Publications by authors named "Bruce C McGorum"

19 Publications

  • Page 1 of 1

Establishment of a model for equine small intestinal disease: effects of extracorporeal blood perfusion of equine ileum on metabolic variables and histological morphology - an experimental ex vivo study.

BMC Vet Res 2019 Nov 8;15(1):400. Epub 2019 Nov 8.

Department for Companion Animals and Horses, University Equine Hospital, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210, Vienna, Austria.

Background: In horses a number of small intestinal diseases is potentially life threatening. Among them are Equine Grass Sickness (EGS), which is characterised by enteric neurodegeneration of unknown aetiology, as well as reperfusion injury of ischaemic intestine (I/R), and post-operative ileus (POI), common after colic surgery. The perfusion of isolated organs is successfully used to minimize animal testing for the study of pathophysiology in other scenarios. However, extracorporeal perfusion of equine ileum sourced from horses slaughtered for meat production has not yet been described. Therefore the present study evaluated the potential of such a model for the investigation of small intestinal diseases in an ex vivo and cost-efficient system avoiding experiments in live animals.

Result: Nine ileum specimens were sourced from horses aged 1-10 years after routine slaughter at a commercial abattoir. Ileum perfusion with oxygenated autologous blood and plasma was successfully performed for 4 h in a warm isotonic bath (37.0-37.5 °C). Ileum specimens had good motility and overall pink to red mucosa throughout the experiment; blood parameters indicated good tissue vitality: 82 ± 34 mmHg mean arterial partial pressure of oxygen (pO) compared to 50 ± 17 mmHg mean venous pO 48 ± 10 mmHg mean arterial partial pressure of carbon dioxide (pCO) compared to 66 ± 7 mmHg venous pCO and 9.8 ± 2.8 mmol/L mean arterial lactate compared to 11.6 ± 2.7 mmol/L venous lactate. There was a mild increase in ileum mass reaching 105 ± 7.5% of the pre-perfusion mass after 4 hours. Histology of haematoxylin and eosin stained biopsy samples taken at the end of perfusion showed on average 99% (±1%) histologically normal neurons in the submucosal plexus and 76.1% (±23.9%) histologically normal neurons in the myenteric plexus and were not significantly different to control biopsies.

Conclusion: Extracorporeal, normothermic perfusion of equine ileum over 4 h using autologous oxygenated blood/plasma perfusate showed potential as experimental model to test whether haematogenous or intestinal exposure to neurotoxins suspected in the pathogenesis of EGS can induce neuronal damage typical for EGS. Also, this model may allow investigations into the effect of pharmaceuticals on I/R injury, as well as into the pathogenesis of equine POI.
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http://dx.doi.org/10.1186/s12917-019-2145-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839147PMC
November 2019

A study of residual lesions in horses that recovered from clinical signs of chronic equine dysautonomia.

J Vet Intern Med 2019 Sep 22;33(5):2302-2311. Epub 2019 Jul 22.

Royal (Dick) School of Veterinary Studies and The Roslin Institute, The University of Edinburgh, Midlothian, United Kingdom.

Background: Equine dysautonomia (ED) causes degeneration and loss of autonomic neurons. Approximately 50% of chronic cases recover, but it is unclear how they survive neuronal loss.

Objectives: To assess lesions, autonomic neuron numbers, interstitial cells of Cajal (ICC), and neurodegeneration in recovered cases.

Animals: Thirteen cases (group ED), euthanized 10.3 ± 5.2 (1-16) years from diagnosis and 6 age-matched controls (group C).

Methods: Prospective, case control; routine post mortem examination, neuron counts in peripheral and enteric ganglia and immunohistochemical assessment of neural networks (Protein gene product [PGP] 9.5), ICC (c-kit), and neurodegeneration (beta-amyloid precursor protein and ubiquitin) in intestine.

