Melbourne Veterinary School - Research Publications
Now showing items 1-12 of 206
The genome sequence of the European golden eagle, Aquila chrysaetos chrysaetos Linnaeus 1758.
(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.
Tetrathiomolybdate Treatment Attenuates Bleomycin-Induced Angiogenesis and Lung Pathology in a Sheep Model of Pulmonary Fibrosis
(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.
One Health in Indigenous Communities: A Critical Review of the Evidence.
(MDPI AG, 2021-10-28)
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.
Evaluation of microRNA expression in a sheep model for lung fibrosis
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.
The efficacy and safety of pinocembrin in a sheep model of bleomycin-induced pulmonary fibrosis
(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.
Mathematical modeling and simulation in animal health. Part III: Using nonlinear mixed-effects to characterize and quantify variability in drug pharmacokinetics
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.
Effect of distal ulnar ostectomy on carpal joint stability during weight bearing in the dog
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.
Determination of testosterone esters in the hair of male greyhound dogs using liquid chromatography-high resolution mass spectrometry
The doping of greyhound dogs with testosterone is done in an attempt to improve their athletic performance, but such doping cannot easily be confirmed, especially in male dogs owing to the natural presence of endogenous testosterone. As testosterone is usually administered as its esters, their direct detection in hair would provide confirmatory evidence of the administration of a pharmaceutical product. This article demonstrates that the use of a liquid chromatography-high resolution mass spectrometry method with heated electrospray ionisation (HESI) combined with the use of amino solid-phase extraction (SPE) cartridges for sample clean-up, is suitable for the sensitive determination of propionate, phenyl propionate, isocaproate, decanoate, and enanthate esters of testosterone in greyhound hair. The method is linear over the range, 0.1 μg/kg-10 μg/kg, for all the testosterone esters analysed. The limits of detection (LOD) are 0.05 μg/kg for testosterone phenyl propionate, isocaproate, and decanoate, 0.025 μg/kg for testosterone propionate, and 0.25 μg/kg for testosterone enanthate. This method was applied to hair samples collected from male greyhounds before and after a single administration of a product containing several testosterone esters, each of which could be detected up to 100 days post-administration. The study also demonstrates that tail hair is the specimen of choice for the analysis of testosterone in dog hair and that washing of dogs does not impact the analysis of testosterone esters in hair. This method may be useful in racing regulation for the detection of illegitimate use of testosterone in all species.
Retrospective evaluation of cats with elapid snake envenomation associated neurotoxicity requiring mechanical ventilation: 12 cases (2005-2014)
OBJECTIVE: To retrospectively determine the population and outcome characteristics of a cohort of Australian elapid snake envenomed cats requiring mechanical ventilation (MV). DESIGN: Retrospective observational study (2005-2014). SETTING: Academic veterinary emergency and critical care service. ANIMALS: Twelve cats undergoing MV for elapid snake envenomation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The medical records were searched to identify cats requiring MV as part of treatment for elapid snake envenomation. Signalment, the indication for, duration of and complications associated with MV, duration of hospitalization, and survival to hospital discharge were recorded for each of the enrolled cases. Seven cats (58.3%) underwent MV because of presumed unsustainable respiratory effort and 5 cats (41.7%) for respiratory arrest. Eleven cats (91.7%) were successfully weaned from MV and survived to hospital discharge. No cats developed ventilator associated pneumonia or pneumothorax. The median duration of MV was 19.5 hours for the survivors (range 7.0-37.0 hours) and median duration of hospitalization was 3.5 days (range 2.4-14.9 days). CONCLUSIONS: Cats requiring MV for elapid snake envenomation have a favorable outcome and require a relatively short period of MV. Complications encountered are unlikely to influence outcome.
