Asthma is characterized by chronic lower airway inflammation that results in airway remodeling, which can lead to a permanent decrease in lung function. The pathophysiology driving the development of asthma is complex and heterogenous. Animal models have been and continue to be essential for the discovery of molecular pathways driving the pathophysiology of asthma and novel therapeutic approaches. Animal models of asthma may be induced or naturally occurring. Species used to study asthma include mouse, rat, guinea pig, cat, dog, sheep, horse, and nonhuman primate. Some of the aspects to consider when evaluating any of these asthma models are cost, labor, reagent availability, regulatory burden, relevance to natural disease in humans, type of lower airway inflammation, biological samples available for testing, and ultimately whether the model can answer the research question(s). This review aims to discuss the animal models most available for asthma investigation, with an emphasis on describing the inciting antigen/allergen, inflammatory response induced, and its translation to human asthma.
Background Further development of surgical techniques for equine cervical stabilisation is necessary to make the procedure less technically demanding, reduce complications and improve outcomes. Objective To describe clinical outcomes and owner reports in horses undergoing placement of an interbody fusion device and polyaxial pedicle screw and rod construct for cervical vertebral fusion in horses with cervical vertebral compressive myelopathy. Study design Retrospective case series. Methods Data were retrieved from medical records of 10 horses undergoing cervical vertebral fusion (2015‐2019). Records were evaluated for signalment, duration of clinical signs, number and location of compression sites, grade of ataxia, duration of hospitalisation and complications. Long‐term follow‐up was obtained through clinical re‐evaluation, postoperative radiographs and owner contact. Results Breeds were mixed. Median age was 24 (range 12‐168) months. There were 2/10 mares, 4/10 geldings and 4/10 stallions. Preoperative grade of ataxia ranged from 1‐3/5. Fusion was performed at one (n = 3) or two (n = 7) sites. Two horses were euthanised within the first year. In 6 of 8 horses with ≥1‐year follow‐up, ataxia improved by 1‐3 grades, with an average improvement of 1.25 grades. In four horses, ataxia improved to grade 0‐1. In two horses the gait was unaffected, but neck comfort improved. Complications included seroma formation (n = 9), pain (n = 5), fever (n = 4), upper respiratory tract obstruction (n = 2), azotemia (n = 2), screw breakage (n = 2), progression of neurological signs (n = 1), Horner's Syndrome (n = 1), dysphagia (n = 1), hives (n = 1), implant infection (n = 1) and nondisplaced fracture (n = 1). Main limitations Small case series, heterogeneous patient population. Conclusions This technique resulted in ≥1 grade gait improvement in 6/10 cases operated and 6/8 cases for which ≥1‐year follow‐up was available, similar to other methods. Fatal complications related to implant placement did not occur. This technique may represent a safer alternative to current techniques of ventral interbody fusion with similar outcomes.
Detection of equine acute kidney injury (AKI) is hindered by limited markers of early renal damage in horses. N-acetyl-β-D-glucosaminidase (NAG), a lysosomal enzyme in renal tubular epithelium released into urine during tubular insult, has shown promise for early identification of AKI in humans and other species. We validated an assay for NAG in equine urine and measured urinary NAG in 7 azotemic and 7 non-azotemic client-owned adult horses. The enzymatic NAG assay was validated using within- and between-run coefficients of variation (CVs), recovery following standard addition, and linearity of dilution. Intra- and inter-run CVs (21% and 3.2%, respectively), average recovery following standard addition (99–109%), and linearity under serial dilution ( R2 = 0.997) were satisfactory. Urine NAG index was significantly correlated with urinary fractional excretion of sodium (FENa; ρ = 0.76, p < 0.001) and plasma creatinine (ρ = 0.74, p = 0.001). Median urine NAG indices were higher in azotemic horses ( p = 0.006), in horses with increased urinary FENa ( p = 0.006), and in horses with increased urine gamma-glutamyl transferase index ( p = 0.032). Urine NAG can be measured in horses and shows positive correlation with 2 current renal biomarkers. Additional work is needed to establish normal equine reference intervals and characterize the increase of urine NAG index in horses in relation to tubular injury.
Plasma cell-free DNA (cfDNA) is a biomarker of ischemia, systemic inflammation, and mortality in humans with gastrointestinal disease. Cell-free DNA has not been investigated as a biomarker for equine colic, to our knowledge. We hypothesized that cfDNA could be measured accurately in neat equine plasma using a benchtop fluorometer and that plasma cfDNA would be elevated in emergency patients compared to healthy horses. Plasma was obtained from blood collected in Roche DNA stabilizing tubes. We used the Qubit 4 fluorometer and 1× dsDNA HS assay kit to measure cfDNA concentration in neat patient plasma and following DNA extraction of plasma with a commercial kit. Assay precision and linearity of dilution were satisfactory for neat plasma cfDNA, but DNA spike and recovery results were variable. Further, cfDNA concentrations in paired neat plasma and extracted-plasma samples ( n = 66) were not correlated. Median extracted-plasma cfDNA was higher in emergency patients ( n = 50) and a subgroup of colic patients ( n = 36), compared to healthy horses ( n = 19). Our results with extracted-plasma samples provide proof of concept for further investigation of plasma cfDNA as a biomarker in horses.
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