.6°; P = .383; CI95  = -4.2°-5.3°) when varus stress was applied to the loaded limb. Palpation detected increased valgus score after ulnectomy. CONCLUSION: Distal ulnectomy with excision of the lateral styloid process induces a slight increase in valgus in canine cadaver carpi. The clinical consequences of that valgus on carpal function and health should be assessed in clinical patients.