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.
Gomez D, Toribio R, Caddey B, Costa M, Vijan S, Dembek K.Antimicrobial drug-associated diarrhea (AAD) is the most common adverse effect in horses receiving antimicrobials. Little information on how oral administration of antimicrobials alters intestinal microbiota in horses is available. Objective: Investigate changes of the fecal microbiota in response to oral administration of antimicrobials. Methods: Twenty healthy horses. Methods: Prospective, longitudinal study. Horses were randomly assigned to 4 groups comprising 4 horses each: group 1 (metronidazole); group 2 (erythromycin); group 3 (doxycycline); group 4 (sulfadiazine/trimethoprim, SMZ-TMP);...
Coomer RPC, Terschuur JA, Pressanto MC, Walker I.To assess the efficacy of commercial intra-articular blood-derived allogeneic-induced mesenchymal stem cells (CIMSCs) to treat tarsometatarsal lameness in horses. Methods: This was a retrospective cohort study. Methods: Records from 167 adult light breed horses with bilateral tarsometatarsal lameness. Methods: Horses with tarsometatarsal lameness were retrospectively selected from medical records. Diagnosis followed subjective graded lameness assessment before and after intra-articular analgesia, with graded radiographic tarsal examination. Horses were excluded if they were diagnosed or treate...
Sundra T, Gough S, Rossi G, Kelty E, Rendle D.Oral omeprazole is the accepted treatment for equine squamous gastric disease (ESGD); however, it is not universally effective. Esomeprazole results in more consistent and pronounced acid suppression in men and is more effective than omeprazole in the treatment of oesophageal and gastric disease. Pharmacodynamic and pilot clinical studies have indicated esomeprazole might also be more effective than omeprazole in horses. Objective: To compare the efficacy and safety of oral esomeprazole and omeprazole pastes in the treatment of ESGD and, where present, concurrent equine glandular gastric disea...
Estrada RJ, Alvarado GJ, Vargas A, Vargas J, Vargas D, Chacón R, Razquin P, Vindas R.To determine the proximal diffusion distance of radiopaque contrast medium and mepivacaine/methylene blue solution and incidence of inadvertent intrasynovial and intravascular injections of modified sesamoid nerve block (MASB) when compared with traditional plantar nerve analgesia techniques of the equine distal hind limb. Methods: Ex vivo model: 18 hind limbs; and in vivo model: 5 horses in a crossover study. Methods: In the ex vivo model, a mepivacaine/methylene blue solution was used to compare the diffusion distance between MASB, basisesamoid block (BSB), and traditional low plantar block ...
Elliott SM, Giancola SC, Moorman V.To determine if targeted blocking of frontal and infratrochlear nerves provided anesthesia for the approach to a frontonasal sinusotomy. Methods: Two part study: Part 1 randomized crossover design; Part 2 proof of concept. Methods: N = 12; six each in Parts 1 and 2. Methods: Part 1: Each horse had either frontal and infratrochlear nerve blocks or a line block performed with 2% mepivacaine hydrochloride. Mechanical nociceptive thresholds (MNT) were obtained at five sites along a proposed frontonasal sinusotomy prior to injection, and at 10, 60, and 120 min after blocking. After a 4 day ...
McCarthy MB, Duesterdieck-Zellmer KF, Larson MK.To determine whether Botulinum neurotoxin type A (BoNT-A) ameliorates the effects of interleukin 1 (IL-1) on equine articular cartilage, or exerts negative effects on normal equine articular cartilage homeostasis in vitro. Methods: Articular cartilage explants from 6 healthy femoropatellar joints of 3 adult horses. Methods: Explants were allocated to the IL-1 challenged or unchallenged group, then exposed to 1 of 6 concentrations of BoNT-A (0, 1, 10, 50, 100, or 500 pg/mL) for 96 hours. To assess BoNT-A's effects on inflammation, prostaglandin E2 (PGE2) was measured in media via ELISA. Matrix ...
