Melbourne Veterinary School - Research Publications
Now showing items 1-12 of 166
Fibroblastic Subtype has a Favourable Prognosis in Appendicular Osteosarcoma of Dogs
(ELSEVIER SCI LTD, 2020-04-01)
Osteosarcoma (OS) is an aggressive malignant bone neoplasm that occurs mostly in the appendicular skeleton of dogs and people. OS is classified based on the presence of malignant stroma and the formation of extracellular matrix into osteoblastic, chondroblastic and fibroblastic forms. This study investigated the correlation between the three histological subtypes of canine OS and clinical outcome. Additionally, we examined whether there was any difference in the immunolabelling of desmin, S100 and neuron-specific enolase (NSE) between the three histological subtypes. Formalin-fixed and paraffin wax-embedded tissues from 87 dogs with primary OS were available for this study. The survival times were correlated with appendicular OS subtypes in dogs that were treated surgically, received adjuvant chemotherapy and had no pulmonary metastasis at the time of diagnosis. Dogs with an appendicular fibroblastic OS had significantly prolonged mean average survival times (546 ± 105 days) in comparison with dogs having appendicular osteoblastic (257 ± 48 days) or appendicular chondroblastic (170 ± 28 days) OS (P = 0.003, Log Rank). The results also revealed that the appendicular chondroblastic subtype is a significant indicator for poor prognosis in dogs compared with the fibroblastic or osteoblastic subtypes (P = 0.006, Cox regression). Moreover, the findings indicated that there was no significant correlation between the localization of desmin, NSE or S100 and histological subtypes. Importantly, dogs with appendicular fibroblastic OS were found to have a better prognosis when compared with dogs with other subtypes. This may suggest that histological subtypes of appendicular OS have diverse behaviour and could be used to categorize patients for risk-based assessment.
Examination of Novel Immunomodulatory Effects of L-Sulforaphane
The dietary isothiocyanate L-sulforaphane (LSF), derived from cruciferous vegetables, is reported to have several beneficial biological properties, including anti-inflammatory and immunomodulatory effects. However, there is limited data on how LSF modulates these effects in human immune cells. The present study was designed to investigate the immunomodulatory effects of LSF (10 µM and 50 µM) on peripheral blood mononuclear cell (PBMC) populations and cytokine secretion in healthy adult volunteers (n = 14), in the presence or absence of bacterial (lipopolysaccharide) and viral (imiquimod) toll-like receptor (TLRs) stimulations. Here, we found that LSF reduced pro-inflammatory cytokines interleukin (IL)-6, IL-1β, and chemokines monocyte chemoattractant protein (MCP)-1 irrespective of TLR stimulations. This result was associated with LSF significantly reducing the proportion of natural killer (NK) cells and monocytes while increasing the proportions of dendritic cells (DCs), T cells and B cells. We found a novel effect of LSF in relation to reducing cluster of differentiation (CD) 14+ monocytes while simultaneously increasing monocyte-derived DCs (moDCs: lineage-Human Leukocyte Antigen-DR isotype (HLA-DR)+CD11blow-high CD11chigh). LSF was also shown to induce a 3.9-fold increase in the antioxidant response element (ARE) activity in a human monocyte cell line (THP-1). Our results provide important insights into the immunomodulatory effects of LSF, showing in human PBMCs an ability to drive differentiation of monocytes towards an immature monocyte-derived dendritic cell phenotype with potentially important biological functions. These findings provide insights into the potential role of LSF as a novel immunomodulatory drug candidate and supports the need for further preclinical and phase I clinical studies.
