Abstract
OBJECTIVE
Design and evaluate immune responses of neonatal foals to a mRNA vaccine expressing the virulence-associated protein A (VapA) of Rhodococcus equi.
ANIMALS
Cultured primary equine respiratory tract cells; Serum, bronchoalveolar lavage fluid (BALF), and peripheral blood mononuclear cells (PBMCs) from 30 healthy Quarter Horse foals.
METHODS
VapA expression was evaluated by western immunoblot in cultured equine bronchial cells transfected with 4 mRNA constructs encoding VapA. The mRNA construct with greatest expression was used to immunize foals at ages 2 and 21 days in 5 groups: (1) 300 μg nebulized mRNA (n = 6); (2) 600 μg nebulized mRNA (n = 4); (3) 300 μg mRNA administered intramuscularly (IM) (n = 5); (4) 300 μg VapA IM (positive controls; n = 6); or (5) nebulized water (negative controls; n = 6). Serum, BALF, and PBMCs were collected at ages 3, 22, and 35 days and tested for relative anti-VapA IgG1, IgG4/7, and IgA activities using ELISA and cell-mediated immunity by ELISpot.
RESULTS
As formulated, nebulized mRNA was not immunogenic. However, a significant increase in anti-VapA IgG4/7 activity (P < .05) was noted exclusively in foals immunized IM with VapA mRNA by age 35 days. The proportion of foals with anti-VapA IgG1 activity > 30% of positive control differed significantly (P = .0441) between negative controls (50%; 3/6), IM mRNA foals (100%; 5/5), and IM VapA (100%; 6/6) groups. Natural exposure to virulent R equi was immunogenic in some negative control foals.
CLINICAL RELEVANCE
Further evaluation of the immunogenicity and efficacy of IM mRNA encoding VapA in foals is warranted.
Abstract
OBJECTIVE
To compare dexmedetomidine-ketamine (DK; 0.1 and 10 mg/kg, respectively) with midazolam (M; 1.0 mg/kg) or 0.9% sodium chloride (S; 0.2 mL/kg) administered IM in the forelimb (F) or hindlimb (H) in eastern box turtles (Terrapene carolina carolina).
ANIMALS
20 clinically healthy, captive adult eastern box turtles.
METHODS
In a randomized, blinded, complete crossover study with 1-week washout periods, turtles were administered each of 3 treatments: F-DKS, F-DKM, or H-DKM. Palpebral reflex, muscle tone, and withdrawal responses were serially assessed and used to calculate cumulative sedation scores at each 5-minute time point. The ability to intubate was evaluated. At 60 minutes, atipamezole (1.0 mg/kg) and either flumazenil (F-DKM, H-DKM; 0.05 mg/kg) or 0.9% sodium chloride (F-DKS; 0.5 mL/kg) were administered IM.
RESULTS
All treatments resulted in clinically relevant anesthetic effects. F-DKM produced significantly higher sedation scores than H-DKM or F-DKS at all time points between 10 and 60 minutes (P < .05). Sedation score variability was observed with all treatments with significantly higher variability for H-DKM (P < .05). Intubation was successful in 32, 89, and 11% of turtles in F-DKS, F-DKM, and H-DKM, respectively. Median (range) recovery time was 10 (5–22), 16 (7–45), and 12 (4–28) minutes for F-DKS, F-DKM, and H-DKM, respectively.
CLINICAL RELEVANCE
In eastern box turtles, forelimb dexmedetomidine-ketamine resulted in clinically relevant anesthetic effects that were heightened with the addition of midazolam. Hindlimb administration of midazolam-dexmedetomidine-ketamine resulted in reduced and more variable anesthetic effects compared to forelimb administration, supporting a hepatic first-pass effect.
Abstract
OBJECTIVE
Effect of photobiomodulation therapy (PBMT) in patients with CCLR after TPLO surgery by measuring C-reactive protein (CRP), percentage weight bearing, lameness using a short form of a composite measure pain scale, evaluated by the clinician and owners, and surgical site infection.