Lagounova M, MacNicol JL, Weese JS, Pearson W.Synbiotics are often provided to horses receiving antibiotics to protect against microbiome disturbances, despite a lack of evidence for efficacy. The purpose of this study was to evaluate the effect of a synbiotic product in horses receiving antibiotics. Sixteen actively racing Standardbred horses were randomly allocated (four-way crossover) to one of four groups: antibiotics (10 days; AB), synbiotics (28 days; PROBIOPlusTM; PBP), PBP + AB, or Control. The fecal microbiome was investigated using 16S rRNA sequencing, and fecal dry matter (DM; %), pH, and scores (FS; 0-9) were measured. Data we...
Chen Q, Wang Z, Chen H.Aromatase inhibitors (AIs) can indirectly cause increased testosterone in animals, which leads to the improvement of the athletic ability of horses. For the protection of horses and the consideration of fair competition, AIs were listed as prohibited drugs by the Federation Equestre Internationale (FEI). There were several disadvantages using traditional pretreatment methods before analyzing these drugs from biological samples. A rapid and green pretreatment method has been developed by utilizing the hydrophobic deep eutectic solvent (DES)-based vortex-assisted liquid-liquid microextraction (D...
Trsan J, Nottle BF, Pusterla N.This study was designed to determine the effect of PPG and/or flunixin meglumine on SAA response when used at clinical dosing regimens in healthy adult horses. Six healthy adult horses were enrolled in a crossover study design including one control and three treatment groups: no treatment (control); PPG alone (intramuscularly q12h for 72h); flunixin meglumine alone (intravenously q24h for 72h); and PPG (intramuscularly q12h for 72h) and flunixin meglumine (intravenously q24h for 72h). Whole blood was collected at 0, 24, 48, 72, 96 and 120 hours post-initial drug administration to measure SAA u...
Elder E, Wong D, Johnson K, Robertson H, Marner M, Dembek K.Bacterial sepsis is the leading cause of death in foals and is associated with hypothalamic-pituitary-adrenocortical axis (HPAA) dysfunction. HPAA function can be evaluated by an arginine-vasopressin (AVP) stimulation test. Objective: Administration of AVP will stimulate a dose-dependent rise in systemic adrenocorticotropin-releasing hormone (ACTH) and cortisol in neonatal foals. There will be no response seen in corticotropin-releasing hormone (CRH) and baseline AVP will be within reference interval. Methods: Twelve neonatal foals, <72 hours old. Methods: HPAA function was assessed in foals...
Haugaard SL, McGovern KF, Tallon R, Gough R, Watrobska N.Horses commonly receive hyoscine butylbromide (HB) prior to hospital admission for colic. This could alter the appearance of the small intestine (SI) on ultrasound scan and affect clinical decision making. The aim of this study was to assess the impact of HB on ultrasonographically assessed SI motility and heart rate. Six horses hospitalised for medical colic with no significant abnormalities on baseline abdominal ultrasound examination were included. Ultrasound was performed in three locations (right inguinal, left inguinal and hepatoduodenal window) before and at 1, 5, 15, 30, 45, 60, 90, an...
Clark B, Steel C, Vokes J, Shan JR, Gedye K, Lovett A, Sykes BW.Rebound gastric hyperacidity (RGH) secondary to hypergastrinemia has been suggested to contribute to the rapid recurrence of equine squamous gastric disease (ESGD) in horses after discontinuation of omeprazole. Objective: To evaluate changes in serum gastrin and chromogranin A (CgA) concentrations in response to medium-term (57-day) omeprazole treatment and after omeprazole discontinuation. Methods: Fourteen mature Thoroughbred racehorses in simulated race training. Methods: Horses received 2.28 g of oral omeprazole PO q24h for 57 days within a 61-day period, excluding a withholding period...
Atai T, Ozmaie S, Anoushepour A.This research was performed to compare the effects of prednisolone and fluorometholone on intraocular pressure (IOP) and Schirmer tear test (STT) in the normal equine eye. Sixteen normal mares aged between 6 and 10 years were used for this study. Horses were randomly assigned to two groups. Eight horses in the first group received 0.2 mL of topical 1% prednisolone in one eye and the contralateral eye was used as control (0.2 mL of saline was instilled). The second group received 0.2 mL of 0.1% fluorometholone in a randomly selected eye and the contralateral eye served as control and received 0...
