A one-health approach to identifying and mitigating the impact of endocrine disorders on human and equine athletes.

Endocrinopathies affect multiple species in ever-increasing percentages of their populations, creating an opportunity to apply one-health approaches to determining creative preventative measures and therapies in athletes. Obesity and alterations in insulin and glucose dynamics are medical concerns that play a role in whole-body health and homeostasis in both horses and humans. The role and impact of endocrine disorders on the musculoskeletal, cardiovascular, and reproductive systems are of particular interest to the athlete. Elucidation of both physiologic and pathophysiologic mechanisms involved in disease processes, starting in utero, is important for development of prevention and treatment strategies for the health and well-being of all species. This review focuses on the unrecognized effects of endocrine disorders associated with the origins of metabolic disease; inflammation at the intersection of endocrine disease and related diseases in the musculoskeletal, cardiovascular, and reproductive systems; novel interventions; and diagnostics that are informed via multiomic and one-health approaches. Readers interested in further details on specific equine performance conditions associated with endocrine disease are invited to read the companion Currents in One Health by Manfredi et al, JAVMA, February 2023.

Identification of Host Factors Associated with the Development of Equine Herpesvirus Myeloencephalopathy by Transcriptomic Analysis of Peripheral Blood Mononuclear Cells from Horses.

Equine herpesvirus-1 is the cause of respiratory disease, abortion, and equine herpesvirus myeloencephalopathy (EHM) in horses worldwide. EHM affects as many as 14% of infected horses and a cell-associated viremia is thought to be central for EHM pathogenesis. While EHM is infrequent in younger horses, up to 70% of aged horses develop EHM. The aging immune system likely contributes to EHM pathogenesis; however, little is known about the host factors associated with clinical EHM. Here, we used the "old mare model" to induce EHM following EHV-1 infection. Peripheral blood mononuclear cells (PBMCs) of horses prior to infection and during viremia were collected and RNA sequencing with differential gene expression was used to compare the transcriptome of horses that did (EHM group) and did not (non-EHM group) develop clinical EHM. Interestingly, horses exhibiting EHM did not show respiratory disease, while non-EHM horses showed significant respiratory disease starting on day 2 post infection. Multiple immune pathways differed in EHM horses in response to EHV-1. These included an upregulation of IL-6 gene expression, a dysregulation of T-cell activation through AP-1 and responses skewed towards a T-helper 2 phenotype. Further, a dysregulation of coagulation and an upregulation of elements in the progesterone response were observed in EHM horses.

Use of tube cystostomy in the surgical management of obstructive urolithiasis in a Bactrian camel.

CASE DESCRIPTION: A 6-year-old castrated male Bactrian camel was evaluated because of a 14hour history of oliguria and stranguria that progressed to anuria. CLINICAL FINDINGS: Perineal urethral pulsations and intermittent tail flagging with no accompanying urination were observed. Ultrasonography of the urethra revealed multiple hyperechoic foci with shadowing artifact indicative of calculi present in the penile urethra distal to the sigmoid flexure. Rectal palpation revealed a pulsating hard urethra and intact distended urinary bladder. Further clinical examination was not possible because of challenges associated with handling the camel. TREATMENT AND OUTCOME: Urethral catheterization through a perineal urethral incision failed to achieve urinary bladder decompression. Tube cystostomy was performed to prevent bladder rupture. Urethrocystography performed 3 days after surgery revealed a urethral rupture at the level of the prepuce. Five weeks after surgery, the camel could urinate a steady stream via the urethrotomy site. Seven weeks after surgery, the cystostomy tube was removed, and the urethrotomy site was modified to provide a permanent urethral opening via perineal urethrostomy. During 6 years of subsequent periodic follow-up by telephone, the owner reported that the camel continued to do well and urinate through the revised opening. CLINICAL RELEVANCE: To the authors' knowledge, this is the first detailed description of a tube cystostomy in an adult camel with obstructive urolithiasis that includes information on the patient's long-term outcome. This technique was a viable option in the surgical management of obstructive urolithiasis in this camel and may be useful for other large camelids as well.

Metabolic perturbations in Welsh Ponies with insulin dysregulation, obesity, and laminitis.

BACKGROUND: Metabolomics, the study of small-molecule metabolites, has increased understanding of human metabolic diseases, but has not been used to study equine metabolic syndrome (EMS). OBJECTIVES: (1) To examine the serum metabolome of Welsh Ponies with and without insulin dysregulation before and during an oral sugar test (OST). (2) To identify differences in metabolites in ponies with insulin dysregulation, obesity, or history of laminitis. ANIMALS: Twenty Welsh Ponies (mean ± SD; 13.8 ± 9.0 years) classified as non-insulin dysregulated [CON] (n = 10, insulin < 30 mU/L) or insulin dysregulated [ID] (n = 10, insulin > 60 mU/L) at 75 minutes after administration of Karo syrup, obese (n = 6) or nonobese (n = 14), and history of laminitis (n = 9) or no history of laminitis (n = 11). METHODS: Case-control study. Metabolomic analysis was performed on serum obtained at 0 minutes (baseline) and 75 minutes during the OST. Data were analyzed with multivariable mixed linear models with significance set at P ≤ .05. RESULTS: Metabolomic analysis of 646 metabolites (506 known) detected significant metabolite differences. At baseline, 55 metabolites (insulin response), 91 metabolites (obesity status), and 136 metabolites (laminitis history) were different. At 75 minutes, 51 metabolites (insulin response), 102 metabolites (obesity status), and 124 metabolites (laminitis history) were different. CONCLUSIONS AND CLINICAL IMPORTANCE: Use of metabolomics could have diagnostic utility for early detection of EMS and provide new knowledge regarding the pathophysiology of metabolic perturbations associated with this condition that might lead to improved clinical management.

Cavernous sinus syndrome in a Holstein bull.

A 13-month-old Holstein bull was presented for right-sided exophthalmos. Ophthalmologic examination noted that the animal was visual in both eyes, but that the right pupil was persistently dilated and very sluggish to constrict when stimulated with a bright light and that normal ocular motility was absent. Fundic examination of the right eye was normal as was a complete ophthalmologic examination of the left eye. Radiographs at presentation did not reveal the presence of sinusitis or other skull abnormalities. Initial treatment comprised intravenous antibiotics and anti-inflammatories for orbital inflammation over a 14-day period. There was no perceptible change in the appearance or neuro-ophthalmologic examination of the right eye during hospitalization. The animal was discharged to the owner's care, but 3 weeks later was found recumbent with unilateral strabismus of the left eye and a fixed right pupil. Due to the inability to rise and rapid deterioration, humane euthanasia was performed, and a full postmortem examination, preceded by a MRI, was performed that identified abscesses extending bilaterally through the round foramina obliterating the cavernous sinus region, as well as abscessation of the right mandible, right trigeminal neuritis, right-sided sinusitis, and right-sided otitis media. Cavernous sinus syndrome should be considered in cattle with a combination of exophthalmos and neuro-ophthalmologic abnormalities involving cranial nerves III, IV, V, and VI, whose branches are located within the cavernous sinus.