SAMPLE
54 client-owned dogs with CCLR undergoing unilateral TPLO surgery were enrolled in this study between April 5, 2021, through April 10, 2022.
METHODS
The study population was randomly assigned to either a treatment group receiving PMBT (24 dogs) or a control group (30 dogs). PMBT was performed on the treatment group immediately after induction, and 6 hours, 24 hours, 48 hours, and 8 weeks postoperatively. The control group received sham PMBT (device turned off) at the same time. Evaluation of CRP, CMPS-SF, evidence of SSI, and %WB were evaluated for all dogs 24 hours preoperatively, and then 24 hours, 48 hours, and 8 weeks postoperatively. Owners completed CMPS-SF and subjective evaluations weekly for 8 weeks postoperatively.
RESULTS
No statistically significant differences were found between treatment groups when evaluating CRP, %WB, and CMPS-SF by the clinician and weekly evaluation of the CMPS-SF by owners. Although no statistically significant differences were found in patients developing surgical site infections between treatment groups, SSI was only observed in patients in the control group (5/30, 16.6%). Most were minor/superficial infections (4/30 13.3%), and a single dog (1/30, 3.3%) had a major/deep surgical site infection.
CLINICAL RELEVANCE
Although with promising but not statistically significant differences between groups, surgical site infections may be reduced after PBMT application.
Abstract
OBJECTIVE
To determine the K-constant for body surface area calculation from body weight in corn snakes (Pantherophis guttatus) through the use of computed tomography (CT) measurements.
ANIMALS
12 adult corn snakes held by North Carolina State University for research purposes underwent CT between November 2022 and January 2023.
METHODS
Each snake had a CT scan, physical examination, and body weight measurement. CT images were uploaded into software able to perform 3-D reconstruction and measure body surface area. The species-specific K-constant was determined using nonlinear regression analysis between body surface area and (body weight in grams)2/3.
RESULTS
The mean body weight of the 12 adult corn snakes was 228 g, with a mean body surface area of 505.1 cm2. The calculated K-constant was 13.6 (P < .001). The resulting formula for body surface area in corn snakes is BSA in cm2 = 13.6 X (body weight in grams)2/3.
CLINICAL RELEVANCE
The body surface area formula developed for corn snakes will allow for improved dosing accuracy for medications with low therapeutic safety margins. Additional pharmacokinetic and pharmacodynamic studies are necessary to determine the safety and efficacy of individual medications.
Abstract
OBJECTIVE
Compare 3 methods of nucleus pulposus (NP) volume measurement using the rabbit lumbar spines as a preclinical model to determine the effectiveness of prophylactic intervertebral disk fenestration in dogs.
ANIMALS
Twelve 9-month-old, skeletally mature female entire New Zealand White rabbits weighing between 3.5 to 4.5 kg.
METHODS
NP volume measurements of dissected rabbit lumber spines between L1 and L6 were made and compared using gross measurements, reconstructed MRI images, and water volumetry based on Archimedes’ principle. Water volumetry was used as the true gold standard volume measurement in this study.
RESULTS
The true volume (mean ± SD) of the nucleus pulposus NP as measured by water volumetry increased caudally from L1/L2 (16.26 ± 3.32 mm3) to L5/L6 (22.73 ± 6.09 mm3). Volume estimates made by MRI were significantly higher than those made using water volumetry at all sites (L1/L2 [P = .044], L2/L3 [P = .012], L3/L4 [P = .015], L4/L5 [P < .001], and L5/L6 [P < .001]). Gross measurements also significantly overestimated volume when compared to water volumetry at all sites; L1/L2 (P = .021), L2/L3 (P = .025), L3/L4 (P = .001), L4/L5 (P < .001), and L5/L6 (P < .001). MRI and gross volume estimates were significantly different at L4/L5 (P = .035) and L5/L6 (P = .030).
CLINICAL RELEVANCE
The findings of this preclinical model might be relevant to veterinary surgeons who perform prophylactic fenestration for which there is no reliable method to determine the amount of NP to be removed. Preclinical ex vivo and in vivo fenestration studies with pre- and postoperative NP volume assessment are required.
