Veterinary Medicine Commons^™

A Cluster Of Trace-Concentration Methamphetamine Identifications In Racehorses Associated With A Methamphetamine-Contaminated Horse Trailer: A Report And Analysis, Kimberly Brewer, Theodore F. Shults, Jacob Machin, Sucheta Kudrimoti, Rodney L. Eisenberg, Petra Hartman, Caroline Wang, Clara Fenger, Pierre Beaumier, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Three low concentration methamphetamine “positive” tests were linked to use of a methamphetamine-contaminated trailer to transport the affected horses. This incident establishes methamphetamine as a human-use substance that can inadvertently enter the environment of racing horses, resulting in urinary methamphetamine “positives;” an interim regulatory cut-off of 15 ng/mL for methamphetamine in post-race urine is proposed.

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 …

Large Deletions At The Shox Locus In The Pseudoautosomal Region Are Associated With Skeletal Atavism In Shetland Ponies, Nima Rafati, Lisa S. Andersson, Sofia Mikko, Chungang Feng, Terje Raudsepp, Jessica Pettersson, Jan Janecka, Ove Wattle, Adam Ameur, Gunilla Thyreen, John E. Eberth, John Huddleston, Maika Malig, Ernest Bailey, Evan E. Eichler, Göran Dalin, Bhanu Chowdary, Leif Andersson, Gabriella Lindgren, Carl-Johan Rubin

Maxwell H. Gluck Equine Research Center Faculty Publications

Skeletal atavism in Shetland ponies is a heritable disorder characterized by abnormal growth of the ulna and fibula that extend the carpal and tarsal joints, respectively. This causes abnormal skeletal structure and impaired movements, and affected foals are usually killed. In order to identify the causal mutation we subjected six confirmed Swedish cases and a DNA pool consisting of 21 control individuals to whole genome resequencing. We screened for polymorphisms where the cases and the control pool were fixed for opposite alleles and observed this signature for only 25 SNPs, most of which were scattered on genome assembly unassigned scaffolds. …

In Vivo-Expressed Proteins Of Virulent Leptospira Interrogans Serovar Autumnalis N2 Elicit Strong Igm Responses Of Value In Conclusive Diagnosis, Veerapandian Raja, Santhanam Shanmughapriya, Murugesan Kanagavel, Sergey Artiushin, Sridhar Velineni, John F. Timoney, Kalimuthusamy Natarajaseenivasan

Maxwell H. Gluck Equine Research Center Faculty Publications

Leptospirosis is a serious zoonosis that is underdiagnosed because of limited access to laboratory facilities in Southeast Asia, Central and South America, and Oceania. Timely diagnosis of locally distributed serovars of high virulence is crucial for successful care and outbreak management. Using pooled patient sera, an expression gene library of a virulent Leptospira interrogans serovar Autumnalis strain N2 isolated in South India was screened. The identified genes were characterized, and the purified recombinant proteins were used as antigens in IgM enzyme-linked immunosorbent assay (ELISA) either singly or in combination. Sera (n = 118) from cases of acute leptospirosis along …

Tissue Restricted Splice Junctions Originate Not Only From Tissue-Specific Gene Loci, But Gene Loci With A Broad Pattern Of Expression, Matthew S. Hestand, Zheng Zeng, Stephen J. Coleman, Jinze Liu, James N. Macleod

Maxwell H. Gluck Equine Research Center Faculty Publications

Cellular mechanisms that achieve protein diversity in eukaryotes are multifaceted, including transcriptional components such as RNA splicing. Through alternative splicing, a single protein-coding gene can generate multiple mRNA transcripts and protein isoforms, some of which are tissue-specific. We have conducted qualitative and quantitative analyses of the Bodymap 2.0 messenger RNA-sequencing data from 16 human tissue samples and identified 209,363 splice junctions. Of these, 22,231 (10.6%) were not previously annotated and 21,650 (10.3%) were expressed in a tissue-restricted pattern. Tissue-restricted alternative splicing was found to be widespread, with approximately 65% of expressed multi-exon genes containing at least one tissue-specific splice junction. …