Resveratrol Promotes Hypertrophy in Wildtype Skeletal Muscle and Reduces Muscle Necrosis and Gene Expression of Inflammatory Markers in Mdx Mice
Duchenne muscular dystrophy (DMD) is a progressive fatal neuromuscular disorder with no cure. Therapies to restore dystrophin deficiency have been approved in some jurisdictions but long-term effectiveness is yet to be established. There is a need to develop alternative strategies to treat DMD. Resveratrol is a nutraceutical with anti-inflammatory properties. Previous studies have shown high doses (100-400 mg/kg bodyweight/day) benefit mdx mice. We treated 4-week-old mdx and wildtype mice with a lower dose of resveratrol (5 mg/kg bodyweight/day) for 15 weeks. Voluntary exercise was used to test if a lower dosage than previously tested could reduce exercise-induced damage where a greater inflammatory infiltrate is present. We found resveratrol promoted skeletal muscle hypertrophy in wildtype mice. In dystrophic muscle, resveratrol reduced exercise-induced muscle necrosis. Gene expression of immune cell markers, CD86 and CD163 were reduced; however, signalling targets associated with resveratrol's mechanism of action including Sirt1 and NF-κB were unchanged. In conclusion, a lower dose of resveratrol compared to the dosage used by other studies reduced necrosis and gene expression of inflammatory cell markers in dystrophic muscle suggesting it as a therapeutic candidate for treating DMD.
The Effect of Pet Insurance on Presurgical Euthanasia of Dogs With Gastric Dilatation-Volvulus: A Novel Approach to Quantifying Economic Euthanasia in Veterinary Emergency Medicine
(FRONTIERS MEDIA SA, 2020-12-08)
Euthanasia of companion animals in veterinary emergency medicine is a common cause of death. Euthanasia is economic when it is the consequence of the pet owner's inability to afford essential treatment while a viable medical alternative to euthanasia exists. Gastric dilatation-volvulus (GDV) is an acute life-threatening emergency condition of dogs; if left untreated, rapid death is highly likely. Surgical treatment leads to survival of around 80-90% of dogs; however, such treatment is costly. Therefore, pre-surgical euthanasia may be largely economically motivated. Having pet insurance, a financial instrument to reduce the burden of unforeseen veterinary medical costs on pet owners, would be expected to abolish the risk for pre-surgical economic euthanasia. We therefore aimed to determine whether pet insurance attenuates the risk of pre-surgical economic euthanasia in dogs with GDV. Non-referred dogs (n = 260) with GDV and known insurance status seen at 24 emergency clinics over a 2-year period were included. Relevant data (e.g., insurance status, age, comorbidities, outcome) were retrospectively extracted from a pet insurer's claim records (insured animals) or from electronic medical records of participating hospitals (non-insured animals). Forty-one percent of dogs (106 of 260 dogs) did not survive to hospital discharge; 82 (77%) of non-survivors died before surgery, all through euthanasia. The pre-surgical euthanasia rate was 10% in insured and 37% in non-insured dogs (p < 0.001). When adjusted for the effect of age, deposit size, comorbidities, and blood lactate concentration, the absence of insurance increased the odds of pre-surgical euthanasia by a factor of 7.4 (95% CI 2.0 to 37; p = 0.002). Of dogs undergoing surgery, 86% survived to hospital discharge. Overall, 80% of insured animals and 53% of non-insured animals survived to hospital discharge (p < 0.001). Thus, insurance was associated with a marked decrease in risk of pre-surgical euthanasia indicating that the cause of pre-surgical euthanasia of dogs with GDV is predominantly economic in nature. The rate of pre-surgical euthanasia in dogs with GDV may emerge as a suitable marker to quantify economic decision making of pet owners and to measure the impact of financial interventions aimed at mitigating economic duress associated with cost of veterinary emergency care.
SYSTEMIC INFECTION DUE TO CANDIDA PARAPSILOSIS IN A DOMESTIC FERRET (MUSTELA PUTORILIS FURO)
(ELSEVIER SCIENCE INC, 2014-01-01)
An 18-month-old castrated male ferret (Mustela putorius furo) was presented to the veterinary hospital for acute collapse but died despite initiation of emergency treatment. The body was submitted for a complete postmortem examination. The pathologist determined the ferret was suffering from severe necrotizing encephalitis, necrogranulomatous mediastinal lymphadenitis, and ulcerative dermatitis attributable to systemic Candida parapsilosis. This is the first report of systemic Candida parapsilosis in a ferret.
