American journal of veterinary research最新文献

Objective: To assess the pharmacokinetics of a single application of transdermal flunixin meglumine in southern white rhinoceros (Ceratotherium simum simum).

Methods: Healthy adult white rhinoceros were prospectively enrolled in the study from June through September 2024. Baseline blood samples were collected prior to drug administration. A single (3.3 mg/kg) dose of commercially available transdermal flunixin meglumine was applied topically at 2 primary sites: the nuchal hump extending behind the ears and the skin overlying the spine from the shoulder to ischium. Blood samples were collected under behavioral restraint at 2 to 4 time points for each rhinoceros following a sparse-sampling model. Drug assay validation and plasma drug concentrations were determined using HPLC-MS-MS.

Results: Successful application of transdermal flunixin meglumine was achieved in 13 individuals. Twelve individuals were included in compartmental analysis. The time to maximum plasma concentration was 7.2 hours. The peak plasma concentration was 0.31 μg/mL. The elimination half-life was 28.6 hours. Mild behavioral changes were observed in 6 animals and included quiet mentation, rubbing at the application site, lethargy, and mild ataxia. All side effects were noted to be resolved 24 hours after drug application.

Conclusions: Transdermal flunixin meglumine was absorbed and measurable plasma concentrations achieved in all southern white rhinoceros. The side effects observed included short-duration behavioral changes.

Clinical relevance: This study reports successful use and pharmacokinetic parameters of transdermal flunixin meglumine at 3.3 mg/kg when applied to the neck and topline in southern white rhinoceros.

Objective: To determine if and how oral itraconazole alters the gastrointestinal microbiome of cats.

Methods: This was a single-arm, longitudinal exploratory study performed in a university setting. Healthy cats were administered 5 mg/kg/day of itraconazole solution orally with food during alternating weeks over a 5-week time period. Rectal swabs were collected at 2 time points before treatment and serially during and after treatment over 31 weeks. Bacterial and fungal populations were quantified by 16S and internal transcribed spacer 3 and 4 sequencing, respectively. Changes in α diversity, β diversity, and differential abundance were evaluated over time.

Results: There were no significant changes in bacterial α diversity, β diversity (R2 = 0.0077; P = .550), or relative abundance between the 2 pretreatment time points indicating stable microbial populations before itraconazole exposure in 16 cats. Time was a significant determinant of β diversity during and after itraconazole treatment (R2 = 0.0181; P = .002), and several α-diversity indices significantly decreased in the posttreatment timeframe. Ruminococcus torques (-1.916; 95% CI, -2.971 to -0.861), Acidaminococcus spp (-1.291; 95%, CI -1.866 to -0.716), and Blautia hansenii (-1.475, 95% CI, -2.295 to -0.691) relative abundances were significantly decreased at weeks 1, 5, and 9, respectively. The final fungal internal transcribed spacer dataset only included 5 taxa limiting analysis and interpretation.

Conclusions: These findings provide preliminary evidence for possible dysbiosis in the feline gastrointestinal tract during itraconazole treatment. However, many changes in differential abundance were small and no longer significant posttreatment.

Clinical relevance: Itraconazole administration might induce gastrointestinal bacterial dysbiosis in cats. Alternate methods for fungal microbiome assessment should be used in future feline studies.

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: 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 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: 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.