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Topic:Pathogenesis
Pathogenesis in horses refers to the biological mechanisms that lead to the development and progression of diseases within equine species. This process involves a complex interaction between the horse's immune system, genetic predispositions, environmental factors, and infectious agents such as bacteria, viruses, or parasites. Understanding pathogenesis is essential for identifying how diseases manifest and progress in horses, which can inform diagnostic and therapeutic strategies. Research in this area often focuses on specific diseases, examining factors such as pathogen entry, immune response, tissue damage, and recovery processes. This page compiles peer-reviewed research studies and scholarly articles that explore the mechanisms, contributing factors, and implications of pathogenesis in equine health.
Arterial calcification in race horses. Calcification of large arteries has been sporadically reported in horses. The pathogenesis is still unknown, but recent studies in humans suggest that this is a regulated biomineralizing process. This study surveyed the prevalence, distribution, and severity of vascular calcification in Thoroughbred and Standardbred racehorses. Histopathologic, ultrastructural imaging, and energy dispersive X-ray elemental analyses were used to examine the lesions. Calcification of the tunica media, predominantly the pulmonary artery, was found in 82% of horses (83/101). Young adult horses (mean [SD] age in ye...
[Genetics of recurrent airway obstruction (RAO)]. Recurrent airway obstruction (RAO) is a multifactorial and polygenic disease. Affected horses are typically 7 years of age or older and show exercise intolerance, increased breathing effort, coughing, airway neutrophilia, mucus accumulation and hyperreactivity as well as cholinergic bronchospasm. The environmental factors responsible are predominantly allergens and irritants in haydust, but the immunological mechanisms underlying RAO are still unclear. Several studies have demonstrated a familiar predisposition for RAO and it is now proven that the disease has a genetic basis. In offspring, th...
Clinical pathology of the foal. The neonatal foal is in a period of transition between fetal and extrauterine life. The clinicopathologic findings in this period often reflect the in utero environment; thus, results need to be interpreted with the knowledge of changes that intrauterine life may produce. These changes can also assist the veterinarian in identifying a foal at high risk for developing clinical problems. The veterinarian should also be aware of the normal variations in clinicopathologic findings that occur as the foal matures. As with results from all diagnostic testing, the clinicopathologic results need to be ...
A novel application of quantile regression for identification of biomarkers exemplified by equine cartilage microarray data. Identification of biomarkers among thousands of genes arrayed for disease classification has been the subject of considerable research in recent years. These studies have focused on disease classification, comparing experimental groups of effected to normal patients. Related experiments can be done to identify tissue-restricted biomarkers, genes with a high level of expression in one tissue compared to other tissue types in the body. Results: In this study, cartilage was compared with ten other body tissues using a two color array experimental design. Thirty-seven probe sets were identified as...
Seasonal changes in circadian peripheral plasma concentrations of melatonin, serotonin, dopamine and cortisol in aged horses with Cushing’s disease under natural photoperiod. Equine pituitary pars intermedia dysfunction (PPID) is a common and serious condition that gives rise to Cushing's disease. In the older horse, it results in hyperadrenocorticism and disrupted energy metabolism, the severity of which varies with the time of year. To gain insight into the mechanism of its pathogenesis, 24-h profiles for peripheral plasma melatonin, serotonin, dopamine and cortisol concentrations were determined at the winter and summer solstices, and the autumn and spring equinoxes in six horses diagnosed with Cushing's disease and six matched controls. The nocturnal rises in p...
In vitro culture of equine respiratory mucosa explants. An in vitro model of the upper respiratory tract of the horse was developed to investigate mechanisms of respiratory diseases. Four tissues of the upper respiratory tract of three horses were collected. Explants were maintained in culture at an air-liquid interface for 96h. At 0, 24, 48, 72 and 96h of cultivation, a morphometric analysis was performed using light microscopy, scanning electron microscopy and transmission electron microscopy. The explants were judged on morphometric changes of epithelium, basement membrane and connective tissue. Viability was evaluated using a fluorescent Termin...
[Hereditary diseases in the horse: I. Monogenetic diseases]. Overall, monogenetic hereditary diseases are less important for the breeding industry than polygenetic diseases because they are relatively rare. For the individual animal, however, these diseases have often a dramatic outcome and many of these diseases presently known are lethal. For several of them the exact pathogenesis is known and DNA-tests are available to confirm the exact diagnosis.
