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Topic:Inflammation

Inflammation is a biological response of the horse's body to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a complex process that involves the activation of immune cells, the release of inflammatory mediators, and changes in blood flow. In horses, inflammation can manifest in various forms, affecting different tissues and organs, including the joints, respiratory system, and skin. The inflammatory response is an essential component of the horse's immune system, aiming to eliminate the initial cause of cell injury, clear out damaged cells and tissues, and establish tissue repair. This topic page gathers peer-reviewed research studies and scholarly articles that explore the mechanisms, effects, and management of inflammation in equine health.
The effects of dexamethasone and prednisolone on pituitary and ovarian function in the mare.
Equine veterinary journal    July 20, 2010   Volume 42, Issue 5 438-443 doi: 10.1111/j.2042-3306.2010.00034.x
Ferris RA, McCue PM.Persistent mating induced endometritis is among the most common causes of infertility in the mare. Recently, improved pregnancy rates have been reported when corticosteroids were administered to 'problem mares' specifically, to modulate the post mating inflammatory response; however, the effect of treatment on pituitary and ovarian function requires further study. Objective: To evaluate the effects of prolonged treatment with glucocorticoids on pituitary and ovarian function. Methods: Eighteen cycling Quarter Horse mares in early oestrus were assigned randomly to one of 3 treatment groups: dex...
Histopathology and computed tomography of age-associated degeneration of the equine temporohyoid joint.
Equine veterinary journal    July 20, 2010   Volume 42, Issue 5 425-430 doi: 10.1111/j.2042-3306.2010.00036.x
Naylor RJ, Perkins JD, Allen S, Aldred J, Draper E, Patterson-Kane J, Piercy RJ.The aetiology of temporohyoid osteoarthropathy (THO) is unknown; both primary infectious and degenerative causes have been suggested. Objective: There is a significant association between increasing age and severity of temporohyoid joint degeneration. To examine the histopathology of the temporohyoid articulation in aged horses and to compare the appearance of the joint with computed tomography (CT) and peripheral quantitative CT (pQCT). Methods: pQCT scans of the temporohyoid articulations were obtained bilaterally from 31 horses (range age 1-44 years) post mortem and images were graded by 2 ...
Diagnostic utility of computed tomography imaging in equine intracranial conditions.
Equine veterinary journal    July 20, 2010   Volume 42, Issue 5 393-399 doi: 10.1111/j.2042-3306.2010.00086.x
Lacombe VA, Sogaro-Robinson C, Reed SM.The use of computer tomography (CT) and contrast-enhanced CT (CCT) to image the head is common. However, the validity of CT as a neurodiagnostic indicator of intracranial diseases in horses is unknown. Objective: To define the validity of CT and CCT in horses with suspected intracranial disorders. Methods: The validity of CT imaging was estimated by comparing clinical, clinicopathological and histopathological findings to CT findings in 15 horses presented for intracranial disorders, for which pre- and post contrast CT images and post mortem examination of the brain and skull were reviewed. Po...
Peritoneal concentrations of transforming growth factor beta in horses with colic.
Equine veterinary journal    July 20, 2010   Volume 42, Issue 5 451-455 doi: 10.1111/j.2042-3306.2010.00102.x
Argüelles D, Casteljins G, Carmona JU, Armengou L, Climent F, Prades M.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...
Ascending placentitis in the mare: an update.
Reproduction in domestic animals = Zuchthygiene    July 16, 2010   Volume 45 Suppl 2 28-34 doi: 10.1111/j.1439-0531.2010.01633.x
LeBlanc MM.Ascending placentitis is a common cause of premature birth, abortion and delivery of compromised, ill foals. Recent experimental models have investigated diagnostic procedures and treatment strategies in an attempt to improve live foal rate. Diagnostics such as transrectal and transabdominal ultrasonography are used to evaluate foetal well-being and placental separation, while measurement of plasma progestins or oestrogen identifies a stressed or hypoxic foetus. Treatment is directed at stopping spread of infection, maintaining uterine quiescence and blocking production of pro-inflammatory cyt...