Results: Postmortem findings in group ED were small intestinal dilation (4/12, 33%) and muscular hypertrophy (4/12, 33%), and gastric mucosal hypertrophy (3/11, 27%) and ulceration (4/11, 36%). Neuron density was lower in group ED (mean 39% lower for cranial cervical ganglion [P < .001], median 44% lower in celiacomesenteric ganglion [P = .01]). In intestine, neuronal depletion was worst in ileum (median 100% lower in submucosal plexus [P < .001], 91% lower in myenteric plexus [P = .004]). Group ED had less PGP 9.5 staining in ileal myenteric plexus (mean 66% lower [P = .04]) and circular muscle (median 75% lower [P = .006]). In ileum, there was less c-kit staining in myenteric plexus (median 57% lower [P = .02]) but not muscularis externa. Beta-amyloid precursor protein and ubiquitin results were not indicitive of neurodegeneration.

Conclusions And Clinical Importance: Intact ICC in muscularis externa might help maintain motility after neuronal loss. Treatment supporting ICC function warrants investigation.
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http://dx.doi.org/10.1111/jvim.15567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766533PMC
September 2019

The Effect of Race Training on the Basal Gene Expression of Alveolar Macrophages Derived From Standardbred Racehorses.

J Equine Vet Sci 2019 04 29;75:48-54. Epub 2019 Jan 29.

The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, UK.

Mild-to-moderate equine asthma is prevalent in young racehorses, particularly early in their training period. Although the precise etiopathogenesis remains undetermined, it is possible that the susceptibility of this population might partly reflect an exercise-associated immune derangement at the level of the airway. We performed a genome-wide basal gene expression scan on alveolar macrophages (AMs) isolated from Standardbred racehorses before and after commencement of competition race training with a view to identifying any exercise-associated gene expression modulation consistent with functional alterations, which might reflect training-associated immunological derangement. Microarray technology was used to analyze the basal gene expression profiles of bronchoalveolar fluid-derived AMs, harvested from six systemically healthy Standardbred racehorses before (T0) and after (T1) entry into training. In addition, AM lipopolysaccharide (LPS)-induced TNF-α and IL-10 release at T0 and T1 was assessed. Although the data revealed significant interhorse heterogeneity in relation to the magnitude of individual gene expression at each timepoint, within each horse, several inflammatory-related genes [e.g., chemokine ligands, interferons, and nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB)] declined in expression from T0 to T1. Entry into training did not significantly alter AM LPS-induced TNF-α or IL-10 release. The data support a direct effect of training on AM basal gene expression, particularly with respect to immune-related genes. The pattern of training-associated differential gene expression may indicate relative downregulation of inflammatory-related genes, consistent with an immunosuppressive effect of training and an increased susceptibility to opportunistic pathogens.
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http://dx.doi.org/10.1016/j.jevs.2019.01.010DOI Listing
April 2019

Equine Dysautonomia.

Vet Clin North Am Equine Pract 2018 Apr 3;34(1):113-125. Epub 2018 Feb 3.

The Dick Vet Equine Hospital, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Easter Bush, Roslin, Midlothian EH25 9RG, GBR.

Equine dysautonomia (ED; also known as equine grass sickness) is a neurological disease of unknown cause, which primarily affects grazing adult horses. The clinical signs reflect degeneration of specific neuronal populations, predominantly within the autonomic and enteric nervous systems, with disease severity and prognosis determined by the extent of neuronal loss. This review is primarily focused on the major clinical decision-making processes in relation to ED, namely, (1) clinical diagnosis, (2) selection of appropriate ancillary diagnostic tests, (3) obtaining diagnostic confirmation, (4) selection of treatment candidates, and (5) identifying appropriate criteria for euthanasia.
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http://dx.doi.org/10.1016/j.cveq.2017.11.010DOI Listing
April 2018

Alterations in amino acid status in cats with feline dysautonomia.

PLoS One 2017 23;12(3):e0174346. Epub 2017 Mar 23.

Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, Roslin, Midlothian, United Kingdom.

