Large or Food Animal and Equine Medicine Commons^™

Gabapentin, A Human Therapeutic Medication And An Environmental Substance Transferring At Trace Levels To Horses: A Case Report., Kimberly Brewer, Jacob Machin, George Maylin, Clara Fenger, Abelardo Morales-Briceño, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Gabapentin, 1-(Aminomethyl)cyclohexaneacetic acid, MW 171.240, is a frequently prescribed high dose human medication that is also used recreationally. Gabapentin is orally absorbed; the dose can be 3,000 mg/day and it is excreted essentially unchanged in urine. Gabapentin is stable in the environment and routinely detected in urban wastewater. Gabapentin randomly transfers from humans to racing horses and is at times detected at pharmacologically ineffective / trace level concentrations in equine plasma and urine. In Ohio racing between January 2019 and July 2020,18 Gabapentin identifications, all less than 2 ng/ml in plasma, were reported. These identifications were ongoing because the horsemen …

Sporadic Worldwide “Clusters” Of Feed Driven Zilpaterol Identifications In Racing Horses: A Review And Analysis, Jacob Machin, Kimberly Brewer, Abelardo Morales Briceno, Clara Fenger, George Maylin, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Zilpaterol is a β2-adrenergic agonist medication approved in certain countries as a cattle feed additive to improve carcass quality. Trace amounts of Zilpaterol can transfer to horse feed, yielding equine urinary “identifications” of Zilpaterol. These “identifications” occur because Zilpaterol is highly bioavailable in horses, resistant to biotransformation and excreted as unchanged Zilpaterol in urine, where it has a 5 day or so terminal half-life.

In horses, urinary steady-state concentrations are reached 25 days (5 half-lives) after exposure to contaminated feed. Zilpaterol readily presents in horse urine, yielding clusters of feed related Zilpaterol identifications in racehorses. The first cluster, April …

Advances In Gene Ontology Utilization Improve Statistical Power Of Annotation Enrichment, Eugene Waverly Hinderer Iii, Robert M. Flight, Rashmi Dubey, James N. Macleod, Hunter N. B. Moseley

Maxwell H. Gluck Equine Research Center Faculty Publications

Gene-annotation enrichment is a common method for utilizing ontology-based annotations in gene and gene-product centric knowledgebases. Effective utilization of these annotations requires inferring semantic linkages by tracing paths through edges in the ontological graph, referred to as relations. However, some relations are semantically problematic with respect to scope, necessitating their omission or modification lest erroneous term mappings occur. To address these issues, we created the Gene Ontology Categorization Suite, or GOcats—a novel tool that organizes the Gene Ontology into subgraphs representing user-defined concepts, while ensuring that all appropriate relations are congruent with respect to scoping semantics. Here, we demonstrate the …

Systematic Review Of Gastrointestinal Nematodes Of Horses From Australia, Muhammad A. Saeed, Ian Beveridge, Ghazanfar Abbas, Anne Beasley, Jenni Bauquier, Edwina Wilkes, Caroline Jacobson, Kris J. Hughes, Charles El-Hage, Ryan O'Handley, John Hurley, Lucy Cudmore, Peter Carrigan, Lisa Walter, Brett Tennent-Brown, Martin K. Nielsen, Abdul Jabbar

Maxwell H. Gluck Equine Research Center Faculty Publications

Background: Equine gastrointestinal nematodes (GINs) have been the subject of intermittent studies in Australia over the past few decades. However, comprehensive information on the epidemiology of equine GINs, the efficacy of available anthelmintic drugs and the prevalence of anthelmintic resistance (AR) in Australasia is lacking. Herein, we have systematically reviewed existing knowledge on the horse GINs recorded in Australia, and main aspects of their pathogeneses, epidemiology, diagnoses, treatment and control.

Methods: Six electronic databases were searched for publications on GINs of Australian horses that met our inclusion criteria for the systematic review. Subsets of publications were subjected to review epidemiology, …

Phylogenetic Analysis And Characterization Of A Sporadic Isolate Of Equine Influenza A H3n8 From An Unvaccinated Horse In 2015, Chithra C. Sreenivasan, Sunayana S. Jandhyala, Sisi Luo, Ben M. Hause, Milton Thomas, David E. B. Knudsen, Pamela Leslie-Steen, Travis Clement, Stephanie E. Reedy, Thomas Chambers, Jane Christopher-Hennings, Eric Nelson, Dan Wang, Radhey S. Kaushik, Feng Li

Maxwell H. Gluck Equine Research Center Faculty Publications

Equine influenza, caused by the H3N8 subtype, is a highly contagious respiratory disease affecting equid populations worldwide and has led to serious epidemics and transboundary pandemics. This study describes the phylogenetic characterization and replication kinetics of recently-isolated H3N8 virus from a nasal swab obtained from a sporadic case of natural infection in an unvaccinated horse from Montana, USA. The nasal swab tested positive for equine influenza by Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR). Further, the whole genome sequencing of the virus confirmed that it was the H3N8 subtype and was designated as A/equine/Montana/9564-1/2015 (H3N8). A BLASTn search revealed …