Pinetre J, Delcourt V, Becher F, Garcia P, Barnabé A, Loup B, Popot MA, Fenaille F, Bailly-Chouriberry L.Many innovative biotherapeutics have been marketed in the last decade. Monoclonal antibodies (mAbs) and Fc-fusion proteins (Fc-proteins) have been developed for the treatment of diverse diseases (cancer, autoimmune diseases, and inflammatory disorders) and now represent an important part of targeted therapies. However, the ready availability of such biomolecules, sometimes characterized by their anabolic, anti-inflammatory, or erythropoiesis-stimulating properties, raises concerns about their potential misuse as performance enhancers for human and animal athletes. In equine doping control labo...
Gonzalez GA, Betbeze C, Wills R, Eddy A, Mochal-King C, Fontenot RL.To evaluate corneal sensitivity and adverse events following subconjunctival administration of three local anesthetics in horses. Methods: Randomized, masked, crossover study. Methods: Twelve healthy adult mares. Methods: The subconjunctival space of the treated eye was injected with 0.2 mL of liposomal bupivacaine (1.3%), ropivacaine (0.5%), or mepivacaine (2%). All horses received each medication once and the contralateral eye received saline (control). Corneal touch threshold (CTT) was measured using a Cochet-Bonnet esthesiometer before sedation, after sedation, and at specified intervals...
Skiöldebrand E, Adepu S, Lützelschwab C, Nyström S, Lindahl A, Abrahamsson-Aurell K, Hansson E.This study aimed to test a novel treatment combination (TC) (equivalent to sildenafil, mepivacaine, and glucose) with disease-modifying properties compared to Celestone® bifas® (CB) in a randomized triple-blinded phase III clinical study in horses with mild osteoarthritis (OA). Joint biomarkers (reflecting the articular cartilage and subchondral bone remodelling) and clinical lameness were used as readouts to evaluate the treatment efficacy. Unassigned: Twenty horses with OA-associated lameness in the carpal joint were included in the study and received either TC (n = 10) or CB (n = ...
Beaumont RE, Smith EJ, Zhou L, Marr N, Thorpe CT, Guest DJ.We investigated how Interleukin 1 beta (IL-1β) impacts equine tenocyte function and global gene expression in vitro and determined if these effects could be rescued by pharmacologically inhibiting nuclear factor-κB (NF-B) or interleukin 1 signalling. Equine superficial digital flexor tenocytes were cultured in three-dimensional (3D) collagen gels and stimulated with IL-1β for two-weeks, with gel contraction and interleukin 6 (IL6) measured throughout and transcriptomic analysis performed at day 14. The impact of three NF-B inhibitors on gel contraction and IL6 secretion were measured in 3D ...
Dirikolu L, Lehner AF.Anabolic androgenic steroids are synthetic substances related to the male sex hormones (androgens). These agents promote the growth of skeletal muscle (anabolic effects) and the development of male sexual characteristics (androgenic effects). Anabolic steroids have been illegally used for many years as performance-enhancing drugs in human, equine, and canine sports and as growth promoters in livestock reared to provide meat for human consumption. The analytical challenge to developing effective means of control within these fields has been exacerbated by the reported endogenous nature of some ...
Li Z, He Y, Ge L, Quan R, Chen J, Hu Y, Sa R, Liu J, Ran D, Fu Q, Shi H.Equine herpesvirus type 1 (EHV-1) poses a global threat to equines. The anticancer agent berbamine (BBM), a bioactive alkaloid, has been shown to inhibit viral infection. However, whether BBM can inhibit EHV-1 infection remains unclear. This study investigated the effect of BBM treatment on EHV-1 infection. Quantitative PCR (qPCR), immunoblotting, the Reed-Muench method, and pathological examination were employed to study the ability of BBM to inhibit EHV-1 infection, viral DNA replication, viral protein production, virion secretion, and cytopathogenesis in vitro and in vivo. The in vitro stud...
Black JB, Frampton AR.Equine herpesvirus type 1 (EHV-1) is a highly transmissible pathogen that leads to a variety of clinical disease outcomes in infected horses. A major sequela that can occur after an EHV-1 infection is a neurological disease termed equine herpesvirus myeloencephalopathy (EHM). Clinical manifestations of EHM include fever, ataxia, incontinence, and partial to full paralysis, which may ultimately lead to the euthanization of the infected horse. To develop an effective treatment strategy for EHM, it is critical that the specific virus-host interactions that lead to EHM be investigated so that safe...