Abstract
OBJECTIVE
To determine if plasma concentrations of symmetric dimethylarginine (SDMA), N-acetyl-beta-d-glucosaminidase (NAG), GGT, ALT, AST, lactate, total calcium, and ionized calcium (iCa) and the calcium:phosphorus ratio are clinically relevant biomarkers to detect early stages of tubular lesions in snakes.
ANIMALS
6 adult corn snakes (Pantherophis guttatus).
METHODS
Corn snakes were administered 11 injections of gentamicin at 50 mg/kg, SC, q 24 h in an experimental model of induced tubular necrosis. Plasma biochemistry and blood gas analyses were performed at baseline and after the 3rd and 11th injections. Parameters were compared between time points using a paired Wilcoxon test. In 3 individuals, renal biopsies were collected at baseline before starting injections and at the 3rd and 11th injections, while renal tissue samples were procured after euthanasia in all individuals.
RESULTS
Renal proximal and distal tubular necrosis and hepatic steatosis were present in all individuals at necropsy. Compared to baseline, decreased blood concentrations of lactate, ionized calcium, and total calcium and a decreased calcium:phosphorus ratio were noted. A significant decrease of lactate and ionized calcium was observed after 3 days. Conversely, no changes in SDMA, NAG, ALT, AST, GGT, and sodium were detected.
CLINICAL RELEVANCE
Ionized calcium and lactate concentrations were the earliest parameters to decrease compared to baseline values in this experimental model. While SDMA is a sensitive indicator of renal disease in mammals, this biomarker did not increase in a model of induced acute tubular necrosis in corn snakes.
Abstract
OBJECTIVE
This study aimed to develop a sound database for the hematological reference intervals of thoroughbred foals in Trinidad, West Indies from birth to 1 month of age.
ANIMALS
89 foals.
METHODS
Whole blood samples were taken from 89 foals throughout Trinidad at approximately 1 day, 1 week, and 1 month of age. These foals were examined to be classified as healthy or free from disease. Complete blood count (CBC), microscopic analysis of blood smears, and conventional PCR for Theileria equi and Babesia caballi were performed.
RESULTS
Of the 89 foals, 67 were deemed healthy and suitable for establishing reference intervals. Foals in this study had lower mean hemoglobin and hematocrit values for all 3 times of sampling when compared to their North American counterparts. Age had a significant effect on hemoglobin, hematocrit, white blood cell (WBC), neutrophil, and platelet counts of the foals from birth to 1 month of age.
CLINICAL RELEVANCE
Variations in reference intervals can occur due to differences in demographic, physiological, and environmental factors such as age, gender, breed, and geographical location. Given the changes in the hematological values over time, this study provides clinicians with valuable information that can be used to monitor the health status of newborn foals and detect disease conditions.
Abstract
OBJECTIVE
To identify protective equine rotavirus group A (ERVA) VP8 epitopes and demonstrate that immunizing hens with synthetic peptides based on these epitopes would yield high-titered, neutralizing egg yolk antibodies for potential application in foals.
ANIMALS
26 rotavirus-positive, client-owned foals were included in the study. Five white leghorn hens were used for antibody production.
METHODS
Chicken antibodies were raised against 3 synthetic epitope peptides from the VP8 protein of the common ERVA P-type, P4[12] using CD40-targeted streptavidin-peptide complexes. Antipeptide serum- and egg yolk antibodies were subject to ELISA and in vitro virus neutralization assays to evaluate binding and neutralization activities. Lyophilized anti-VP8 egg yolk antibodies were orally administered (30 g; q 24 h for 5 days) to foals with rotaviral diarrhea. Physical examinations were performed daily. The duration of diarrhea and any adverse effects were recorded.