Regional pulmonary veno-occlusion: a newly identified lesion of equine exercise-induced pulmonary hemorrhage. Exercise-induced pulmonary hemorrhage (EIPH) is common in horses following intense exertion, occurring in up to 75% of racing Thoroughbreds and Standardbreds. In spite of this, the pathogenesis of EIPH is poorly understood. In 7 racing Thoroughbred horses with EIPH, 6 sections were collected from the left and right lung, representing the cranial, middle, and caudal region of the dorsal and ventral lung (84 sites total). Grossly, both right and left lungs had numerous dark brown to blue-black foci along the caudodorsal visceral pleura. Tissue sections were stained with hematoxylin-eosin, Masson...
Characterisation of the inflammatory reaction in equine idiopathic focal eosinophilic enteritis and diffuse eosinophilic enteritis. Idiopathic focal eosinophilic enteritis (IFEE) and diffuse eosinophilic enteritis (DEE) are primary eosinophilic intestinal conditions without a known cause that are associated with an increasing number of surgical colic cases. Histology may be helpful in defining disease aetiology and pathogenesis. Objective: To characterise further the inflammatory infiltrate in equine IFEE and to compare the condition with DEE. Methods: Twenty-three IFEE cases and 5 DEE cases were examined by light microscopy including immunohistology to identify infiltrating leucocytes. Inflammatory infiltrates in mucosa a...
Equine gastrointestinal motility research: where we are and where we need to go. Equine gastrointestinal motility is a central issue in cases of equine colic, post operative convalescence and alimentary conditions encountered in practice. There are significant syndromes of intestinal dysmotility in the horse such as obstructive disorders and post operative ileus that are still poorly understood. This review describes the various areas of research that aim to elucidate the pathogenesis of intestinal hypo- or hypermotility by research methods, which include studies at the cellular level, and those that employ in vitro or in vivo techniques of evaluating the physiology and me...
Epiphyseal cartilage canal blood supply to the distal femur of foals. The developmental pattern of the cartilage canal blood supply to epiphyseal growth cartilage has been linked to osteochondrosis (OC) in the tarsus of foals. This pattern has not yet been described in the distal femur, another site frequently affected by OC. Objective: To describe the developmental pattern of the blood supply to the distal femoral epiphyseal growth cartilage in 8 Standardbred foals age 0-7 weeks. Methods: One foal was sacrificed weekly from birth to age 7 weeks (n=8) to undergo a barium perfusion procedure to demonstrate vessels within cartilage canals of one hindlimb. The dist...
[Construction of an infectious clone of equine infectious anemia virus by N-glycosylation reverse-mutations]. To elucidate the role of N-glycosylation in fetal donkey dermal cell (FDD)-attenuated equine infectious anemia virus (EIAV), we constructed an N-glycosylation reverse-mutation molecular clone, pLGN191N236N246. This viral molecular clone was derived from the infectious clone pLGFD3-8 by site-directed mutagenesis. This clone was used to transfect fetal donkey dermal (FDD) cells. Infectious characteristics of transfectants were monitored by RT-PCR, indirect immune fluorescence and reverse transcriptase activity assay. After three passages in FDD cells, viral replications in the supernatant of cel...
Peripheral blood mononuclear cells represent a reservoir of bovine papillomavirus DNA in sarcoid-affected equines. Bovine papillomaviruses of types 1 and 2 (BPV-1 and -2) chiefly contribute to equine sarcoid pathogenesis. However, the mode of virus transmission and the presence of latent infections are largely unknown. This study established a PCR protocol allowing detection of <or=10 copies of the BPV-1/-2 genes E5 and L1. Subsequent screening of peripheral blood mononuclear cell (PBMC) DNA derived from horses with and without BPV-1/2-induced skin lesions demonstrated the exclusive presence of E5, but not L1, in PBMCs of BPV-1/2-infected equines. To validate this result, a blind PCR was performed from ...
A subset of equine sarcoids harbours BPV-1 DNA in a complex with L1 major capsid protein. Bovine papillomavirus type 1 or 2 (BPV-1, BPV-2) are accepted causal factors in equine sarcoid pathogenesis. Whereas viral genomes are consistently found and expressed within lesions, intact virions have never been detected, thus permissiveness of sarcoids for BPV-1 replication remains unclear. To reassess this issue, an immunocapture PCR (IC/PCR) was established using L1-specific antibodies to capture L1-DNA complexes followed by amplification of the viral genome. Following validation of the assay, 13 sarcoid-bearing horses were evaluated by IC/PCR. Samples were derived from 21 tumours, 4 per...
The equine endometrosis: new insights into the pathogenesis. This paper describes the histomorphological and immunohistochemical characterisation of phenotypic variations of endometrosis as well as potential etiological factors which may influence disease progression. In total, 779 endometrial biopsies were examined. These biopsies were taken in the breeding and non-breeding season (n=509), on defined days during the estrous cycle (n=70) and before and after experimentally induced bacterial endometritis (n=200). In addition to conventional histopathology, selected biopsies were investigated using alcianblue staining as well as immunohistochemical method...