Advances in the diagnosis and treatment of chronic infectious and post-mating-induced endometritis in the mare.
Reproduction in domestic animals = Zuchthygiene    July 16, 2010   Volume 45 Suppl 2 21-27 doi: 10.1111/j.1439-0531.2010.01634.x
LeBlanc MM.Rapid physical uterine clearance is paramount for fertility. Mares that are unable to clear the by-products of insemination or foaling quickly may develop post-mating-induced or acute endometritis. If endometritis is not promptly resolved, the infection can become chronic. Endometritis can be difficult to identify because clinical signs, ultrasonographic and laboratory findings can vary between uterine pathogens. Some micro-organisms are associated with an influx of neutrophils and fluid into the uterine lumen while others are associated with only heavy debris on cytological specimens. Identif...
IL-4 activates equine neutrophils and induces a mixed inflammatory cytokine expression profile with enhanced neutrophil chemotactic mediator release ex vivo.
American journal of physiology. Lung cellular and molecular physiology    July 16, 2010   Volume 299, Issue 4 L472-L482 doi: 10.1152/ajplung.00135.2009
Lavoie-Lamoureux A, Moran K, Beauchamp G, Mauel S, Steinbach F, Lefebvre-Lavoie J, Martin JG, Lavoie JP.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...
Optimization of a procedure to accurately detect equine TNFα in serum samples.
Veterinary immunology and immunopathology    July 6, 2010   Volume 138, Issue 1-2 118-123 doi: 10.1016/j.vetimm.2010.06.018
Lavoie-Lamoureux A, Maghni K, Lavoie JP.The systemic component of chronic inflammatory diseases may lead to clinical complications. High levels of TNFα, a pro-inflammatory cytokine, are found in human patients with COPD and asthma. Horses are also susceptible to an array of chronic inflammatory disorders possibly associated with systemic inflammation, including respiratory diseases. Currently, there is no commercially available ELISA validated to assess TNFα in equine serum samples. Moreover, the reported normal mean concentration of serum TNFα in horses vary greatly. Hence, we sought to optimize and validate a procedure to quant...
Deciphering membrane-associated molecular processes in target tissue of autoimmune uveitis by label-free quantitative mass spectrometry.
Molecular & cellular proteomics : MCP    July 4, 2010   Volume 9, Issue 10 2292-2305 doi: 10.1074/mcp.M110.001073
Hauck SM, Dietter J, Kramer RL, Hofmaier F, Zipplies JK, Amann B, Feuchtinger A, Deeg CA, Ueffing M.Autoimmune uveitis is a blinding disease presenting with autoantibodies against eye-specific proteins as well as autoagressive T cells invading and attacking the immune-privileged target tissue retina. The molecular events enabling T cells to invade and attack the tissue have remained elusive. Changes in membrane protein expression patterns between diseased and healthy stages are especially interesting because initiating events of disease will most likely occur at membranes. Since disease progression is accompanied with a break-down of the blood-retinal barrier, serum-derived proteins mask the...
Evaluation of the role of superoxide anions in endotoxin-induced impairment of beta-adrenoceptor-mediated vasodilation in equine digital veins.
American journal of veterinary research    July 3, 2010   Volume 71, Issue 7 773-779 doi: 10.2460/ajvr.71.7.773
Mallem MY, Thuleau A, Noireaud J, Desfontis JC, Gogny M.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...
Associations of horse age, joint type, and osteochondral injury with serum and synovial fluid concentrations of type II collagen biomarkers in Thoroughbreds.
