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Topic:Pathophysiology
Pathophysiology in horses involves the study of functional changes that occur in the body as a result of disease or injury. This field examines the mechanisms through which diseases develop and progress, as well as how they affect the body's normal physiological processes. In equine research, pathophysiology encompasses a wide range of conditions, including respiratory disorders, musculoskeletal injuries, gastrointestinal diseases, and metabolic syndromes. Understanding these processes helps in identifying potential therapeutic targets and developing effective treatment strategies. This page collects peer-reviewed research studies and scholarly articles that explore the underlying mechanisms, clinical manifestations, and implications of various pathophysiological conditions in equine health.
Chronic laminitis: foot management. Laminitis is a disease of the suspensory apparatus of the distal phalanx, which can advance to the chronic stage with varying degrees of structural failure. Because the disease may ultimately lead to mechanical failure of the digit, a foot management plan is required to effectively and mechanically treat these cases. Many laminitis cases can be successfully rehabilitated back to athletic soundness, light use, breeding, or pasture soundness, whereas others suffer from permanent instability and never enjoy an acceptable level of comfort. To understand how to minimize damage in the acute laminiti...
Clara cell secretory protein increases phagocytic and decreases oxidative activity of neutrophils. Horses suffer from recurrent airway obstruction, an asthma-like condition induced by repeat inhalation of environmental substances present in barn air. Clara cell secretory protein (CCSP) is much reduced during active inflammation when neutrophils predominate in the airways, and in chronic asthmatics. We sought to investigate morphologic and functional interactions of CCSP with neutrophils. Bronchoalveolar and blood neutrophils from healthy control animals, and from animals with recurrent airway obstruction in remission and exacerbation, were evaluated by immuno-cytochemistry and immuno-electr...
The role of activated neutrophils in the early stage of equine laminitis. Despite ongoing research and a widening range of treatment options, laminitis remains a severely damaging condition with poorly understood pathophysiology. Results obtained from cytokine regulation studies during the last decade have highlighted the inflammatory nature of laminitis. This review will describe the role of systemic activation and local infiltration of neutrophils in laminar tissues in the induction of laminitis. Particular emphasis is placed on the role of neutrophil activation in subsequent vascular dysfunction and oxidative and proteolysis imbalances that are pathways previousl...
The effect of cooling on the contractility of equine digital small lamellar arteries: modulating role of the endothelium. The equine hoof displays thermoregulatory functions, and the blood vessels lying under the hoof wall are temperature sensitive. The aim of this study was to investigate the effect of cooling on the contractile responses to α-adrenoceptor and 5-HT receptor stimulation in equine small lamellar arteries using wire myography. The role of the endothelium in the response mediated by 5-HT was also evaluated. Moderate cooling caused a reduction of the contraction induced by depolarizing Krebs solution (DKS, containing 118 mm KCl) and the maximal contraction caused by UK-14304 (α(2)-adrenoceptor agon...
Peritoneal concentrations of transforming growth factor beta in horses with colic. In man, peritoneal transforming growth factor beta (TGF-beta) is associated with peritoneal diseases and subsequent adhesion formation. No studies on plasma and peritoneal TGF-beta concentrations in horses with colic are available. Objective: 1) To determine both plasma and peritoneal TGF-beta(1) and TGF-beta(3) concentrations in horses with different types of colic (not previously subjected to abdominal surgery); 2) to compare these concentrations according to the type of peritoneal fluid (transudate, modified transudate and exudate); and 3) to compare and correlate plasma and peritoneal conc...
IL-4 activates equine neutrophils and induces a mixed inflammatory cytokine expression profile with enhanced neutrophil chemotactic mediator release ex vivo. Neutrophils are potent contributors to the lung pathophysiological changes occurring in allergic airway inflammation, which typically involve T helper type 2 (Th2) cytokine overexpression. We have previously reported that equine pulmonary endothelial cells are activated by the Th2 cytokine IL-4 and express chemotactic factors for neutrophils after stimulation. We have further explored the possible mechanisms linking Th2-driven inflammation and neutrophilia by studying the effects of recombinant equine IL-4, a prototypical Th2 cytokine, on peripheral blood neutrophils (PBN) isolated from normal...
Toxicological effects of aflatoxins in horses. Aflatoxins are a group of mycotoxins principally produced by Aspergillus flavus and A. parasiticus, which are both natural contaminants of food and feedstuff. Aflatoxin B(1) is the most prevalent member of this group that is normally detected and is the most powerful hepatocarcinogen known. Few naturally occurring episodes of aflatoxicosis in horses have been reported in the literature. Indeed, the published information about aflatoxin exposure, metabolism and the effects on horses is limited and controversial, possibly indicating a lack of awareness rather than the rarity of the occurrence. T...