A survey of northern Victorian dairy farmers to investigate dairy calf management: colostrum feeding and management
OBJECTIVES: To describe colostrum management practices carried out in northern Victorian dairy herds and to identify weaknesses in these areas that may affect calf health and welfare by comparing the results with the current industry recommendations METHODS: A questionnaire to obtain information about colostrum management and calf-rearing practices was sent to commercial dairy farming clients of Rochester Veterinary Practice between June and September 2013. The questionnaire consisted of a general herd overview and colostrum harvesting practices. RESULTS: The response rate was 39% (58/150). Many dairy producers were not meeting the current industry recommendations in the following areas: (1) time of removal calf from the dam, (2) relying on calf suckling colostrum from the dam to achieve adequate passive transfer, (3) failing to supplement calves with colostrum, (4) feeding inadequate volumes of colostrum, (5) delayed colostrum harvesting, (6) pooling of colostrum, (7) failing to objectively assess colostrum quality or relying on visual assessment and (8) storing colostrum for a prolonged periods of time at ambient temperatures. CONCLUSION: The results from this survey highlight the need for greater awareness of industry standards for colostrum management and feeding hygiene.
Tumour cells surviving in vivo cisplatin chemotherapy display elevated c-myc expression
(NATURE PUBLISHING GROUP, 1996-03-01)
The c-myc oncogene has been extensively implicated in cell proliferation, cell differentiation and programmed cell death. Aberrant expression of the c-myc gene product has been observed in a range of tumours and has also been implicated in cisplatin (cis-dichlorodiammineplatinum)-mediated chemoresistance. A solid transplantable tumour model in syngeneic DA rats was subjected to treatment with cisplatin to determine the impact of such therapy on endogenous c-myc gene expression. Serially transplanted tumours were intravenously treated with a single cisplatin dose (1 mg/kg) and c-myc expression analysed 2 and 7 days after treatment. The surviving tumour cells display a significant 2-fold elevation in c-myc expression at 48 h and 7 days after treatment. Primary cell cultures have been derived from untreated in vivo tumours of the same model and subjected to treatment with a c-myc phosphorothioate antisense oligomer. Administration of 5 microM c-myc antisense oligomer directed at the initiation codon and first four codons of c-myc mRNA results in total inhibition of c-myc expression and coincident suspension of cell growth for a period of 4 days in culture. Antisense therapies directed at the c-myc gene may well prove an effective tool for treating tumours in conjunction with cisplatin as these findings show that tumour cells surviving cisplatin chemotherapy display elevated c-myc expression.
ASPECTS OF THE DIAGNOSIS, PATHOGENESIS AND EPIDEMIOLOGY OF CANINE PARVOVIRUS
(AUSTRALIAN VETERINARY ASSN, 1983-01-01)
Between 18 July 1980 and 2 January 1981, 188 samples (145 faeces and 43 intestinal contents) were submitted from dogs with suspected canine parvovirus (CPV) enteritis. CPV was demonstrated in 56 (30%) of these samples; the weekly rate of positive CPV identification was remarkably constant at approximately 30% even though clinical and often post-mortem findings strongly supported a diagnosis of CPV enteritis. The simplest, most sensitive and most rapid method for detection of virus was haemagglutination (HA) which was twice as sensitive as isolation of virus and 8 times as sensitive as electron microscopy (EM). Forty nine of 56 (88%) samples positive for CPV were from dogs less than 1 year old and 44 (79%) CPV-positive samples were from pups less than 6 months old; only one sample from a pup less than 2 months old (pup was 7 weeks old) was positive. An additional 68 samples (53 faeces and 15 intestinal contents) were submitted from Beagle dogs that were part of a colony of approximately 1200 dogs. Epidemiological data pinpoints the entry of CPV into the colony in November 1978 at which time most dogs including pups less than 6 months of age developed antibody to CPV without developing clinical disease. From these data an overview of some aspects of the pathogenesis and epidemiology of CPV is constructed.
