Pharmacology in horses involves the study and application of drugs and medications to diagnose, treat, and prevent diseases and conditions in equine species. This field encompasses the understanding of pharmacokinetics and pharmacodynamics specific to horses, including how drugs are absorbed, distributed, metabolized, and excreted by the equine body. Commonly studied pharmacological agents in horses include non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, sedatives, and anthelmintics. Research in equine pharmacology focuses on determining appropriate dosages, understanding drug interactions, and minimizing adverse effects. This page compiles peer-reviewed research studies and scholarly articles that investigate the efficacy, safety, and regulatory aspects of pharmacological interventions in equine veterinary practice.
Lindinger MI.The TCO2 (total carbon dioxide) test is performed on the blood of racehorses as a means of combatting the practice of administering alkalizing agents for the purpose of enhancing performance. The purposes of this review are to present an overview of the factors contributing to TCO2 and to review the literature regarding TCO2 in adult Standardbred and Thoroughbred horses to demonstrate the range of variability of TCO2 in horses. Most of the research published on the topic of TCO2 or bicarbonate measurement in racehorses was accessed and reviewed. PubMed and Google Scholar were the primary sear...
Aleman MR, True A, Scalco R, Crowe CM, Costa LRR, Chigerwe M.Irreversible sensorineural auditory loss has been reported in humans treated with aminoglycosides but not in horses. Objective: Investigate if auditory loss occurs in horses treated using the recommended IV daily dosage of gentamicin for 7 consecutive days. Methods: Ten healthy adult horses (7-15 years; females and males, 5 each). Methods: Prospective study. Physical and neurological examinations and renal function tests were performed. Gentamicin sulfate was administered at a dosage of 6.6 mg/kg via the jugular vein on alternating sides for 7 days. Gentamicin peak and trough concentratio...
Balko JA, Fogle C, Stuska SJ, Fogle JE, Posner LP.Butorphanol-azaperone-medetomidine (BAM™) has not been evaluated in horses. Objective: The objective of this study was to evaluate BAM™ for chemical restraint of feral horses. Methods: Retrospective and prospective descriptive studies. Methods: Data were collected retrospectively from medical records of 28 feral horses immobilised with BAM™ over a 6-year period. Prospectively, 0.0125 mL/kg bwt of BAM™ (butorphanol 27.3 mg/mL, azaperone 9.1 mg/mL and medetomidine 10.9 mg/mL) intramuscularly (im) was administered to eight stallions via dart, and once recumbent, 1.0 mg/kg bwt ketamin...
Cunneen A, Pratt S, Perkins N, McEwen M, Truchetti G, Rainger J, Farry T, Kidd L, Goodwin W.To evaluate the use of ketamine-medetomidine-midazolam total intravenous infusion as part of a balanced anaesthetic technique for surgical castration in horses. Five healthy Standardbred cross colts were premedicated with IV acepromazine (0.01-0.02 mg/kg), medetomidine (7 µg/kg) and methadone (0.1 mg/kg) and anaesthesia induced with IV ketamine (2.2 mg/kg) and midazolam (0.06 mg/kg). Horses were anaesthetised for 40 min with an IV infusion of ketamine (3 mg/kg/h), medetomidine (5 µg/kg/h) and midazolam (0.1 mg/kg/h) while routine surgical castration was performed. Cardiorespiratory variables...
Martin F, Eydal M, Höglund J, Tydén E.The equine roundworm Parascaris univalens has developed resistance to the three anthelmintic substances most commonly used in horses. The mechanisms responsible for resistance are believed to be multi-genic, and transport proteins such as the P-glycoprotein (Pgp) family have been suggested to be involved in resistance in several parasites including P. univlaens. To facilitate further research into the mechanisms behind drug metabolism and resistance development in P. univalens we aimed to develop an in vitro model based on larvae. We developed a fast and easy protocol for hatching P. univalens...
Jiménez BLM, Elghandour MMMY, Adegbeye MJ, Tirado González DN, Tirado Estrada G, Salem AZM, Pacheco EBF, Pliego AB.In the race against deadly diseases, multiple drugs have been developed as a treatment strategy in livestock. Each treatment is based on a specific mechanism to find a suitable drug. Antibiotics have become a fundamental part of the equine industry to treat bacterial diseases. These antibiotics have specific doses and side effects, and understanding each parameter allows veterinarians to avoid or limit the adverse effects of such drugs. Use of antibiotics causes microbial imbalance, decreased microbial diversity and richness in both cecal and fecal samples. Antibiotics reduced metabolites prod...
