American journal of veterinary research最新文献

Objective: To evaluate the diagnostic performance of a post-/pre-thyrotropin-releasing hormone (TRH) plasma ACTH ratio for the diagnosis of pituitary pars intermedia dysfunction (PPID) in horses.

Methods: This was a prospective, case-controlled study conducted monthly from January through December 2018 on 21 horses with PPID and 63 control horses. The ratios were calculated by dividing the plasma ACTH concentration obtained 30 minutes after IV injection of TRH by the pre-TRH plasma ACTH concentration. The effect of PPID and month were assessed using a linear mixed-effect model, and the diagnostic performance of the ratio, including accuracy, sensitivity, and specificity, was assessed via receiver operating characteristic curves. Diagnostic cutoff values were calculated via the Youden index when relevant.

Results: Both PPID status and month had a significant effect on post-/pre-TRH plasma ACTH ratio, with higher ratios in horses with PPID in 7 of 12 months. The diagnostic performance of the post-/pre-TRH plasma ACTH ratio varied by month, with accuracies ranging from fair to good but consistently low positive likelihood ratios.

Conclusions: The post-/pre-TRH ACTH ratio allows evaluation of the pituitary pars intermedia response, validating the use of the TRH stimulation test in the diagnosis of PPID. However, the post-/pre-TRH plasma ACTH ratio does not improve the diagnostic characteristics of a TRH stimulation test.

Clinical relevance: The TRH stimulation test is recommended for evaluation of the pars intermedia of the equine pituitary gland in the context of diagnosing PPID, but the use of the post-/pre-TRH plasma ACTH ratio does not provide superior performance over the post-TRH ACTH concentration alone.

Objective: To investigate the ability of the equine orthobiologic Alpha2EQ to control inflammation in cultured synovial fibroblasts.

Methods: Equine synovial fibroblasts (n = 16) were cultured in a monolayer, and a targeted transcriptomic analysis (NanoString nCounter) was performed to screen for upregulated inflammatory gene expression. Cells were classified according to their IL-6 expression level. In the first experiment, high IL-6 expression (n = 4) and low IL-6 expression (4) cells were treated with Alpha2EQ, and in the second, cells with basal IL-6 expression were stimulated with 10 ng/mL IL-1β (4) before treatment. Allogeneic Alpha2EQ was pooled from sound healthy horses (n = 6) at a dose of 25% vol/vol of cell culture media. Twenty-four hours later, RNA was isolated for NanoString gene expression analysis. The t tests assessed differences in mean gene expression fold changes between baseline and treatment, while one-way ANOVA or Wilcoxon signed-rank tests were used for multiple comparisons (P < .05).

Results: Alpha2EQ downregulated inflammatory genes in 2 cell culture models. Compared to baseline, Alpha2EQ treatment significantly reduced expression of IL-6, IL-15, and CCL2/MCP1 in IL-6HIGH synovial fibroblasts by 1.88- to 4.21-fold, as well as expression of IL-1β, CCL5/RANTES, and PPBP/CXCL7 by 2.14- to 4.07-fold in a 10 ng/mL IL-1β model. In addition, CXCL6/GCP-2 and TNF-α were significantly downregulated by Alpha2EQ in both models (2.64- to 5.38-fold).

Conclusions: Alpha2EQ reduces inflammation by modulating the expression of cytokines and chemokines by synovial cells.

Clinical relevance: This study provides early insights into Alpha2EQ's anti-inflammatory mechanisms in vitro and evidence to support its clinical use in the treatment of equine osteoarthritis.

Objective: Osteoarthritis (OA) is a aging-associated degenerative joint disease. The objective was to determine relative senescence gene expression in joints and leukocytes of OA horses toward considering senotherapeutics to manage OA.

Methods: To define local (joint) and systemic (peripheral blood mononuclear cells [PBMCs]) senescence burden, synovial fluid cell single-cell RNA sequencing and PBMC mRNA sequencing datasets (n = 65 samples) were examined. Differential analyses were conducted using limma to compare OA versus control. A custom 3,043-gene senescence set curated from published metadata was applied to differential analyses to investigate senescence-specific pathways. Senescence genes were divided into 8 categories; scores were calculated with fast gene set enrichment analysis with P value computed via permutation and log2 fold change ranks.