VIRUSES AND VIRUS-LIKE PARTICLES IN THE FECES OF DOGS WITH AND WITHOUT DIARRHEA
(AUSTRALIAN VETERINARY ASSN, 1984-01-01)
Negative staining electron microscopy was used to identify viruses in 157 normal and 29 diarrhoeal faecal samples collected from 156 dogs admitted to an animal shelter during an 8 month period (March to October) in 1982. Seven distinct viral types were detected: 21-26 nm parvovirus-like particles, 28-31 nm astrovirus-like particles, a previously undescribed 34-35 nm "round" virus particle, coronavirus, coronavirus-like particles ( CVLP ), rotavirus and papova-like virus. Parvovirus-like particles alone were detected in 14 diarrhoeal and 50 normal faeces, astrovirus-like particles in 3 normal faeces, "round" viruses in 4 normal faeces, coronavirus in 2 diarrhoeal and 5 normal faeces, CVLP in one diarrhoeal and one normal faeces, rotavirus in 2 normal faeces, papova-like virus in one normal faeces, both parvovirus-like particles and coronavirus in 2 diarrhoeal and 2 normal faeces, parvovirus-like particles and rotavirus in one normal faeces and parvovirus-like and papova-like virus in one normal faeces. The significance of these findings in canine and human disease is discussed.
VIRUS AND VIRUS-LIKE PARTICLES IN THE FECES OF CATS WITH AND WITHOUT DIARRHEA
Negative staining electron microscopy was used to identify viruses in 166 normal and 62 diarrhoeal faecal samples from 208 cats admitted to an animal shelter during a 16-month period (March 1984 to June 1985). On the basis of size and shape 7 distinct viral types were detected: 24 nm parvovirus-like particles, 30 nm astrovirus, 30 nm picornavirus-like particles, reovirus, rotavirus, coronavirus and a 75 nm "togavirus-like" particle. The incidence of these particles in the 208 cats was 11%, 7%, 6%, 0.4%, 5%, 1% and 1% respectively. Virus isolation studies using 40 of the faecal samples succeeded in isolating reovirus 1 in 2 cases. Immune electron microscope studies demonstrated the presence of antibody in a human serum to cat astrovirus, but failed to clarify the identity of the parvovirus-like particles and picornavirus-like particles, other than showing that some of the parvovirus-like particles were not related to feline panleukopenia virus. It was found that parvovirus-like particles, astrovirus, picornavirus-like particles, reovirus and rotavirus could be excreted by cats with normal faeces as well as cats with diarrhoeal faeces. Parvovirus-like particles, astrovirus, picornavirus-like particles and rotavirus could be excreted in high concentration in normal faeces. There was no simple relationship between age and diarrhoea in the population of cats studied. Age was not a critical factor in the excretion of parvovirus-like particles, astrovirus, picornavirus-like particles and rotavirus. The incidence of diarrhoea was not clearly associated with the seasons.
Determination of angiotensin I-converting enzyme activity in equine blood: lack of agreement between methods of analysis
(KOREAN SOC VETERINARY SCIENCE, 2011-03-01)
Angiotensin-I converting enzyme (ACE) is a key regulator of blood pressure, electrolytes and fluid homeostasis through conversion of angiotensin I into angiotensin II. Recently, a genetic polymorphism of the ACE gene, which accounts for 47% of the variation of ACE activity in blood, has been advocated as a biomarker of athletic aptitude. Different methods of analysis and determination of ACE activity in plasma have been used in human and equine research without a consensus of a "gold standard" method. Different methods have often been used interchangeably or cited as being comparable in the existing literature; however, the actual agreement between assays has not been investigated. Therefore, in this study, we evaluated the level of agreement between three different assays using equine plasma obtained from 29 horses. Two spectrophotometric assays using Furylacryloylphenylalanyl-glycyl-glycine as substrate and one fluorimetric assay utilizing o-aminobenzoic acid-FRK-(Dnp)P-OH were employed. The results revealed that the measurements from the different assays were not in agreement, indicating that the methods should not be used interchangeably for measurement of equine ACE activity. Rather, a single method of analysis should be adopted to achieve comparable results and critical appraisal of the literature is needed when attempting to compare results obtained from different assays.