Complete Genome Sequence Of Noncytopathic Bovine Viral Diarrhea Virus 1 Contaminating A High-Passage Rk-13 Cell Line, Bora Nam, Ganwu Li, Ying Zheng, Jianqiang Zhang, Kathleen M. Shuck, Peter J. Timoney, Udeni B. R. Balasuriya

Maxwell H. Gluck Equine Research Center Faculty Publications

A high-passage rabbit kidney RK-13 cell line (HP-RK-13[KY], originally derived from the ATCC CCL-37 cell line) used in certain laboratories worldwide is contaminated with noncytopathic bovine viral diarrhea virus (ncpBVDV). On complete genome sequence analysis, the virus strain was found to belong to BVDV group 1b.

Recurrent Streptococcus Equi Subsp. Zooepidemicus Bacteremia In An Infant, Joshua R. Watson, Amy Leber, Sridhar Velineni, John F. Timoney, Monica I. Ardura

Maxwell H. Gluck Equine Research Center Faculty Publications

We describe a case of an infant with recurrent bacteremia caused by Streptococcus equi subsp. zooepidemicus, likely transmitted from mother to infant. Our case highlights the importance of an epidemiological history and molecular diagnostics in ascertaining insights into transmission, pathogenesis, and optimal management.

Changes In Serum Strongylus Vulgaris-Specific Antibody Concentrations In Response To Anthelmintic Treatment Of Experimentally Infected Foals, Martin Krarup Nielsen, Jessica Scare, Holli Sullivan Gravatte, Jennifer Lynn Bellaw, Julio C. Prado, Craig Robert Reinemeyer

Maxwell H. Gluck Equine Research Center Faculty Publications

Strongylus vulgaris is the most pathogenic nematode parasite of horses. Its extensive migration in the mesenteric blood vessels can lead to life-threatening intestinal infarctions. Recent work has shown that this parasite is still identified among managed horse populations. A serum enzyme-linked immunosorbent assay (ELISA) has been developed for the detection of migrating larvae of S. vulgaris. Previous work has documented an increase in ELISA values following larvicidal treatment with ivermectin and suggested that the target parasite antigen is primarily produced by the later larval stages. The aim of this study was to experimentally inoculate cohorts of foals with S. …

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 …

Sudden Death, Aortic Rupture In Horses, Literature Review, Case Studies Reported And Risk Factors, Abelardo Morales Briceño, Aniceto Mendez, Kimberly Brewer, Charlie Hughes, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Sudden deaths of horses in multiple equestrian disciplines have been attributed to acute and chronic respiratory and cardiovascular diseases. The aim of this study was to perform a review of aortic rupture in horses analyzing, case studies and assessing risk factors. The literature has reported a total of 137 cases of aortic rupture in horses for 28 years (1986-2014), with approximately five horses dying of aortic rupture per year. Histopathologically, there are observed discrete macroscopic degenerative changes in the intima layer only in the aorta. The histological evaluation in the beginning portion of the aorta of the heart evidenced degenerative …

Bovine Colostrum Supplementation Optimises Earnings, Performance And Recovery In Racing Thoroughbreds, C. K. Fenger, Thomas Tobin, P. J. Casey, Edward A. Roualdes, J. L. Langemeier, D. M. Haines

Maxwell H. Gluck Equine Research Center Faculty Publications

Bovine colostrum (BC) is the first milk produced by cows after calving and contains numerous beneficial substances for the immunity and development of the newborn calf. Because of the growth and immune factors in BC, it has become an attractive supplement for use by athletes to support immunity and health during athletic performance. In order to evaluate the effects of oral BC supplementation on equine athletes, this study evaluated the earnings, performance, recovery and incidence of upper respiratory infections (URTI) in racing horses. The study design was a randomized cross-over racing performance study. 21 horses in race training were randomly …

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 …

Clones Of Streptococcus Zooepidemicus From Outbreaks Of Hemorrhagic Canine Pneumonia And Associated Immune Responses, Sridhar Velineni, John F. Timoney, Kim Russell, Heidi J. Hamlen, Patricia Pesavento, William D. Fortney, P. Cynda Crawford