RESULTS
CD40-targeted vaccination of hens generated high titers of anti-VP8 serum and egg yolk antibodies after just 3 immunizations. These antibodies prevented in vitro infection of ERVA with titers of 128 in the serum and 94.5 in the yolk. Oral administration (30 g; q 24 h for 5 days) of lyophilized hyperimmune egg yolk to foals with rotaviral diarrhea did not reveal any adverse effects of the treatment.
CLINICAL RELEVANCE
This study demonstrated that antibodies raised against neutralizing epitopes of the ERVA VP8 protein could prevent ERVA infection in vitro. Based on these results and previous work in other animals, in vivo evaluation of the therapeutic efficacy of anti-VP8 egg yolk antibodies is warranted.
Abstract
OBJECTIVE
To evaluate the plasma concentrations and determine pharmacokinetic parameters of atorvastatin and its primary active metabolites (para- and ortho-hydroxyatorvastatin) after administration of a single oral dose in orange-winged Amazon parrots (Amazona amazonica).
ANIMALS
8 adult orange-winged Amazon parrots (4 male, 4 female) of varying ages.
METHODS
A compounded oral suspension of atorvastatin 10 mg/mL was administered via oral gavage at 20 mg/kg to each bird. Blood samples were collected at 10 different time points from 0 to 30 hours postadministration to evaluate plasma levels of atorvastatin, para-hydroxyatorvastatin, and ortho-hydroxyatorvastatin. Pharmacokinetic analysis was performed using noncompartmental analysis and commercially available software.
RESULTS
Mean ± SD atorvastatin half-life, tmax, and Cmax were 5.96 ± 11.50 hours, 1.60 ± 0.80 hours, and 82.60 ± 58.30 ng/mL, respectively. For para-hydroxyatorvastatin, the half-life, tmax, and Cmax were 6.46 ± 54.20 hours, 5.00 ± 2.51 hours, and 34.10 ± 16.00 ng/mL, respectively, and 5.58 ± 9.92 hours, 3.38 ± 2.10 hours, and 7.35 ± 3.96 ng/mL for ortho-hydroxyatorvastatin.
CLINICAL RELEVANCE
The plasma concentrations and pharmacokinetic profile shown support the therapeutic use of atorvastatin at the dose evaluated in this species based on human pharmacokinetic data. While 20 mg/kg PO q24 hours could be used as a starting dosage until further studies evaluating multiple dose administration and efficacy in this species become available, the high interindividual variability results warrant monitoring of the treatment response to make dosing adjustments if needed.
Abstract
OBJECTIVE
To compare the influence of fluid on carboplatin elution, and assess the feasibility of ultrafiltration (UF) probe sampling
SAMPLE
20 samples of 5 mg carboplatin in 1.0 mL 30% poloxamer 407 eluting in Dulbecco’s phosphate-buffered saline (DPBS) or canine plasma and 6 samples of UF probe sampling in 0.01 mg/mL carboplatin in DPBS or plasma.
METHODS
Carboplatin-gel specimens in dialysis tubing (12- to 14-kDa pores) were placed in 100 mL of DPBS or canine plasma (37 °C and 600 rpm stirring) in a nonlidded and lidded experiment. Samples were collected in decreasing frequency for 96 hours. The 0.01-mg/mL carboplatin solutions in DPBS and plasma were sampled 6 times by UF probe (30-kDa pores) or direct aspiration. Platinum was measured using inductively coupled plasma mass spectrometry.
RESULTS
High fluid evaporation was noted in the nonlidded but not the lidded experiment. A burst release was seen in plasma (first 2 hours) and DPBS (first 5 hours) with the highest hourly increase in the first hour in both DPBS (6,040 ppb/h) and plasma (2,612 ppb/h), with no further increase after the first 22 hours. Platinum content in the specimens was higher at 96 hours than the surrounding fluid. Higher platinum concentrations were measured by both direct and UF probe sampling in DPBS than in plasma.
CLINICAL RELEVANCE
Platinum concentrations measured in DPBS were higher than in plasma, but elution patterns were similar. Ultrafiltration probes can be used to sample platinum in vitro and could be used in vivo to measure local unbound Pt tissue concentrations in local chemotherapy delivery.
