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Topic:Neutrophils

Neutrophils are a type of white blood cell that play a significant role in the immune system of horses. They are involved in the body's defense mechanisms against infections and are typically one of the first responders to microbial invasion or tissue damage. Neutrophils function by engulfing and destroying pathogens through processes such as phagocytosis and the release of antimicrobial substances. In horses, the number and activity of neutrophils can be indicative of immune status and are often assessed in the context of infectious diseases, inflammation, and other health conditions. This page compiles peer-reviewed research studies and scholarly articles that explore the function, regulation, and clinical implications of neutrophils in equine health.
Pharmacologic characterization of novel adenosine A2A receptor agonists in equine neutrophils.
American journal of veterinary research    September 4, 2007   Volume 68, Issue 9 981-987 doi: 10.2460/ajvr.68.9.981
Sun WC, Moore JN, Hurley DJ, Vandenplas ML, Linden JM, Murray TF.To evaluate anti-inflammatory effects of several novel adenosine receptor agonists and to determine their specificity for various adenosine receptor subtypes on neutrophils, cells heterologously expressing equine adenosine receptors, or equine brain membranes. Methods: Neutrophils isolated from 8 healthy horses. Methods: Radioligand binding experiments were performed to compare binding affinities of adenosine receptor agonists to equine adenosine A(1), A(2A), and A(3) receptor subtypes. Effects of these agonists on endotoxin-induced production of reactive oxygen species (ROS) by equine neutrop...
Inhibitory effect of curcuminoids and tetrahydrocurcuminoids on equine activated neutrophils and myeloperoxidase activity.
Physiological research    July 26, 2007   Volume 57, Issue 4 577-587 doi: 10.33549/physiolres.931086
Franck T, Kohnen S, Grulke S, Neven P, Goutman Y, Peters F, Pirotte B, Deby-Dupont G, Serteyn D.In the horse, the inflammation response to various pathologies (intestinal strangulations, laminitis, etc.) involves an excessive stimulation of the polymorphonuclear neutrophils releasing reactive oxygen species (ROS) and myeloperoxidase (MPO). The aim of the present work was to study the effect of natural polyphenols, curcuminoids and tetrahydrocurcuminoids (THC) on isolated stimulated equine neutrophils and on the activity of purified MPO. The ROS production and the release of MPO by activated neutrophils were measured by chemiluminescence and ELISA techniques, respectively. The activity of...
Effects of stimulation of adenosine A2A receptors on lipopolysaccharide-induced production of reactive oxygen species by equine neutrophils.
American journal of veterinary research    June 5, 2007   Volume 68, Issue 6 649-656 doi: 10.2460/ajvr.68.6.649
Sun WC, Moore JN, Hurley DJ, Vandenplas ML, Murray TF.To assess the anti-inflammatory effects of an adenosine analogue on lipopolysaccharide (LPS)-stimulated equine neutrophils. Methods: Neutrophils obtained from 10 healthy horses. Methods: An adenosine analogue (5'-N-ethylcarboxamidoadenosine [NECA]) was tested for its ability to inhibit production of reactive oxygen species (ROS) in LPS-stimulated equine neutrophils. Selective adenosine receptor antagonists were used to identify the receptor subtype responsible for effects. To assess the mechanism of action of NECA, cAMP concentrations were measured, and effects of dibutyryl cAMP (a stable anal...
IL-4 stimulates the expression of CXCL-8, E-selectin, VEGF, and inducible nitric oxide synthase mRNA by equine pulmonary artery endothelial cells.
American journal of physiology. Lung cellular and molecular physiology    May 15, 2007   Volume 292, Issue 5 L1147-L1154 doi: 10.1152/ajplung.00294.2006
Huang H, Lavoie-Lamoureux A, Moran K, Lavoie JP.Little is known concerning the possible contribution of T helper 2 (Th2)-type cytokines to the recruitment of neutrophils into the lung tissue. In the present study, endothelial cells from equine pulmonary arteries were cultured in the presence of recombinant equine (re) IL-4 and reIL-5, and the cytokine mRNA expression of molecules implicated in the chemotaxis and migration of neutrophils was studied using real-time RT-PCR. The functional response of reIL-4-induced endothelial cell stimulation on neutrophil migration was also studied using a chemotaxis chamber. ReIL-4 either increased the exp...