Equine Arteritis Virus Elicits A Mucosal Antibody Response In The Reproductive Tract Of Persistently Infected Stallions, Mariano Carossino, Bettina Wagner, Alan T. Loynachan, R. Frank Cook, Igor F. Canisso, Lakshman Chelvarajan, Casey L. Edwards, Bora Nam, John F. Timoney, Peter J. Timoney, Udeni B. R. Balasuriya

Maxwell H. Gluck Equine Research Center Faculty Publications

Equine arteritis virus (EAV) has the ability to establish persistent infection in the reproductive tract of the stallion (carrier) and is continuously shed in its semen. We have recently demonstrated that EAV persists within stromal cells and a subset of lymphocytes in the stallion accessory sex glands in the presence of a significant local inflammatory response. In the present study, we demonstrated that EAV elicits a mucosal antibody response in the reproductive tract during persistent infection with homing of plasma cells into accessory sex glands. The EAV-specific immunoglobulin isotypes in seminal plasma included IgA, IgG1, IgG3/5, and IgG4/7. Interestingly, seminal …

Medication Migration: The Charles Town Naproxen Experience And Why It Matters To All Racing Jurisdictions, Clara Fenger, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

No abstract provided.

Allelic Variation In Cxcl16 Determines Cd3+ T Lymphocyte Susceptibility To Equine Arteritis Virus Infection And Establishment Of Long-Term Carrier State In The Stallion, Sanjay Sarkar, Ernest Bailey, Yun Young Go, R. Frank Cook, Ted Kalbfleisch, John E. Eberth, R. Lakshman Chelvarajan, Kathleen M. Shuck, Sergey Artiushin, Peter J. Timoney, Udeni B. R. Balasuriya

Maxwell H. Gluck Equine Research Center Faculty Publications

Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of horses and other equid species. Following natural infection, 10–70% of the infected stallions can become persistently infected and continue to shed EAV in their semen for periods ranging from several months to life. Recently, we reported that some stallions possess a subpopulation(s) of CD3⁺ T lymphocytes that are susceptible to in vitro EAV infection and that this phenotypic trait is associated with long-term carrier status following exposure to the virus. In contrast, stallions not possessing the CD3⁺ T …

Enhanced Bovine Colostrum Supplementation Shortens The Duration Of Respiratory Disease In Thoroughbred Yearlings, Clara K. Fenger, Thomas Tobin, Patrick J. Casey, Edward A. Roualdes, John L. Langemeier, Ruel Cowles, Deborah M. Haines

Maxwell H. Gluck Equine Research Center Faculty Publications

Bovine colostrum (BC) is used in humans as a nutritional supplement for immune support and has been shown to reduce Respiratory disease (RD). Other nutritional supplements, minerals and vitamins including mannan oligosaccharides (MOS), zinc and vitamins A, C and E have also been used for immune support. The aim of this prospective blinded randomized clinical trial was to evaluate the effects of a BC, MOS, zinc and vitamin based enhanced bovine colostrum supplement (BCS) on incidence and duration of RD occurring in yearling horses. 109 yearlings on two Thoroughbred farms in Central Kentucky were randomly assigned to treatment or placebo …

Comparison Of The Equine Reference Sequence With Its Sanger Source Data And New Illumina Reads, Jovan Rebolledo-Mendez, Matthew S. Hestand, Stephen J. Coleman, Zheng Zeng, Ludovic Orlando, James N. Macleod, Ted Kalbfleisch

Maxwell H. Gluck Equine Research Center Faculty Publications

The reference assembly for the domestic horse, EquCab2, published in 2009, was built using approximately 30 million Sanger reads from a Thoroughbred mare named Twilight. Contiguity in the assembly was facilitated using nearly 315 thousand BAC end sequences from Twilight's half brother Bravo. Since then, it has served as the foundation for many genome-wide analyses that include not only the modern horse, but ancient horses and other equid species as well. As data mapped to this reference has accumulated, consistent variation between mapped datasets and the reference, in terms of regions with no read coverage, single nucleotide variants, and small …

Protective Efficacy Of Centralized And Polyvalent Envelope Immunogens In An Attenuated Equine Lentivirus Vaccine, Jodi K. Craigo, Corin Ezzelarab, Sheila J. Cook, Chong Liu, David Horohov, Charles J. Issel, Ronald C. Montelaro

Maxwell H. Gluck Equine Research Center Faculty Publications

Lentiviral Envelope (Env) antigenic variation and related immune evasion present major hurdles to effective vaccine development. Centralized Env immunogens that minimize the genetic distance between vaccine proteins and circulating viral isolates are an area of increasing study in HIV vaccinology. To date, the efficacy of centralized immunogens has not been evaluated in the context of an animal model that could provide both immunogenicity and protective efficacy data. We previously reported on a live-attenuated (attenuated) equine infectious anemia (EIAV) virus vaccine, which provides 100% protection from disease after virulent, homologous, virus challenge. Further, protective efficacy demonstrated a significant, inverse, linear relationship …

