OBJECTIVE: To evaluate the effects of aging on phenylbutazone (PBZ) disposition in older horses (≥ 25 years old) compared to young adults (4 to 10 years old) by characterizing the pharmacokinetic profile of PBZ and its active metabolite, oxyphenbutazone (OPBZ), following a 2.2-mg/kg dose, IV. We hypothesized that the disposition of PBZ will be affected by age.
METHODS: 16 healthy horses (8 young adults aged 4 to 10 years and 8 geriatric horses ≥ 25 years old).
METHODS: Horses were administered a single 2.2-mg/kg PBZ dose, IV. Plasma samples were collected at designated time points and frozen at -80 °C until assayed using liquid chromatography-tandem mass spectrometry. Pharmacokinetic analyses were performed using Phoenix WinNonlin, version 8.0 (Certara). Both clinical and pharmacokinetic data were compared between age groups using independent samples t tests, with P < .05 considered significant.
RESULTS: Baseline characteristics did not differ between groups, with the exception of age, weight, and plasma total solids. Plasma concentrations of PBZ were best described by a two-compartment model. The maximum plasma concentration of OPBZ was reached at 5 hours for both age groups, and the metabolite-to-parent-drug area-under-the-curve ratios were approximately 20% for both groups. None of the pharmacokinetic parameters of PBZ or its metabolite, OPBZ, differed significantly between age groups.
CONCLUSIONS: The hypothesis was rejected as there was no significant difference in PBZ disposition in young-adult horses compared to geriatric horses. Our data do not support the need for dose adjustments of PBZ in clinically healthy geriatric horses.

A 1-year-old Miniature Horse filly was presented for chronic lethargy and hyporexia. Elevated liver enzymes, bile acids, and ammonia were noted on bloodwork. The primary differential diagnosis was a portosystemic shunt (PSS). Three-phase computed tomographic angiography findings were consistent with a transhepatic portosystemic shunt. Percutaneous liver biopsy confirmed severe diffuse hepatic changes, most likely due to chronic pyrrolizidine alkaloid toxicosis, and medical management was elected. Based on an extensive literature review, this is the first report of a transhepatic portosystemic collateral vessel in a horse. Computed tomographic angiography is feasible and useful for the diagnosis of PSS in miniature horses.

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.

Pulmonary function testing is critical to the diagnosis of equine asthma (EA), an important cause of respiratory disease in the horse, but its clinical use has remained elusive, unfortunately, due to the complexity of reference methods, esophageal balloon/pneumotachography (EBP) and forced oscillatory mechanics (FOM), so we sought a non-invasive, portable method for use in horses through rapid interruption of airflow for equilibration of alveolar pressure with proximal airway pressure, termed flow interruption (FI). Resistance (RINT) was computed as the relationship between the change in pressure at the nose before and immediately after interruption and flow immediately before interruption. A pilot study in 5 healthy university-owned animals using EBP and FI showed good correspondence between the two methods: RINT (0.33 +/- 0.05 cm H2O/l/s) and RL (0.31 +/- 0.06 cm H2O/l/s). In 2 separate populations of client-owned horses, with random assignment of methods to FI v EBP (n = 8), RINT showed good correlation with RL in horses, (rs =.995, p = .0002) and accords with RL, with no significant difference between RINT and RL. Using FOM (n = 12), RINT (0.67 +/- 0.31 cmH2O/l/s) has good correlation with RRS measured with FOM (r =.834, p = .0001), but is consistently smaller than RRS (0.74 +/- 0.33 cmH2O/l/s) . Histamine bronchoprovocation (HBP) was performed in a subset of these horses: FI classified one horse in 6 as less reactive than did EBP, and FI classified one horse in 7 as less reactive than did FOM.

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.

The equine uterus is highly interrogated during estrus prior to breeding and establishing pregnancy. Many studies in mares have been performed during estrus under the influence of high estrogen concentrations, including the equine estrual microbiome. To date, it is unknown how the uterine microbiome of the mare is influenced by cyclicity; while, the equine vaginal microbiome is stable throughout the estrous cycle. We hypothesized that differences would exist between the equine endometrial microbiome of mares in estrus and anestrus. The aim of this study was two-fold: to characterize the resident endometrial microbiome of healthy mares during anestrus and to compare this with estrus. Double-guarded endometrial swabs were taken from healthy mares during estrus (n=16) and in the following non-breeding season during anestrus (n=8). Microbial population was identified using 16S rRNA sequencing. Our results suggest that the equine uterine microbiome in estrus has a low diversity and low richness, while during anestrus, a higher diversity and higher richness were seen compared to estrus. Despite this difference, both the estrus and anestrus endometrial microbiome were dominated by Proteobacteria, Firmicutes, and Bacteroidota. The composition of the microbial community between anestrus and estrus was significantly different. This may be explained by the difference in the composition of the endometrial immune milieu based on the stage of the cycle. Further research investigating the function of the equine endometrial microbiome and dynamics changes within the uterine environment is required.