Plasma concentrations of myeloperoxidase in endurance and 3-day event horses after a competition.
Equine veterinary journal. Supplement    April 4, 2007   Issue 36 298-302 doi: 10.1111/j.2042-3306.2006.tb05557.x
Art T, Franck T, Gangl M, Votion D, Kohnen S, Deby-Dupont G, Serteyn D.In man, exercise of any type has been shown to induce neutrophil degranulation and respiratory burst activity, as well as an increase in plasma myeloperoxidase (MPO), a specific enzyme of neutrophil azurophilic granules with a strong oxidative activity. Until now, it is not known whether this is the same in horses. Objective: To study whether degranulation of blood neutrophils may be induced by exercise by measuring the total concentration of MPO and assess the possible influence of type of competition on this exercise-induced adjustment. Methods: Blood was sampled before, and 30 min after, th...
Prevalence of inflammatory airway disease in national hunt horses referred for investigation of poor athletic performance.
Equine veterinary journal. Supplement    April 4, 2007   Issue 36 529-534 doi: 10.1111/j.2042-3306.2006.tb05599.x
Allen KJ, Tremaine WH, Franklin SH.Inflammatory airway disease (IAD) is thought to be an important cause of poor performance in young Thoroughbred racehorses. However, little study has been made of IAD in older National Hunt (NH) horses. Objective: To determine the prevalence of IAD in NH racehorses referred for investigation of poor athletic performance and identify some of the risk factors that may be associated with IAD in this group of horses. Methods: Tracheal mucus was graded, and tracheal wash (TW) and bronchoalveolar lavage (BAL) performed after treadmill exercise in 91 NH horses referred to the University of Bristol. C...
Hypersegmentation of equine neutrophils.
Veterinary clinical pathology    February 22, 2007   Volume 36, Issue 1 4-5 doi: 10.1111/j.1939-165x.2007.tb00172.x
Tvedten H, Riihimäki M.No abstract available
Cellular basis of chronic obstructive pulmonary disease in horses.
International review of cytology    February 7, 2007   Volume 257 213-247 doi: 10.1016/S0074-7696(07)57006-3
Marinkovic D, Aleksic-Kovacevic S, Plamenac P.Chronic obstructive pulmonary disease (COPD) is an inflammatory obstructive disease of the airways characterized with hypersensitivity of the airway tissues to various allergens, most commonly the fungi contained in the poor-quality hay and straw bedding-Saccharopolyspora rectivirgula, Aspergillus fumigatus, and Thermoactinomyces vulgaris. It is manifested clinically in middle-aged horses with recurrent episodes of dyspnea, chronic cough, and their reduced athletic and working capacity. Pulmonary emphysema and lack of pulmonary collapse are the most common gross lesion. Pathohistological findi...
Influx of neutrophils and persistence of cytokine expression in airways of horses after performing exercise while breathing cold air.
American journal of veterinary research    February 3, 2007   Volume 68, Issue 2 185-189 doi: 10.2460/ajvr.68.2.185
Davis MS, Williams CC, Meinkoth JH, Malayer JR, Royer CM, Williamson KK, McKenzie EC.To determine effects of exercise performed while breathing cold air on expression of cytokines and influx of neutrophils in airways of horses. Methods: 9 adult horses. Methods: In a crossover study, bronchoalveolar lavage fluid (BALF) was obtained 24 and 48 hours after each of 2 submaximal exercise sessions performed by horses while breathing warm (25 degrees C) or cold (-5 degrees C) air. Total and differential nucleated cell counts were determined for each BALF sample. Relative mRNA expression of cytokines in BALF cells was quantified by use of a reverse transcription-PCR assay. Results: Hor...
Neutrophil myeloperoxidase measurements in plasma, laminar tissue, and skin of horses given black walnut extract.
American journal of veterinary research    January 4, 2007   Volume 68, Issue 1 81-86 doi: 10.2460/ajvr.68.1.81
Riggs LM, Franck T, Moore JN, Krunkosky TM, Hurley DJ, Peroni JF, de la Rebière G, Serteyn DA.To compare measurements of myeloperoxidase (MPO) in plasma, laminar tissues, and skin obtained from control horses and horses given black walnut heartwood extract (BWHE). Methods: 22 healthy 5- to 15-year-old horses. Methods: Horses were randomly assigned to 4 groups as follows: a control group given water (n = 5) and 3 experimental groups given BWHE (17) via nasogastric intubation. Experimental groups consisted of 5, 6, and 6 horses that received BWHE and were euthanatized at 1.5, 3, and 12 hours after intubation, respectively. Control horses were euthanatized at 12 hours after intubation. Pl...