Makra Z, Eördögh R, Fábián I, Veres-Nyéki K.To compare the corneal anaesthetic effect of 0.5% bupivacaine, 2% lidocaine and 0.4% oxybuprocaine on normal equine eyes. Methods: Prospective, blinded crossover study. Methods: A group of 10 clinically healthy horses. Methods: Corneal sensitivity was determined in each eye by measuring corneal touch threshold (CTT). The study had three phases. Each subject was randomly given one of the three treatments followed by a 72 hour washout period. Every horse received all treatments. Baseline CTT was recorded prior to anaesthetic instillation (T0) then CTT was measured 5 and 10 minutes after (T1 and ...
Pusterla N, James K, Bain F, Barnett DC, Chappell D, Gaughan E, Craig B, Schneider C, Vaala W, Papich M.The aim of this study was to determine if bi-weekly administration of diclazuril at half the label dose would reduce seroprevalence and magnitude of titers to S. neurona in healthy horses naturally exposed to the apicomplexan protozoal parasite. 12 healthy adult horses were moved from a low-risk exposure to a farm with high exposure rate to S. neurona in their horse population. The horses were randomly assigned to either a treatment or a control group. Treatment consisted in the administration of half the label dose (0.5 mg/kg) of diclazuril (Protazil) pelleted top dress twice weekly (every 3-...
Troya-Portillo L, López-Sanromán J, Villalba-Orero M, Santiago-Llorente I.Standing surgery under sedation reduces anesthetic-related mortality in horses. Medetomidine, alone and combined with morphine in a constant rate infusion (CRI), has been described for standing surgery but their cardiorespiratory, sedative and antinociceptive effects have never been compared. The addition of ketamine could improve analgesia in these procedures with minimal cardiorespiratory consequences. The objectives were to compare the cardiorespiratory effects, quality of sedation, antinociception and ataxia produced by administration of a medetomidine-based CRI with morphine, ketamine or ...
Turner TA.Barbiturate overdose as a method of euthanasia is becoming unacceptable. This has made alternative methods of euthanasia very important. Gunshot or captive bolt euthanasia is among methods that are acceptable, but they may not be esthetically acceptable. This has led to the use of other methods of euthanasia. Inducing anesthesia prior to euthanasia offers an easier method of control. Adjunctive techniques using intravenous potassium or magnesium salts administered intravenously and intracardiac administration of potassium chloride or intrathecal lidocaine offer alternatives that work well and ...
Wilson WD, Magdesian KG.Antimicrobial drugs play an important, often central, role in the therapeutic management of mature horses and foals with a variety of illnesses, including those requiring critical care. Antimicrobial use must be based on rational principles involving thorough patient evaluation and sound clinical judgment that indicate a high likelihood that the patient has a bacterial infection and that antimicrobials are indicated to promote recovery. The aim of antimicrobial treatment is to inflict an insult on infecting bacteria sufficient to kill the organism or render it susceptible to inactivation by na...
Schellenberg LM, Regenthal R, Abraham G.The present study addresses the effect of the Rho-kinase (ROCK) inhibitor Y-27632 on the β-adrenoceptor density and β-agonist-stimulated intracellular second messenger cAMP formation in primary equine bronchial epithelial cells (EBEC). Y-27632 significantly decreased the β-adrenoceptor number (B) without markedly affecting the receptor affinity (dissociation constant, K) to the radioligand [I]-iodocyanopindolol (ICYP). In contrast, Y-27632 augmented the β-agonist-stimulated intracellular cAMP production. Herein, Y-27632 markedly increased the maximal cAMP responses (E) (isoproterenol >...
O'Banion MP, Sundman E, Edmonds M, Davis J.Dipyrone is a non-opioid, nonsteroidal anti-inflammatory drug with antipyretic and analgesic properties commonly used in horses. Dipyrone is rapidly hydrolyzed to the primary active metabolite 4-methylaminoantipyrine (4-MAA). The purpose of this study was to determine the pharmacokinetic profile of 4-MAA following repeated and escalating doses of intravenously administered dipyrone. Twenty-six horses were randomly allocated to five treatment groups (one placebo group and four dipyrone groups [30 mg/kg q8h, 30 mg/kg q12h, 60 mg/kg q8h, and 90 mg/kg q12h]) and treated for nine consecutive da...
Hussein KH, Elmeligy E, Khalphallah A, Al-Lethie AA.This study was performed to investigate the effects of cyclopentolate on ultrasonographic parameters of eye structures, intraocular pressure (IOP), tear production, and pupil size in normal donkeys. Sixteen eyes of eight clinically healthy adult donkeys (2-2.5 years old) weighing 295 ± 34 kg (mean ± standard deviation) were used in this study. Cyclopentolate hydrochloride 1% was instilled in a randomly selected eye and the other eye received normal saline drops as a control. The effect of cyclopentolate was evaluated by ultrasonography. Additionally, changes in IOP and tear production were ...