Copy Number Variation In The Horse Genome, Sharmila Ghosh, Zhipeng Qu, Pranab J. Das, Erica Fang, Rytis Juras, E. Gus Cothran, Sue Mcdonell, Daniel G. Kenney, Teri L. Lear, David L. Adelson, Bhanu P. Chowdhary, Terje Raudsepp

Maxwell H. Gluck Equine Research Center Faculty Publications

We constructed a 400K WG tiling oligoarray for the horse and applied it for the discovery of copy number variations (CNVs) in 38 normal horses of 16 diverse breeds, and the Przewalski horse. Probes on the array represented 18,763 autosomal and X-linked genes, and intergenic, sub-telomeric and chrY sequences. We identified 258 CNV regions (CNVRs) across all autosomes, chrX and chrUn, but not in chrY. CNVs comprised 1.3% of the horse genome with chr12 being most enriched. American Miniature horses had the highest and American Quarter Horses the lowest number of CNVs in relation to Thoroughbred reference. The Przewalski horse …

The Mare Reproductive Loss Syndrome And The Eastern Tent Caterpillar: A Toxicokinetic/Statistical Analysis With Clinical, Epidemiologic, And Mechanistic Implications, Manu Sebastian, Marie G. Gantz, Thomas Tobin, J. Daniel Harkins, Jeffrey M. Bosken, Charlie Hughes, Lenn R. Harrison, William V. Bernard, Dana L. Richter, Terrence D. Fitzgerald

Maxwell H. Gluck Equine Research Center Faculty Publications

During 2001, central Kentucky experienced acute transient epidemics of early and late fetal losses, pericarditis, and unilateral endophthalmitis, collectively referred to as mare reproductive loss syndrome (MRLS). A toxicokinetic/statistical analysis of experimental and field MRLS data was conducted using accelerated failure time (AFT) analysis of abortions following administration of Eastern tent caterpillars (ETCs; 100 or 50 g/day or 100 g of irradiated caterpillars/day) to late-term pregnant mares. In addition, 2001 late-term fetal loss field data were used in the analysis. Experimental data were fitted by AFT analysis at a high (P < .0001) significance. Times to first abortion (“lag time”) and abortion rates were dose dependent. Lag times decreased and abortion rates increased exponentially with dose. Calculated dose × response data curves allow interpretation of abortion data in terms of “intubated ETC equivalents.” Analysis suggested that field exposure to ETCs in 2001 in central Kentucky commenced on approximately April 27, was initially equivalent to approximately 5 g of intubated ETCs/day, and increased to approximately 30 g/day at the outbreak peak. This analysis accounts for many aspects of the epidemiology, clinical presentations, and manifestations of MRLS. It allows quantitative interpretation of experimental and field MRLS data and has implications for the basic mechanisms underlying MRLS. The results support suggestions that MRLS is caused by exposure to or ingestion of ETCs. The results also show that high levels of ETC exposure produce intense, focused outbreaks of MRLS, closely linked in time and place to dispersing ETCs, as occurred in central Kentucky in 2001. With less intense exposure, lag time is longer and abortions tend to spread out over time and may occur out of phase with ETC exposure, obscuring both diagnosis of this syndrome and the role of the caterpillars.

Hordenine : Pharmacology, Pharmacokinetics And Behavioural Effects In The Horse, M. Frank, T. J. Weckman, T. Wood, W. E. Woods, Chen L. Tai, Shih-Ling Chang, A. Ewing, J. W. Blake, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Hordenine is an alkaloid occurring naturally in grains, sprouting barley, and certain grasses. It is occasionally found in post race urine samples, and therefore we investigated its pharmacological actions in the horse. Hordenine (2.0 mgkg bodyweight [bwt]) was administered by rapid intravenous (iv) injection to 10 horses. Typically, dosed horses showed a tlehmen response and defecated within 60 secs. All horses showed substantial respiratory distress. Respiratory rates increased about 250 per cent and heart rates were approximately double that of resting values. All animals broke out in a sweat shortly after iv injection, but basal body temperature was not affected. …

Pharmacokinetics And Protein Binding Of Morphine In Horses, Joan Combie, Thomas E. Nugent, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Morphine could be detected in horses dosed with 0.1 mg of drug/kg of body weight for up to 48 hours in blood and 144 hours in urine. This dose of morphine elicited no observ­able effects and is a suggested an­algesic dose. Computer analysis revealed that a 3-compartment open system was the best fitting model with a serum half life of 87.9 minutes and a urine half life of 101.1 minutes. Binding to equine serum proteins was linear over a drug con­centration range of 3.88 x 10-5M to 3.50 x 10-aM and averaged 31.6%. In RBC-partitioning experiments, 78.1 % of the …