UNASSIGNED: Anatomical location-dependent differences in transdermal opioid penetration are well described in human patients. Although this has been investigated in horses with fentanyl, there is no literature available on location-dependent plasma buprenorphine concentrations when administered as a transdermal matrix-type patch.
UNASSIGNED: This study aims to compare the plasma concentrations achieved from the matrix-type transdermal buprenorphine patches placed at different anatomical sites (metacarpus, gaskin, and ventral tail base) in healthy adult horses.
UNASSIGNED: This is a randomized experimental study with a Latin square design.
UNASSIGNED: Six adult horses were given each of three treatments with a minimum 10-day washout period. For each treatment, two 20 μg h-1 matrix-type buprenorphine patches were applied to the ventral aspect of the tail base (TailTDP), metacarpus region (MetacarpusTDP), or gaskin region (GaskinTDP). Whole blood samples (for determination of buprenorphine concentration) and physiological variables were collected before (0 h) and at 0.5, 2, 4, 6, 8, 10, 12, 16, 24, 32, 48, 56, 72, 96 and 120 h after patches were applied. The patches were removed 96 h following placement and were analyzed for residual buprenorphine content. Buprenorphine concentrations were measured in plasma by LC-MS/MS. A mixed-effects model was used to analyze the physiological variables.
UNASSIGNED: Between the three treatment groups, there was no change in physiological variables across timepoints as compared to baseline and when compared to each other in a single horse and between horses (p > 0.3). When comparing all three locations, the buprenorphine uptake was observed to be more consistent with respect to measurable plasma concentrations >0.1 ng ml-1 when applied to the ventral aspect of the tail base. In the TailTDP group, the mean plasma buprenorphine concentrations were >0.1 ng ml-1 from 2 to 32 h. The highest group mean was 0.25 ng ml-1 noted at 4 h.
UNASSIGNED: The metacarpal and gaskin regions presented more erratic and inconsistent buprenorphine uptake and plasma concentrations as compared to the ventral aspect of the tail base. Further research must be directed at investigating the optimal dose, achievable duration of analgesia, change in measurable plasma concentrations, and behavioral and systemic effects.

The use of mesenchymal stem cells (MSCs) in human and veterinary clinical applications has become a subject of increasing importance due to their roles in immunomodulation and regenerative processes. MSCs are especially relevant in equine medicine because they may have the ability to treat prevalent musculoskeletal disorders, among other conditions. However, recent evidence suggests that the components secreted by MSCs, particularly extracellular vesicles (EVs), are responsible for these properties. EVs contain proteins and nucleic acids, which possess an active role in intercellular communication and can be used as therapeutics. However, because the intersection of equine veterinary medicine with EVs remains a relatively new field, there is a demand to identify biomarkers that can discern and enrich for therapeutic EVs, progressing their clinical efficacy. In this study, we identified and characterized 84 miRNAs, between three equine donors involved in immunomodulation in cell and EV subjects. We discovered distinct groups of shared miRNAs, like miR-21-5p and miR-451a, that are abundant and enriched between the donors\' EVs, respectively. By mapping and comparing the MSC-EV miRNA expression, we discovered many pathways that are involved in immunomodulation and tissue regenerative processes related to equine clinical applications. Therefore, the miRNAs highlighted in this article can be used as valuable biomarkers for screening MSC-derived EVs for potential equine therapy.

UNASSIGNED: Although relatively uncommon, lymphoma is the most prevalent haematopoietic neoplasia in horses, and multicentric lymphoma remains the most common presentation of the disease. The pathogenesis of equine lymphoma is still poorly understood and the diagnosis is usually confirmed at an advanced stage of the disease, compromising the prognosis. This study investigated the clinical, pathological, and molecular features of a case of equine multicentric lymphoma.
UNASSIGNED: An apparently healthy 5-year-old crossbreed mare hospitalized at the Centre of Animal Reproduction of Vairão, Portugal, suddenly presented clinical signs of supraorbital oedema and mandibular lymph node enlargement, developing fever, facial oedema, and generalized lymphadenopathy. The mare ended up dying twenty-four days after the first clinical signs due to multisystem organ failure. Haematological and biochemical analyses, necropsy, and microscopic and molecular evaluation of affected tissues were performed. At necropsy, the main findings were multiple multinodular lesions, distributed along the serous surface of oropharynx, trachea, pericardium, gastrointestinal tract, and mesentery. Microscopically, these consisted of solid proliferations of neoplastic round cells that exhibited immunopositivity for CD3 (T cells). Based on these findings, a medium-grade multicentric T-cell lymphoma was diagnosed.
UNASSIGNED: There is still very little research regarding the molecular characterization of lymphoma in horses. As an entity itself is quite heterogeneous, it is important to describe the interspecies particularities to understand its development and behaviour.