Serial alterations in digital hemodynamics and endothelin-1 immunoreactivity, platelet-neutrophil aggregation, and concentrations of nitric oxide, insulin, and glucose in blood obtained from horses following carbohydrate overload.
American journal of veterinary research    January 4, 2007   Volume 68, Issue 1 87-94 doi: 10.2460/ajvr.68.1.87
Eades SC, Stokes AM, Johnson PJ, LeBlanc CJ, Ganjam VK, Buff PR, Moore RM.To quantify changes in endothelium-derived factors and relate those changes to various aspects of digital hemodynamics during the prodromal stages of carbohydrate overload (CHO)-induced laminitis in horses. Methods: 20 adult horses without abnormalities of the digit. Methods: Digital and jugular venous blood samples were collected at 1-hour intervals (for assessment of endothelin-1 [ET-1] immunoreactivity and measurement of glucose, insulin, and nitric oxide [NO] concentrations) or 4-hour intervals (CBC and platelet-neutrophil aggregate assessment) for 8 hours or 16 hours after induction of CH...
Elevated amount of Toll-like receptor 4 mRNA in bronchial epithelial cells is associated with airway inflammation in horses with recurrent airway obstruction.
American journal of physiology. Lung cellular and molecular physiology    December 8, 2006   Volume 292, Issue 4 L936-L943 doi: 10.1152/ajplung.00394.2006
Berndt A, Derksen FJ, Venta PJ, Ewart S, Yuzbasiyan-Gurkan V, Robinson NE.Recurrent airway obstruction (RAO) is characterized by neutrophilic airway inflammation and obstruction, and stabling of susceptible horses triggers acute disease exacerbations. Stable dust is rich in endotoxin, which is recognized by Toll-like receptor (TLR) 4. In human bronchial epithelium, TLR4 stimulation leads to elevation of interleukin (IL)-8 mRNA expression. The zinc finger protein A20 negatively regulates this pathway. We hypothesized that TLR4 and IL-8 mRNA and neutrophil numbers are elevated and that A20 mRNA is not increased in RAOs during stabling compared with controls and with R...
Se18.9, an anti-phagocytic factor H binding protein of Streptococcus equi.
Veterinary microbiology    November 28, 2006   Volume 121, Issue 1-2 105-115 doi: 10.1016/j.vetmic.2006.11.023
Tiwari R, Qin A, Artiushin S, Timoney JF.Evasion of phagocytosis is an important virulence determinant of Streptococcus equi (S. equi subsp. equi), the cause of equine strangles and distinguishes it from the closely related but much less virulent S. zooepidemicus (S. equi subsp. zooepidemicus). We describe Se18.9, a novel H factor binding protein secreted by S. equi but not by S. zooepidemicus that reduces deposition of C3 on the bacterial surface and significantly reduces the bactericidal activity of equine neutrophils suspended in normal serum for both S. equi and S. zooepidemicus. Se18.9 is secreted abundantly by actively dividing...
Myeloperoxidase concentration in bronchoalveolar lavage fluid from healthy horses and those with recurrent airway obstruction.
Canadian journal of veterinary research = Revue canadienne de recherche veterinaire    October 18, 2006   Volume 70, Issue 4 291-296 
Art T, Franck T, Lekeux P, de Moffarts B, Couëtil L, Becker M, Kohnen S, Deby-Dupont G, Serteyn D.The aim of this work was to measure the myeloperoxidase (MPO) concentration in bronchoalveolar lavage (BAL) fluid collected from horses with recurrent airway obstruction (RAO), both in crisis and in remission, as well as from healthy horses. Seven horses with RAO were exposed to moldy hay until the maximum change in pleural pressure was greater than 1.5 kPa. At that point, BAL was performed, and the total cell counts and percentages in the fluid were immediately determined. To measure the MPO concentration in BAL-fluid supernatant, we used a specific enzyme-linked immunosorbent assay with poly...
Effect of tracheal mucus and tracheal cytology on racing performance in Thoroughbred racehorses.