Chemical stability of morphine and methadone, and of methadone in combination with acepromazine, medetomidine or xylazine, during prolonged storage in syringes
OBJECTIVE: To assess the chemical and physical stability of morphine and methadone stored in syringes for 12 months and of methadone when mixed with acepromazine, medetomidine or xylazine. METHODS: A high-performance liquid chromatography (HPLC) technique was developed and validated for the analysis of morphine and methadone. Morphine and methadone were dispensed into syringes and stored at 25°C/60% relative humidity (RH) and 40°C/75% RH. Solutions containing mixtures of methadone combined with acepromazine, medetomidine or xylazine were stored in syringes at 25°C/60%RH. At initiation, after 1 week and then 1, 3, 6, 9 and 12 months, samples were analysed by HPLC for the quantification of the morphine or methadone. Measured concentrations were assessed as a function of storage time and temperature using linear regression statistics to calculate stability. RESULTS: When stored at 40°C/75%RH as pre-dispensed syringes, severe physical and chemical changes were observed after the third month for both morphine and methadone. In contrast, at 25°C/60%RH both drugs remained chemically stable for 12 months, with concentration variations not exceeding a 5% change from initiation as stipulated in VICH stability guidelines. When in combination with acepromazine or xylazine, methadone also remained chemically stable, but the combination with medetomidine failed stability criteria prior to 6 months. Precipitation compromised the physical stability of methadone in all unsealed syringes prior to 9 months' storage. CONCLUSION: Pre-dispensing morphine or methadone into unsealed syringes compromises the drugs' physical stability. Mixing of methadone with other drugs can degrade its chemical stability.
Impact of diet on faecal output and caecotroph consumption in rabbits
OBJECTIVES: To assess the impact of four rabbit diets (hay only, extruded diet with hay, muesli with hay and muesli only) on faecal pellet size, faecal output and caecotrophy. MATERIALS AND METHODS: Thirty-two Dutch rabbits were studied over 17 months. Faecal pellet size and weight were measured in weeks 3, 9, 21 and 43 and faecal output in weeks 10, 22 and 45. Number of uneaten caecotrophs was recorded weekly. RESULTS: Faecal pellets were consistently smaller and lighter in rabbits fed muesli only, and the size of pellets produced by those fed muesli with hay decreased over the course of the study. Faecal output was greatest in rabbits with the highest hay intake. Uneaten caecotrophs were found in greatest frequency in rabbits fed muesli. CLINICAL SIGNIFICANCE: Muesli diets have a negative effect on faecal output and caecotroph ingestion and may therefore predispose to digestive disorders. Higher hay intake is associated with greater faecal output and fewer uneaten caecotrophs and may assist in preventing the gastrointestinal stasis.
Evidence for marsh mallow (Malva parviflora) toxicosis causing myocardial disease and myopathy in four horses
REASON FOR PERFORMING THE STUDY: Investigation of toxicosis caused by Malva parviflora was required after 4 horses from the same farm developed severe muscle fasciculations, tachycardia, sweating and periods of recumbency leading to death or euthanasia after ingesting the plant. OBJECTIVES: To describe historical, clinical, clinicopathological and pathological findings of 4 horses with suspected M. parviflora toxicosis. The role of cyclopropene fatty acids (found in M. parviflora) and mechanism for toxicosis are proposed. STUDY DESIGN: Case series. METHODS: Historical, physical examination, clinicopathological and pathological findings are reported. Due to similarities with atypical myopathy or seasonal pasture myopathy acyl carnitine profiles were performed on sera from 2 cases and equine controls. Presence of cyclopropene fatty acids was also examined in sera of 2 cases. RESULTS: M. parviflora had been heavily grazed by the horses with little other feed available. Horse 1 deteriorated rapidly and was subjected to euthanasia. Horse 2 was referred to hospital where severe myocardial disease and generalised myopathy was determined; this horse was subjected to euthanasia 36 h after admission. Horse 3 died rapidly and Horse 4 was subjected to euthanasia at onset of clinical signs. Post-mortem examinations performed on 3 horses revealed acute, multifocal cardiac and skeletal myonecrosis. Myocyte glycogen accumulation was absent when examined in Horse 2. Acyl carnitine profiles revealed increased C14-C18 acyl carnitine concentrations in cases relative to controls. Cyclopropene fatty acids were detected in sera of cases but not controls. CONCLUSION: These findings suggest aetiology different to that of atypical myopathy or seasonal pasture myopathy. We hypothesise that cyclopropene fatty acids in M. parviflora interfere with fatty acid β-oxidation in horses in negative energy balance, causing the clinical signs and abnormal acyl carnitine profiles. These equine cases suggest a pathophysiological course that closely mimics the human genetic condition very long chain acyl CoA dehydrogenase deficiency.