Results: Synovial fluid single-cell RNA sequencing data revealed cell type-specific heterogeneity in senescence gene expression. Fast gene set enrichment analysis pathway analysis confirmed enrichment/upregulation in inflammatory and stress-induced senescence in dendritic, cycling, CD8 T, and gamma delta T cells. Senescence-associated secretory phenotype pathways were predominantly represented in cycling cells. Senescence genes aryl hydrocarbon receptor (AHR), IL-1 receptor antagonist (IL1RN), heme oxygenase 1 (HMOX1), plasminogen activator, urokinase receptor (PLAUR), and tissue inhibitor of metalloproteinase 1 (TIMP1) were upregulated in multiple synovial fluid cell types. In contrast, genes in most senescence categories were downregulated in PBMCs.

Conclusions: Senescence pathways were differentially expressed in aged horses with OA, with upregulation of senescence genes in the joint and downregulation in PBMCs.

Clinical relevance: Therapeutic strategies targeting senescent cells may be a disease-modifying strategy to treat equine OA.

Objective: To assess the prevalence of burnout (BO), secondary traumatic stress (STS), and compassion satisfaction (CS) and identify associated individual, clinic, and dog-handling factors among veterinary professionals.

Methods: A cross-sectional online questionnaire was distributed to veterinary professionals in Canada and US (2023 to 2024). The questionnaire collected individual, clinic, and dog-handling information and measured ProQOL (BO, STS, CS). Logistic regression models examined associations between these factors and ProQOL.

Results: Participants (n = 691) had moderate BO (71.2%), STS (71.8%), and CS (74.3%); 2.4% reported high STS, and none had high BO. Veterinarians had lower odds of moderate/high BO (OR, 0.50; 95% CI, 0.32 to 0.78) and CS (OR, 0.12; 95% CI, 0.021 to 0.64) compared with nonveterinarians. Below-normal personality traits were associated with moderate/high BO and/or STS: extraversion (BO: OR, 2.25; 95% CI, 1.47 to 3.46), agreeableness (BO: OR, 2.02; 95% CI, 1.29 to 3.18; STS: OR, 1.60; 95% CI, 1.07 to 2.39), conscientiousness (BO: OR, 3.91; 95% CI, 2.41 to 6.34; STS: OR, 3.81; 95% CI, 2.47 to 5.88), emotional stability (BO: OR, 1.96; 95% CI, 1.24 to 3.11), and openness (BO: OR, 1.64; 95% CI, 1.05 to 2.56; STS: OR, 1.88; 95% CI, 1.26 to 2.81). Stress-reducing certification was associated with moderate/high BO (OR, 2.04; 95% CI, 1.14 to 3.64).

Conclusions: Personality traits and individual factors were associated with ProQOL, whereas handling techniques were not.

Clinical relevance: Findings provide exploratory evidence for workplace strategies to reduce BO and STS and enhance CS while generating hypotheses for future intervention research.

Objective: To evaluate the impact of anesthesia and body temperature changes on a point-of-care viscoelastic coagulation monitoring device (VCM-Vet, Entegrion Corp) parameters in New Zealand white rabbits (Oryctolagus cuniculus).

Methods: Purpose-bred New Zealand white rabbits were anesthetized in a research facility as part of a randomized, complete crossover study. Each rabbit was anesthetized using isoflurane twice (7 days apart), with or without a heated anesthesia circuit (Heated ZDS Qube; Darvall), over approximately 2 weeks. Lateral saphenous venipuncture was performed within 5 minutes of anesthetic induction (baseline) and at 50 minutes after anesthetic induction (T50) during each event. Fresh whole blood was immediately tested using a single VCM-Vet analyzer, providing 2 tracings per event. Statistical analysis was performed using a linear mixed model with significance at P < .05.

Results: 10 approximately 4-month-old intact male apparently healthy rabbits were included. All rabbits were normothermic (median, 39.3 °C; range, 38.5 to 39.8 °C) at baseline, and all rectal temperatures were lower at T50 compared to baseline (median, 1.6 °C; range, 0.7 to 2.1 °C). There was no statistically significant difference in any clot parameter between baseline and T50 nor between different rectal temperatures; however, there were statistical differences in 4 clot parameters between nonheated and heated anesthetic events.