López-Sanromán FJ, Freilich GM, Gomez-Cisneros D, Varela M, Santiago I, Manso-Díaz G.The objective of the present study was to compare, using accelerometry, the gait changes produced after administration of a dose of 0.2 mg/kg of morphine at the walk in healthy horses. Six mature horses were used, and all animals received two different treatments with, at least, two weeks interval in between. Treatments administered consisted of a single dose of 10 ml of saline solution or a total of 0.2 mg/kg of morphine diluted in 10 ml of saline solution. A three-dimensional accelerometric device was used to collect data continuously while horses were walking. The walking test was performed...
Watanabe R, Huruta H, Ueno Y, Nukada T, Niwa H, Shinyashiki N, Kano R.Luliconazole (LCZ) is an imidazole antifungal medication that exhibits excellent activity against dermatophytes. As a topical cream and lotion (approved for human use), LCZ has demonstrated a broad spectrum of activity against human dermatophytoses. Objective: This is the first study to investigate the in vitro susceptibility of clinical isolates from horse dermatophytoses to LCZ. Methods: No animals were used in this study. Methods: In the present study, the in vitro susceptibilities of clinical isolates of dermatophytes to LCZ, clotrimazole (CTZ), miconazole (MCZ) and terbinafine (TRF) wer...
Sampaio B, Ortiz I, Resende H, Felix M, Varner D, Hinrichs K.Exposure to the calcium ionophore A23187 may present a "universal" sperm treatment for IVF, as it bypasses capacitation pathways. However, success in utilizing A23187 is variable, especially in equine spermatozoa. Notably, albumin is used during A23187 treatment but paradoxically is thought to suppress A23187 action. Essentially no critical data are available on the effects of A23187 and albumin concentrations, ratios, or addition protocols on changes in intracellular calcium ([Ca] ) in any cell type. To determine factors that affect the action of A23187 on [Ca] in equine and murine spermatozo...
Willette C, Aarnes TK, Lerche P, Ricco-Pereira C, Ballash GA, Bednarski RM.To assess anesthetic induction, recovery quality and cardiopulmonary variables after intramuscular (IM) injection of three drug combinations for immobilization of horses. Methods: Randomized, blinded, three-way crossover prospective design. Methods: A total of eight healthy adult horses weighing 470-575 kg. Methods: Horses were administered three treatments IM separated by ≥1 week. Combinations were tiletamine-zolazepam (1.2 mg kg), ketamine (1 mg kg) and detomidine (0.04 mg kg) (treatment TKD); ketamine (3 mg kg) and detomidine (0.04 mg kg) (treatment KD); and tiletamine-zolazepam (2.4 mg ...
Reed RA, Epstein KL, Bramski JH, Diehl KA, Ryan CA.To determine the effect of xylazine on intracranial pressure (ICP) in standing compared to isoflurane-anesthetized horses. Methods: Prospective, crossover study design. Methods: University Teaching Hospital. Methods: Six adult horses donated to the University. Horses were determined to be healthy via physical examination, complete blood count, and neurological evaluation. Methods: Horses were anesthetized, maintained on isoflurane in oxygen in left lateral recumbency, and ventilated to normocapnia. Horses were instrumented for intraparenchymal measurement of ICP, invasive blood pressure, pulse...
Arnold C, Pilla R, Chaffin K, Lidbury J, Steiner J, Suchodolski J.Diarrhea is an adverse effect of antimicrobial therapy in horses. This matched, case-controlled study compared the fecal microbiome and metabolome of horses on antibiotics that developed diarrhea (AAD, = 17) to those that did not develop diarrhea (ABX, = 15) and to a control population not exposed to antibiotics (CON, = 31). Fecal samples were collected from horses that were matched for diet and antimicrobial agent (including dose, route, and duration of therapy). Illumina sequencing of 16S rRNA genes was performed, and QIIME 2.0 was used to generate alpha and beta diversity metrics. Untarg...
Ellis JS, Mama KR, Rao S, Sadler RA, Marinkovich M, Clancy MM, Howard LL, Lamberski N, Kinney ME.Przewalski's horses () are an endangered equid species. Anesthesia administered by remote delivery is often needed to provide medical care. Behavioral and physiologic parameters were prospectively compared in 14 horses (8 females and 6 males, 3-18 yr) after a single-dart or staged two-dart anesthesia induction protocol with intramuscular medetomidine (0.06 mg/kg), butorphanol (0.05 mg/kg), thiafentanil (0.02 mg/kg), and ketamine (1 mg/kg). Seven horses were randomly assigned to receive all drugs in a single dart, and the other seven to receive medetomidine and butorphanol 10 min prior to thiaf...