Feline dysautonomia (FD) is a multiple system neuropathy of unknown aetiology. An apparently identical disease occurs in horses (equine grass sickness, EGS), dogs, rabbits, hares, sheep, alpacas and llamas. Horses with acute EGS have a marked reduction in plasma concentrations of the sulphur amino acids (SAA) cyst(e)ine and methionine, which may reflect exposure to a neurotoxic xenobiotic. The aim of this study was to determine whether FD cats have alterations in amino acid profiles similar to those of EGS horses. Amino acids were quantified in plasma/serum from 14 FD cats, 5 healthy in-contact cats which shared housing and diet with the FD cats, and 6 healthy control cats which were housed separately from FD cats and which received a different diet. The adequacy of amino acids in the cats' diet was assessed by determining the amino acid content of tinned and dry pelleted foods collected immediately after occurrences of FD. Compared with controls, FD cats had increased concentrations of many essential amino acids, with the exception of methionine which was significantly reduced, and reductions in most non-essential amino acids. In-contact cats also had inadequate methionine status. Artefactual loss of cysteine during analysis precluded assessment of the cyst(e)ine status. Food analysis indicated that the low methionine status was unlikely to be attributable to dietary inadequacy of methionine or cystine. Multi-mycotoxin screening identified low concentrations of several mycotoxins in dry food from all 3 premises. While this indicates fungal contamination of the food, none of these mycotoxins appears to induce the specific clinico-pathologic features which characterise FD and equivalent multiple system neuropathies in other species. Instead, we hypothesise that ingestion of another, as yet unidentified, dietary neurotoxic mycotoxin or xenobiotic, may cause both the characteristic disease pathology and the plasma SAA depletion.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0174346PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363954PMC
August 2017

Designing a field trial of an equine grass sickness vaccine: A questionnaire-based feasibility study.

Vet J 2016 Jul 4;213:64-71. Epub 2016 May 4.

Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK.

Without an experimental model of equine grass sickness (EGS), a randomised controlled field trial (RCT) represents the only method of evaluating the efficacy of Clostridium botulinum type C vaccination in preventing naturally occurring disease. Clinical trial feasibility is an important aspect of preliminary work undertaken prior to initiating RCTs, estimating parameters that are important for study design. This cross-sectional study aimed to assess the feasibility of conducting a nationwide RCT of a candidate vaccine for EGS based on responses from a sample of British equine veterinary practices (n = 119/284). Seventy-three percent of practices had attended ≥1 EGS case within the preceding 2 years (median four cases), and 51.3% regularly attended recurrently affected premises. Veterinary surgeons had greater confidence diagnosing acute/subacute EGS based solely on history and clinical signs compared to chronic EGS. Ninety-one percent of respondents (n = 103/113) considered the proposed RCT to be important/very important to equine veterinary research. Ninety-one percent of respondents (n = 102/112) indicated preparedness to assist in owner recruitment and 92.9% (n = 104/112) indicated willingness to participate in a RCT. The most frequent reasons for practices declining to participate were low incidence of EGS (n = 4), did not believe clients would wish to participate (n = 3) and amount of paperwork/data collection involved (n = 2). There was considerable support amongst participating veterinary practices for a RCT evaluating the efficacy of Clostridium botulinum vaccination for the prevention of EGS in Britain. Substantial proportions of participating practices would be prepared to participate in the RCT and regularly attended EGS-affected premises that would meet trial inclusion criteria.
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http://dx.doi.org/10.1016/j.tvjl.2016.05.001DOI Listing
July 2016

Proteomic Profiling of Cranial (Superior) Cervical Ganglia Reveals Beta-Amyloid and Ubiquitin Proteasome System Perturbations in an Equine Multiple System Neuropathy.

Mol Cell Proteomics 2015 Nov 13;14(11):3072-86. Epub 2015 Sep 13.