American journal of veterinary research    July 3, 2010   Volume 71, Issue 7 741-749 doi: 10.2460/ajvr.71.7.741
Nicholson AM, Trumble TN, Merritt KA, Brown MP.To determine the effects of horse age, osteochondral injury, and joint type on a synthesis biomarker and 3 degradative biomarkers of type II collagen in Thoroughbreds. Methods: Healthy rested adult (3- to 12-year-old) Thoroughbreds (n = 19), yearling (1- to 2-year-old) Thoroughbreds (40), and Thoroughbred racehorses (2 to 7 years old) undergoing arthroscopic surgery for removal of osteochondral fragments that resulted from training or racing (41). Methods: Samples of blood and metacarpophalangeal, metatarsophalangeal, or carpal joint synovial fluid (SF) were collected from all horses. Commerci...
Immunohistochemical identification of collagen in the equine lung.
Veterinary pathology    June 22, 2010   Volume 47, Issue 5 982-990 doi: 10.1177/0300985810375051
Furness MC, Bienzle D, Caswell JL, Delay J, Viel L.Recurrent airway obstruction (RAO) in the horse is a disease characterized by reversible bronchoconstriction and by mucus and neutrophil accumulation in the airways. It has been hypothesized that in horses with RAO, remodeling changes occur that are similar to those described in humans with asthma. Although collagen fibrils are present surrounding normal airways, they are a prominent feature of airway remodeling in human asthma with evidence of enhanced collagen III and I fibril deposition. An immunolabeling method was developed to identify collagen I and III in equine lung and to describe the...
A surgical tendonitis model in horses: technique, clinical, ultrasonographic and histological characterisation.
Veterinary and comparative orthopaedics and traumatology : V.C.O.T    June 21, 2010   Volume 23, Issue 4 231-239 doi: 10.3415/VCOT-09-10-0106
Schramme M, Hunter S, Campbell N, Blikslager A, Smith R.Tendon injuries are common in all athletic activities in both humans and horses. Research of treatment modalities for this disease has typically been performed on a model of collagenase-induced tendonitis. This model has several disadvantages. Our hypothesis was that a reproducible core lesion could be created surgically in superficial digital flexor tendons (SDFT), which could then be evaluated consistently using ultrasonography. Methods: Four horses free of forelimb lameness were used in this study. Each horse underwent general anaesthesia and a synovial resector was used to create a core le...
Patient variation in veterinary medicine: part I. Influence of altered physiological states.
Journal of veterinary pharmacology and therapeutics    June 19, 2010   Volume 33, Issue 3 213-226 doi: 10.1111/j.1365-2885.2009.01139.x
Martinez M, Modric S.In veterinary medicine, the characterization of a drug's pharmacokinetic (PK) properties is generally based upon data that are derived from studies that employ small groups of young healthy animals, often of a single breed. These are also the data from which population predictions are often generated to forecast drug exposure characteristics in the target population under clinical conditions of use. In veterinary medicine, it is rare to find information on the covariates that can influence drug exposure characteristics. Therefore, it is important to recognize some of the factors that can alter...
Age-related differences in prostaglandin E2 synthesis by equine cartilage explants and synoviocytes.
Journal of veterinary pharmacology and therapeutics    June 19, 2010   Volume 33, Issue 3 268-276 doi: 10.1111/j.1365-2885.2009.01131.x
Briston L, Dudhia J, Lees P.Time- and concentration-related actions of lipopolysaccharide (LPS) on the synthesis of prostaglandin E(2) (PGE(2)) were investigated in cartilage explants and synoviocytes harvested from 3 age groups of horses, all with clinically normal joint function: group A 20 years. Cartilage explants from group A horses were least and those from group C were most sensitive to LPS. Significant increases in PGE(2) concentration (P <or= 0.01) were obtained in group C horses in response to LPS concentrations of 1.0 microg/mL (and higher) after exposure for 24, 36 and 48 h, whereas explants from group A h...
Identification, validation and qualification of biomarkers for osteoarthritis in humans and companion animals: mission for the next decade.
Veterinary journal (London, England : 1997)    June 15, 2010   Volume 185, Issue 2 95-97 doi: 10.1016/j.tvjl.2010.05.026
Mobasheri A, Henrotin Y.No abstract available
Endocrinopathic laminitis.