Pagliara E, Nicolo A, Rossi C, Cammaresi C, Donadio G, Bertuglia A.Perineural anaesthesia is an essential part of lameness investigation in horses. Painful reactions to injections imply a high risk of accidents for veterinarians. To evaluate the efficacy of two topical anaesthetic creams on desensitization of the skin at two perineural injection sites and to evaluate the effects these formulations may have on pain perception distally to the application sites. Randomized, blind, prospective study. 14 healthy horses were randomly divided in two groups of 7 horses each, one treated with EMLA and one with PLIAGLIS preparations. The mechanical nociceptive thresh...
Millares-Ramirez EM, Lavoie JP.Severe asthma in horses is characterized by structural changes that thicken the lower airway wall, a change that is only partially reversible by current treatments. Increased vascularization contributes to the thickening of the bronchial wall in humans with asthma and is considered a potential new therapeutic target. Objective: To determine the presence of angiogenesis in the bronchi of severely asthmatic horses, and if present, to evaluate its reversibility by treatment with corticosteroids. Methods: Study 1: Bronchial samples from asthmatic horses in exacerbation (7), in remission (7), and a...
Trailovic SM, Rajkovic M, Marjanovic DS, Neveu C, Charvet CL. sp. is the only ascarid parasitic nematode in equids and one of the most threatening infectious organisms in horses. Only a limited number of compounds are available for treatment of horse helminthiasis, and sp. worms have developed resistance to the three major anthelmintic families. In order to overcome the appearance of resistance, there is an urgent need for new therapeutic strategies. The active ingredients of herbal essential oils are potentially effective antiparasitic drugs. Carvacrol is one of the principal chemicals of essential oil from , , , , and herbs. However, the antiparasi...
Adler DMT, Frellesen JF, Karlsen CV, Jensen LD, Dahm ASQ, Berg LC.To investigate the in vitro effects of clinically relevant concentrations of the local anesthetics (LAs) bupivacaine, lidocaine, lidocaine with preservative (LP), mepivacaine, and ropivacaine on equine chondrocyte and fibroblast-like synoviocyte (FLS) viability. Methods: Chondrocytes and FLSs of the metacarpophalangeal joints of 4 healthy adult horses. Methods: Viability of chondrocytes and FLSs was determined with 3 assays: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), and trypan blue (TB) exclusion (only FLS). Viability was assessed after 30...
Loomes K.Aerosolized salbutamol has been associated with hypokalemia in horses undergoing colic surgery. The objective of this study was to evaluate the effect of aerosolized salbutamol on arterial potassium concentration ([K +]) in healthy anaesthetized horses undergoing elective surgery. Anesthetic records were reviewed from healthy adult horses undergoing elective surgery over a 3-year period with two complete sets of arterial electrolyte (sodium [Na +], potassium [K +], chloride [Cl -], calcium [Ca 2+]) concentration measurements. Records were excluded if intra-operative electrolyte supplementation...
Sandbaumhüter FA, Gittel C, Larenza-Menzies MP, Theurillat R, Thormann W, Braun C.The enantioselectivity of the pharmacokinetics of methadone was investigated in anesthetized Shetland ponies after a single intravenous (0.5 mg/kg methadone hydrochloride; n = 6) or constant rate infusion (0.25 mg/kg bolus followed by 0.25 mg/kg/h methadone hydrochloride; n = 3) administration of racemic methadone. Plasma concentrations of l-methadone and d-methadone and their major metabolites, l- and d-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), respectively, were analyzed by CE with highly sulfated γ-cyclodextrin as chiral selector and electrokinetic analyte injection from...
Amaral A, Fernandes C, Szóstek-Mioduchowska A, Rebordão MR, Skarzynski DJ, Ferreira-Dias G.Endometrosis is a reproductive pathology that is responsible for mare infertility. Our recent studies have focused on the involvement of neutrophil extracellular traps enzymes, such as elastase (ELA), in the development of equine endometrosis. Noscapine (NOSC) is an alkaloid derived from poppy opium with anticough, antistroke, anticancer, and antifibrotic properties. The present work investigates the putative inhibitory in vitro effect of NOSC on collagen type I alpha 2 chain () mRNA and COL1 protein relative abundance induced by ELA in endometrial explants of mares in the follicular or mid-lu...
Verhaar N, Breves G, Hewicker-Trautwein M, Pfarrer C, Rohn K, Burmester M, Schnepel N, Neudeck S, Twele L, Kästner S.Ischaemic postconditioning (IPoC) has been shown to ameliorate ischaemia reperfusion injury in different species and tissues. Objective: To assess the feasibility of IPoC in equine small intestinal ischaemia and to assess its effect on histomorphology, electrophysiology and paracellular permeability. Methods: Randomised in vivo experiment. Methods: Experimental jejunal ischaemia was induced for 90 min in horses under general anaesthesia. In the control group (C; n = 7), the jejunum was reperfused without further intervention. In the postconditioning group (IPoC; n = 7), reocclusion was im...
