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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.
Lipopolysaccharide and interferon gamma activate nuclear factor kappa B and induce cyclo-oxygenase-2 in equine vascular smooth muscle cells. Equine endotoxaemia is an important cause of morbidity and mortality in horses caused by the interaction of bacterial lipopolysaccharide (LPS) with cells such as macrophages and vascular smooth muscle. In this study we isolated equine vascular smooth muscle from a variety of vessels and stimulated it with LPS and human interferon (hIFN)-gamma. Using reverse transcriptase polymerase chain reaction (rt-PCR) and Western blot analysis we show that cyclooxygenase-2 (COX-2) is readily expressed in equine vascular smooth muscle. Vascular smooth muscle cells produced prostaglandin E2 in response to LP...
Biochemical characterisation of navicular hyaline cartilage, navicular fibrocartilage and the deep digital flexor tendon in horses with navicular disease. The study hypothesis was that navicular disease is a process analogous to degenerative joint disease, which leads to changes in navicular fibrocartilage and in deep digital flexor tendon (DDFT) matrix composition and that the process extends to the adjacent distal interphalangeal joint. The objectives were to compare the biochemical composition of the navicular articular and palmar cartilages from 18 horses with navicular disease with 49 horses with no history of front limb lameness, and to compare navicular fibrocartilage with medial meniscus of the stifle and collateral cartilage of the hoof...
Detection of EHV-1 and EHV-4 in placental sections of naturally occurring EHV-1- and EHV-4-related abortions in the UK: use of the placenta in diagnosis. EHV-1 and EHV-4 abortion diagnosis is based upon detailed examination of the aborted fetus. However, in some cases, only the placenta is available for examination. Furthermore, the contribution of lesions in the placenta to pathogenesis and diagnosis of EHV-1 and EHV-4 abortion has been neglected. Objective: To assess the utility of placental examination in equine herpesvirus-1 (EHV-1) and EHV-4 abortion diagnosis. Methods: Sections of allantochorion from 49 herpesvirus abortions were analysed by PCR, in situ hybridisation and immunostaining. Results: Virus-specific nested PCR confirmed the pr...
Effects of hypothyroidism and withholding of feed on plasma lipid concentrations, concentration and composition of very-low-density lipoprotein, and plasma lipase activity in horses. To evaluate selected concentrations of blood lipids and lipase activities in euthyroid and hypothyroid horses deprived of feed for 96 hours. Methods: 4 healthy adult mares and 4 thyroidectomized adult mares. Methods: Horses were deprived of feed for 96 hours. Blood samples were collected at 24-hour intervals and analyzed to determine concentrations of non-esterified fatty acid (NEFA), triglyceride (TG), total cholesterol (TC), and very-low-density lipoprotein (VLDL) as well as composition of VLDL. Plasma lipase activities were measured after feed was withheld for 96 hours and 12 days after res...
Submural histopathologic changes attributable to peracute laminitis in horses. To describe submural histopathologic changes attributable to peracute laminitis in horses. Methods: 20 adult horses. Methods: A concurrent-control design was used to compare laminar lesions in 10 horses subjected to carbohydrate-induced laminitis with laminar characteristics of 10 sex- and aged-matched control horses with normal feet. Horses in the treatment group were administered an overload of carbohydrate. Tissues were obtained by biopsy 4 to 8 hours after onset of lameness or 72 hours after administration of the carbohydrate overload when lameness did not develop. Sections were stained wi...
Phylogenetic relationship of equine Actinobacillus species and distribution of RTX toxin genes among clusters. Equine Actinobacillus species were analysed phylogenetically by 16S rRNA gene (rrs) sequencing focusing on the species Actinobacillus equuli, which has recently been subdivided into the non-haemolytic A. equuli subsp. equuli and the haemolytic A. equuli subsp. haemolyticus. In parallel we determined the profile for RTX toxin genes of the sample of strains by PCR testing for the presence of the A. equuli haemolysin gene aqx, and the toxin genes apxI, apxII, apxIII and apxIV, which are known in porcine pathogens such as Actinobacillus pleuropneumoniae and Actinobacillus suis. The rrs-based phylo...