§Division of Neurobiology, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, UK; Euan MacDonald Centre for Motor Neuron Disease Research, University of Edinburgh, Edinburgh, UK

Equine grass sickness (EGS) is an acute, predominantly fatal, multiple system neuropathy of grazing horses with reported incidence rates of ∼2%. An apparently identical disease occurs in multiple species, including but not limited to cats, dogs, and rabbits. Although the precise etiology remains unclear, ultrastructural findings have suggested that the primary lesion lies in the glycoprotein biosynthetic pathway of specific neuronal populations. The goal of this study was therefore to identify the molecular processes underpinning neurodegeneration in EGS. Here, we use a bottom-up approach beginning with the application of modern proteomic tools to the analysis of cranial (superior) cervical ganglion (CCG, a consistently affected tissue) from EGS-affected patients and appropriate control cases postmortem. In what appears to be the proteomic application of modern proteomic tools to equine neuronal tissues and/or to an inherent neurodegenerative disease of large animals (not a model of human disease), we identified 2,311 proteins in CCG extracts, with 320 proteins increased and 186 decreased by greater than 20% relative to controls. Further examination of selected proteomic candidates by quantitative fluorescent Western blotting (QFWB) and subcellular expression profiling by immunohistochemistry highlighted a previously unreported dysregulation in proteins commonly associated with protein misfolding/aggregation responses seen in a myriad of human neurodegenerative conditions, including but not limited to amyloid precursor protein (APP), microtubule associated protein (Tau), and multiple components of the ubiquitin proteasome system (UPS). Differentially expressed proteins eligible for in silico pathway analysis clustered predominantly into the following biofunctions: (1) diseases and disorders, including; neurological disease and skeletal and muscular disorders and (2) molecular and cellular functions, including cellular assembly and organization, cell-to-cell signaling and interaction (including epinephrine, dopamine, and adrenergic signaling and receptor function), and small molecule biochemistry. Interestingly, while the biofunctions identified in this study may represent pathways underpinning EGS-induced neurodegeneration, this is also the first demonstration of potential molecular conservation (including previously unreported dysregulation of the UPS and APP) spanning the degenerative cascades from an apparently unrelated condition of large animals, to small animal models with altered neuronal vulnerability, and human neurological conditions. Importantly, this study highlights the feasibility and benefits of applying modern proteomic techniques to veterinary investigations of neurodegenerative processes in diseases of large animals.
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http://dx.doi.org/10.1074/mcp.M115.054635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638047PMC
November 2015

Grazing livestock are exposed to terrestrial cyanobacteria.

Vet Res 2015 Feb 25;46:16. Epub 2015 Feb 25.

While toxins from aquatic cyanobacteria are a well-recognised cause of disease in birds and animals, exposure of grazing livestock to terrestrial cyanobacteria has not been described. This study identified terrestrial cyanobacteria, predominantly Phormidium spp., in the biofilm of plants from most livestock fields investigated. Lower numbers of other cyanobacteria, microalgae and fungi were present on many plants. Cyanobacterial 16S rDNA, predominantly from Phormidium spp., was detected in all samples tested, including 6 plant washings, 1 soil sample and ileal contents from 2 grazing horses. Further work was performed to test the hypothesis that ingestion of cyanotoxins contributes to the pathogenesis of some currently unexplained diseases of grazing horses, including equine grass sickness (EGS), equine motor neuron disease (EMND) and hepatopathy. Phormidium population density was significantly higher on EGS fields than on control fields. The cyanobacterial neurotoxic amino acid 2,4-diaminobutyric acid (DAB) was detected in plant washings from EGS fields, but worst case scenario estimations suggested the dose would be insufficient to cause disease. Neither DAB nor the cyanobacterial neurotoxins β-N-methylamino-L-alanine and N-(2-aminoethyl) glycine were detected in neural tissue from 6 EGS horses, 2 EMND horses and 7 control horses. Phormidium was present in low numbers on plants where horses had unexplained hepatopathy. This study did not yield evidence linking known cyanotoxins with disease in grazing horses. However, further study is warranted to identify and quantify toxins produced by cyanobacteria on livestock fields, and determine whether, under appropriate conditions, known or unknown cyanotoxins contribute to currently unexplained diseases in grazing livestock.
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http://dx.doi.org/10.1186/s13567-015-0143-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342207PMC
February 2015

Constitutive apoptosis in equine peripheral blood neutrophils in vitro.

Vet J 2014 Dec 29;202(3):536-42. Epub 2014 Aug 29.