Evaluation of the role of superoxide anions in endotoxin-induced impairment of beta-adrenoceptor-mediated vasodilation in equine digital veins. To investigate the role of superoxide anions in the lipopolysaccharide (LPS)-induced impairment of beta-adrenoceptor-mediated equine digital vein (EDV) vasodilation. Methods: EDVs isolated from forelimbs of 24 healthy adult horses. Methods: Endothelium-intact or endothelium-denuded EDV rings were incubated with or without LPS (10 microg/mL) of Escherichia coli (O55:B5) for 4 hours. Cumulative concentration-relaxation curves resulting from administration of isoprenaline, a nonselective beta-adrenoceptor agonist, or from administration of SR 58611A, a selective beta(3)-adrenoceptor agonist, were...
Glycan profiling of a defect in decorin glycosylation in equine systemic proteoglycan accumulation, a potential model of progeroid form of Ehlers-Danlos syndrome. Defects in glycosylation of decorin can result in systemic hereditary disease. A mutation in the galactosyl transferase I gene is the underlying defect of a progeroid form of Ehlers-Danlos syndrome. We have previously described pathological changes in equine systemic proteoglycan accumulation (ESPA, formerly degenerative suspensory ligament desmitis) as consisting of excessive presence of decorin and other proteoglycans in organs and structures with a high content of connective tissue. Using liquid chromatography/mass spectrometry, and one- and two-dimensional immunoblotting we have determined...
The use of adrenocorticotrophic hormone as a potential biomarker of pituitary pars intermedia dysfunction in horses. Elevated concentrations of plasma adrenocorticotrophic hormone (ACTH) in horses with pituitary disturbances are often associated with dysfunction of the pituitary's pars intermedia. The majority of such animals exhibit an increased susceptibility to laminitis, particularly during the autumn. The 24h plasma ACTH profiles of horses with pituitary pars intermedia dysfunction (PPID), and those of matched controls, were determined in March, June, September and December. Differences in ACTH concentrations between the groups were significant (P<0.0001), regardless of photoperiod, and persisted thr...
Exploring lay perceptions of the causes of crib-biting/windsucking behaviour in horses. Crib-biting/windsucking behaviour has important consequences for equine health and welfare. Lay perceptions of health and illness are of interest to medical sociologists, providing important information to medical practitioners, but have infrequently been applied in veterinary research. Objective: To demonstrate how lay epidemiology can be applied within veterinary research by exploring the lay perceptions regarding the causes of crib-biting/windsucking behaviour in horses. Methods: Informants were recruited from professional and amateur horse owners who had or had not owned/cared for a horse ...
Corticosteroid-associated laminitis. A direct causal association between corticosteroid use and laminitis has yet to be proven scientifically, and there have been few studies specifically addressing this aspect. New evidence, however, is improving the understanding of the causes of laminitis, particularly related to endocrine factors. The focus of this article is discussing the circumstances under which steroids might cause this condition.
Hyperinsulinemic laminitis. Laminitis occurring in association with hyperinsulinemia is frequently encountered in today's equine population. New evidence suggests that hyperinsulinemia is the direct cause of this form of laminitis, rather than insulin resistance per se. The mechanism by which elevated serum insulin concentrations result in lamellar dysfunction is currently under investigation by many researchers and the use of a new insulin infusion model for investigating the pathogenesis of insulin-associated laminitis will doubtless enhance progress in this field of research. By focusing on the metabolic and vascular ...
The relationship between digital perfusion pressure and hoof lamellar blood flow in isoflurane-anesthetized horses. Digital perfusion pressure (DPP) equals mean arterial pressure (MAP) at the hoof coronet minus digital interstitial pressure (DIP) within the hoof. To test whether lamellar blood flow (LBF) changes proportionately to DPP, anesthesia was induced and maintained with isoflurane in six horses to target a MAP of 60 mmHg. Arterial, venous, and hoof interstitial pressures were measured in each pelvic limb. LBF was measured using fluorescent microspheres during dobutamine infusions targeting either 60 (low), 80 (medium), or 100 (high) mmHg MAP. Following euthanasia, hoof lamina was collected for micro...