Equine veterinary journal    July 27, 2006   Volume 38, Issue 4 300-304 doi: 10.2746/042516406777749191
Holcombe SJ, Robinson NE, Derksen FJ, Bertold B, Genovese R, Miller R, de Feiter Rupp H, Carr EA, Eberhart SW, Boruta D, Kaneene JB.Accumulations of mucus within the trachea are often found during endoscopic examinations of the airways of poorly performing racehorses, but the clinical importance of this finding is unknown. Objective: To determine the effect of tracheal mucus, pharyngeal lymphoid hyperplasia (PLH) and cytological indices of tracheal aspirate on racing performance in Thoroughbred horses assessed by race place and whether the horse was raced. Methods: Endoscopic examination of the nasopharynx, larynx and trachea was performed, and a tracheal aspirate obtained monthly at Thistledown racetrack from April to Dec...
The effect of aerosolized and intravenously administered clenbuterol and aerosolized fluticasone propionate on horses challenged with Aspergillus fumigatus antigen.
Veterinary research communications    July 14, 2006   Volume 30, Issue 6 623-635 doi: 10.1007/s11259-006-3346-9
Laan TT, Bull S, van Nieuwstadt RA, Fink-Gremmels J.Beta-agonists have been shown to display anti-inflammatory properties in several experimental models. The aim of this study was to investigate the anti-inflammatory properties of clenbuterol (CB), administered either intravenously or by aerosol, in comparison with fluticasone propionate (FP) in recurrent airway obstruction (RAO)-susceptible horses. Eight horses, of which five were known to be susceptible to RAO, underwent an inhalation challenge with Aspergillus fumigatus (AF) antigen and were treated with CB intravenously, CB by aerosol, or FP by aerosol. Twenty-four hours after the challenge...
Matrix metalloproteinase-9 in laminae of black walnut extract treated horses correlates with neutrophil abundance.
Veterinary immunology and immunopathology    July 5, 2006   Volume 113, Issue 3-4 267-276 doi: 10.1016/j.vetimm.2006.05.010
Loftus JP, Belknap JK, Black SJ.We sought to determine whether a correlation exists between neutrophil infiltration and tissue matrix metalloproteinase-9 (MMP-9) content in digital laminae collected during the prodromal and acute phases of laminitis in horses treated with an aqueous black walnut heartwood extract (BWE). Hoof laminar tissue was obtained at the onset of leukopenia and at the onset of clinical signs of lameness from BWE-treated horses and at equivalent times from control horses. Thin sections of laminae were screened for neutrophils by immunohistochemistry with an anti-CD13 monoclonal antibody and extracts of t...
Rapid, multiwell colorimetric assay for measuring neutrophil chemoattractant activity in bronchoalveolar lavage fluid of horses with recurrent airway obstruction. Hall JA, Hoyt D, Zuver C, Skinner MM, Schlipf JW.The criteria used to diagnose recurrent airway obstruction (RAO) in affected horses include demonstration of reversible lower airway obstruction and greater than 25% neutrophils in bronchoalveolar lavage fluid (BALF). Additional objective laboratory tests are needed to improve diagnostic accuracy and to monitor response to treatment. The goal of this study was to determine if neutrophil chemoattractant activity of BALF could be measured by using a previously described, rapid, multiwell colorimetric assay for chemotaxis. In this assay, neutrophils that have migrated through a membrane filter ar...
Evidence for the expression and enzymatic activity of haem oxygenase-1 in the lungs of horses.
The Veterinary record    June 13, 2006   Volume 158, Issue 23 795-797 doi: 10.1136/vr.158.23.795
Wyse CA, Nixon C, McLaughlin M, Dowell FJ, Philbey AW.The aim of this study was to characterise the expression of haem oxygenase-1 (HO-1) in healthy lung tissue from horses and to measure its activity. Samples of lung tissue were collected from six horses euthanased for reasons other than respiratory disease. HO-1 expression and activity were detected in type II alveolar epithelial cells, macrophages and neutrophils in all the samples examined. The activity was dependent on the presence of NADPH and inhibited quantitatively by the addition of increasing concentrations of a competitive inhibitor of HO-1, tin mesoporphyrin IX.
Importance of using guarded techniques for the preparation of endometrial cytology smears in mares.