Royal (Dick) School of Veterinary Studies and the Roslin Institute, University of Edinburgh, Roslin, Midlothian EH25 9RG, UK. Electronic address:

The aim of this study was to characterise constitutive apoptosis in equine peripheral blood neutrophils, including assessment of factors that potentially modulate neutrophil survival through alteration of the rate of constitutive apoptosis. Cells underwent spontaneous time-dependent constitutive apoptosis when aged in culture for up to 36 h, developing the structural and functional features of apoptosis observed in many cell types, including human neutrophils. Neutrophils undergoing apoptosis also had diminished zymosan activated serum (ZAS)-stimulated chemiluminescence, but maintained responsiveness to phorbol myristate acetate (PMA). The constitutive rate of equine neutrophil apoptosis was promoted by lipopolysaccharide (LPS), tumour necrosis factor α and phagocytosis of opsonised ovine erythrocytes, while it was inhibited by dexamethasone and ZAS (a source of C5a). Formyl-Met-Leu-Phe, leukotriene B4, platelet activating factor and PMA had no demonstrable effect on equine neutrophil apoptosis. There was a difference between equine and human neutrophil apoptosis in response to LPS and the time-dependence of the response to dexamethasone.
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http://dx.doi.org/10.1016/j.tvjl.2014.08.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274315PMC
December 2014

Chronic pleuropulmonary fibrosis and elastosis of aged donkeys: similarities to human pleuroparenchymal fibroelastosis.

Chest 2014 Jun;145(6):1325-1332

The Donkey Sanctuary, Sidmouth, Devon, England. Electronic address:

Background: Donkey pulmonary fibrosis (DPF) is a spontaneous syndrome of aged donkeys with a high prevalence (35%). No previous detailed characterization of DPF has been performed. We sought to determine the similarities between DPF and recognized patterns of human pulmonary fibrosis.

Methods: Whole lungs were collected from 32 aged donkeys at routine necropsy. Gross examination revealed pulmonary fibrosis in 19 donkeys (DPF cases), whereas 13 (control cases) had grossly normal lungs. Eighteen whole inflated ex vivo lungs (11 DPF cases, seven control cases) were imaged with high-resolution CT (HRCT) scan, whereas the remainder were sectioned and photographed. Tissue samples were collected from all lungs for histopathologic evaluation using a standardized protocol. HRCT images and histology sections underwent independent blinded review. Lung tissue was analyzed for herpes virus, fungal hyphae, mycobacteria, and dust content.

Results: Ten of 19 DPF lungs were categorized as being consistent with pleuroparenchymal fibroelastosis (PPFE) according to previously defined histologic and imaging criteria. All 10 PPFE-like lungs had marked pleural and subpleural fibrosis, predominantly within the upper lung zone, with accompanying intraalveolar fibrosis and elastosis. Asinine herpesvirus was ubiquitously expressed within control and DPF lung tissue. No other etiologic agents were identified.

Conclusions: Many cases of DPF share key pathologic and imaging features with human PPFE, a rare interstitial pneumonia. Consequently, further study of DPF may help to elucidate the etiopathogenesis of human PPFE.
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http://dx.doi.org/10.1378/chest.13-1306DOI Listing
June 2014

Viraemic frequencies and seroprevalence of non-primate hepacivirus and equine pegiviruses in horses and other mammalian species.

J Gen Virol 2014 Aug 9;95(Pt 8):1701-1711. Epub 2014 May 9.

Roslin Institute, University of Edinburgh, Easter Bush, Edinburgh, UK.

