construction-realistic-whole-body-three-dimensional-equine-skeletal

Construction of a Realistic, Whole-Body, Three-Dimensional Equine Skeletal Model using Computed Tomography Data

Therapies based upon whole-body biomechanical assessments are successful for injury prevention and rehabilitation in human athletes. Similar approaches ...

University of Georgia College of Veterinary Medicine

Infections with respiratory pathogens such as respiratory syncytial virus and rhinovirus have been associated with the development of long-term chronic airway disease. To better understand the events responsible for this clinical outcome, a rodent model of virus-induced chronic airway disease has been characterized. Upon infection with Sendai virus (parainfluenza virus type-1), Brown Norway (BN) rats develop an asthma-like clinical syndrome, while Fischer 344 (F344) rats fully recover. Our previous studies demonstrated that after infection, tumor necrosis factor-alpha (TNF-alpha) expression is substantially higher in BN rats compared to F344 rats, and this may at least partially mediate the virus-induced airway abnormalities. To investigate the underlying mechanism(s) for the increased TNF-alpha expression, the role of nuclear factor-kappaB (NF-kappaB), an important regulator of TNF-alpha gene transcription, was examined. Supershift electrophoretic mobility shift assays (EMSAs) indicate that normal F344 rats predominantly express the p65 subunit of NF-kappaB in the lungs, and virus infection temporarily increases expression of the p50 subunit. In contrast, normal BN rats have higher expression of the p50 subunit in the pulmonary tract. Upon infection, p50-subunit expression in BN rats increases to levels higher than those observed in virus-infected F344 rats. Interestingly, treatment of infected BN rats with dexamethasone at doses known to prevent virus-induced airway abnormalities increases pulmonary expression of the p65 subunit, and decreases TNF-alpha mRNA levels in the lungs. Furthermore, direct inhibition of TNF-alpha also increases pulmonary expression of p65 in virus-infected BN, but not F344, rats. Taken together, these results suggest that differential expression of NF-kappaB subunits may play an important role in the development of post-viral chronic airway abnormalities.

Differential expression of nuclear factor-kappaB mediates increased pulmonary expression of tumor necrosis factor-alpha and virus-induced asthma.

Weanling Brown Norway (BN) rats are susceptible to persistent steroid-responsive pulmonary abnormalities following resolution of an acute respiratory virus infection. In contrast, Fischer 344 (F344) rats recover without complications. Previous studies determined that NF-κB activation and subunit composition were markedly different between these 2 rat strains. This study examined whether viral infection also resulted in altered pulmonary expression of IκBα and IκBβ, 2 inhibitory regulators of NF-κB. Western blot analyses of total pulmonary protein extracted from BN and F344 rats at 7, 10, and 14 days after inoculation (n = 5 per group) did not reveal virus-induced differences in IκBβ expression. In contrast, a lower molecular weight form of IκBα appeared in the BN rats at 14 days postinfection, and it was still present at 21 days after infection (n = 5 per group). The change in IκBα expression observed in the susceptible BN but not the resistant F344 animals occurs when the epithelium is proliferating during the repair phase, and it correlates with the development of the persistent virus-induced airway inflammation and pulmonary functional abnormalities. These results further implicate differential regulation of NF-κB in the pathogenesis of virus-induced asthma.

Rats susceptible to virus-induced asthma have a persistent virus-induced change in the predominant pulmonary form of the NF-κB inhibitor IκBα.

Evolutionary aspects of animal models.

Although vitamin D is critical to calcium/phosphorus homeostasis, bone formation and remodeling, there is evolution-based variation between species in vitamin D metabolism and susceptibility to rickets and osteomalacia. Most herbivores produce vitamin D in response to sunlight, but dogs and cats have generally lost the ability as carnivore diets are rich in vitamin D. Nutritional deficiencies and/or poor exposure to sunlight can induce rickets in birds, swine, cattle and sheep, but horses are less susceptible as they have evolved a calcium homeostasis that is quite different than other animals. Adaptations to specific environments also affect disease incidence: llamas/alpacas out of their natural high altitude intense solar radiation environments are highly susceptible to vitamin D deficiency. The pathology of rickets/osteomalacia is similar across species, however fibrous osteodystrophy is more common and may also be present. Rickets/osteomalacia were likely more common in animals before the advent of commercial diets, but can be difficult to definitively diagnose especially in single archeological specimens. Consideration of species susceptibility, location - especially in terms of latitude, and any available information on diet, season of occurrence, husbandry practices or descriptions of affected animals can support the diagnosis of metabolic bone disease in animals.

The pathology of vitamin D deficiency in domesticated animals: An evolutionary and comparative overview.

Canine distemper virus (CDV), human measles virus (HMV), and rinderpest virus (RPV) of cattle are morbilliviruses that have caused devastating outbreaks for centuries. This paper seeks to reconstruct the evolutionary history of CDV.

Article	Year
Differential expression of nuclear factor-kappaB mediates increased pulmonary expression of tumor necrosis factor-alpha and virus-induced asthma. Viral immunology\| PubMed ID: 19326995	2009
Rats susceptible to virus-induced asthma have a persistent virus-induced change in the predominant pulmonary form of the NF-κB inhibitor IκBα. Veterinary pathology\| PubMed ID: 20817891	2010
Evolutionary aspects of animal models. Veterinary pathology\| PubMed ID: 22983990	2012
The pathology of vitamin D deficiency in domesticated animals: An evolutionary and comparative overview. International journal of paleopathology\| PubMed ID: 29544996	2018
New world origin of canine distemper: Interdisciplinary insights. International journal of paleopathology\| PubMed ID: 30743216	2019

Elizabeth W. Uhl

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