Maxwell H. Gluck Equine Research Center Faculty Publications

Acute hemorrhagic pneumonia caused by Streptococcus zooepidemicus has emerged as a major disease of shelter dogs and greyhounds. S. zooepidemicus strains differing in multilocus sequence typing (MLST), protective protein (SzP), and M-like protein (SzM) sequences were identified from 9 outbreaks in Texas, Kansas, Florida, Nevada, New Mexico, and Pennsylvania. Clonality based on 2 or more isolates was evident for 7 of these outbreaks. The Pennsylvania and Nevada outbreaks also involved cats. Goat antisera against acutely infected lung tissue as well as convalescent-phase sera reacted with a mucinase (Sz115), hyaluronidase (HylC), InlA domain-containing cell surface-anchored protein (INLA), membrane-anchored protein (MAP), SzP, …

Current Therapeutic Approaches To Equine Protozoal Myeloencephalitis, L. Dirikolu, Jonathan H. Foreman, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Equine protozoal myeloencephalitis is the most important infectious neurologic disease of horses in the Western Hemisphere. Equine protozoal myeloencephalitis can interfere with a horse's ability to race, work, and perform; untreated, EPM can be lethal. Antemortem diagnosis of EPM is challenging, requiring careful evaluation of the animal's history, clinical signs, and laboratory data, with rigorous exclusion of other causes.

Therapeutic approaches to EPM are evolving. First-generation therapeutic approaches for EPM were based on the classic anti–Toxoplasma gondii pyrimethamine–sulfonamide combinations; treatment is prolonged and can be associated with a considerable relapse rate, which may be associated with the difficulty in …

A Toxicology And Clinical Study Of Post Race Epitaxis Associated With Exercise Induced Pulmonary Hemorrhage In Thoroughbred Race Horses At The Racecourse Rinconada, Caracas, Venezuela, Abelardo Morales Briceno, Diana Villoria Leon, Kimberly Brewer, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

The aim of this study was to describe cases of epistaxis associated with post-race Exercise Induced Pulmonary Hemorrhage (EIPH) in Thoroughbred horses at the Hippodrome "La Rinconada", Caracas, Venezuela, through a clinic pathological study. We studied a total of 29 cases of epistaxis post-race in Thoroughbred horses at the Hippodrome La Rinconada, Caracas, Venezuela, which is 2,950 meters above sea level. The study included horses between the ages of 2-5 years, 16 stallions and 13 mares, weighing between 450-510 kg. They underwent a clinical examination, although horses presenting with epistaxis were in an emergency situation. Samples of blood and urine …

Evaluation Of Mass Spectrometric Methods For Detection Of The Anti-Protozoal Drug Imidocarb, A. F. Lehner, J. A. Hitron, J. May, C. Hughes, R. Eisenberg, N. Schwint, D. P. Knowles, P. Timoney, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Imidocarb [N,N'-bis[3-(4,5-dihydro-1H-imidazol-2-yl)phenyl]urea, C₁₉H₂₀N₆O₁, m.w. 348.41] is a symmetrical carbanilide derivative used to treat disease caused by protozoans of the Babesia genus. Imidocarb, however, is also considered capable of suppressing Babesia-specific immune responses, allowing Babesia-positive horses to pass a complement fixation test (CFT) without eliminating the infection. This scenario could enable Babesia-infected horses to pass CFT-based importation tests. It is imperative to unequivocally identify and quantify equine tissue residues of imidocarb by mass spectrometry to address this issue. As a pretext to development of sensitive tissue assays, we have investigated possibilities of mass …