Broberg MN, Knych H, Bondesson U, Pettersson C, Tidstedt B, Stanley S, Thevis M, Hedeland M.LGD-3303 is a Selective Androgen Receptor Modulator (SARM) that is prohibited in both equine and human sports due to its anabolic properties. The aim of this study was to investigate the equine in vivo metabolite profile of LGD-3303 and identify drug metabolites that can be suitable as new and improved analytical targets for equine doping control. This was performed by an oral administration of 0.05 mg·kg LGD-3303 to horses, where blood and urine samples were collected up to 96 h after administration. The in vivo samples consisting of plasma, urine and hydrolyzed urine were analyzed utilizi...
Marchenko VA, Khalikov SS, Biryukov IV, Efremova EA, Ilyin MM, Sazmand A.This study aimed to develop new complex preparations of ivermectin, niclosamide and albendazole based on solid-phase mechanochemical technology, and to evaluate their efficacy against equine nematodosis and cestodosis. Unassigned: Novel formulation of antiparasitic paste were prepared using joint mechano-chemical treatment of ivermectin (0.2 mg/kg bodyweight; BW), niclosamide (10 mg/kg BW) and albendazole (3, 5, 10 mg/kg BW) substances with polyvinylpyrrolidone and arabinogalactan. For the evaluation of activity of different doses of formulations against gastrointestinal tract helminths a tota...
Bishop RC, Wilkins PA, Kemper AM, Stewart RM, McCoy AM.Nonsteroidal anti-inflammatory drug (NSAID) administration carries risks of gastrointestinal toxicity. Selective COX-2 inhibitors ("coxibs") were designed to reduce risks of adverse effects but are still associated with gastrointestinal complications in humans. The effect of coxibs on colonic inflammation and integrity in horses is unknown. The study objective was to compare the effects of the coxib firocoxib and the nonselective NSAID flunixin meglumine on ultrasonographic indicators of colonic inflammation in healthy horses. Twelve healthy adult horses were administered flunixin meglumine (1...
Barton C, Hassel DM.A successful outcome to management of the critical colic patient is highly dependent on how the patient is monitored and treated, particularly, in the perioperative period. In this article, we will provide an update on monitoring techniques, advances in fluid therapy, nutrition management and pharmacotherapeutic agents, inclusive of pain monitoring and management, prokinetics, and management of systemic inflammatory response syndrome and the hypercoagulable state.
Kikuchi M, Nagata SI, Ishige T, Minamijima Y, Hirota KI, Tozaki T, Kakoi H, Kizaki K.Glucocorticoid preparations have anti-inflammatory effects, and are commonly used in the equine clinical setting; however, such treatments can cause a number of side effects. Adrenal insufficiency is an adverse effect induced by the suppression of adrenal function following drug administration. This study aimed to investigate the influence of two glucocorticoid preparations, dexamethasone and hydrocortisone, on adrenocortical function in horses. The usual doses of dexamethasone and hydrocortisone preparations in equine practice were administered intramuscularly to six horses, and peripheral bl...
Fan Y, Lou J, Tam CC, Wen W, Conrad F, Leal da Silva Alves P, Cheng LW, Garcia-Rodriguez C, Farr-Jones S, Marks JD.Equine-derived antitoxin (BAT) is the only treatment for botulism from botulinum neurotoxin serotype G (BoNT/G). BAT is a foreign protein with potentially severe adverse effects and is not renewable. To develop a safe, more potent, and renewable antitoxin, humanized monoclonal antibodies (mAbs) were generated. Yeast displayed single chain Fv (scFv) libraries were prepared from mice immunized with BoNT/G and BoNT/G domains and screened with BoNT/G using fluorescence-activated cell sorting (FACS). Fourteen scFv-binding BoNT/G were isolated with K values ranging from 3.86 nM to 103 nM (median K 2...