Investigations into the role of the thyrohyoid muscles in the pathogenesis of dorsal displacement of the soft palate in horses. Contributes to the understanding of the pathogenesis of dorsal displacement of the soft palate during exercise so that management of this condition could be enhanced. Objective: That the thyrohyoid muscles play an important role in the stability of the laryngo-palatal relationship and that dysfunction of these muscles leads to dorsal displacement of the soft palate (DDSP) during exercise. Methods: Ten horses were exercised on a high-speed treadmill under 4 different treatment conditions: control conditions (n = 10), after resection of thyrohyoid muscles (TH, n = 10), after sham-treatment (n = ...
Mucin genes in horse airways: MUC5AC, but not MUC2, may play a role in recurrent airway obstruction. Increased mucin gene expression may be an important cause of mucus accumulation observed in recurrent airway obstruction (RAO)-affected horses. To date, however, no mucin gene sequences are available for the horse. Objective: To identify equine homologues of gel-forming mucins and investigate their expression at different airway generations of healthy and RAO-affected horses. Methods: Two equine homologues were identified by cloning and sequencing fragments of equine (eq)MUC5AC and eqMUC2. Results: Semiquantitative RT-PCR on RNA from airways (generations 1, 5, 10, 15; small airways and parench...
Inhaled endotoxin and organic dust particulates have synergistic proinflammatory effects in equine heaves (organic dust-induced asthma). Equine heaves is a naturally occurring organic dust-induced asthma characterized by airway neutrophilia, mucus hypersecretion and obstructive lung dysfunction. However, the relative role of different dust components in disease severity remains unclear. Objective: This study investigated the relative contribution of inhaled endotoxin and organic dust particulates (mainly mould spores) in inducing heaves in heaves-susceptible horses. Methods: Control and heaves-susceptible horses received inhalation challenges with hay dust suspension (HDS) before and after lipopolysaccharide (LPS) depletion. He...
A case of equine granulocytic ehrlichiosis provides molecular evidence for the presence of pathogenic anaplasma phagocytophilum (HGE agent) in Germany. Based on seroprevalence studies and tick infection rates, tick-borne human granulocytic ehrlichiosis (HGE) is thought to occur in Germany, but to date no clinical case has been detected. Reported here are the first ehrlichial sequences derived from a German horse that fell ill with granulocytic ehrlichiosis. The analysis of three different genes (16S rRNA gene, groESL, and ankA) revealed up to 100% identity with ehrlichial sequences derived from patients with HGE in other countries or from infected ticks in Germany. Thus, the current lack of clinical cases of HGE in Germany is unlikely to resu...
Effects of hydrochloric, acetic, butyric, and propionic acids on pathogenesis of ulcers in the nonglandular portion of the stomach of horses. To identify the pathogenesis of gastric ulcers by comparing injury to the nonglandular gastric mucosa of horses caused by hydrochloric acid (HCl) or volatile fatty acids (VFAs). Methods: Gastric tissues from 30 horses. Methods: Nonglandular gastric mucosa was studied by use of Ussing chambers. Short-circuit current (Isc) and potential difference were measured and electrical resistance calculated for tissues after addition of HCl and VFAs to normal Ringer's solution (NRS). Tissues were examined histologically. Results: Mucosa exposed to HCl in NRS (pH, 1.5) had a significant decrease in Isc, co...
Effects of hydrochloric, valeric, and other volatile fatty acids on pathogenesis of ulcers in the nonglandular portion of the stomach of horses. To identify in vitro effects of hydrochloric acid, valeric acid, and other volatile fatty acids (VFAs) on the pathogenesis of ulcers in the nonglandular portion of the equine stomach. Methods: Gastric tissues from 13 adult horses. Methods: Nonglandular gastric mucosa was studied by use of Ussing chambers. Short-circuit current (Isc) and potential difference were measured and electrical resistance and conductance calculated after tissues were bathed in normal Ringer's solution (NRS) or NRS and hydrochloric, valeric, acetic, propionic, and butyric acids. Treated tissues were examined histologica...
Identification of equine cecal bacteria producing amines in an in vitro model of carbohydrate overload. Acute laminitis has been associated with the overgrowth of gram-positive bacteria within the equine hindgut, causing the release of factor(s) leading to ischemia-reperfusion of the digits. The products of fermentation which trigger acute laminitis are, as yet, unknown; however, vasoactive amines are possible candidates. The objectives of this study were to use an in vitro model of carbohydrate overload to study the change in populations of cecal streptococci and lactobacilli and to establish whether certain species of these bacteria were capable of producing vasoactive amines from amino acids....