Raisis AL, Mosing M, Hosgood GL, Secombe CJ, Adler A, Waldmann AD.Electrical impedance tomography (EIT) provides clinically useful lung images; however, it would be an advantage to extract additional cardiovascular information from the data. The aim of this study was to evaluate if cardiac-related changes measured by EIT can be used to measure pulse rate (PR) under physiological as well as high and low blood pressure states in anaesthetised horses. Electrical impedance tomography data and PR from seven horses anaesthetised in dorsal recumbency were recorded over 1 min during mechanical ventilation and 1 min of apnoea. Data were collected at four measurement ...
Atta EH, de Sousa AM, Schirmer MR, Bouzas LF, Nucci M, Abdelhay E.The standard regimen for HLA-identical sibling bone marrow transplant (BMT) in severe aplastic anemia (SAA) is cyclophosphamide (Cy) and horse antithymocyte globulin (ATG). Horse ATG has been replaced by rabbit ATG in many countries due to the unavailability of the former product. This study was designed to assess if these ATG preparations are interchangeable in the preparative regimen for matched related BMT in SAA. Forty consecutive BMTs were retrospectively analyzed: 20 received Cy plus horse ATG and 20 received Cy plus rabbit ATG as the preparative regimen. Conditioning with rabbit ATG was...
Charvet CL, Guégnard F, Courtot E, Cortet J, Neveu C.The control of parasitic nematodes impacting animal health relies on the use of broad spectrum anthelmintics. However, intensive use of these drugs has led to the selection of resistant parasites in livestock industry. In that respect, there is currently an urgent need for novel compounds able to control resistant parasites. Nicotine has also historically been used as a de-wormer but was removed from the market when modern anthelmintics became available. The pharmacological target of nicotine has been identified in nematodes as acetylcholine-gated ion channels. Nicotinic-sensitive acetylcholin...
Muir WW.N-Methyl-D-aspartate (NMDA) is a synthetic chemical binding molecule (ligand) that selectively binds to the "slow response" glutamate NMDA receptor (NMDAR). NMDARs are important for normal brain function and play a central role in learning, memory, and the development of central nervous system hyperactive states. Diverse chemicals belonging to various drug families have demonstrated NMDAR antagonistic effects. Ketamine has been shown to produce antihyperalgesic effects produced by incision and tissue or nerve damage, and has become popular in equine practice as an anesthetic and more recently ...
Clarke KW, Paton BS.The effects of administration of one of four opiates (pethidine 1 mg/kg bodyweight (bwt), morphine 0.1 mg/kg bwt, methadone 0.1 mg/kg bwt, and butorphanol 0.05 mg/kg bwt) given intravenously to horses and ponies already sedated with detomidine (10 micrograms/kg bwt) were investigated. Behavioural, cardiovascular and respiratory effects of the combinations were compared with those occurring with detomidine alone. Addition of the opiate increased the apparent sedation and decreased the response of the animal to external stimuli. At doses used, butorphanol produced the most reliable response. Sid...
Little D, Brown SA, Campbell NB, Moeser AJ, Davis JL, Blikslager AT.To determine the effect of meloxicam and flunixin meglumine on recovery of ischemia-injured equine jejunum. Methods: 18 horses. Methods: Horses received butorphanol tartrate; were treated IV with saline (0.9% NaCl) solution (SS; 12 mL; n = 6), flunixin meglumine (1.1 mg/kg; 6), or meloxicam (0.6 mg/kg; 6) 1 hour before ischemia was induced for 2 hours in a portion of jejunum; and were allowed to recover for 18 hours. Flunixin and SS treatments were repeated after 12 hours; all 3 treatments were administered immediately prior to euthanasia. Selected clinical variables, postoperative pain scores...
Venner M, Kerth R, Klug E.Tulathromycin is a new injectable macrolide antibiotic used for the treatment of pulmonary diseases of swine and cattle. In this study, 37 foals with sonographic evidence of lung abscesses were treated with tulathromycin (2.5mg/kg intramuscularly [IM] once weekly, group 1) and 33 foals (group 2) with a combination of azithromycin (10mg/kg per os [PO] once daily for the first seven days of therapy, thereafter every other day) and rifampin (10mg/kg PO twice daily). The bacterial aetiological agent was not determined. The foals were only mildly sick and the median number of pulmonary abscesses wa...
Klöppel H, Leece EA.To compare alfaxalone with ketamine for total intravenous anaesthesia in ponies undergoing castration. Methods: Prospective, randomised, blinded clinical study. Methods: Forty-two, 12-month-old Welsh Mountain ponies. Methods: Ponies were assigned randomly to receive ketamine or alfaxalone. After administration of romifidine 100 μg kg(-1) and butorphanol 50 μg kg(-1) intravenously (IV), sedation and response to tactile stimulation were scored. If sedation was insufficient, romifidine 30 μg kg(-1) was administered IV. Anaesthesia was induced with ketamine 2.2 mg kg(-1) or alfaxalone 1 mg kg(-...