Smith HL, Berglund AK, Robertson JB, Schnabel LV, McMullen RJ, Gilger BC, Oh A.The objective of the study was to determine the effect of gentamicin on CD3+ T-lymphocyte proliferation and cell viability using an in vitro cell culture model as a means of investigating the mechanism of action of low-dose intravitreal gentamicin injection. Methods: Three adult horses with no evidence of ophthalmic or systemic disease. Methods: Peripheral blood lymphocytes were treated with gentamicin at concentrations 37.5 μg/mL, 112.5 μg/mL, 187 μg/mL, 375 μg/mL, or 750 μg/mL then stimulated to proliferate with concanavalin A (ConA). 4',6-diamidino-2-phenylindole (DAPI) and c...
Yocom A, Contino E, Kawcak C.Bisphosphonates are a group of drugs that can reduce bone resorption by incorporating into the crystal structure of exposed hydroxyapatite where they are taken up by osteoclasts. Bisphosphonates have several other mechanisms of action including reducing pain and inflammation and altering macrophage function. There are two types of bisphosphonates-nitrogenous and non-nitrogenous, the latter of which is used in horses. This article provides a literature-based review of the proposed mechanisms of action and therapeutic uses of bisphosphonates including a brief review of bone response to disease. ...
Science (New York, N.Y.)August 26, 1983
Volume 221, Issue 4613 823-828 doi: 10.1126/science.6308762
Campbell WC, Fisher MH, Stapley EO, Albers-Schönberg G, Jacob TA.Ivermectin is the 22,23-dihydro derivative of avermectin B1, a macrocyclic lactone produced by an actinomycete, Streptomyces avermitilis. It is active at extremely low dosage against a wide variety of nematode and arthropod parasites, apparently by virtue of its action on the mediation of neurotransmission by gamma-aminobutyric acid. It is now in commercial use in various countries for the treatment and control of parasites in cattle, horses, and sheep, and is expected to become available for use in swine and dogs. Since studies with the drug in man are in a preliminary stage, it is not yet kn...
Jahrling PB, Geisbert TW, Geisbert JB, Swearengen JR, Bray M, Jaax NK, Huggins JW, LeDuc JW, Peters CJ.A passive immunization strategy for treating Ebola virus infections was evaluated using BALB/ c mice, strain 13 guinea pigs, and cynomolgus monkeys. Guinea pigs were completely protected by injection of hyperimmune equine IgG when treatment was initiated early but not after viremia had developed. In contrast, mice were incompletely protected even when treatment was initiated on day 0, the day of virus inoculation. In monkeys treated with one dose of IgG on day 0, onset of illness and viremia was delayed, but all treated animals died. A second dose of IgG on day 5 had no additional beneficial e...
Chindera K, Mahato M, Sharma AK, Horsley H, Kloc-Muniak K, Kamaruzzaman NF, Kumar S, McFarlane A, Stach J, Bentin T, Good L.To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles whe...
Brayton CF.Dimethyl sulfoxide (DMSO) is a very simple compound that has stimulated much controversy in the scientific and popular literature. Fig. 1 It is an aprotic solvent. Therapeutic and toxic agents that are not soluble in water are often soluble in DMSO. DMSO has a very strong affinity for water; on exposure to air, pure DMSO is rapidly diluted. DMSO's physiologic and pharmacologic properties and effects are incompletely understood. Properties that are considered to be particularly important to its therapeutic and toxic effects include: its own rapid penetration and enhanced penetration of other su...
Durham AE, Frank N, McGowan CM, Menzies-Gow NJ, Roelfsema E, Vervuert I, Feige K, Fey K.Equine metabolic syndrome (EMS) is a widely recognized collection of risk factors for endocrinopathic laminitis. The most important of these risk factors is insulin dysregulation (ID). Clinicians and horse owners must recognize the presence of these risk factors so that they can be targeted and controlled to reduce the risk of laminitis attacks. Diagnosis of EMS is based partly on the horse's history and clinical examination findings, and partly on laboratory testing. Several choices of test exist which examine different facets of ID and other related metabolic disturbances. EMS is controlled ...