Neuropharmacological sequelae of persistent CNS viral infections: lessons from Borna disease virus. Borna Disease Virus (BDV) is a neurotropic RNA virus that is worldwide in distribution, causing movement and behavior disorders in a wide range of animal species. BDV has also been reported to be associated with neuropsychiatric diseases of humans by serologic study and by recovery of nucleic acid or virus from blood or brain. Natural infections of horses and sheep produce encephalitis with erratic excited behaviors, hyperkinetic movement or gait abnormalities; naturally infected cats have ataxic "staggering disease." Experimentally infected primates develop hyperactivity, aggression, disinhib...
Systemic concentrations of antioxidants and biomarkers of macromolecular oxidative damage in horses with grass sickness. The aetiopathogenesis of equine grass sickness (EGS) is unknown. The role of free radical-mediated neuronal damage has not previously been investigated in this condition. Objective: To investigate the potential contribution of oxidative damage and antioxidant status to neurodegeneration in EGS. Methods: Systemic levels of surrogate biomarkers were determined in 10 horses with acute EGS and in 2 control populations; 10 healthy horses co-grazing with the 10 EGS horses at the onset of clinical disease, and 10 healthy mares grazing where EGS has not been reported. Results: EGS horses had alteratio...
Detection of papillomavirus-DNA in mesenchymal tumour cells and not in the hyperplastic epithelium of feline sarcoids. We examined 12 formalin-fixed paraffin-embedded feline skin tumours which had the histopathological features of fibropapillomas for the presence of papillomavirus (PV) DNA using touchdown polymerase chain reaction (PCR), DNA sequencing and nonradioactive in situ hybridization. Nine of the tumours contained a 102-bp PCR product demonstrated using consensus PV primers that amplify a portion of the L1 gene. The nucleotide sequences are closely related, but not identical to that of ovine PV type 2, rabbit oral PV and reindeer PV. The deduced amino acid sequences had strong homologies with the majo...
Equine amplification and virulence of subtype IE Venezuelan equine encephalitis viruses isolated during the 1993 and 1996 Mexican epizootics. To assess the role of horses as amplification hosts during the 1993 and 1996 Mexican Venezuelan equine encephalitis (VEE) epizootics, we subcutaneously infected 10 horses by using four different equine isolates. Most horses showed little or no disease and low or nonexistent viremia. Neurologic disease developed in only 1 horse, and brain histopathologic examination showed meningeal lymphocytic infiltration, perivascular cuffing, and focal encephalitis. Three animals showed mild meningoencephalitis without clinical disease. Viral RNA was detected in the brain of several animals 12-14 days after...
Hemolytic activity of Prevotella intermedia and Prevotella nigrescens strains: influence of abiotic factors in solid and liquid assays. The influence of growth medium, hemin and menadione, blood source and atmosphere of incubation on the expression of hemolytic activity of 25 strains of Prevotella intermedia and Prevotella nigrescens was evaluated. The best hemolytic activity was observed for samples of both species growing in brain heart infusion agar and incubated in Brewer-like anaerobic jars for 48 h. Hemolysis was less intense and occurred later in the presence of hemin and menadione in solid media. beta-Hemolysis was detected for medium supplemented with horse or human blood and alpha-hemolysis was observed when sheep bl...
Down-regulation of MHC class I expression by equine herpesvirus-1. There is good evidence that cytotoxic T lymphocytes play an important role in the clearance of equine herpesvirus-1 (EHV1) in horses. We have demonstrated that, in common with other alphaherpesviruses, EHV1 infection can lead to dramatic down-regulation of MHC class I expression at the cell surface, a common strategy for pathogen evasion of the host immune response. This down-regulation is specific for MHC class I and does not reflect a general shut-off of host-cell protein synthesis. The use of monoclonal antibodies that recognize different MHC class I epitopes has demonstrated that the effec...
Influence of liver copper status of mare and newborn foal on the development of osteochondrotic lesions. To elucidate the highly contentious role of copper in the pathogenesis of osteochondrosis. Objective: There would be no relationship between liver copper concentration of mares and foals and incidence of radiographically detectable osteochondrotic lesions in foals and yearlings was tested. Methods: Liver copper concentration was assessed in biopsies taken within 4 days after birth from both mares and foals and from the same foals at age 5 months. Biopsies were taken in the standing, sedated animal under ultrasonographic guidance. Radiographs were taken of both hocks (lateromedial, dorsoplantar...