Non-primate hepacivirus (NPHV), equine pegivirus (EPgV) and Theiler's disease associated virus (TDAV) are newly discovered members of two genera in the Flaviviridae family, Hepacivirus and Pegivirus respectively, that include human hepatitis C virus (HCV) and human pegivirus (HPgV). To investigate their epidemiology, persistence and clinical features of infection, large cohorts of horses and other mammalian species were screened for NPHV, EPgV and TDAV viraemia and for past exposure through serological assays for NPHV and EPgV-specific antibodies. NPHV antibodies were detected in 43% of 328 horses screened for antibodies to NS3 and core antibodies, of which three were viraemic by PCR. All five horses that were stablemates of a viraemic horse were seropositive, as was a dog on the same farm. With this single exception, all other species were negative for NPHV antibodies and viraemia: donkeys (n=100), dogs (n=112), cats (n=131), non-human primates (n=164) and humans (n=362). EPgV antibodies to NS3 were detected in 66.5% of horses, including 10 of the 12 horses that had EPgV viraemia. All donkey samples were negative for EPgV antibody and RNA. All horse and donkey samples were negative for TDAV RNA. By comparing viraemia frequencies in horses with and without liver disease, no evidence was obtained that supported an association between active NPHV and EPgV infections with hepatopathy. The study demonstrates that NPHV and EPgV infections are widespread and enzootic in the study horse population and confirms that NPHV and potentially EPgV have higher frequencies of viral clearance than HCV and HPgV infections in humans.
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http://dx.doi.org/10.1099/vir.0.065094-0DOI Listing
August 2014

The equine alveolar macrophage: functional and phenotypic comparisons with peritoneal macrophages.

Vet Immunol Immunopathol 2013 Oct 20;155(4):219-28. Epub 2013 Jul 20.

The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9PS, UK. Electronic address:

Alveolar macrophages (AMs) constitute the first line of defence in the lung of all species, playing a crucial role in the regulation of immune responses to inhaled pathogens. A detailed understanding of the function and phenotype of AMs is a necessary pre-requisite to both elucidating their role in preventing opportunistic bacterial colonisation of the lower respiratory tract and developing appropriate preventative strategies. The purpose of the study was to characterise this important innate immune cell at the tissue level by making functional and phenotypic comparisons with peritoneal macrophages (PMs). We hypothesised that the tissue of origin determines a unique phenotype of AMs, which may constitute an appropriate therapeutic target for certain equine respiratory diseases. Macrophages isolated from the lung and the peritoneal cavity of 9 horses were stimulated with various toll like receptor (TLR) ligands and the production of nitrite, tumour necrosis factor alpha (TNFα), interleukin (IL) 10 and indoleamine 2,3-dioxygenase (IDO) were measured by the Griess reaction and enzyme linked immunosorbent assay (ELISA) and/or quantitative polymerase chain reaction, respectively. Cells were also compared on the basis of phagocytic-capacity and the expression of several cell surface markers. AMs, but not PMs, demonstrated increased TNFα release following stimulation with LPS, polyinosinic polycytidylic acid (Poly IC) and heat-killed Salmonella typhinurium and increased TNFα and IDO mRNA expression when stimulated with LPS. AMs showed high expression of the specific macrophage markers cluster of differentiation (CD) 14, CD163 and TLR4, whereas PMs showed high expression of TLR4 only. AMs, but not PMs, demonstrated efficient phagocytic activity. Our results demonstrate that AMs are more active than PMs when stimulated with various pro-inflammatory ligands, thus supporting the importance of the local microenvironment in the activation status of the macrophage. This information provides a valuable knowledge base on which to improve our understanding of the role of macrophages and their microenvironment in equine innate immunity.
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http://dx.doi.org/10.1016/j.vetimm.2013.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795452PMC
October 2013

Nonprimate hepaciviruses in domestic horses, United kingdom.

Emerg Infect Dis 2012 Dec;18(12):1976-82

University of Edinburgh, Edinburgh, Scotland, UK.