Costa GL, Cristarella S, Quartuccio M, Interlandi C.To evaluate the anti-nociceptive and sedative effects of slow intravenous (IV) injection of tramadol, romifidine, or a combination of both drugs in ponies. Methods: Within-subject blinded. Methods: Twenty ponies (seven male, 13 female, weighing mean ± SD 268.0 ± 128 kg). Methods: On separate occasions, each pony received one of the following three treatments IV; romifidine 50 μg kg(-) (R) tramadol 3 mg kg(-1) given over 15 minutes (T) or tramadol 3 mg kg(-1) followed by romifidine 50 μg kg(-1) (RT). Physiologic parameters and caecal borborygmi (CB) were measured and sedation ...
Tedesco DEA, Guerrini A.Milk thistle, Silybum marianum, is a medicinal plant grown for its bioactive compounds with well-documented antioxidant and hepatoprotective properties. Milk thistle has a well-established pharmacological reputation for treatments of human liver disease, but it is also used in animals. This review summarizes the experimental evidence of milk thistle's effects on animals when administered as silymarin extract (feed additive) or a feed ingredient, if administered as seed or expeller/cake with the seed residue still containing the bioactive components. The use as a feed additive or feed ingredien...
Lankveld DP, Bull S, Van Dijk P, Fink-Gremmels J, Hellebrekers LJ.Ketamine is widely used in equine anaesthesia. Beside its anaesthetic and analgesic properties, ketamine possesses a cytokine-modulating activity. However, to date, no data are available regarding the inhibitory effect of ketamine on the cytokine response in horses. In horses, cytokines such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) play a pivotal role in the pathogenesis of equine endotoxaemia following gastrointestinal disorders. Hence, the objective of this study was to assess the influence of ketamine on LPS-induced TNF-alpha and IL-6 formation in an equine macro...
Guedes AGP, Aristizabal F, Sole A, Adedeji A, Brosnan R, Knych H, Yang J, Hwang SH, Morisseau C, Hammock BD.This study determined the pharmacokinetics, antinociceptive, and anti-inflammatory effects of the soluble epoxide hydrolase (sEH) inhibitor t-TUCB (trans-4-{4-[3-(4-Trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid) in horses with lipopolysaccharide (LPS)-induced radiocarpal synovitis. A total of seven adult healthy mares (n = 4-6/treatment) were administered 3 μg LPS into one radiocarpal joint and t-TUCB intravenously (i.v.) at 0 (control), 0.03, 0.1, 0.3, and 1 mg/kg in a blinded, randomized, crossover design with at least 3 weeks washout between. Two investigators independe...
MacAllister CG, Sifferman RL, McClure SR, White GW, Vatistas NJ, Holste JE, Ericcson GF, Cox JL.A multicentre, blinded, randomised complete-block, field trial was conducted with 140 horses and foals age 4 weeks-28 years to determine if omeprazole paste is effective and safe in promoting healing of spontaneous gastric ulcers under a variety of field conditions and in different breeds and ages of horses. Horses in the study had gastric ulceration as determined by gastroscopy and were divided into replicates of 4 or 5 animals. One horse in each replicate was assigned randomly to receive an empty omeprazole syringe (sham-dosed control) and the remaining horses received omeprazole paste once ...
Cudmore LA, Muurlink T, Whittem T, Bailey SR.Pro-inflammatory cytokines, such as IL-1β and TNFα, play a major role in activating leukocytes and endothelial cells during the systemic inflammatory response to endotoxin in the horse. β2 agonist drugs, such as clenbuterol, inhibit leukocyte activation. This study aimed to determine the effects of oral clenbuterol on clinical and leukocyte responses, including production of TNFα, in an in vivo endotoxin challenge model. In a randomised crossover design, horses received either clenbuterol or a placebo product prior to the administration of low dose endotoxin (30 ng/kg over 30 min). Clinica...
Furr M, Kennedy T, MacKay R, Reed S, Andrews F, Bernard B, Bain F, Byars D.Equine protozoal myeloencephalitis (EPM) is a neurologic disease of horses most commonly caused by the protozoan parasite Sarcocystis neurona. Until recently the only treatment option was the combination of a sulfonamide with pyrimethamine. The present study was performed to assess the efficacy of ponazuril, an anticoccidial triazine-based compound, as a treatment for naturally occurring EPM. One hundred one horses with EPM were randomly allocated to treatment with ponazuril 15% oral paste at either 5 or 10 mg/kg body weight for 28 consecutive days. Horses were evaluated clinically and by anal...