Theriogenology    January 20, 2006   Volume 66, Issue 2 423-430 doi: 10.1016/j.theriogenology.2005.12.007
Aguilar J, Hanks M, Shaw DJ, Else R, Watson E.Material for endometrial cytology can be collected by veterinarians using guarded or unguarded swabs, or digitally with a gloved hand, and is an important diagnostic tool in establishing the endometrial health of mares prior to breeding. The aim of this study was to determine whether the use of unguarded endometrial samples is a reliable indicator of the presence of neutrophils in the uterus. Duplicate endometrial smears were collected from 41 genitally normal, non-pregnant fertile mares by both double-guarded swabs (DGS) and in an unguarded manner by digital scraping (DS) of the endometrium. ...
Development of an enzyme-linked immunosorbent assay for specific equine neutrophil myeloperoxidase measurement in blood. Franck T, Grulke S, Deby-Dupont G, Deby C, Duvivier H, Peters F, Serteyn D.Equine inflammatory disease is accompanied by a neutrophil activation resulting in the release of granulocytic enzyme myeloperoxidase (MPO). To measure MPO in horse plasma as marker of neutrophil activation, the authors purified equine neutrophil MPO and developed a specific enzyme immunoassay using 2 specific polyclonal antibodies obtained from rabbit (primary antibody) and guinea pig (secondary antibody). The sandwich complex "primary antibody-MPO-secondary antibody" was detected using a goat anti-guinea pig immunoglobulin antibody conjugated to alkaline phosphatase. The enzyme-linked immuno...
Dynamic changes in circulating leukocytes during the induction of equine laminitis with black walnut extract.
Veterinary immunology and immunopathology    November 10, 2005   Volume 110, Issue 3-4 195-206 doi: 10.1016/j.vetimm.2005.09.015
Hurley DJ, Parks RJ, Reber AJ, Donovan DC, Okinaga T, Vandenplas ML, Peroni JF, Moore JN.Administration of black walnut heartwood extract (BWHE) via nasogastric tube induces acute laminitis in horses. However, the processes responsible for the development of laminitis, including laminitis induced with BWHE, remain unclear. The results of recent studies indicate that administration of BWHE initiates an inflammatory response in the laminar tissues and that this response may be due to extravasation of activated leukocytes from the circulation. This study examines the effects of BWHE administration on the dynamics of circulating neutrophils and monocytes, and the capacity of blood leu...
Influence of repeated artificial insemination (IS) on functional properties of uterine neutrophils of mares.
Animal reproduction science    November 3, 2005   Volume 89, Issue 1-4 258-261 
Görgens A, Leibold W, Klug E, Schuberth HJ, Martinsson , Zerbe H.No abstract available
Effect of acute airway inflammation on the pulmonary antioxidant status.
Experimental lung research    October 6, 2005   Volume 31, Issue 7 653-670 doi: 10.1080/01902140591007092
Deaton CM, Marlin DJ, Smith NC, Harris PA, Dagleish MP, Schroter RC, Kelly FJ.Effects of acute airway inflammation induced by organic dust inhalation on pulmonary antioxidant status were investigated in healthy horses and horses affected by recurrent airway obstruction. Exposure to organic dust induced acute airway neutrophilia, which was associated with increases in elastase and decreases in ascorbic acid concentrations in bronchoalveolar lavage fluid. However, markers of oxidative stress were unaffected, as was hydrogen peroxide in breath condensate. Decreases in ascorbic acid correlated with increased respiratory resistance (P = .001) when both groups were combined. ...
Leukocyte emigration in the early stages of laminitis.
Veterinary immunology and immunopathology    September 19, 2005   Volume 109, Issue 1-2 161-166 doi: 10.1016/j.vetimm.2005.08.017
Black SJ, Lunn DP, Yin C, Hwang M, Lenz SD, Belknap JK.The mechanisms that initiate the pathophysiologic changes in the digital laminae in equine laminitis are poorly understood. Due to the fact that (1) the horse at risk of laminitis has many similarities clinically to the human sepsis patient and (2) our recent finding of marked laminar proinflammatory cytokine expression at the developmental time point of the black walnut extract (BWE) model of laminitis, we tested the possibility that, similar to organ damage in human sepsis, leukocyte emigration is an early event in laminitis. Using immunoperoxidase methods with an anti-equine CD13 monoclonal...