Whittle BJ, Moncada S, Vane JR.The activity of prostacyclin (PGI2), PGE1 or PGD2 as inhibitors of platelet aggregation in plasma from human, dog, rabbit, rat, sheep and horse was investigated. Prostacyclin was the most potent inhibitor in all species. PGD2 was a weak inhibitor in dog, rabbit and rat plasma whereas PGE1 and prostacyclin were highly active. Theophylline or dipyridamole potentiated the inhibition of human platelet aggregation by prostacyclin, PGE1 or PGD2. Compound N-0164 abolished the inhibition by PGD2 of human platelet aggregation but did not inhibit the effects of PGE1 or prostacyclin. The results suggest ...
The intestinal tract is a rich and complex environment and its microbiota has been shown to have an important role in health and disease in the host. Several factors can cause disruption of the normal intestinal microbiota, including antimicrobial therapy, which is an important cause of diarrhea in horses. This study aimed to characterize changes in the fecal bacterial populations of healthy horses associated with the administration of frequently used antimicrobial drugs. Results: Twenty-four adult mares were assigned to receive procaine penicillin intramuscularly (IM), ceftiofur sodium IM, tr...
Adams MR, Register TC, Golden DL, Wagner JD, Williams JK.Although estrogen replacement therapy is associated with reduced risk of coronary heart disease and reduced extent of coronary artery atherosclerosis, the effects of combined (estrogen plus progestin) hormone-replacement therapy are uncertain. Some observational data indicate that users of combined hormone replacement consisting of continuously administered oral conjugated equine estrogens (CEE) and oral sequentially administered (7 to 14 days per month) medroxyprogesterone acetate (MPA) experience a reduction in risk similar to that of users of CEE alone. However, the effects of combined, con...
Lafont R, Dinan L.Ecdysteroids are widely used as inducers for gene-switch systems based on insect ecdysteroid receptors and genes of interest placed under the control of ecdysteroid-response elements. We review here these systems, which are currently mainly used in vitro with cultured cells in order to analyse the role of a wide array of genes, but which are expected to represent the basis for future gene therapy strategies. Such developments raise several questions, which are addressed in detail. First, the metabolic fate of ecdysteroids in mammals, including humans, is only poorly known, and the rapid catabo...
de Waal DT.This review focuses on equine piroplasmosis with specific reference to its distribution, diagnosis and clinical and pathological signs. The more common used drugs are discussed both with reference to treatment and chemosterilization. Areas requiring further research are also briefly mentioned.
Giguère S, Viel L, Lee E, MacKay RJ, Hernandez J, Franchini M.Work in humans and laboratory animals has identified a central role for cytokines and chemokines in development and persistence of lower airway inflammation. The objectives of this study were to determine interleukin (IL)-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha induction in bronchoalveolar lavage (BAL) of control horses and horses with heaves both during remission and exacerbation of the disease, and to determine the effect of therapy with inhaled fluticasone propionate on the cytokine profile of horses with heaves. IL-1 beta an...
Aitken RJ, Gibb Z, Mitchell LA, Lambourne SR, Connaughton HS, De Iuliis GN.The prolonged incubation of human spermatozoa in vitro was found to induce a loss of motility associated with the activation of mitochondrial reactive oxygen species generation in the absence of any change in mitochondrial membrane potential. The increase in mitochondrial free radical production was paralleled by a loss of protein thiols and a concomitant rise in the formation of 4-hydroxynonenal, an electrophilic product of lipid peroxidation that was found to directly suppress sperm movement. These results prompted a search for nucleophiles that could counteract the action of such cytotoxic ...
Patnaik A, Chau V, Li F, Montelaro RC, Wills JW.The only retrovirus protein required for the budding of virus-like particles is the Gag protein; however, recent studies of Rous sarcoma virus (RSV) and human immunodeficiency virus have suggested that modification of Gag with ubiquitin (Ub) is also required. As a consequence, the release of these viruses is reduced in the presence of proteasome inhibitors, which indirectly reduce the levels of free Ub within the cell. Here we show that the budding of equine infectious anemia virus (EIAV) from infected equine cells is largely unaffected by these drugs, although use of one inhibitor (MG-132) re...
Corning S.The small strongyles of horses, also known as cyathostomins, are considered the most prevalent and pathogenic parasites of horses today. The clinical syndrome of larval cyathostominosis which occurs as a result of mass emergence of inhibited stages has a high fatality rate despite the best standard of care given to affected horses. Management of the challenge level of cyathostomins to prevent the syndrome is preferable. Many different management programmes have been tried over the past two decades, with mixed success. Programmes have relied heavily on repeated use of anthelmintic treatments th...