Valverde A, Gunkelt C, Doherty TJ, Giguère S, Pollak AS.Lidocaine constant rate infusions (CRIs) are common as an intraoperative adjunct to general anaesthesia, but their influence on quality of recovery has not been thoroughly determined. Objective: To determine the effects of an intraoperative i.v. CRI of lidocaine on the quality of recovery from isoflurane or sevoflurane anaesthesia in horses undergoing various surgical procedures, using a modified recovery score system. Objective: The administration of intraoperative lidocaine CRI decreases the quality of recovery in horses. Methods: Lidocaine (2 mg/kg bwt bolus followed by 50 microg/kg bwt/min...
Nogueira SA, Torres SM, Malone ED, Diaz SF, Jessen C, Gilbert S.Imiquimod is an immune response modifier with potent antiviral and antitumour activity. The objective of this pilot study was to evaluate the efficacy of an imiquimod 5% cream (Aldaratrade mark: 3M, Saint Paul, MN, USA) as a topical treatment for equine sarcoids. Fifteen horses with a total of 19 tumours were enrolled, including mixed (7), fibroblastic (5), flat (3), verrucous (2), and nodular (2) types. Baseline data included history, physical examination, tumour location, measurement and digital photography. Imiquimod was applied by the owners three times a week until complete resolution of ...
Naylor RJ, Taylor AH, Knowles EJ, Wilford S, Linnenkohl W, Mair TS, Johns IC.Ex vivo evidence suggests that cyclo-oxygenase (COX) 2-preferential inhibitor nonsteroidal anti-inflammatory drugs (NSAIDs), such as meloxicam, have a less detrimental effect on intestinal healing than flunixin meglumine (FM). Whether this translates to a beneficial effect in horses with naturally occurring strangulating small intestinal (SSI) lesions is unknown. Objective: To compare the clinical outcome of horses with naturally occurring SSI lesions treated with meloxicam or FM. Methods: Randomised prospective study. Methods: Cases presenting to the Royal Veterinary College Equine Referral H...
Prieto D, Simonsen U, Hernández M, García-Sacristán A.1. Penile small arteries (effective internal lumen diameter of 300 600 microm) were isolated from the horse corpus cavernosum and mounted in microvascular myographs in order to investigate the mechanisms underlying the endothelium-dependent relaxations to acetylcholine (ACh) and bradykinin (BK). 2. In arteries preconstricted with the thromboxane analogue U46619 (3-30 nM), ACh and BK elicited concentration-dependent relaxations, pD2 and maximal responses being 7.71+/-0.09 and 91+/-1 % (n=23), and 8.80+/-0.07 and 89+/-2% (n=24) for ACh and BK, respectively. These relaxations were abolished by me...
Williams DC, Aleman M, Tharp B, Fletcher DJ, Kass PH, Steffey EP, LeCouteur RA, Holliday TA.The administration of certain sedatives has been shown to promote sleep in humans. Related agents induce sleep-like behavior when administered to horses. Interpretation of electroencephalograms (EEGs) obtained from sedated horses should take into account background activity, presence of sleep-related EEG events, and the animal's behavior. Objective: Sedatives induce states of vigilance that are indistinguishable on EEGs from those that occur naturally. Methods: Six healthy horses. Methods: Digital EEG with video was recorded after administration of 1 of 4 sedatives (acepromazine, butorphanol, ...
Sheats MK, Pescosolido KC, Hefner EM, Sung EJ, Adler KB, Jones SL.Neutrophil infiltration is a prominent feature in a number of pathologic conditions affecting horses including recurrent airway obstruction, ischemia-reperfusion injury, and laminitis. Cell signaling components involved in neutrophil migration represent targets for novel anti-inflammatory therapies. In order to migrate into tissue, neutrophils must respond to chemoattractant signals in their external environment through activation of adhesion receptors (i.e. integrins) and reorganization of the actin cytoskeleton. Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS), a highly conserved actin...
Lohmann KL, Vandenplas ML, Barton MH, Bryant CE, Moore JN.Lipopolysaccharide (LPS) antagonists inhibit the response of inflammatory cells to LPS, presumably by competitive inhibition, and may be of therapeutic value in the treatment of endotoxemia and sepsis. The inhibitory effects of some LPS antagonists are restricted to certain host species, however, as the same molecules can have significant endotoxic activity in other species. This species-specific recognition appears to be mediated by Toll-like receptor 4 (TLR4) and/or MD-2. We have shown previously that LPS from Rhodobacter sphaeroides ( RsLPS) is an LPS antagonist in human cells but an agonis...
Johnson CB, Taylor PM.We have investigated in eight ponies the effects of three different end-tidal concentrations of halothane, isoflurane and methoxyflurane on median (F50) and 95% spectral edge (F95) frequencies of the EEG and the second differential (DD) of the middle latency auditory evoked potential (MLAEP). The three concentrations of each agent were chosen to represent approximately the minimum alveolar concentration (MAC), 1.25 MAC and 1.5 MAC for each agent. During halothane anaesthesia, F95 decreased progressively as halothane concentration increased, from mean 13.9 (SD 2.6) at 0.8% to 11.9 (1.1) at 1.2%...