Although the origin of hepatitis C virus infections in humans remains undetermined, a close homolog of this virus, termed canine hepacivirus (CHV) and found in respiratory secretions of dogs, provides evidence for a wider distribution of hepaciviruses in mammals. We determined frequencies of active infection among dogs and other mammals in the United Kingdom. Samples from dogs (46 respiratory, 99 plasma, 45 autopsy samples) were CHV negative by PCR. Screening of 362 samples from cats, horses, donkeys, rodents, and pigs identified 3 (2%) positive samples from 142 horses. These samples were genetically divergent from CHV and nonprimate hepaciviruses that horses were infected with during 2012 in New York state, USA. Investigation of infected horses demonstrated nonprimate hepacivirus persistence, high viral loads in plasma (10(5)-10(7) RNA copies/mL), and liver function test results usually within reference ranges, although several values ranged from high normal to mildly elevated. Disease associations and host range of nonprimate hepaciviruses warrant further investigation.
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http://dx.doi.org/10.3201/eid1812.120498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557883PMC
December 2012

Evaluation of formalin-fixed ileum as the optimum method to diagnose equine dysautonomia (grass sickness) in simulated intestinal biopsies.

J Vet Diagn Invest 2010 Mar;22(2):248-52

Division of Veterinary Clinical Sciences, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian, EH25 9RG, United Kingdom.

Equine dysautonomia, or grass sickness, is a frequently fatal disease of unknown etiology, manifested as poor gastrointestinal motility and colic as a result of degenerative changes in the autonomic nervous system. Examination of ileal biopsies collected at laparotomy is currently the best antemortem diagnostic method to distinguish equine dysautonomia from colic cases, which can present with similar signs, but their value has not been previously critically evaluated. Using simulated biopsies collected postmortem from 23 cases of equine dysautonomia and 11 of colic, the sensitivity and specificity of 1-cm long, formalin-fixed ileal biopsies was 100% for the diagnosis of equine dysautonomia. There was therefore no advantage to using larger biopsies or examining jejunum either in addition to or instead of ileal biopsies. Furthermore, although cryostat sections of ileum, 1-cm long, had a sensitivity of 100%, the specificity was only 73%, meaning that 27% of cases would have been misclassified, resulting in unnecessary euthanasia. Increasing the size of the cryostat or examining jejunum in addition to ileum cryostat sections did not significantly improve the specificity. Results of the current study indicate that in diagnostic practice, 1-cm long, formalin-fixed biopsies are likely to be the most suitable for accurate diagnosis, despite the slower turnaround time compared with cryostat sections.
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http://dx.doi.org/10.1177/104063871002200214DOI Listing
March 2010

Evaluation of equine laminar vein function: harvesting, dissection and the use of functional methods to distinguish between veins and arteries.

J Pharmacol Toxicol Methods 2008 Mar-Apr;57(2):92-9. Epub 2008 Jan 19.

Department of Biological and Biochemical Science, Glasgow Caledonian University, Cowcaddens Road, Glasgow, United Kingdom.

Introduction: Pharmacological evaluation of the unique equine laminar microvasculature is crucial to understanding its role in health and in diseases such as laminitis. However, separating the distinctive characteristics of arterial versus venous components of this complex vascular network has previously proved to be extremely difficult. Encased in a hard hoof capsule, isolation of individual blood vessels presents a considerable challenge. Exacerbating this difficulty, the laminar venous network is adapted to sustain high intravascular pressures and consequently has thickened walls, making the normally straightforward visual distinction between arteries and veins problematic. Here we describe a novel harvesting and dissection method coupled with a functional analysis procedure that facilitates distinction of arteries and veins.

Methods: Laminar tissue was recovered from the hoof of euthanized, clinically normal horses by dissection at the coronary band and stored in cold Krebs-Henseleit physiological salt solution prior to further dissection in the laboratory to remove 2 mm segments of vessels 100-500 microm in diameter. Active length tension measurements were made to evaluate optimal conditions for experimentation, and based on the differences in contractility and appearance, an experimental protocol was set up to allow a) initial distinction between arteries and veins and b) in vitro pharmacological evaluation.

Results: Active length tension studies clearly revealed the presence of two populations of vessels distinguished by either a large or a lower maximal contraction that subsequent histological evaluation confirmed to be arteries and veins respectively. Functional distinction using relative contractility to 60 mM potassium salt solution then demonstrated equine laminar veins to have increased sensitivity to the agonist endothelin 1 (ET-1) compared to arteries.