Conclusions: Anesthesia and mildly decreased body temperature did not significantly impact the viscoelastography assessment.

Clinical relevance: Although thromboelastography reference intervals have been established in rabbits, the use of the VCM-Vet analyzer is understudied in this species. Future research is needed to determine VCM-Vet reference intervals for rabbits.

Objective: To evaluate the relationship between goniometric stifle range of motion (gROM), active stifle range of motion (aROM), and stifle osteoarthritis (sOA) in dogs with cranial cruciate ligament disease (CCLD) and to assess the association between gROM and aROM in CCL-affected and control dogs.

Methods: Dogs weighing 20 to 40 kg with CCLD before surgery (CCL-Dogs) and orthopedically healthy controls (C-Dogs) were enrolled between August 1, 2020, and August 1, 2021. Objective gait analysis was performed on a treadmill using a 2-D marker-based system. Goniometric stifle extension (gSE) and goniometric stifle flexion (gSF) were measured 3 times by 3 observers. sOA was scored on a scale from 1 (none) to 4 (severe). Spearman rank correlation (r) described associations between sOA, gROM, and aROM.

Results: 15 CCL-Dogs and 10 C-Dogs were included. These preliminary data demonstrated that in CCL-Dogs, gROM (r = -0.644) and gSE (r = -0.751) showed significant correlations with sOA. No significant correlations were found between sOA and active stifle flexion (r = -0.160), active stifle extension (r = -0.138), aROM (r = 0.036), or gSF (r = 0.198). No significant correlation was observed between aROM and gROM in either CCL-Dogs (r = -0.346) or C-Dogs (r = -0.127).

Conclusions: In C-Dogs and CCL-Dogs, aROM and gROM are not associated. In CCL-Dogs, sOA is associated with reduced gROM and gSE, indicating that gROM rather than aROM reflects joint impairment.

Clinical relevance: Goniometric measurement of stifle extension may serve as a practical indicator of osteoarthritic severity and functional limitation in dogs with CCLD.

Objective: To establish an ultrasound protocol for identifying the muscular structures of the ventromedial hip region that contribute to coxofemoral joint stability, with comparative MRI and gross anatomic dissection confirmation of accurate structure identification.

Methods: High-frequency B-mode ultrasonography and 3-Tesla MRI were utilized to bilaterally investigate the muscular anatomy of the ventromedial hip region in 5 normal adult canine pelvis cadaver specimens (n = 10) from September 1, 2024, through August 30, 2025. Ultrasonographic and MRI appearance and anatomic relationships of the evaluated structures were documented and assessed for consistency. Structure identification was confirmed through ultrasound-guided dye placement (using 2 separate specimens for each evaluated structure) followed by gross anatomical dissection.

Results: High-quality ultrasound and MRI images of the pectineus, iliopsoas, adductor longus, adductor magnus et brevis, gracilis, and external obturator muscles were acquired in all specimens. The ultrasonographic approach for evaluating muscles of the ventromedial hip region was documented. Specimen dissection immediately following ultrasound-guided dye injections confirmed accurate identification of all 6 muscles on both attempts, performed separately by 2 clinicians. Structure identification and anatomical descriptions were consistent amongst MRI, ultrasound, and dissection.

Conclusions: This study provides foundational knowledge in ultrasound and MRI anatomy of the ventromedial hip region and demonstrates methods for effective ultrasonographic evaluation of this region.

Clinical relevance: These findings provide a foundation for diagnosing soft tissue injuries in the ventromedial hip region and guiding rehabilitation strategies in dogs with hip disease.

Objective: To compare IM and IV administration of 18F-sodium fluoride (18F-NaF) for PET-CT imaging of atherosclerosis in orange-winged Amazon parrots (Amazona amazonica) and to evaluate the effects of uptake time and acquisition duration on image quality using a reduced radiotracer dose.

Methods: From June to July 2025, parrots underwent 2 18F-NaF micro-PET-micro-CT scans at the University of California-Davis, each in a cross-over design (IM vs IV). A 0.1-mCi dose was used with a 30-minute uptake period and 30-minute dynamic acquisition. Images were reconstructed into 5-, 10-, and 15-minute frames to assess the effects of acquisition duration and uptake time. Standardized uptake values and target-to-background ratios were calculated in arterial lesions and control tissues.

