Mouse models have been essential to generate supporting data for the research of infectious diseases. Burkholderia pseudomallei, the etiological agent of melioidosis, has been studied using mouse models to investigate pathogenesis and efficacy of novel medical countermeasures to include both vaccines and therapeutics. Previous characterization of mouse models of melioidosis have demonstrated that BALB/c mice present with an acute infection, whereas C57BL/6 mice have shown a tendency to be more resistant to infection and may model chronic disease. In this study, either BALB/c or C57BL/6 mice were exposed to aerosolized human clinical isolates of B. pseudomallei. The bacterial strains included HBPUB10134a (virulent isolate from Thailand), MSHR5855 (virulent isolate from Australia), and 1106a (relatively attenuated isolate from Thailand). The LD50 values were calculated and serial sample collections were performed in order to examine the bacterial burdens in tissues, histopathological features of disease, and the immune response mounted by the mice after exposure to aerosolized B. pseudomallei. These data will be important when utilizing these models for testing novel medical countermeasures. Additionally, by comparing highly virulent strains with attenuated isolates, we hope to better understand the complex disease pathogenesis associated with this bacterium.
F(2)-isoprostanes are useful markers for assessing oxidant injury; however, the validity of measuring urinary 15-F(2t)-isoprostane concentration by enzyme-linked immunosorbent assay (ELISA) has not been evaluated in veterinary species. The current study assesses the agreement between 2 commercially available urinary isoprostane kits and gas chromatography and negative ion chemical ionization-mass spectrometry (GC/NICI-MS). The results indicate that only feline urinary isoprostane measurement by glucuronidase (GL)-ELISA has acceptable agreement with GC/NICI-MS. Urinary isoprostane concentration was highly variable in critically ill animals, but there were too many variations between healthy and critically ill animals to draw meaningful conclusions. Currently, GC/NICI-MS is the only method that can be recommended for the assessment of urinary isoprostanes in dogs, cattle, and horses. Feline urinary isoprostanes can be assessed by GL-ELISA, but caution is still warranted when comparing data from manuscripts using different methods given the relatively low Spearman rank correlation coefficient. Future studies may require large sample sizes or focused inclusion criteria to account for variability in isoprostane concentration.
Oxidative stress refers to the cellular injury and pathologic change that occurs when there is an imbalance favoring oxidants over antioxidants within a living organism. In human medicine, oxidative stress has been implicated in numerous disease processes, which has led to further research into the clinical benefits and efficacy of antioxidant therapy. The evaluation of oxidative stress in the horse has been limited primarily to ischemia-reperfusion injury of the gastrointestinal tract, recurrent airway obstruction, exercise, osteoarthritis, equine motor neuron disease, and pituitary pars intermedia dysfunction. Each of these is examined in this review in terms of the current evidence for oxidative stress as well as the evidence for current antioxidant therapy in equine medicine and the potential of future research and therapies. Oxidative stress research is currently an emerging field with relevance to the equine critical patient.
Infection with Burkholderia pseudomallei causes the disease melioidosis, which often presents as a serious suppurative infection that is typically fatal without intensive treatment and is a significant emerging infectious disease in Southeast Asia. Despite intensive research there is still much that remains unknown about melioidosis pathogenesis. New animal models of melioidosis are needed to examine novel aspects of pathogenesis as well as for the evaluation of novel therapeutics. The objective of the work presented here was to develop a subacute to chronic caprine model of melioidosis and to characterize the progression of disease with respect to clinical presentation, hematology, clinical microbiology, thoracic radiography, and gross and microscopic pathology. Disease was produced in all animals following an intratracheal aerosol of 104 CFU delivered, with variable clinical manifestations indicative of subacute and chronic disease. Bronchointerstitial pneumonia was apparent microscopically by day 2 and radiographically and grossly apparent by day 7 post infection (PI). Early lesions of bronchopneumonia soon progressed to more severe bronchointerstitial pneumonia with pyogranuloma formation. Extrapulmonary dissemination appeared to be a function of pyogranuloma invasion of pulmonary vasculature, which peaked around day 7 PI. Histopathology indicated that leukocytoclastic vasculitis was the central step in dissemination of B. pseudomallei from the lungs as well as in the establishment of new lesions. While higher doses of organism in goats can produce acute fatal disease, the dose investigated and resulting disease had many similarities to human melioidosis and may warrant further development to provide a model for the study of both natural and bioterrorism associated disease.
We studied the forelimb interosseus muscle in horses, Equus caballus, to determine the muscular properties inherent in its function. Some authors have speculated that the equine interosseus contains muscle fibers at birth only to undergo loss of these fibers through postnatal ontogeny. We describe the muscle fibers in eight interosseus specimens from adult horses. These fibers were studied histochemically using myosin ATPase studies and immunocytochemically using several antibodies directed against type I and type II myosin heavy chain antibodies. We determined that 95% of the fibers were type I, presumed slow-twitch fibers. All fibers exhibited normal morphological appearance in terms of fiber diameter and cross-sectional area, suggesting that the muscles are undergoing normal cycles of recruitment. SDS-PAGE studies of myosin heavy chain isoforms were consistent with these observations of primarily slow-twitch muscle. Fibers were determined to be approximately 800 microm long when studied using nitric acid digestion protocols. Short fiber length combined with high pinnation angles suggest that the interosseus muscle is able to generate large amounts of force but can produce little work (measured as pulling the distal tendon proximally). While the equine interosseus muscle has undergone a general reduction of muscle content during its evolution, it remains composed of a significant muscular component that likely contributes to forelimb stability and elastic storage of energy during locomotion.
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