The Veterinary clinics of North America. Equine practice    June 11, 2010   Volume 26, Issue 2 233-237 doi: 10.1016/j.cveq.2010.04.009
McGowan CM.In laminitis occurring in the field, as opposed to laminitis occurring during hospitalization or severe illness, endocrinopathic laminitis is the predominant form of laminitis. Prevalent causes of endocrinopathic laminitis are ECS and EMS. Exclusion of inflammatory or weight bearing causes of laminitis and focussing on the identification and treatment of underlying endocrine conditions will improve laminitis management strategies.
Endocrinopathic laminitis: reducing the risk through diet and exercise.
The Veterinary clinics of North America. Equine practice    June 9, 2010   Volume 26, Issue 2 371-378 doi: 10.1016/j.cveq.2010.04.005
Menzies-Gow NJ.Certain individual animals appear predisposed to recurrent pasture-associated laminitis, but the exact mechanisms underlying their predisposition remain a fundamental question in laminitis research. The risk of endocrinopathic laminitis can be reduced if steps are taken to improve insulin sensitivity and reduce inflammation using strategies based on exercise and diet. Exercise has been shown to reduce insulin resistance and suppress inflammation, and dietary manipulation can significantly affect insulin sensitivity.
A morphological and quantitative immunohistochemical study of the interstitial cells of Cajal in the normal equine intestinal tracts.
Equine veterinary journal    June 9, 2010   Volume 42, Issue 4 358-366 doi: 10.1111/j.2042-3306.2010.00031.x
Pavone S, Mandara MT.The interstitial cells of Cajal (ICC) play a key role in the control of intestinal motility and have been implicated in several human gastrointestinal dysmotility syndromes, in equine grass sickness and in other intestinal disorders where a significant reduction in ICC density was observed. Objective: To investigate the density of ICC in clinically normal horses, ICC c-Kit expression was evaluated by image analysis in order to obtain numerical data. Methods: Intestinal samples from the jejunum to small colon from 5 clinically normal horses were studied. Immunohistochemical labelling of ICC was...
Corticosteroid-associated laminitis.
The Veterinary clinics of North America. Equine practice    June 8, 2010   Volume 26, Issue 2 277-285 doi: 10.1016/j.cveq.2010.04.001
Bailey SR.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.
Experimental induction of recurrent airway obstruction with inhaled fungal spores, lipopolysaccharide, and silica microspheres in horses.
American journal of veterinary research    June 2, 2010   Volume 71, Issue 6 682-689 doi: 10.2460/ajvr.71.6.682
Beeler-Marfisi J, Clark ME, Wen X, Sears W, Huber L, Ackerley C, Viel L, Bienzle D.To evaluate experimental induction of recurrent airway obstruction (RAO) with inhaled fungal spores, lipopolysaccharide, and silica microspheres in horses. Methods: 7 horses with and 3 horses without a history of RAO. Methods: RAO-susceptible horses ranged in age from 17 to approximately 30 years, and control horses ranged in age from 7 to approximately 15 years. Pure mold cultures were derived from repeated culture of hay and identified via gene amplification and sequencing. Pulmonary function testing and bronchoalveolar lavage were performed before and after nebulization with a suspension of...
In vitro expression of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in cultured equine articular cells.
American journal of veterinary research    June 2, 2010   Volume 71, Issue 6 615-622 doi: 10.2460/ajvr.71.6.615
Byron CR, Barger AM, Stewart AA, Pondenis HC, Fan TM.To determine concentrations of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) in equine chondrocytes and synoviocytes and to quantify changes in the OPG:RANKL ratio in response to exogenous factors. Methods: Samples of articular cartilage and synovium with grossly normal appearance obtained from metacarpophalangeal and metatarsophalangeal joints of 5 adult (1- to 8-year-old) horses. Methods: Cell cultures of chondrocytes and synoviocytes were incubated with human recombinant interleukin-1beta (hrIL-1beta; 10 ng/mL), lipopolysaccharide (LPS; 10 microg/mL), ...
