Veterinary Biosciences - Research Publications
Permanent URI for this collection
Search Results
1 - 10 of 32
-
ItemNo Preview AvailableEvidence for dopamine production and distribution of dopamine D2 receptors in the equine gastrointestinal mucosa and pancreas(PUBLIC LIBRARY SCIENCE, 2024-02-27)Insulin dysregulation in horses is characterised by hyperinsulinaemia and/or tissue insulin resistance and is associated with increased risk of laminitis. There is growing evidence in other species that dopamine attenuates insulin release from the pancreas; however, this has yet to be examined in horses. The present study aimed to identify whether there are cells capable of producing or responding to dopamine within the equine gastrointestinal mucosa and pancreas. Tissue samples were collected from the stomach, small and large intestines, and pancreas of six mature horses following euthanasia. Samples of stomach contents and faeces were also collected. Immunohistochemistry was performed to identify tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine production, and dopamine D2 receptors in tissue sections. Additional immunostaining for glucagon, insulin and chromogranin A was performed to identify α cells, β cells and enteroendocrine cells, respectively. Gastric parietal cells expressed both TH and D2 receptors, indicating that they are capable of both producing and responding to dopamine. Dopamine was quantified in stomach contents and faeces by high-performance liquid chromatography with electrochemical detection, with similar concentrations found at both sites. Dopamine D2 receptors were expressed in duodenal epithelial cells but not more distally. A subset of enteroendocrine cells, located sporadically along the gastrointestinal tract, were found to be immunopositive for the D2 receptor. In pancreatic islets, TH was present in α cells, while D2 receptors were strongly expressed in β cells and variably expressed in α cells. These findings are consistent with studies of other species; however, dynamic studies are required to further elucidate the role of dopamine in the modulation of insulin and glucagon secretion in horses. This descriptive study provides preliminary evidence for a potential role of dopamine to act as a paracrine messenger in the gastrointestinal mucosa and endocrine pancreas of horses.
-
ItemNo Preview AvailableDevelopment of a body condition index to estimate adiposity in ponies and horses from morphometric measurements(WILEY, 2024-03)BACKGROUND: There is a high prevalence of obesity in ponies and pleasure horses. This may be associated with equine metabolic syndrome and an increased risk of laminitis. Body condition scoring (BCS) systems are widely used but are subjective and not very sensitive. OBJECTIVES: To derive a body condition index (BCI), based on objective morphometric measurements, that correlates with % body fat. STUDY DESIGN: Retrospective cohort study. METHODS: Morphometric measurements were obtained from 21 ponies and horses in obese and moderate body condition. Percentage body fat was determined using the deuterium dilution method and the BCI was derived to give the optimal correlation with body fat, applying appropriate weightings. The index was then validated by assessing inter-observer variation and correlation with % body fat in a separate population of Welsh ponies; and finally, the correlation between BCI and BCS was evaluated in larger populations from studies undertaken in Australia, the United Kingdom and the United States. RESULTS: The BCI correlated well with adiposity in the ponies and horses, giving a Pearson r value of 0.74 (P < 0.001); however, it was found to slightly overestimate the % body fat in leaner animals and underestimate in more obese animals. In field studies, the correlation between BCI and BCS varied particularly in Shetlands and miniature ponies, presumably due to differences in body shape. MAIN LIMITATIONS: Further work may be required to adapt the BCI to a method that is more applicable for Shetlands and miniature ponies. CONCLUSIONS: This BCI was able to provide an index of adiposity which compared favourably with condition scoring in terms of accuracy of estimating adiposity; and was more consistent and repeatable when used by inexperienced assessors. Therefore, this may be a useful tool for assessing adiposity; and may be more sensitive than condition scoring for tracking weight gain or weight loss in individual animals.
-
ItemIdentifying possible thresholds for nonstructural carbohydrates in the insulin dysregulated horse(WILEY, 2023-11)BACKGROUND: Identifying intake levels of nonstructural carbohydrates (NSCs) that limit the postprandial insulinaemic response in the insulin dysregulated (ID) horse may help reduce hyperinsulinaemia-associated laminitis (HAL) risk. OBJECTIVE: To determine if ID horses have thresholds for pure sources of starch and sugar, above which there is an augmented insulin response. STUDY DESIGN: Randomised crossover experiment. METHODS: Fourteen adult horses (6 ID and 8 noninsulin dysregulated, NID; matched for bodyweight) were randomly fed eight dietary treatments. Dietary treatments were formulated using a base of low-nonstructural carbohydrate pellet (LNSC; 0.04 g of water-soluble carbohydrates (WSCs)/kg bwt and 0.01 g of starch/kg bwt), to which pure sugar (dextrose) or starch (50:50 mix of waxy-maize and oat starch powder) sources were titrated to create diets with increasing amounts of either WSC (0.06-0.17 g WSC/kg bwt), or starch (0.03-0.1 g starch/kg bwt). Horses were fed each dietary treatment at a rate of 1 g/kg bwt once over 12 weeks. Serial blood samples were collected pre- and up to 240 min postprandially. Insulin was determined via RIA and diet analytes were determined via wet chemistry. Statistical analysis was performed with a mixed effect model. Positive incremental area under the curve for insulin (IAUCi) was calculated for all horses and dietary treatments. RESULTS: There was no significant effect of diet in NID horses but diets with NSC >0.1 g/kg bwt produced an augmented response in ID horses compared with the LNSC (p < 0.05). ID horses IAUCi were also significantly different to all NID IAUCi for diets with NSC >0.1 g/kg (p < 0.04). Apparent thresholds for sugar and starch addition varied. CONCLUSIONS: Based on this study, using supplemental pure starch and sugar sources, ID horses seem to have an apparent threshold for NSC of around 0.1 g/kg bwt/meal, above which significantly increased insulin responses are seen compared with NID horses.