Leclere M, Lavoie-Lamoureux A, Joubert P, Relave F, Setlakwe EL, Beauchamp G, Couture C, Martin JG, Lavoie JP.Recent studies suggest that airway smooth muscle remodeling is an early event in the course of asthma. Little is known of the effects of long-term antigen avoidance and inhaled corticosteroids on chronically established airway remodeling. We sought to measure the effects of inhaled corticosteroids and antigen avoidance on airway remodeling in the peripheral airways of horses with heaves, a naturally occurring asthma-like disease. Heaves-affected adult horses with ongoing airway inflammation and bronchoconstriction were treated with fluticasone propionate (with and without concurrent antigen av...
Afable MG, Shaik M, Sugimoto Y, Elson P, Clemente M, Makishima H, Sekeres MA, Lichtin A, Advani A, Kalaycio M, Tiu RV, O'Keefe CL, Maciejewski JP.A combination of horse anti-thymocyte globulin and cyclosporine produces responses in 60-70% of patients with severe aplastic anemia. We performed a phase II study of rabbit anti-thymocyte globulin and cyclosporine as first-line therapy for severe aplastic anemia. Methods: Twenty patients with severe aplastic anemia treated with rabbit anti-thymocyte globulin were compared to 67 historical control cases with matched clinical characteristics treated with horse anti-thymocyte globulin. Results: Response rates at 3, 6 and 12 months were similar for patients treated with rabbit anti-thymocyte glob...
Rojas G, Jiménez JM, Gutiérrez JM.A simple methodology for hyperimmune horse plasma fractionation, based on caprylic acid precipitation, is described. Optimal conditions for fractionation were studied; the method gives best results when concentrated caprylic acid was added to plasma, whose pH had been adjusted to 5.8, until a final caprylic acid concentration of 5% was reached. The mixture was vigorously stirred during caprylic acid addition and then for 60 min; afterwards the mixture was filtered. Non-immunoglobulin proteins precipitated in these conditions, whereas a highly enriched immunoglobulin preparation was obtained in...
Harder A, Schmitt-Wrede HP, Krücken J, Marinovski P, Wunderlich F, Willson J, Amliwala K, Holden-Dye L, Walker R.There are three major classes of anthelmintics for veterinary use: the benzimidazoles/prebenzimidazoles, the tetrahydropyrimidines/imidazothiazoles, and the macrocyclic lactones. In nematodes, there are five targets for the existing anthelmintics: the nicotinergic acetylcholine receptor which is the target of tetrahydropyrimidines/imidazothiazoles and indirectly that of the acetylcholineesterase inhibitors; the GABA receptor which is the target of piperazine, the glutamate-gated chloride channel as the target of the macrocyclic lactones, and beta-tubulin as the target of prebenzimidazoles/benz...
Scepek S, Coorssen JR, Lindau M.Using the patch-clamp technique, we studied the role of protein phosphorylation and dephosphorylation on the exocytotic fusion of secretory granules with the plasma membrane in horse eosinophils. Phorbol 12-myristate 13-acetate (PMA) had no effect on the amplitude and dynamics of degranulation, indicating that the formation of fusion pores is insensitive to activation of protein kinase C (PKC). Fusion pore expansion, however, was accelerated approximately 2-fold by PMA, and this effect was abolished by staurosporine. Elevating intracellular Ca2+ to 1.5 microM also resulted in a 2-fold accelera...
Atta EH, Dias DS, Marra VL, de Azevedo AM.The best antithymocyte globulin preparation for first-line immune suppression in patients with severe aplastic anemia is still not clear. The aim of this study was to compare hematological response and overall survival in patients submitted to horse or rabbit antithymocyte globulin as first-line treatment for severe aplastic anemia. We retrospectively compared 71 consecutive patients with severe aplastic anemia, classified according to the antithymocyte globulin preparation. Analyses included variables related to patients and to immune suppression. Forty two patients (59.1%) received horse and...