Results: Eight older parrots were scanned. Atherosclerotic lesions were identified in 6 of 8 parrots. Both image noise and background activity were higher in IM than IV scans, particularly at shorter acquisition durations. Lesion conspicuity and quantitative stability improved at longer uptake times (≥ 45 minutes) and acquisitions (≥ 10 minutes). The IM administration produced slower equilibration but comparable or higher late-phase lesion uptake, consistent with gradual tracer release.

Conclusions: The IM 18F-NaF administration provides diagnostic-quality PET images with lesion detectability approaching that of the IV administration, while being technically simpler and safer for parrots.

Clinical relevance: An optimized protocol for PET imaging in psittacine birds using a similar scanner is proposed with the administration of approximately 0.3 mCi 18F-NaF IM or IV, a 1-hour uptake period, and a 10- to 15-minute acquisition to balance image quality, diagnostic sensitivity, procedural simplicity, and radiation safety.

Objective: To describe the pharmacokinetics of the IV formulation of levetiracetam administered intranasally and calculate the absolute bioavailability. Our hypothesis was that levetiracetam would show near complete absorption following a single intranasal dose.

Methods: 8 healthy dogs (4 female, 4 male) from a canine colony were used in a crossover study comparing the pharmacokinetics of intranasal and IV levetiracetam. The study occurred from August through September 2024. A 100-mg dose of levetiracetam was administered via the intranasal and IV routes on separate occasions. Blood was collected from jugular catheters over a 24-hour period following dose administration. Plasma levetiracetam concentrations were analyzed using high-pressure liquid chromatography. Noncompartmental analysis was performed to describe the pharmacokinetics.

Results: Median (minimum to maximum), maximal concentration, time to maximal concentration, and elimination half-life for the intranasal route were 7.85 µg/mL (range, 3.37 to 14.16), 0.98 hours (range, 0.22 to 1.00), and 2.83 hours (range, 2.44 to 3.76), respectively. Median (minimum to maximum) bioavailability was 61% (range, 34% to 85%). The maximal concentration achieved fell within the human reference interval for levetiracetam in 5 of 8 dogs.

Conclusions: Levetiracetam was absorbed to a moderate degree following the intranasal route of administration and appeared to be well tolerated.

Clinical relevance: Levetiracetam is absorbed via the nasal administration route and could be considered a feasible route of administration for at-home rescue protocols. Although concentrations within the human reference interval were achieved in a majority of dogs, a clinical trial is necessary to determine if this method of administration would be effective in a clinical setting.

Objective: To describe the pharmacokinetic parameters of tramadol and its main metabolites, O-desmethyltramadol (M1) and N-desmethyltramadol, and clinically detectable adverse effects after a single orally administered high dose of tramadol in rabbits (Oryctolagus cuniculus).

Methods: 6 experimental and 1 control healthy intact male rabbits of commercial origin were included in February 2025. Following administration of a 30-mg/kg oral dose of tramadol, plasma concentrations of tramadol, M1, and N-desmethyltramadol were determined by UHPLC-MS at 12 predetermined time points. Pharmacokinetic parameters were calculated using commercial software. Fecal production and sedation were evaluated before and after the experiment.

Results: The mean tramadol maximum plasmatic concentration was 91 ± 38 ng/mL, the average time to reach maximum plasmatic concentration was 40 minutes, the terminal half-life was 4.0 ± 2.4 hours, and the mean area under the curve from the first dose to infinity was 192 ± 45 ng/hmL. The M1 metabolite reached concentrations compatible with previously described analgesic effects in rabbits after 10 minutes and for up to 3 hours after administration in some individuals, whereas tramadol did not reach analgesic concentrations. Mild sedation was detected in 4 rabbits at the 20 minute- to 6-hour time points, and fecal production increased from 24 to 48 hours after tramadol administration. No clinically relevant adverse effects were noted.

Conclusions: Administration of 30 mg/kg tramadol, PO, in rabbits results in plasma concentrations of M1 compatible with analgesia.

Clinical relevance: The short duration of action warrants further studies with long-acting formulations of tramadol.