Discussion: In vitro evaluation of laminar vessels is possible despite anatomical obstacles. Furthermore, a clear distinction can be made between laminar veins and arteries using functional characteristics providing vessels of a similar size range are selected. Utilising these novel procedures, investigators can unambiguously analyse the pharmacological characteristics of equine laminar veins and arteries to decipher the physiological mechanisms responsible for the control of laminar blood flow.
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http://dx.doi.org/10.1016/j.vascn.2007.10.005DOI Listing
June 2008

The involvement of mast cells and mast cell proteinases in the intestinal response to equine cyathostomin infection.

Vet Immunol Immunopathol 2007 Jan 21;115(1-2):35-42. Epub 2006 Nov 21.

Division of Veterinary Clinical Science, University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG, United Kingdom.

Cyathostomins (Cyathostominae) are regarded as the most pathogenic equine nematode worldwide. These nematodes are difficult to control in equine populations due to emerging anthelmintic resistance and evasion of encysted larval cyathostomins to regular modern anthelmintics. Mast cells and their proteinases have been shown to play a role in the mammalian immune response to nematode infections. Involvement of mast cells and mast cell proteinases in the equine immune response to cyathostomin infection is proposed. A technique was established to perform immunohistochemical staining using polyclonal rabbit anti-equine mast cell proteinase-1 (eqMCP-1) and anti-equine tryptase on formalin-fixed large intestinal sections, from horses classified as cyathostomin positive and negative at the time of death based upon larval enumeration. Quantitative analysis of antibody labelled mast cells was used to detect mast cell proteinases in equine large intestinal sections positive and negative for cyathostomin larvae. This demonstrated an increase in equine tryptase labelled mucosal and submucosal mast cells in cyathostomin positive horses. This study has established an immunohistochemical technique to demonstrate mast cell proteinases in formalin-fixed large intestinal sections. This technique may be used to determine possible involvement of mast cells and their proteinases in the equine immune response to cyathostomin larvae. Further studies are required to define a specific role.
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http://dx.doi.org/10.1016/j.vetimm.2006.10.015DOI Listing
January 2007

Suspected complex regional pain syndrome in 2 horses.

J Vet Intern Med 2006 Jul-Aug;20(4):1014-7

Division of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Large Animal Hospital, Easter Bush Veterinary Centre, Roslin, Midlothian, UK.

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http://dx.doi.org/10.1892/0891-6640(2006)20[1014:scrpsi]2.0.co;2DOI Listing
October 2006

Lymphoproliferative disease resembling lymphomatoid granulomatosis in a thoroughbred mare.

J Vet Intern Med 2004 Nov-Dec;18(6):904-6

Department of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG, UK.

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http://dx.doi.org/10.1892/0891-6640(2004)18<904:ldrlgi>2.0.co;2DOI Listing
January 2005

Alopecia areata with lymphocytic mural folliculitis affecting the isthmus in a thoroughbred mare.

Vet Dermatol 2004 Aug;15(4):260-5

Hospital for Small Animals, The University of Edinburgh, The Royal (Dick) School of Veterinary Studies, Easter Bush Veterinary Center, Roslin, Midlothian, EH25 9RG, UK.

A 13-year-old, thoroughbred mare was presented with an 8-year history of multifocal, generalized, noninflammatory alopecia and a 3-month history of alopecia, erythema and scaling of the white star on the forehead and muzzle. Histopathological examination of biopsy samples from multiple sites on the body (mane, neck, shoulder, flank and gluteal region) showed a subtle lymphocytic inflammatory infiltrate affecting and surrounding the anagen hair bulbs, consistent with a diagnosis of alopecia areata. The biopsy sample from the star on the forehead showed atrophic hair follicles with perifollicular and mural mononuclear folliculitis affecting the isthmus. Immunohistochemical staining with a CD3 marker confirmed the T-lymphocytic origin of the inflammatory infiltrate in all the samples. The concurrent presence of lymphocytic infiltration at the bulbar and isthmic level of the hair follicles in the same horse is unusual. This finding may represent a variation of the histological appearance of alopecia areata.
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http://dx.doi.org/10.1111/j.1365-3164.2004.00392.xDOI Listing
August 2004
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