Naturally arising point mutations in non-essential domains of equine infectious anemia virus Rev alter Rev-dependent nuclear-export activity. Equine infectious anemia virus (EIAV) exhibits a high rate of genetic variation in vivo, and results in a clinically variable disease in infected horses. In vivo populations of EIAV have been characterized by the presence of distinct, genetic subpopulations of Rev that differ in phenotype and fluctuate in dominance in a manner coincident with each clinical stage of disease. This study examined the specific mutations that arose in vivo and altered the phenotype. The Rev protein was found to be highly conserved, and only 10 aa mutations were observed at a frequency greater than 10 % in the sampl...
Effects of neuraminidase on equine isolated bronchi. It has been demonstrated in mammals that the airway hyper-responsiveness, which accompanies viral infections, is the result of increased reflex bronchoconstriction due to inhibition of muscarinic prejunctional receptors, which belong to M2 subtypes. Multiple mechanisms account for virus-induced M2 receptor dysfunction. Viral neuraminidase may deglycosylate the M2 receptor, decreasing acetylcholine affinity. Equine influenza remains a common viral respiratory disease of horses worldwide, which results in loss to the equine industry, by decreasing performance, convalescence time and loss of peak...
Truncation of cytoplasmic tail of EIAV Env increases the pathogenic necrosis. Equine Infectious Anemia Virus (EIAV), like other lentiviruses, has a transmembrane glycoprotein with an unusually long cytoplasmic tail (CT). Viral envelope (Env) proteins having CT truncations just downstream the putative membrane-spanning domain (PMSD) are assumed to exist among all wild-type budded virions, and also in some cell-adapted strains. To determine whether CT-truncated Env proteins can cause particularly deleterious effects on the Env expressing cells and/or their neighboring cells, plasmids encoding codon-optimized env gene including full-length (pE863) or CT-truncated (pE686* a...
Early changes in biomarkers of skeletal metabolism and their association to the occurrence of osteochondrosis (OC) in the horse. Diagnosis of osteochondrosis (OC) is based on clinical signs and radiography, but alternative methods for detection at an early stage would be useful. Objective: To determine in the juvenile horse the relationship between serum concentrations of a number of biomarkers that reflect changes in cartilage and bone turnover and age, feeding level, growth, and the occurrence of OC. Methods: Foals were assigned to a high (n = 20) or moderate (n = 19) feeding level group from birth to age 1 year. Bodyweight, withers height and cannon width were measured. Osteoarticular status was assessed radiographic...
Effect of paddock vs. stall housing on 24 hour gastric pH within the proximal and ventral equine stomach. Stall housing has been suggested as a risk factor for ulcer development in the equine stomach; however, the exact pathogenesis for this has not been established. Objective: To investigate the effect of 3 environmental situations (grass paddock, stall alone or stall with adjacent companion) on pH in the proximal and the ventral stomach. Methods: Six horses with permanently implanted gastric cannulae were used in a randomised, cross-over, block design. Each horse rotated through each of three 24 h environmental situations. Horses remained on their normal diet (grass hay ad libitum and grain b.i....
Venezuelan equine encephalitis virus capsid protein inhibits nuclear import in Mammalian but not in mosquito cells. Venezuelan equine encephalitis virus (VEEV) represents a continuous public health threat in the United States. It has the ability to cause fatal disease in humans and in horses and other domestic animals. We recently demonstrated that replicating VEEV interferes with cellular transcription and uses this phenomenon as a means of downregulating a cellular antiviral response. VEEV capsid protein was found to play a critical role in this process, and its approximately 35-amino-acid-long peptide, fused with green fluorescent protein, functioned as efficiently as did the entire capsid. We detected a...
Characterization of equine arteritis virus particles and demonstration of their hemolytic activity. Equine arteritis virus (EAV), a member of the newly established family Arteriviridae, is a small, positive-stranded RNA virus. It carries two protein complexes in its envelope, gp5/M and the recently described gp2b/gp3/gp4 complex. We report here on several basic features of EAV replication in cell culture and on the protein composition of virus particles. We have also characterized gp2b, gp3, and gp4 expressed using a baculovirus system in insect cells. Finally, we provide evidence that EAV possess hemagglutinating and hemolytic activity. The hemolysis assay might be useful for determining wh...
