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.
Macias A, Delvescovo B, Donaldson SF, Divers TJ, Donnelly CG.Ursodeoxycholic acid (UDCA), a secondary bile acid (BA) with therapeutic applications, is standard therapy for cholestatic hepatopathies in humans. In recent years, its use has been increasingly explored in equine medicine for similar indications. Pharmacokinetic data for UDCA in horses are currently lacking. This study aimed to describe the pharmacokinetic parameters following a single intragastric administration of 15 mg/kg in nine healthy, fasted horses and to characterize the changes in their BA profiles. Plasma concentrations of UDCA were measured at specific time points using liquid ch...
Morales CJ, Sykes BW, McKemie DS, Kass PH, Knych HK.Current treatment options for equine gastric ulcer syndrome (EGUS), such as omeprazole-a proton pump inhibitor (PPI)-have notable limitations, including the need for administration on an empty stomach. Potassium-competitive acid blockers (P-CABs), such as vonoprazan, are a newer class of acid suppressants that offer several advantages over PPIs in humans and may provide similar benefits in horses. Objective: To describe the pharmacokinetics and effect of a single oral dose of vonoprazan on intragastric pH in horses. We hypothesised that vonoprazan would follow linear kinetics across the doses ...
Bombardi C, Salamanca G, Tagliavia C, Grandis A, Zamith Cunha R, Gramenzi A, De Silva M, Zannoni A, Chiocchetti R.The amygdala is composed of several nuclei, including the lateral nucleus which is the main receiving area for the input from cortical and subcortical brain regions. It mediates fear, anxiety, stress, and pain across species. Evidence suggests that the endocannabinoid system may be a promising target for modulating these processes. Cannabinoid and cannabinoid-related receptors have been identified in the amygdala of rodents, carnivores, and humans, but not in horses. This study aimed to investigate the gene expression of cannabinoid receptors 1 (CB1R) and 2 (CB2R), transient receptor potential...
Mountessou BYG, Mouafon IL, Maharjan R, Tchamgoue J, Tiani GLM, Dibouloul P, Choudhary MI, Kouam SF.Four previously undescribed phenazine-derived pigments (1-4), along with seventeen known compounds, were isolated from a strain cultured on solid rice medium. Structural elucidation of the new compounds was achieved through extensive spectroscopic analysis, while known compounds were identified by comparison with literature data. The antimicrobial and cytotoxic activities of the isolated compounds were assessed. Compounds 2, 5, and 11 exhibited weak antifungal activity against at 200 μM, while compounds 5, 6, 11, 12, 15, and 20 demonstrated moderate antibacterial effects against at the sam...
Bacon EK, Finno CJ, Donnelly CG, Haase B, Knych HK, Velie BD.Clinical assessments of equine sedation typically rely on subjective observations, the accuracy of which is paramount to the safety of equine veterinary procedures. Methods: To assess the degree in which subjective clinical sedative evaluations reflect pharmacokinetic measurements of equine drug metabolism, xylazine hydrochloride, an alpha-2 adrenoreceptor agonist, was administered to 36 horses of varying breed and age at a dosage of 0.5 mg/kg body weight. Subjective clinical parameters were scored at 5-, 15-, 30-, 45- and 60-minutes post xylazine administration and included responsiveness to ...
Jantunen N, Raekallio M, Obrochta B, Tapio H, Gracia Calvo L, Rivera Pöyhönen R, Hagman K, Karikoski N.To assess the effects of a 4 hour detomidine constant rate infusion (CRI) with and without a vatinoxan CRI on energy metabolism and urine composition. Methods: Randomized, blinded, crossover study. Methods: Eight Finnhorses, 587 (550-620) kg [median (range)] and 13 (4-16) years old. Methods: Horses were administered an intravenous (IV) detomidine loading dose (0.01 mg kg) followed by 240 minutes CRI (0.015 mg kg hour) (DET) and the same detomidine protocol combined with an IV vatinoxan loading dose (0.15 mg kg) and CRI (0.05 mg kg hour) (DET+VAT). Blood samples for glucose, insulin, non-esteri...
Tarillion M, Hertzsch R, Richter A.Since 28.01.2022, veterinary medicinal products must be used in accordance with the conditions of authorization (Regulation (EU) 2019/6, Article 106). This entails further restrictions on therapeutic freedom, e. g., with regard to dose deviations. To date, there is no data available in equine medicine on the scope of off-label use as any use deviating from the expert information for antibiotics, on the basis of which the feasibility of implementing the new regulations in Germany can be assessed.To collect data on the off-label use of antibiotics, a Germany-wide anonymous online survey was th...