Youn HJ, Lakritz J, Kim DY, Rottinghaus GE, Marsh AE.The purpose of this study was to determine whether alcohol extracts of herbs (Sophora flavescens Aiton, Sinomenium acutum (Thunb.) Rehder and E.H. Wilson, Pulsatilla koreana (Yabe ex Nakai) Nakai ex T. Mori, Ulmus macrocarpa Hance and Torilis japonica (Houtt.) DC.) from South Korea, possess in vitro anti-protozoal activity against cultures of Toxoplasma gondii and Neospora caninum. These herbs have been used as human anti-parasitics in Asian countries for many years. Alcohol extracts of these herbs were serially diluted to final concentrations ranging from 625 to 19.5 ng/ml in media and added ...
Ochi S, Oda M, Nagahama M, Sakurai J.Clostridium perfringens alpha-toxin is able to lyse various erythrocytes. Exposure of horse erythrocytes to alpha-toxin simultaneously induced hot-cold hemolysis and stimulated production of diacylglycerol and phosphorylcholine. When A23187-treated erythrocytes were treated with the toxin, these events were dependent on the concentration of extracellular Ca2+ . Incubation with the toxin of BAPTA-AM-treated horse erythrocytes caused no hemolysis or production of phosphorylcholine, but that of the BAPTA-treated erythrocytes did. When Quin 2-AM-treated erythrocytes were incubated with the toxin i...
Wang YX, Kotlikoff MI.We investigated the muscarinic activation of Ca(2+)-activated Cl- currents [ICl(Ca)] in voltage-clamped equine tracheal myocytes. The threshold of cytosolic free Ca2+ concentration ([Ca2+]i) required for activation of ICl(Ca) was 202 +/- 22 nM, and full activation of the current occurred at 771 +/- 31 nM. Hexahydro-sila-difenidol (M3 antagonist) inhibited the methacholine-induced phasic [Ca2+]i increase and ICl(Ca) in a concentration-dependent manner, whereas methoctramine (M2 antagonist) only slightly attenuated the [Ca2+]i increase and ICl(Ca) (14.8 and 21.4%, respectively), consistent with ...
Jamila N, Khairí·ªn M, Yeong KK, Osman H, Murugaiyah V.Context: Garcinia hombroniana Pierre, known as manggis hutan in Malaysia is a rich source of xanthones and benzophenones. Objective: This study was aimed to isolate and characterize potential cholinesterase inhibitors from the extracts of G. hombroniana bark and investigate their interactions with the enzymes. Methods: The dichloromethane extract afforded five triterpenoids which were characterized by NMR and mass spectral techniques. Cholinesterase inhibitory assay and molecular docking were performed to get insight of the inhibitory activity and molecular interactions of the compounds. The c...
Peffers MJ, Milner PI, Tew SR, Clegg PD.SOX9 is a transcription factor that is essential for cartilage extracellular matrix (ECM) formation. Osteoarthritis (OA) is characterised by a loss of cartilage ECM. In chondrocytes SOX9 gene expression is regulated by osmotic loading. Here we characterise SOX9 mRNA regulation through static and cyclical application of hyperosmotic conditions in normal and OA monolayer equine chondrocytes. Furthermore, we investigate whether extracellular signal-regulated protein kinase (ERK)1/2 mitogen-activated protein kinases (MAPK) pathways have a role in this regulation of SOX9. Methods: Equine chondrocyt...
Leclere M.Immune suppressive therapies target exaggerated and deleterious responses of the immune system. Triggered by exogenous or endogenous factors, these improper responses can lead to immune or inflammatory manifestations, such as urticaria, equine asthma, or autoimmune and immune-mediated diseases. Glucocorticoids are the most commonly used immune suppressive drugs and the only ones supported by robust evidence of clinical efficacy in equine medicine. In some conditions, combining glucocorticoids with other pharmacologic and nonpharmacologic treatments, such as azathioprine, antihistamine, broncho...
Tyma JF, Epstein KL, Whitfield-Cargile CM, Cohen ND, Giguère S.OBJECTIVE To determine the effects of oral omeprazole administration on the fecal and gastric microbiota of healthy adult horses. ANIMALS 12 healthy adult research horses. PROCEDURES Horses were randomly assigned to receive omeprazole paste (4 mg/kg, PO, q 24 h) or a sham (control) treatment (tap water [20 mL, PO, q 24 h]) for 28 days. Fecal and gastric fluid samples were collected prior to the first treatment (day 0), and on days 7, 28, 35, and 56. Sample DNA was extracted, and bacterial 16S rRNA gene sequences were amplified and sequenced to characterize α and β diversity and differential ...