Establishment and characterization of equine fibroblast cell lines transformed in vivo and in vitro by BPV-1: model systems for equine sarcoids. It is now widely recognized that BPV-1 and less commonly BPV-2 are the causative agents of equine sarcoids. Here we present the generation of equine cell lines harboring BPV-1 genomes and expressing viral genes. These lines have been either explanted from sarcoid biopsies or generated in vitro by transfection of primary fibroblasts with BPV-1 DNA. Previously detected BPV-1 genome variations in equine sarcoids are also found in sarcoid cell lines, and only variant BPV-1 genomes can transform equine cells. These equine cell lines are morphologically transformed, proliferate faster than parental ...
Equine laminitis: membrane type matrix metalloproteinase-1 (MMP-14) is involved in acute phase onset. Enzymatic separation at the hoof lamellar dermal-epidermal interface may play a role in the development of laminitis and characterising and locating matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of MMPs or TIMPs) in lamellar tissues may further understanding of pathogenesis. Objective: To clone and sequence the cDNA encoding lamellar MMP-14 and TIMP-2, and quantify their transcription in normal and laminitic tissue; and to develop antibody to locate MMP-14 in lamellar tissues. Methods: Tissue samples were obtained from an oligofructose induced model of laminitis. Tot...
Early migration of Sarcocystis neurona in ponies fed sporocysts. Sarcocystis neurona is the most important cause of equine protozoal myeloencephalitis (EPM), a neurologic disease of the horse. In the present work, the kinetics of S. neurona invasion is determined in the equine model. Six ponies were orally inoculated with 250 x 10(6) S. neurona sporocysts via nasogastric intubation and killed on days 1, 2, 3, 5, 7, and 9 postinoculation (PI). At necropsy, tissue samples were examined for S. neurona infection. The parasite was isolated from the mesenteric lymph nodes at 1, 2, and 7 days PI; the liver at 2, 5, and 7 days PI; and the lungs at 5, 7, and 9 days ...
Vaccination of sarcoid-bearing donkeys with chimeric virus-like particles of bovine papillomavirus type 1. Equine sarcoids are fibroblastic skin tumours affecting equids worldwide. While the pathogenesis is not entirely understood, infection with bovine papillomavirus (BPV) type 1 (and less commonly type 2) has been implicated as a major factor in the disease process. Sarcoids very seldom regress and in fact often recrudesce following therapy. Nothing is known about the immune response of the equine host to BPV. Given that the viral genes are expressed in sarcoids, it is reasonable to assume that vaccination of animals against the expressed viral proteins would lead to the induction of an immune re...
Platelet activation in ponies with airway inflammation. Platelet activation occurs in human obstructive airway diseases and in laboratory animal models. However, there is limited evidence that platelets may be involved in equine recurrent airway obstruction (RAO) and other inflammatory diseases. This study investigated whether platelet activation also occurred in RAO. Objective: Platelet function is altered in ponies with active RAO. This alteration can be detected ex vivo by measuring platelet adhesion. Methods: An in vitro platelet adhesion assay measuring acid phosphatase (AcP) activity colorimetrically was adapted for use with equine platelets ...
Equine coronavirus induces apoptosis in cultured cells. Equine coronavirus (ECoV) was first isolated from a diarrheic foal and was found genetically similar to group II coronaviruses. However, its pathological characteristics were not adequately investigated. In our preliminary in vitro investigation, ECoV-induced cell death was observed in bovine kidney-derived MDBK cells. Based on this finding, we investigated whether the ECoV-induced CPE was apoptosis. Following ECoV infection, MDBK cells showed morphological changes such as cell rounding and detachment from the culture surface. Moreover, syncytium formation was observed as the other type of cyt...
Analysis of ORFs 2b, 3, 4, and partial ORF5 of sequential isolates of equine arteritis virus shows genetic variation following experimental infection of horses. Samples from horses experimentally infected with the "large plaque variant (LP3A+)" of equine arteritis virus were analysed. These included 182 nasal swabs collected from day 1 to 14 post-infection (p.i.), and 21 virus isolates obtained from white blood cells of animals that showed a prolonged viraemia between days 30 to 72 p.i. In order to determine the genetic stability of the virus and particularly to characterise the genetic variants found during the prolonged viraemia, partial sequences of open reading frame 5 (ORF5) encoding glycoprotein 5 (GP5) were generated. Viruses with amino acid su...
Glanders: off to the races with Burkholderia mallei. Burkholderia mallei, the etiologic agent of the disease known as glanders, is primarily a disease affecting horses and is transmitted to humans by direct contact with infected animals. The use of B. mallei as a biological weapon has been reported and currently, there is no vaccine available for either humans or animals. Despite the history and highly infective nature of B. mallei, as well as its potential use as a bio-weapon, B. mallei research to understand the pathogenesis and the host responses to infection remains limited. Therefore, this minireview will focus on current efforts to elucida...