Mild-moderate and severe equine asthma (MEA and SEA) are prevalent inflammatory airway conditions affecting horses of numerous breeds and disciplines. Despite extensive research, detailed disease pathophysiology and the differences between MEA and SEA are still not completely understood. Bronchoalveolar lavage fluid cytology, broadly used in clinical practice and in equine asthma research, has limited means to represent the inflammatory status in the lower airways. Lipidomics is a field of science that can be utilized in investigating cellular mechanisms and cell-to-cell interactions. Studies in lipidomics have a broad variety of foci, of which fatty acid and lipid mediator profile analyses and global lipidomics have been implemented in veterinary medicine. As many crucial proinflammatory and proresolving mediators are lipids, lipidomic studies offer an interesting yet largely unexplored means to investigate inflammatory reactions in equine airways. The aim of this review article is to collect and summarize the findings of recent lipidomic studies on equine airway inflammation.

Variation in coat color among equids has attracted significant interest in genetics and breeding research. The range of colors is primarily determined by the type, concentration, and distribution of melanin pigments, with the balance between eumelanin and pheomelanin influenced by numerous genetic factors. Advances in genomic and sequencing technologies have enabled the identification of several candidate genes that influence coat color, thereby clarifying the genetic basis of these diverse phenotypes. In this review, we concisely categorize coat coloration in horses and donkeys, focusing on the biosynthesis and types of melanin involved in pigmentation. Moreover, we highlight the regulatory roles of some key candidate genes, such as MC1R, TYR, MITF, ASIP, and KIT, in coat color variation. Moreover, the review explores how coat color relates to selective breeding and specific equine diseases, offering valuable insights for developing breeding strategies that enhance both the esthetic and health aspects of equine species.

BACKGROUND: This study evaluates the change in an MRI of the proximal metacarpal region in a group of sport horses that returned to work. This retrospective analysis evaluated 18 limbs represented by 17 horses.
RESULTS: The hyperintense signal within the dorsal collagenous part of the proximal suspensory ligament (PSL) on T1W/T2*W GRE sequences decreased or stayed the same in the majority of cases. The hyperintense STIR signal within the dorsal collagenous part of the PSL resolved in the majority of the patients, and the third metacarpal bone (McIII) hyperintense STIR signal resolved in all patients. The dorsal margin irregularity of the PSL stayed the same, and McIII sclerosis and resorption of the palmar margin of McIII stayed the same in the majority of cases. McIII hyperintense STIR signal resolution carries a broad time range, with a mean of 94 days and a range of 47-202 days.
CONCLUSIONS: Complete normalization of the dorsal collagenous part of the PSL does not appear necessary for a return to soundness, but a resolution of the McIII hyperintense STIR signal is expected for horses returning to soundness. A rescan period of 120 days for the proximal metacarpal region is suggested. In addition, there was no significant change in the size of the PSL between the initial and final MRI.

This study aimed to evaluate the feasibility of transcutaneous auricular vagal nerve stimulation (tAVNS) in healthy horses and its effect on heart rate variability (HRV). The study comprised three phases: the selection of mares, their acclimatization to the tAVNS, and the stimulation phase. Stimulation was performed with two electrodes positioned on the right pinna. The settings were 0.5 mA, 250 μs, and 25 Hz for pulse amplitude, pulse width, and pulse frequency, respectively. HRV was analysed before (B1), during (T), and after (B2) the tAVNS. From the 44 mares initially included, only 7 completed the three phases. In these mares, the heart rate (HR) was significantly lower, and frequency domain parameters showed an increased parasympathetic tone in B2 compared with B1. However, in 3/7 mares, the HR was significantly higher during T compared with B1 and B2, compatible with a decreased parasympathetic tone, while in 4/7 mares, the HR was significantly lower and the parasympathetic nervous system index was significantly higher during T and B2 compared with B1. The tAVNS is an economical and easy procedure to perform and has the potential to stimulate vagal activity; however, it was poorly tolerated in the mares included in this study.