Pathological changes caused by Anoplocephala perfoliata in the equine ileocecal junction. Gastrointestinal motility disorders represent a significant cause of morbidity and mortality in horses. Previously regarded as a non-pathogenic tapeworm, Anoplocephala perfoliata has been recently associated with equine colic. In this study, pathological changes related to A. perfoliata at the ileocecal junction were investigated in 31 slaughtered horses. Our results showed a significant relationship between parasitic burden and grading of histopathological lesions in both the mucosa and submucosa. Moreover, in infested horses, hypertrophy of the circular muscle layer was determined. Finally, ...
Evaluation of the effect of phosphodiesterase on equine platelet activation and the effect of antigen challenge on platelet phosphodiesterase activity in horses with recurrent airway obstruction. To determine whether expression of equine platelet activation-dependent surface markers is influenced by phospodiesterase (PDE) isoenzyme activity and whether antigen challenge alters platelet PDE activity in horses with recurrent airway obstruction (RAO). Methods: 16 horses. Methods: 7 healthy horses were used for in vitro experiments, 6 horses with RAO were used for antigen challenge, and 6 healthy horses were used as control animals. Three of the healthy horses had also been used in the in vitro experiments. Effects of PDE inhibition and activation of adenylyl cyclase on CD41/61 and CD62P e...
A pendulum test as a tool to evaluate viscous friction parameters in the equine fetlock joint. An equine fetlock joint pendulum test was studied and the influence of post mortem time and intra-articular lipid solvent on the viscous frictional response examined. Fresh equine digits (group 1, n=6 controls; group 2, n=6 lipid solvent) were mounted on a pendulum tribometer. Assuming that pendular joint damping could be modelled by a harmonic oscillator fluid damping (HOFD), damping time (τ), viscous damping coefficient (c) and friction coefficient (μ) were monitored for 5h under experimental conditions (400N; 20°C). In all experiments, pendular joint damping was found to follow an expone...
Carbohydrate alimentary overload laminitis. In acute laminitis, the suspensory apparatus of the distal phalanx fails at the lamellar dermal/epidermal interface. A grading system for the histopathology of laminitis is based on the consistent pattern of histologic changes to the secondary epidermal lamellae, basal cells, and basement membrane that occur as carbohydrate-induced laminitis develops. The actual trigger factors of carbohydrate-induced laminitis remain unidentified.
The pharmacologic basis for the treatment of developmental and acute laminitis. The treatment of laminitis has been fraught with confusion and controversy for several decades, mainly because of a lack of understanding of the pathophysiology of the disease process. However, recent advances in laminitis research have greatly improved our understanding of the disease process. This article discusses the various treatment options for laminitis in the context of the findings of recent scientific investigations of laminitis pathophysiology.
Black walnut extract: an inflammatory model. The black walnut extract (BWE) model was developed after the discovery that horses bedded on shavings from black walnut trees commonly developed laminitis. The first investigators that consistently induced laminitis with black walnut shavings established that it was only the heartwood of the tree that induced laminitis. The BWE model of laminitis has allowed investigators to determine many of the early pathologic signaling events likely to occur in the developmental and acute clinical stages of the disease process, and has brought inflammatory injury to the forefront of laminitis research. The...
Microbial events in the hindgut during carbohydrate-induced equine laminitis. Equine laminitis is the most serious foot disease of the horse, often resulting in death or euthanasia. Laminitis has long been recognized as an affliction of horses, as has the association of this condition with the ingestion of carbohydrates. Research into the pathophysiology of this condition has been facilitated by the development of reliable models for experimentally inducing laminitis, and DNA-based techniques for profiling complex microbiomes have dramatically increased the knowledge of the microbiology of this disease. Recent studies have provided substantial evidence showing equine hi...
The anatomy and physiology of the suspensory apparatus of the distal phalanx. The equine hoof capsule protects the softer, more sensitive, structures within. Failure of the connection between hoof and bone (suspensory apparatus of the distal phalanx or SADP) results in the crippling lameness of laminitis. Active basal cell proliferation occurs principally in tubular hoof and proximal and distal lamellae. The remaining lamellae are virtually non-proliferative and the hoof wall moves past the stationary distal phalanx, by controlled activation and inhibition of constituent proteases. The lamellar corium derives most of its blood supply from the branches of the terminal ar...
Overview of current laminitis research. All cases of laminitis are characterized by failure of the attachment of the epidermal cells of the epidermal laminae to the underlying basement membrane of the dermal laminae despite the diversity of diseases that underlie the syndrome. The preponderance of evidence supports roles for inflammation, metabolic derangement, endothelial and venous dysfunction, and matrix degradation as causes of laminitis. Inflammation, oxidant stress, and matrix degradation may be factors common to each of these mechanisms that lead to the laminar damage of laminitis. The understanding of the pathophysiology and...
