A state-of-the-art multi-omics approach was applied to improve our understanding of the aetio-pathogenesis of a highly prevalent, performance-limiting disorder of racehorses: mild-to-moderate equine asthma (MMEA). This is a prerequisite to improving prophylactic, management, and therapeutic options for this condition. Although a number of risk factors have been identified, options for intervention are limited.
View Article and Find Full Text PDFBackground: Equine grass sickness (EGS) is a frequently fatal multisystem neuropathy of equids. The aetiology is unknown; proposed causes include toxicoinfection with Clostridium botulinum and a mycotoxicosis. The effect of EGS on the organisation and structural integrity of the skeletal neuromuscular junction (NMJ), the target of botulinum neurotoxins (BoNTs), is unknown.
View Article and Find Full Text PDFThere is a paucity of data relating to the vitamin D status of racehorses. We hypothesised that the management of racehorses in Hong Kong (HK) predisposes to low vitamin D status unless they receive dietary supplementation. Serum concentrations of 25-hydroxyvitamin D (25OHD), 25-hydroxyvitamin D (25OHD) and total 25-hydroxyvitamin D (total 25OHD) for 79 non-grazing HK racehorses were compared with those for 22 racehorses training in the United Kingdom (UK) that grazed for ≥1 h/d, and for which published data exists.
View Article and Find Full Text PDFBackground: Vitamin D deficiency is common in humans and is increasingly linked to the pathogenesis of a multitude of diseases including obesity and metabolic syndrome. The biology of vitamin D in horses is poorly described; the relative contribution of the diet and skin synthesis to circulating concentrations is unclear and associations with the endocrine disease have not been explored.
Objectives: To determine the relationship between management, season and endocrine disease and vitamin D status in horses.
Neurodegenerative disorders are gaining ever more importance in ageing populations of animals and people. Altered insulin signaling and type II diabetes have been linked to the development of Alzheimer's disease (AD) in humans and AD-like neurodegeneration in other long-lived animals. Donkeys are unusual amongst domestic species for their exceptional longevity and are additionally predisposed to abnormalities of insulin metabolism similar to those found in humans.
View Article and Find Full Text PDFBackground: Equine grass sickness (EGS) is a multiple systems neuropathy of grazing horses of unknown aetiology. An apparently identical disease occurs in cats, dogs, rabbits, hares, sheep, alpacas and llamas. Many of the risk factors for EGS are consistent with it being a pasture mycotoxicosis.
View Article and Find Full Text PDFThere is a need to develop platforms delineating inflammatory biology of the distal human lung. We describe a platform technology approach to detect enzyme activity and observe drug inhibition in the distal human lung using a combination of matrix metalloproteinase (MMP) optical reporters, fibered confocal fluorescence microscopy (FCFM), and a bespoke delivery device. .
View Article and Find Full Text PDFBackground: 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.
View Article and Find Full Text PDFBackground: 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.
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.
View Article and Find Full Text PDFEquine 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.
View Article and Find Full Text PDFBackground: An accurate, minimally invasive, ante-mortem diagnostic test for equine grass sickness (EGS) is currently lacking. Although histological examination of haematoxylin and eosin-stained rectal biopsies for chromatolytic neurons is insensitive as a diagnostic test for EGS, we hypothesised that its diagnostic accuracy could be improved by immunolabelling for β-amyloid precursor protein (β-APP), which has increased expression in cranial cervical ganglia (CCG) neuronal perikarya in EGS.
Objectives: To develop a grading scheme for assessing the distribution and intensity of β-APP immunoreactivity within individual rectal submucosal neurons and subsequently to determine the value of the distribution of different grades of neurons in EGS diagnosis.
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.
View Article and Find Full Text PDFDespite frequent use of metered dose inhalers (MDIs) and spacers in equine practice, limited information exists on the efficiency of aerosol delivery using such devices. We determined the particle size distribution within an MDI-generated salbutamol aerosol delivered via an equine spacer using 'best practice' delivery technique and assessed the effect of variations in MDI use technique (shaking prior to each actuation, rapid repetitive actuations, and MDI angulation) on aerosol delivery efficiency. Under optimal conditions, only 53(±18) μg salbutamol per 100 μg actuation was delivered beyond the spacer.
View Article and Find Full Text PDFBackground: The aetiology of equine grass sickness (EGS) is currently unknown. We hypothesised that an acute deficiency of niacin (vitamin B3), which plays a key role in neural homeostasis, may contribute to neurodegeneration in EGS. Niacin deficiency can potentially result from ingestion of niacin antagonists produced by pasture mycotoxigenic fungi.
View Article and Find Full Text PDFWithout 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).
View Article and Find Full Text PDFReasons For Performing Study: Alveolar macrophages (AMs) are the first line of defence against pathogens in the lungs of all mammalian species and thus may constitute appropriate therapeutic target cells in the treatment and prevention of opportunistic airway infections. Therefore, acquiring a better understanding of equine macrophage biology is of paramount importance in addressing this issue in relation to the horse.
Objectives: To compare the transcriptome of equine AMs with that of equine peritoneal macrophages (PMs) and to investigate the effect of lipopolysaccharide (LPS) on equine AM.
Reasons For Performing Study: Objective criteria for predicting survival of chronic grass sickness cases are currently lacking.
Objectives: To determine whether the rate and/or magnitude of bodyweight change during hospitalisation of chronic grass sickness cases can provide an objective predictor of survival to discharge from hospital. Clinicians' recorded indication(s) for euthanasia were also reviewed.
Reasons For Performing Study: Equine grass sickness (EGS) is of unknown aetiology. Despite some evidence suggesting that it represents a toxico-infection with Clostridium botulinum types C and/or D, the effect of EGS on the functional targets of botulinum neurotoxins, namely the soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins, is unknown. Further, while it is commonly stated that, unlike EGS, equine botulism is not associated with autonomic and enteric neurodegeneration, this has not been definitively assessed.
View Article and Find Full Text PDFReasons For Performing Study: Diagnosis of equine grass sickness (EGS) can be challenging. We hypothesised that subgemmal plexus neurons are chromatolytic in EGS. If correct, histopathological examination of gustatory papillae biopsies could aid premortem diagnosis of EGS, and EGS could represent a spontaneous model of subgemmal neuronal chromatolysis to facilitate study of the pathology of structures involved in taste.
View Article and Find Full Text PDFEquine 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.
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