-
ItemA nationwide evaluation of bevacizumab-based treatments in pediatric low-grade glioma in the UK: safety, efficacy, visual morbidity, and outcomes(OXFORD UNIV PRESS INC, 2023-04-06)BACKGROUND: Bevacizumab is increasingly used in children with pediatric low-grade glioma (PLGG) despite limited evidence. A nationwide UK service evaluation was conducted to provide larger cohort "real life" safety and efficacy data including functional visual outcomes. METHODS: Children receiving bevacizumab-based treatments (BBT) for PLGG (2009-2020) from 11 centers were included. Standardized neuro-radiological (RANO-LGG) and visual (logMAR visual acuity) criteria were used to assess clinical-radiological correlation, survival outcomes and multivariate prognostic analysis. RESULTS: Eighty-eight children with PLGG received BBT either as 3rd line with irinotecan (85%) or alongside 1st/2nd line chemotherapies (15%). Toxicity was limited and minimal. Partial response (PR, 40%), stable disease (SD, 49%), and progressive disease (PD, 11%) were seen during BBT. However, 65% progressed at 8 months (median) from BBT cessation, leading to a radiology-based 3 yr-progression-free survival (PFS) of 29%. Diencephalic syndrome (P = .03) was associated with adverse PFS. Pre-existing visual morbidity included unilateral (25%) or bilateral (11%) blindness. Improvement (29%) or stabilization (49%) of visual acuity was achieved, more often in patients' best eyes. Vision deteriorated during BBT in 14 (22%), with 3-year visual-PFS of 53%; more often in patients' worst eyes. A superior visual outcome (P = .023) was seen in neurofibromatosis type 1-associated optic pathway glioma (OPG). Concordance between visual and radiological responses was 36%; optimized to 48% using only best eye responses. CONCLUSIONS: BBTs provide effective short-term PLGG control and delay further progression, with a better sustained visual (best > worst eye) than radiological response. Further research could optimize the role of BBT toward a potentially sight-saving strategy in OPG.
-
ItemNo Preview AvailableAssociations Between Systemic and Cerebral Inflammation in an Ovine Model of Cardiopulmonary Bypass(LIPPINCOTT WILLIAMS & WILKINS, 2023-04)BACKGROUND: Intraoperative inflammation may contribute to postoperative neurocognitive disorders after cardiac surgery requiring cardiopulmonary bypass (CPB). However, the relative contributions of general anesthesia (GA), surgical site injury, and CPB are unclear. METHODS: In adult female sheep, we investigated (1) the temporal profile of proinflammatory and anti-inflammatory cytokines and (2) the extent of microglia activation across major cerebral cortical regions during GA and surgical trauma with and without CPB (N = 5/group). Sheep were studied while conscious, during GA and surgical trauma, with and without CPB. RESULTS: Plasma tumor necrosis factor-alpha (mean [95% confidence intervals], 3.7 [2.5-4.9] vs 1.6 [0.8-2.3] ng/mL; P = .0004) and interleukin-6 levels (4.4 [3.0-5.8] vs 1.6 [0.8-2.3] ng/mL; P = .029) were significantly higher at 1.5 hours, with a further increase in interleukin-6 at 3 hours (7.0 [3.7-10.3] vs 1.8 [1.1-2.6] ng/mL; P < .0001) in animals undergoing CPB compared with those that did not. Although cerebral oxygen saturation was preserved throughout CPB, there was pronounced neuroinflammation as characterized by greater microglia circularity within the frontal cortex of sheep that underwent CPB compared with those that did not (0.34 [0.32-0.37] vs 0.30 [0.29-0.32]; P = .029). Moreover, microglia had fewer branches within the parietal (7.7 [6.5-8.9] vs 10.9 [9.4-12.5]; P = .001) and temporal (7.8 [7.2-8.3] vs 9.9 [8.2-11.7]; P = .020) cortices in sheep that underwent CPB compared with those that did not. CONCLUSIONS: CPB enhanced the release of proinflammatory cytokines beyond that initiated by GA and surgical trauma. This systemic inflammation was associated with microglial activation across 3 major cerebral cortical regions, with a phagocytic microglia phenotype within the frontal cortex, and an inflammatory microglia phenotype within the parietal and temporal cortices. These data provide direct histopathological evidence of CPB-induced neuroinflammation in a large animal model and provide further mechanistic data on how CPB-induced cerebral inflammation might drive postoperative neurocognitive disorders in humans.