Pyrilamine In The Horse: Detection And Pharmacokinetics Of Pyrilamine And Its Major Urinary Metabolite O-Desmethylpyrilamine, L. Dirikolu, A. F. Lehner, J Daniel Harkins, W. E. Woods, W. Karpiesiuk, R. S. Gates, M. Fisher, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Pyrilamine is an antihistamine used in human and veterinary medicine. As antihistamines produce central nervous system effects in horses, pyrilamine has the potential to affect the performance of racehorses. In the present study, O-desmethylpyrilamine (O-DMP) was observed to be the predominant equine urinary metabolite of pyrilamine. After intravenous (i.v.) administration of pyrilamine (300 mg/horse), serum pyrilamine concentrations declined from about 280 ng/mL at 5 min postdose to about 2.5 ng/mL at 8 h postdose. After oral administration of pyrilamine (300 mg/horse), serum concentrations peaked at about 33 ng/mL at 30 min, falling to <2 ng/mL at 8 h postdose. Pyrilamine was not detected in serum samples at 24 h postdosing by either route. After i.v. injection of pyrilamine (300 mg/horse) O-DMP was recovered at a level of about 20 ̄g/mL at 2 h postdose thereafter declining to about 2 ng/mL at 168 h postdose. After oral administration, the O-DMP recovery peaked at about 12 ̄g/mL at 8 h postdose and declined to <2 ng/mL at 168 h postdose. These results show that pyrilamine is poorly bioavailable orally (18%), and can be detected by sensitive enzyme-linked immunosorbent assay tests in urine for up to 1 week after a single administration. Care should be taken as the data suggest that the withdrawal time for pyrilamine after repeated oral administrations is likely to be at least 1 week or longer.

Detection And Confirmation Of Ractopamine And Its Metabolites In Horse Urine After Paylean® Administration, A. F. Lehner, C. G. Hughes, J Daniel Harkins, C. Nickerson, B. Mollett, L. Dirikolu, Jeffrey M Bosken, Fernanda C. Camargo, J. Boyles, A. Troppmann, W. Karpiesiuk, W. E. Woods, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

We have investigated the detection, confirmation, and metabolism of the beta-adrenergic agonist ractopamine administered as Paylean to the horse. A Testing Components Corporation enzyme-linked imunosorbent assay (ELISA) kit for ractopamine displayed linear response between 1.0 and 100 ng/ml, with an 1-50 of 10 ng/ml, and an effective screening limit of detection of 50 ng/mL. The kit was readily able to detect ractopamine equivalents in unhydrolyzed urine up to 24 h following a 300-mg oral dose. Gas chromatography-mass spectrometry (GC-MS) confirmation comprised glucuronidase treatment, solid-phase extraction, and trimethylsilyl derivatization, with selected-ion monitoring of ractopamine-tris(trimethylsilane) (TMS) m/z 267, 250, 179, and 502 …

Development Of A Method For The Detection And Confirmation Of The Alpha-2 Agonist Amitraz And Its Major Metabolite In Horse Urine, A. F. Lehner, C. G. Hughes, W. Karpiesiuk, J Daniel Harkins, L. Dirikolu, Jeffrey M Bosken, Fernanda Camargo, J. Boyles, A. Troppmann, W. E. Woods, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Amitraz (N′-(2,4-dimethylphenyl)-N-[[(2,4-dimethylphenyl)imino] methyl]-N-methyl-methanimidamide) is an alpha-2 adrenergic agonist used in veterinary medicine primarily as a scabicide- or acaricide-type insecticide. As an alpha-2 adrenergic agonist, it also has sedative/tranquilizing properties and is, therefore, listed as an Association of Racing Commissioners International Class 3 Foreign Substance, indicating its potential to influence the outcome of horse races. We identified the principal equine metabolite of amitraz as N-2,4-dimethylphenyl-N′-methylformamidine by electrospray ionization(+)-mass spectrometry and developed a gas chromatographic-mass spectrometric (GC-MS) method for its detection, quantitation, and confirmation in performance horse regulation. The GC-MS method involves derivatization with t-butyldimethylsilyl groups; selected ion monitoring (SIM) of m/z …