UNASSIGNED: Potential synovial penetration following palmar digital nerve blocks has not been investigated.
UNASSIGNED: To evaluate the proximity of needles placed for palmar digital nerve blocks to nearby synovial structures using computed tomography (CT).
UNASSIGNED: Descriptive observational study.
UNASSIGNED: In 18 cadaver forelimbs, sequential injection of the navicular bursa (NB), distal interphalangeal joint (DIPJ) and digital flexor tendon sheath (DFTS) was performed using 3, 5 and 10 mL diluted radiodense contrast medium, respectively. After each synovial injection, 25 gage needles were placed over the palmar digital nerves at the proximal aspect of the ungular cartilages (distal injections) and 1 cm further proximally (proximal injections), and CT examination was performed. Subsequently, needles were removed, and the synovial structures further distended with the same volume as for the first injection. Perineural needle placement and image acquisition were repeated. The distance between the needle tip and adjacent synovial structures was measured (mm) in reconstructed images. Results were analyzed in separate general linear mixed models, to determine the effect of needle position and synovial distension on the distance from the tip of the needle to the NB, DFTS and DIPJ.
UNASSIGNED: Synovial penetration was confirmed following 12/420 (3%) needle placements (NB n = 5, 1 after proximal and 4 after distal injections; DIPJ n = 2, DFTS n = 2, NB or DIPJ n = 3, all after distal injections). The mean distance from the needle tip to the NB and DIPJ was significantly smaller after the second distension (NB: p = 0.025; DIPJ: p < 0.001) and with the distal needle placements (NB: p < 0.001; DIPJ: p < 0.001). For the DFTS, the distance from the needle tip was significantly smaller with the proximal needle placements (p = 0.001).
UNASSIGNED: Ex-vivo study.
UNASSIGNED: There is a small risk of synovial penetration when performing palmar digital nerve blocks, especially when distension of adjacent synovial structures is present.

Understanding the factors which control endothelial cell (EC) function and angiogenesis is crucial for developing the horse as a disease model, but equine ECs remain poorly studied. In this study, we have optimised methods for the isolation and culture of equine aortic endothelial cells (EAoECs) and characterised their angiogenic functions in vitro. Mechanical dissociation, followed by magnetic purification using an anti-VE-cadherin antibody, resulted in EC-enriched cultures suitable for further study. Fibroblast growth factor 2 (FGF2) increased the EAoEC proliferation rate and stimulated scratch wound closure and tube formation by EAoECs on the extracellular matrix. Pharmacological inhibitors of FGF receptor 1 (FGFR1) (SU5402) or mitogen-activated protein kinase (MEK) (PD184352) blocked FGF2-induced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and functional responses, suggesting that these are dependent on FGFR1/MEK-ERK signalling. In marked contrast, vascular endothelial growth factor-A (VEGF-A) had no effect on EAoEC proliferation, migration, or tubulogenesis and did not promote ERK1/2 phosphorylation, indicating a lack of sensitivity to this classical pro-angiogenic growth factor. Gene expression analysis showed that unlike human ECs, FGFR1 is expressed by EAoECs at a much higher level than both VEGF receptor (VEGFR)1 and VEGFR2. These results suggest a predominant role for FGF2 versus VEGF-A in controlling the angiogenic functions of equine ECs. Collectively, our novel data provide a sound basis for studying angiogenic processes in horses and lay the foundations for comparative studies of EC biology in horses versus humans.

Inflammatory bowel disease (IBD) is a chronic disease characterized by different cell infiltrates in the intestine. The aims of this study were to report the clinical and clinicopathological findings in horses with histological changes compatible with IBD in the duodenum. Further, the clinical progression of IBD and survival were investigated. Patient records were reviewed for horses in which histological evidence of IBD was found in duodenal biopsies collected during endoscopy. The histological changes were classified as mild, moderate or severe and the predominant infiltrating cell type was recorded. Clinical improvement was assessed by the owner via a questionnaire at 6 weeks after biopsy, along with survival after one year. In total, 149 horses were included, and the most common clinical signs were weight loss, reduced performance and pain during abdominal palpation. Most horses showed partial malabsorption during an oral glucose absorption test, and the horses with severe IBD had lower serum protein concentrations. Lymphoplasmacytic enteritis was the most common type of IBD (78.5% of cases), while in six horses neutrophilic infiltration of the duodenum was present. Overall, 71% of the cases had improved clinically after six weeks, mostly following treatment with corticosteroids. The results of a second biopsy were a poor predictor of improvement, and the horses that improved after 6 weeks were more likely to be alive after one year.