Equine platelet CD62P (P-selectin) expression: a phenotypic and morphologic study. Acute inflammatory diseases, such as colic, septicemia and endotoxemia are common in equines and have been shown to be correlated to vascular injury and thrombosis. In humans with similar thrombotic conditions, P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1)-mediated platelet-leukocyte adhesion contributes to the pathogenesis of these disorders through the generation of inflammatory mediators and tissue factor. As such, we hypothesized that a P-selectin-PSGL-1 (platelet-leukocyte) interaction, similar to that in humans, may also exist in the horse. The objective of this study was to i...
Equine recurrent airway obstruction: pathogenesis, diagnosis, and patient management. Recurrent airway obstruction is a condition that affects some older horses maintained in confinement. Clinical signs range from exercise intolerance with occasional cough to dyspnea at rest. Bronchoalveolar lavage cytology is characterized by neutrophilic leukocytosis (15%-85%) and is recommended for making the diagnosis in horses with mild to moderate disease. Environmental management combined with periodic bronchodilator and antiinflammatory corticosteroid therapy yields the best prognosis for disease remission.
Transmission of Anaplasma phagocytophila (human granulocytic ehrlichiosis agent) in horses using experimentally infected ticks (Ixodes scapularis). Most human granulocytic ehrlichiosis (HGE) studies carried out in horses use needle inoculation of infected leucocytes or cell cultures. This route of inoculation does not accurately reflect natural infection of the tick-borne agent. To investigate whether tick transmission influences the course of granulocytic ehrlichiosis in the horse model, experimental transmission through infected laboratory-reared Ixodes scapularis ticks was attempted into two healthy horses. One additional horse served as negative control and was exposed to uninfected ticks. Eleven days after exposure to nymphal or adul...
Excessive degradation of type II collagen in articular cartilage in equine osteochondrosis. Articular osteochondrosis (OCD) occurs in both man and animals. The etiology remains to be determined. Studies of OCD lesions in animals may provide clues as to its pathogenesis. The aim of our study was to determine whether there was evidence for increased degradation namely proteoglycan (PG) release and type II collagen cleavage in articular cartilage harvested from OCD lesions. We examined ex vivo explants at post-mortem from equine OCD lesions and macroscopically normal site and age matched cartilage. These were cultured over a 10 day period in serum-free medium. Type II collagen cleavage ...
Effect of nutritional antioxidant supplementation on systemic and pulmonary antioxidant status, airway inflammation and lung function in heaves-affected horses. An oxidant/antioxidant imbalance in favour of oxidants has been identified as playing a decisive role in the pathogenesis of chronic inflammatory airway diseases. Nutritional antioxidant supplementation might reduce oxidative damage by enhancement of the antioxidant defence, thereby modulating inflammatory processes. In a placebo-controlled, blind study, it was tested whether a dietary antioxidant supplement administered for 4 weeks would improve lung function and reduce airway inflammation in heaves-affected horses. Eight horses in clinical remission of heaves were investigated at rest and af...
Animal models of papillomavirus pathogenesis. Tumorigenesis due to papillomavirus (PV) infection was first demonstrated in rabbits and cattle early last century. Despite the evidence obtained in animals, the role of viruses in human cancer was dismissed as irrelevant. It took a paradigm shift in the late 1970s for some viruses to be recognised as 'tumour viruses' in humans, and in 1995, more than 60 years after Rous's first demonstration of CRPV oncogenicity, WHO officially declared that 'HPV-16 and HPV-18 are carcinogenic to humans'. Experimental studies with animal PVs have been a determining factor in this decision. Animal PVs have bee...
Construction of a stable non-mucoid deletion mutant of the Streptococcus equi Pinnacle vaccine strain. Streptococcus equi causes equine strangles, a purulent lymphadenopathy of the head and neck. An avirulent, non-encapsulated strain (Pinnacle) has been used widely in North America as an intranasal vaccine. The aim of the study was to create a specific mutation of the hyaluronate synthase (hasA) gene in Pinnacle to permanently abolish the production of capsule and provide an easily recognisable genetic marker. An internal fragment of hasA was generated by PCR and cloned into pTW100 (Microscience, UK). An encapsulated revertant of Pinnacle was then transformed with the recombinant plasmid by ele...