The efficacy of imiquimod 5% cream (Aldara® in the treatment of aural plaque in horses: a pilot open-label clinical trial.
Veterinary dermatology    May 24, 2010   Volume 21, Issue 5 503-509 doi: 10.1111/j.1365-3164.2009.00877.x
Torres SM, Malone ED, White SD, Koch SN, Watson JL.Aural plaques affect at least 22% of horses and can be asymptomatic or cause ear sensitivity. Immunohistochemical and electron microscopy studies have shown a strong association between aural plaques and papilloma virus. The purpose of this study was to investigate the efficacy of imiquimod 5% cream, an immune response modifier with potent antiviral activity, in the treatment of equine aural plaques. Twenty-one horses were enrolled and 16 completed the study. Imiquimod 5% cream was applied three times a week, every other week. When both ears were affected only the worst affected ear was treate...
Effect of intravenous lidocaine administration on laminar inflammation in the black walnut extract model of laminitis.
Equine veterinary journal    May 22, 2010   Volume 42, Issue 3 261-269 doi: 10.2746/042516409X475760
Williams JM, Lin YJ, Loftus JP, Faleiros RR, Peroni JF, Hubbell JA, Ravis WR, Belknap JK.Laminitis is a serious complication of horses suffering from sepsis/endotoxaemia-related events. Laminitis in horses and organ injury in human sepsis are both reported to involve inflammatory injury to the laminae/organs including early activation of endothelium and leucocytes leading to emigration of neutrophils into the tissue interstitium. In the black walnut extract (BWE) model, systemic inflammatory events coincide with marked increase in laminar mRNA concentrations of inflammatory genes including proinflammatory cytokines (i.e. IL-1beta, IL-6), COX-2, chemokines (i.e. IL-8) and endotheli...
Comparison of endoscopy, histology, and cytokine mRNA of the equine gastric mucosa.
Veterinary research communications    May 18, 2010   Volume 34 Suppl 1 S121-S124 doi: 10.1007/s11259-010-9401-6
Pietra M, Morini M, Perfetti G, Spadari A, Vigo P, Peli A.In recent years, gastric ulceration has been recognized as a common, possibly performance-limiting disease, of adult horses. The aim of this study was to compare endoscopic features, histological diagnosis, and mRNA levels of various cytokines (TNF-alpha, IL-1beta, and IL-13) from horse gastric biopsies. Eleven horses suffering from equine gastric ulcer syndrome and seven horses with normal histological gastric features were assessed. No correlation between endoscopic features and histology (i.e., the gold standard) was observed. Based on histological diagnosis, a significant (p < 0.05) inc...
Enteric dysganglionosis resembling intestinal neuronal dysplasia in a foal with bacterial colitis.
Veterinary pathology    May 13, 2010   Volume 47, Issue 4 654-657 doi: 10.1177/0300985810370006
Giri DK, Quist EM, Ambrus A, Gold J, Porter BF, Bratton GR, Storts RW.A 5-day-old quarter horse colt with a history of hypothermia, agonal breathing, and diarrhea was euthanized. At necropsy, numerous slightly raised, discrete, closely approximated submucosal nodules were observed in the colon and small intestine. Histologically, these nodules were composed of expanded submucosal mesenchyme that contained numerous neurons either individually or in ganglia. Thirty-two percent of these ganglia included 8 or more neurons, in contrast to 6% in an age-matched foal. Some nodules had necrosuppurative inflammation with vasculitis, thrombosis, and bacterial colonization....
Immunohistochemical study of matrix metalloproteinases-2 and -9, macrophage inflammatory protein-2 and tissue inhibitors of matrix metalloproteinases-1 and -2 in normal, purulonecrotic and fungal infected equine corneas.