-
ItemComparison of Feed Digestibility between Ponies, Standardbreds and Andalusian Horses Fed Three Different Diets(MDPI, 2022-01)Ponies and some horse breeds such as Andalusians exhibit an 'easy keeper' phenotype and tend to become obese more readily than other breeds such as Standardbreds. Various hypotheses have been proposed, including differences in appetite or metabolic efficiency. This study aimed to investigate the effect of breed on nutrient digestibility. Ponies, Standardbreds and Andalusian horses were adapted to consuming either a control fibre-based diet (n = 9), a hypercaloric cereal-rich diet (n = 12) or a hypercaloric fat-rich diet (n = 12) over 20 weeks. Total faecal collection was performed over 24 h to determine apparent total tract digestibility of gross energy, dry matter (DM), neutral detergent fibre (NDF), starch, crude protein and crude fat. There was no effect of breed on apparent digestibility for any of the nutrients studied (all p > 0.05). However, there was a significant effect of diet, with animals consuming the cereal-rich or fat-rich diets demonstrating higher digestibility of gross energy, DM, NDF and crude protein compared with those consuming the control diet (all p < 0.05). Animals adapted to the cereal-rich diet demonstrated higher digestibility of starch (p < 0.001) and animals adapted to the fat-rich diet demonstrated higher digestibility of fat (p < 0.001). This study found that horses and ponies had similar nutrient digestibility when adapted to the same diets and management conditions. Limitations included the relatively small number of animals from each breed per diet group and the short period of total faecal collection. The tendency towards increased adiposity in ponies and Andalusian-type horse breeds is more likely to reflect differences in metabolism, rather than differences in feed digestibility.
-
ItemEffects of polymyxin-B on TNF-α production in equine whole blood stimulated with three different bacterial toxins(WILEY, 2018-02)Polymyxin-B is used to treat equine systemic inflammation. Bacterial toxins other than lipopolysaccharide (LPS) contribute to systemic inflammation but the effects of polymyxin-B on these are poorly defined. Whole blood aliquots from six healthy horses diluted 1:1 with RPMI were incubated for 21 hr with 1 μg/ml of LPS, lipoteichoic acid (LTA) or peptidoglycan (PGN) in the presence of increasing concentrations of polymyxin-B (10-3000 μg/ml). A murine L929 fibroblast bioassay was used to measure TNF-α activity. Polymyxin-B significantly inhibited the effects of all three bacterial toxins. Analysis of variance showed the IC50 value for polymyxin-B for TNF-α inhibition caused by LTA (11.19 ± 2.89 μg/ml polymyxin-B) was significantly lower (p = .009) than the values for LPS (46.48 ± 9.93 μg/ml) and PGN (54.44 ± 8.97 μg/ml). There was no significant difference in IC50 values between LPS and PGN (p > .05). Maximum inhibition of TNF-α was 77.4%, 73.0% and 82.7% for LPS, PGN and LTA, respectively and was not significantly different between toxins. At the two highest concentrations of polymyxin-B, TNF-α began to increase. These data suggest that polymyxin-B may inhibit the effects of bacterial toxins other than LPS and might be a more potent inhibitor of LTA than LPS or PGN.
-
Item
-
ItemAn immuno polymerase chain reaction screen for the detection of CJC-1295 and other growth-hormone-releasing hormone analogs in equine plasma(WILEY, 2019-06)CJC-1295 is a 30 amino acid peptide-based drug that stimulates the release of growth hormone (GH) from the pituitary gland. It is unique among performance-enhancing peptides due to the presence of a reactive maleimidopropionic acid group that covalently links the peptide to free thiols on the surface of plasma proteins. Once conjugated, CJC-1295 remains active in the bloodstream for significantly longer than non-conjugated peptide-based drugs that are rapidly excreted. Conjugation of CJC-1295 to plasma proteins prevents its detection by top-down mass-spectrometry-based peptide screening protocols as it effectively becomes a macromolecular protein with an undefined molecular weight. Using a pair of monoclonal antibodies raised against the CJC-1295 peptide, we present an immuno-polymerase chain reaction (I-PCR) assay that is capable of detecting the CJC-1295-protein conjugate at concentrations down to 0.8 pg/mL. Detection of endogenous equine GHRH necessitated a screening threshold for CJC-1295 in equine plasma of 50 pg/mL. The effectiveness of the assay for controlling the illicit use of CJC-1295 was confirmed in equine blood samples after administration in thoroughbred race horses.
-
ItemEquine pituitary pars intermedia dysfunction: current understanding and recommendations from the Australian and New Zealand Equine Endocrine Group(WILEY, 2018-07)The purpose of this article is to provide a review of the current knowledge and opinions about the epidemiology, clinical findings (including sequelae), diagnosis, treatment and monitoring of equine pituitary pars intermedia dysfunction, particularly in the Australian context. This information and the recommendations provided will assist practitioners in making informed decisions regarding the diagnosis and management of this disorder.