Clegg PD, Strassburg S, Smith RK.Injuries to tendons are common in both human athletes as well as in animals, such as the horse, which are used for competitive purposes. Furthermore, such injuries are also increasing in prevalence in the ageing, sedentary population. Tendon diseases often respond poorly to treatment and require lengthy periods of rehabilitation. The tendon has a unique extracellular matrix, which has developed to withstand the mechanical demands of such tensile-load bearing structures. Following injury, any repair process is inadequate and results in tissue that is distinct from original tendon tissue. There ...
Iyer U, Kadambi VJ.Antibody drug conjugates (ADCs) consist of an antibody attached to a cytotoxic drug by means of a linker. ADCs provide a way to couple the specificity of a monoclonal antibody (mAb) to the cytotoxicity of a small-molecule drug and, therefore, are promising new therapies for cancer. ADCs are prodrugs that are inactive in circulation but exert their cytotoxicity upon binding to the target cancer cell. Earlier unsuccessful attempts to generate ADCs with therapeutic value have emphasized the important role each component plays in determining the efficacy and safety of the final ADC. Scientific adv...
Rizk MA, El-Sayed SA, Terkawi MA, Youssef MA, El Said el Sel S, Elsayed G, El-Khodery S, El-Ashker M, Elsify A, Omar M, Salama A, Yokoyama N....A rapid and accurate assay for evaluating antibabesial drugs on a large scale is required for the discovery of novel chemotherapeutic agents against Babesia parasites. In the current study, we evaluated the usefulness of a fluorescence-based assay for determining the efficacies of antibabesial compounds against bovine and equine hemoparasites in in vitro cultures. Three different hematocrits (HCTs; 2.5%, 5%, and 10%) were used without daily replacement of the medium. The results of a high-throughput screening assay revealed that the best HCT was 2.5% for bovine Babesia parasites and 5% for equ...
Wang ZW, Nara M, Wang YX, Kotlikoff MI.The effects of sulfhydryl reduction/oxidation on the gating of large-conductance, Ca(2+)-activated K+ (maxi-K) channels were examined in excised patches from tracheal myocytes. Channel activity was modified by sulfhydryl redox agents applied to the cytosolic surface, but not the extracellular surface, of membrane patches. Sulfhydryl reducing agents dithiothreitol, beta-mercaptoethanol, and GSH augmented, whereas sulfhydryl oxidizing agents diamide, thimerosal, and 2,2'-dithiodipyridine inhibited, channel activity in a concentration-dependent manner. Channel stimulation by reduction and inhibit...
Lyons ET, Tolliver SC, Drudge JH.Small strongyles are highly prevalent in horses and can be found worldwide. Even though over 50 species of these parasites have been described, about 10 species comprise the bulk of the total number present in horses. Efforts to control small strongyles and other equine internal parasites have been undertaken for many years. Some of the early medications and control measures provided questionable activity against endoparasites; whether effective or not, they could be detrimental to the horse. Beginning in the early 1900s, scientific effort was used to evaluate activity of antiparasitic compoun...
England GC, Clarke KW, Goossens L.The sedative effects of a new alpha 2-adrenoceptor agonist, romifidine, were compared with those of xylazine and detomidine. Five horses were treated with two doses of romifidine (40 micrograms/kg body weight and 80 micrograms/kg body weight), two doses of detomidine (10 micrograms/kg body weight and 20 micrograms/kg body weight) and one dose of xylazine (1 mg/kg body weight) given by intravenous injection using a Latin-square design. The dose of 80 micrograms/kg romifidine appeared equipotent to 1 mg/kg xylazine and 20 micrograms/kg detomidine, although at these doses both xylazine and detomi...
Cemazar M, Tamzali Y, Sersa G, Tozon N, Mir LM, Miklavcic D, Lowe R, Teissie J.Electropermeabilization is a method that uses electric field pulses to induce an electrically mediated reorganization of the plasma membrane of cells. Electrochemotherapy combines local or systemic administration of chemotherapeutic drugs such as bleomycin or cisplatin that have poor membrane permeability with electropermeabilization by direct application of electric pulses to the tumors. Preclinical studies have demonstrated excellent antitumor effectiveness of electrochemotherapy on different animal models and various tumor types, minimal toxicity, and safety of the procedure. Based on resul...