Veterinary ophthalmology    May 8, 2010   Volume 13, Issue 2 81-90 doi: 10.1111/j.1463-5224.2009.00757.x
Boveland SD, Moore PA, Mysore J, Krunkosky TM, Dietrich UM, Jarrett C, Paige Carmichael K.Determine the effects of matrix metalloproteinases (MMPs)-2, -9, macrophage inflammatory protein-2 (MIP-2), tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -2 by immunohistochemical expression in fungal affected and purulonecrotic corneas. Methods: Paraffin-embedded equine corneal samples; normal (n = 9), fungal affected (FA; n = 26), and purulonecrotic without fungi (PN; n = 41) were evaluated immunohistochemically for MMP-2, -9, MIP-2, TIMP-1 and -2. The number of immunoreactive inflammatory cells was counted and statistics analyzed. Western blot was performed to detect MMP-2, MMP...
In vivo administration of acepromazine or promethazine to horse decreases the reactive oxygen species production response of subsequently isolated neutrophils to stimulation with phorbol myristate acetate.
Journal of veterinary pharmacology and therapeutics    May 7, 2010   Volume 32, Issue 6 541-547 doi: 10.1111/j.1365-2885.2009.01077.x
Péters F, Franck T, Pequito M, de la Rebière G, Grulke S, Salccicia A, Verwilghen D, Chiavaccini L, Deby-Dupont G, Serteyn D.The previous experiments have shown that some phenothiazines have antioxidant and anti-inflammatory properties in vitro. In this study the inhibition of the production of reactive oxygen species (ROS) by neutrophils was studied in two groups of horses, which received a dose of 0.1 mg/kg of either acepromazine or promethazine intravenously. Blood samples were collected before (T0) and 0.5, 1, 3 and 5 h after drug administration. The chemiluminescence (CML) response of neutrophils was measured ex vivo in the presence of luminol for a period of 10 min and the maximum CML value (peak value) record...
Therapeutic efficacy of undenatured type-II collagen (UC-II) in comparison to glucosamine and chondroitin in arthritic horses.
Journal of veterinary pharmacology and therapeutics    May 7, 2010   Volume 32, Issue 6 577-584 doi: 10.1111/j.1365-2885.2009.01079.x
Gupta RC, Canerdy TD, Skaggs P, Stocker A, Zyrkowski G, Burke R, Wegford K, Goad JT, Rohde K, Barnett D, DeWees W, Bagchi M, Bagchi D.The present investigation evaluated arthritic pain in horses receiving daily placebo, undenatured type II collagen (UC-II) at 320, 480, or 640 mg (providing 80, 120, and 160 mg active UC-II, respectively), and glucosamine and chondroitin (5.4 and 1.8 g, respectively, bid for the first month, and thereafter once daily) for 150 days. Horses were evaluated for overall pain, pain upon limb manipulation, physical examination, and liver and kidney functions. Evaluation of overall pain was based upon a consistent observation of all subjects during a walk and a trot in the same pattern on the same sur...
Evaluation of the effects of transendoscopic diode laser palatoplasty on clinical, histologic, magnetic resonance imaging, and biomechanical findings in horses.
American journal of veterinary research    May 4, 2010   Volume 71, Issue 5 575-582 doi: 10.2460/ajvr.71.5.575
Alkabes KC, Hawkins JF, Miller MA, Nauman E, Widmer W, Dunco D, Kras J, Couetil L, Lescun T, Gautam R.To determine the effects of diode laser palatoplasty on the soft palate in horses. Methods: 6 clinically normal horses and 6 euthanized horses from another study. Methods: 6 horses underwent diode laser palatoplasty (treated horses); 3 received low-dose laser treatment (1,209 to 1,224 J), and 3 received high-dose treatment (2,302 to 2,420 J). Six other horses received no treatment (control horses). The upper respiratory tracts of all treated horses were evaluated immediately following surgery (day 0) and on days 2, 7, 14, 21, 30, and 45. Horses were euthanized on day 45, and magnetic resonance...
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