Cytokine mRNA expressions after racing at a high altitude and at sea level in horses with exercise-induced pulmonary hemorrhage. To determine concentrations of cytokine mRNA in horses with exercise-induced pulmonary hemorrhage (EIPH) after racing. Methods: 97 Thoroughbreds. Methods: Following tracheobronchoscopy, the severity of EIPH was graded (scale of 0 to 4), and venous blood samples were collected from 10 horses in each grade. After RNA isolation and cDNA synthesis, real-time PCR assay was conducted to detect cytokinespecific mRNA for interleukin (IL)-1, IL-6, and IL-10; interferon (INF)-gamma; and tumor necrosis factor (TNF)-alpha. Results: Neither location nor grade of EIPH affected the expression of IL-1 and INF...
Pulmonary intravascular macrophages and endotoxin-induced pulmonary pathophysiology in horses. Endotoxemia causes significant mortality and morbidity in horses. The mechanisms underlying this complex pathophysiology remain unclear. Therefore, effective tools to treat endotoxemia in horses are lacking. Furthermore, the multifactorial and multiorgan pathophysiology of equine endotoxemia has not been fully addressed, especially the lung injury associated with endotoxemia. Within the context of the broader picture of endotoxemia and lung injury, we offer a perspective on the roles of pulmonary intravascular macrophages in endotoxin-induced lung inflammation in horses. L’endotoxémie est u...
Aspartic acid racemization and collagen degradation markers reveal an accumulation of damage in tendon collagen that is enhanced with aging. Little is known about the rate at which protein turnover occurs in living tendon and whether the rate differs between tendons with different physiological roles. In this study, we have quantified the racemization of aspartic acid to calculate the age of the collagenous and non-collagenous components of the high strain injury-prone superficial digital flexor tendon (SDFT) and low strain rarely injured common digital extensor tendon (CDET) in a group of horses with a wide age range. In addition, the turnover of collagen was assessed indirectly by measuring the levels of collagen degradation mark...
Comparative study of the properties of tendinocytes derived from three different sites in the equine superficial digital flexor tendon. This aim of this study was to determine the characteristic differences in tendinocytes derived from three sites of the equine superficial digital flexor tendon (SDFT)-proximally the myotendinous junction (MTJ), mid-metacarpal (mM) and osteotendinous junction (OTJ)-in morphology, proliferation, and ability for synthesis of collagen and matrix metalloproteinases (MMPs). Little difference was observed in cell proliferation. Addition of tumor necrosis factor (TNF) alpha to the culture medium resulted in increased collagen synthesis by tendinocytes from all three sites. The amount of collagen synth...
Evaluation of the possible role of prostaglandin F(2 alpha) in laminitis induced in horses by nasogastric administration of black walnut heartwood extract. To provide insights into the role of prostaglandin F(2 alpha) (PGF(2 alpha)) in the developmental stages of laminitis induced in horses by ingestion of black walnut heartwood extract (BWHE). Methods: 10 adult mixed-breed horses. Methods: Horses were separated into 2 groups and were euthanatized at 12 hours after placebo (water) administration (control horses) or after BWHE administration and development of Obel grade 1 laminitis. Blood samples were obtained to determine plasma PGF(2 alpha) concentrations hourly for the first 4 hours and subsequently every 2 hours after substance administration...
Platelet-activating factor and evidence of oxidative stress in the bronchoalveolar fluid of Thoroughbred colts during race training. Inflammatory airway disease (IAD) is prevalent in young racehorses during training, being the 2nd most commonly diagnosed ailment interrupting training of 2-year-old Thoroughbred racehorses. Objective: That stabling and exercise cause oxidative stress, release of platelet-activating factor (PAF) and inflammation in airways of Thoroughbred colts. Methods: Colts in breeding farms (NC, n = 45), stabled for 30 days (EC, n = 40), and race trained (EX, n = 34). Methods: Cytological profile and parameters of bronchoalveolar lavage fluid (BALF) related to oxidative stress, bioactivity of the proinflam...
Medical implications of obesity in horses–lessons for human obesity. There is growing recognition that obesity is common and represents a significant detriment to the health of companion animals in a manner similar to that by which it is affecting the human population. As is the case for other species, obesity appears to promote insulin resistance in horses and it is through this pathophysiological process that many of the adverse medical consequences of obesity are being characterized. Equine medical conditions that have been described in the context of obesity and insulin resistance differ from those in humans. Chronic human conditions that have been attribut...