A Gc-Ms Method For The Determination Of Isoxsuprine In Biological Fluids Of The Horse Utilizing Electron Impact Ionization, Jeffrey M Bosken, A. F. Lehner, C. G. Hughes, W. E. Woods, F. C. Camargo, J. D. Harkins, J. Boyles, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Isoxsuprine is used to treat navicular disease and other lower-limb problems in the horse. Isoxsuprine is regulated as a class 4 compound by the Association of Racing Commissioners, International (ARCI) and, thus, requires regulatory monitoring. A gas chromatography-mass spectrometry method utilizing electron impact ionization was developed and validated for the quantitation of isoxsuprine in equine plasma or equine urine. The method utilized robotic solid-phase extraction and tri-methyl silyl ether products of derivatization. Products were bis-trimethylsilyl (TMS) isoxsuprine and tris-TMS ritodrine, which released intense quantifier ions m/z 178 for isoxsuprine and m/z 236 for ritodrine that were products of C-C cleavage. …

The Mare Reproductive Loss Syndrome And The Eastern Tent Caterpillar Ii: A Toxicokinetic/Clinical Evaluation And A Proposed Pathogenesis: Septic Penetrating Setae, Thomas Tobin, J. Daniel Harkins, John Ford Roberts, Patricia W. Vanmeter, Tara A. Fuller

Maxwell H. Gluck Equine Research Center Faculty Publications

Reviewing the mare reproductive loss syndrome (MRLS), it is proposed that the fundamental mechanism of this syndrome, which includes early fetal loss, late fetal loss, uveitis, pericarditis, and encephalitis, is tissue penetration by septic barbed setal fragments (septic penetrating setae) from Eastern tent caterpillars (Malacosoma americanum). Once ingested, these barbed setal fragments migrate through moving tissues, followed by rapid hematogenous spread of bacteria, bacterial emboli, and/or septic fragments of setae (septic penetrating setal emboli), collectively referred to as septic materials. Pathogenic bacteria, therefore, enter the horse as hitchhikers on or in the caterpillar setal fragments, and MRLS is caused by …

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.

Clenbuterol In The Horse: Confirmation And Quantitation Of Serum Clenbuterol By Lc-Ms-Ms After Oral And Intratracheal Administration, A. F. Lehner, J Daniel Harkins, W. Karpiesiuk, W. E. Woods, N. E. Robinson, L. Dirikolu, M. Fisher, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Clenbuterol is a β₂ agonist/antagonist bronchodilator, and its identification in post-race samples may lead to sanctions. The objective of this study was to develop a specific and highly sensitive serum quantitation method for clenbuterol that would allow effective regulatory control of this agent in horses. Therefore, clenbuterol-d₉ was synthesized for use as an internal standard, an automated solid-phase extraction method was developed, and both were used in conjunction with a multiple reaction monitoring liquid chromatography-tandem mass spectrometry (LC-MS-MS) method to allow unequivocal identification and quantitation of clenbuterol in 2 mL of serum at concentrations as low as 10 …

Remifentanil In The Horse: Identification And Detection Of Its Major Urinary Metabolite, A. F. Lehner, P. Almeida, J. Jacobs, J Daniel Harkins, W. Karpiesiuk, W. E. Woods, L. Dirikolu, Jeffrey M Bosken, W. G. Carter, J. Boyles, C. Holtz, T. Heller, C. Nattrass, M. Fisher, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Remifentanil (4-methoxycarbonyl-4-[(1-oxopropyl)phyenylamino]-1- piperidinepropionic acid methyl ester) is a μ-opioid receptor agonist with considerable abuse potential in racing horses. The identification of its major equine urinary metabolite, 4-methoxycarbonyl-4-[(1- oxopropyl)phenylamino]-1-piperidinepropionic acid, an ester hydrolysis product of remifentanil is reported. Administration of remifentanil HCl (5 mg, intravenous) produced clear-cut locomotor responses, establishing the clinical efficacy of this dose. ELISA analysis of postadministration urine samples readily detected fentanyl equivalents in these samples. Mass spectrometric analysis, using solid-phase extraction and trimethylsilyl (TMS) derivatization, showed the urine samples contained parent remifentanil in low concentrations, peaking at 1 h. More significantly, a major peak was identified as …