Expression of interleukin (IL)-5 and IL-9 receptors on neutrophils of horses with heaves.
Veterinary immunology and immunopathology    September 12, 2005   Volume 109, Issue 1-2 31-36 doi: 10.1016/j.vetimm.2005.06.017
Dewachi O, Joubert P, Hamid Q, Lavoie JP.Heaves, a condition associated with airway neutrophilia, is believed to result from an allergic response to environmental dust particles. However, the contribution of neutrophils to the allergic response is poorly understood. It has been hypothesized that Th2-type cytokines can directly activate neutrophils to produce pro-inflammatory mediators. The present study focused on the presence of receptors for the Th2-type cytokines interleukin (IL)-5 and IL-9 on peripheral blood neutrophils of horses with heaves. Neutrophils were isolated from peripheral blood of horses with heaves (n=7), and normal...
Effect of plasma transfusion on neutrophil function in healthy and septic foals.
Australian veterinary journal    August 27, 2005   Volume 83, Issue 8 499-505 doi: 10.1111/j.1751-0813.2005.tb13304.x
McTaggart C, Penhale J, Raidala SL.To evaluate the effect of plasma transfusion on phagocytosis and oxidative burst activity of peripheral blood neutrophils from healthy and septic equine neonates with sub-optimal passive transfer of maternal immunity. Methods: Nine healthy and seven septic foals with suboptimal passive transfer of maternal immunity (serum IgG or = 8 g/L. Methods: Foals with serum IgG concentrations or = 11. All foals received between 1 and 3 L of plasma to boost circulating IgG concentrations to > or = 8 g/L. Serum IgG concentrations were determined before and following transfusion by glutaraldehyde coagu...
Components in seminal plasma regulating sperm transport and elimination.
Animal reproduction science    August 17, 2005   Volume 89, Issue 1-4 171-186 doi: 10.1016/j.anireprosci.2005.07.005
Troedsson MH, Desvousges A, Alghamdi AS, Dahms B, Dow CA, Hayna J, Valesco R, Collahan PT, Macpherson ML, Pozor M, Buhi WC.Seminal plasma has been suggested to be involved in sperm transport, and as a modulator of sperm-induced inflammation, which is thought to be an important part of sperm elimination from the female reproductive tract. This article reports on recent experiments on the importance of seminal plasma components in sperm transport and elimination. In Experiment 1, hysteroscopic insemination in the presence (n = 3) or absence (n = 3) of 2 ng/mL PGE showed an increased portion of spermatozoa crossing the utero-tubal junction in the presence of PGE in two mares, while no difference was observed between ...
Temporal regulation of cytokine mRNA expression in equine recurrent airway obstruction.
Veterinary immunology and immunopathology    August 16, 2005   Volume 108, Issue 1-2 237-245 doi: 10.1016/j.vetimm.2005.07.013
Horohov DW, Beadle RE, Mouch S, Pourciau SS.Acute and chronic inflammation of the airway remains an important health problem for equids. "Heaves" or recurrent airway obstruction (RAO) remains one of the most commonly diagnosed conditions affecting the lung of older horses in Europe and the United States. The typical clinical signs of RAO include non-productive coughing, serous nasal discharge, labored expiratory effort, and flaring of the nostrils. Auscultation of the lungs of the affected horse often reveals abnormal respiratory sounds, described as crackles and wheezes, throughout the area of the lung field. These clinical signs occur...
Hemangiosarcoma in 11 young horses.
Journal of veterinary internal medicine    August 13, 2005   Volume 19, Issue 4 564-570 doi: 10.1892/0891-6640(2005)19[564:hiyh]2.0.co;2
Johns I, Stephen JO, Del Piero F, Richardson DW, Wilkins PA.Hemangiosarcoma is a rare neoplasm of horses and hemangiosarcoma in young horses might behave differently than in mature horses. The purpose of this study was to identify the characteristics of hemangiosarcoma occurring in horses < or = 3 years of age. Medical records from 1982 to 2004 were searched for horses < or = 3 years of age with a histopathologic diagnosis of hemangiosarcoma. Eleven records were identified. Thoroughbred and Thoroughbred crosses predominated. Age ranged from 9 days to 3 years. All horses presented with cutaneous or leg swellings or joint effusion. Physical examina...
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