Effect Of Amitraz And Xylazine On Some Physiological Variables Of Horses, A. Queiroz-Neto, A. B. Carregaro, G. Zamur, J Daniel Harkins, Thomas Tobin, M. I. Mataqueiro, S. C. Gonçalves

Maxwell H. Gluck Equine Research Center Faculty Publications

The effect of the intravenous injection of amitraz (0.1 mg/kg) to horses on cardiac activity, respiratory rate, intestinal motor activity, rectal temperature, sweating and masticating was evaluated and compared to the effect of intravenous administration of xylazine (1mg/kg, iv) on heart rate, respiratory rate and intestinal activity. Amitraz caused a significant decrease in heart activity, respiratory rate and intestinal movements, but these effects were not as pronounced as those caused by xylazine. Amitraz also caused a significant relaxation of the rectal smooth muscle, and an apparent increase in sweating and in the frequency of horses found masticating hay. Rectal temperature …

Absence Of Detectable Pharmacological Effects After Oral Administration Of Isoxsuprine, J. Daniel Harkins, G. D. Mundy, S. Stanley, W. E. Woods, R. A. Sams, D. R. Richardson, S. C. Grambow, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Isoxsuprine is reported to be a peripheral vasodilator used in human and veterinary medicine to treat ischaemic vascular disease. In horses, it is generally administered orally to treat navicular disease and other lower limb problems. To deflne the scope and duration of its pharmacological responses after oral administration, 6 horses were dosed with isoxsuprine HCI (1.2 mg/kg bwt) q. 12 h for 8 days and then tested to assess the duration and extent of pharmacological actions. There was no significant difference between isoxsuprine and control treatment values for heart rate, spontaneous activity, sweat production, anal muscle tone, core and skin …

An Overview Of The Methylxanthines And Their Regulation In The Horse, J Daniel Harkins, W. Allen Rees, G. D. Mundy, Scott D. Stanley, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Caffiene, theophylline and theobromine are naturally occurring members of the methylxanthine family;pentoxfylline, dyphylline and enprofylline are structurally related synthetic pharmaceuticals. Caffiene has predominantly central nervous system effects, theophylline, dyphylline and enprofylline have predominantly bronchodilator effects, while theobromine is associated with diuretic responses. Pentoxfylline is thought to increase red cell deformability and facillitate blood flow through capillary beds. The methylxanthines are not highly potent agents; they are typically administered in gram doses and they tend to have relatively long half-lives. They remain detectable in plasma and urine for relatively long periods. Similarly, traces of the naturally occurring members of this family …

The Pharmacologic Effects Of Isoxsuprine, J. Daniel Harkins, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Isoxsuprine is a therapeutic medication used to treat navicular disease and other lower limb problems in horses and is one of the more frequently detected therapeutic agents in racing horses. In crossover studies, horses were administered intravenous and oral isoxsuprine to determine the character and duration of pharmacological effects. Following intravenous administration, isoxsuprine significantly increased heart rate, spontaneous activity, and sweat production. There was an apparent, although statistically insignificant, increase in cutaneous blood flow. Skin temperature decreased below control values, and there was a significant decrease in core temperature. Isoxsuprine also reduced smooth muscle tone. In contrast, after oral dosing, …

Frequency Distribution Of Post Race Urine Ph From Standardbreds Compared With Thoroughbreds: Research And Regulatory Significance, S. D. Stanley, R. A. Sams, J Daniel Harkins, G. D. Mundy, J. Boyles, W. E. Woods, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

The concentration of drugs and drug metabolites in urine samples of racing horses is strongly influenced by urine pH(Tobin, 1981), depending on whether the drugs are weak acids or weak bases. Drugs that are weak acids tend to concentrate in besic urine. In contrast, drugs that are weak bases tend to concentrate in acidic urine. These relationships have a well-established theoretical basis (the Henderson-Hasselbalch relationship) and have been demonstrated repeatedly in experimental animals and man (Tobin, 1981). More recently, evidence suggests that these relationships also occur with clinically and forensically significant agents in equine urine (Wood, et al. 1990; Gerken …