Bazzano M, Laus F, Cerquetella M, Spaterna A, Marchegiani A.Phytocannabinoids have the potential to lower intraocular pressure in both normal and glaucomatous eyes and they have been tested in different animal species, but not in the horse. The present paper describes the tonometric curve of healthy adult Italian Saddle horses after oral administration of cannabidiol oil (CBD). Methods: CBD 20% was administered orally (oily solution) at the dose of 1 mg/kg to 8 adult horses and intraocular pressure (IOP) was evaluated by tonometric curve. Data were then compared to those of the same horses obtained the day before (blank) CBD administration. Results: ...
Sobhy A, Nomir AG, Hamed MA, Abumandour MMA, El-Kammar M.The current study was prepared to compare the efficacy of xylazine-lidocaine HCl and detomidine-lidocaine HCl following caudal epidural injection in horses, evaluating sedation, analgesia, physiological parameters, and hemato-biochemical values. This study was applied to six healthy adult horses (300-350 kg, > 4 years of age). The horses were randomly divided into two equal groups. Group 1 (seven horses) received xylazine (0.17 mg/kg bwt) + lidocaine HCl (0.06 mg/kg bwt), while Group 2 received detomidine (0.03 mg/kg bwt) + lidocaine HCl (0.06 mg/kg bwt) via caudal epidural inje...
El-Ghaly W, El Kamli T, Gongbe AMA, Zaari Lambarki L, El Hamdani M, Lahkak FE, Al Idrissi N, Benmoussa A, Balouch L, Bakkali F, Saffaj T, Jhilal F.The quantification of banned substances in equine antidoping control, especially in racehorse urine, necessitates robust analytical methods with high detection levels due to the extremely low concentrations of the target substances and the significant impact of minor variations on doping test results. Reliable quantification is important for substances near regulatory thresholds, which, if exceeded, are prohibited. This study presents the development and validation of a bioanalytical UHPLC-HRMS method for quantifying doping substances in equine urine, including diazepam and acepromazine with a...
Bardhi A, Barbarossa A, Joubert A, Gehring R, Lambertini C, Romagnoli N.Dried blood spot (DBS) sampling has emerged as a promising microsampling technique in biomedical and clinical research, offering advantages such as reduced invasiveness, minimal blood volume requirements, and enhanced analyte stability. Although well established in human medicine for neonatal screening and diagnostic applications, its potential in veterinary pharmacology remains underexplored. This study investigated the feasibility of using DBS samples to quantify anesthetic agents-ketamine and medetomidine in cats and lidocaine in horses-during routine surgical procedures at a veterinary tea...
Cardinaux EM, Oltmanns H, Beineke A, Meißner J, Geburek F.Flexural limb deformities are a widespread condition in foals. Oxytetracycline is a common conservative treatment option with relaxing effects on the muscle-tendon-unit, potentially mediated through a matrix-metalloproteinase (MMP)-inhibitor mechanism. Its high therapeutic dose for this indication, potential negative side effects, and the guidelines for prudent use of antimicrobials make investigating alternatives desirable. In this study, the influence of substances with potentially similar mechanisms of action, however without antimicrobial properties, on viability and proliferation of juven...
Buzelato Carli I, Fielding L.Many horses receive firocoxib over multiple years, and studies evaluating hematologic and biochemical values in these animals are lacking. Objective: To describe the hematologic and biochemical values of horses receiving long-term firocoxib. Methods: A total of 79 horses receiving long-term firocoxib and 153 horses not receiving long-term firocoxib and not presenting for a specific medical problem. Methods: Retrospective study comparing horses receiving firocoxib (F group) and no firocoxib (NF group). Signalment, hematologic, and biochemical values were compared between the two groups. Simple ...
Bianchi D, Santos RRD, Peleja PL, de Sousa ABB, da Silva Evangelista M, de Almeida Júnior JS, Barata LES, Moraes WP, Minervino AHH. (tropical horse tick) is a tick species commonly found parasitizing horses and other equids in the Amazon region, causing economic losses. Currently, tick control is based on chemical acaricides, usually in a power formulation for topical use. However, its indiscriminate use results in the emergence of resistant tick lineages. Several plant compounds have been tested for their acaricide activity. In the Amazon, several plants are used for oil extraction, resulting in the production of solid residue (waste) that may contain chemical molecules with biological activities. Thus, we aimed to test ...
Chambers A.All anti-doping programmes face financial constraints and monitoring trends in medication use or abuse in a population of racehorses can be difficult and expensive. Obtaining biological samples is the primary method of anti-doping control in individual horses or stables of horses but can be invasive and expensive. Another important practice of anti-doping control has been the confiscation of used and filled syringes by regulators for individual forensic analysis. Pooled samples testing involves the testing of multiple individual samples together as one composite sample. This pooled sample appr...
Hallman IAM, Raekallio MR, Karikoski NP.Vatinoxan is a peripherally acting alpha2-adrenoceptor antagonist used in veterinary medicine to attenuate the side effects of alpha2-adrenoceptor agonists. Vatinoxan also increases insulin response and reduces blood glucose (BG) after intravenous glucose in other species. The aim of this study was to investigate the effects of vatinoxan on BG and insulin concentration in horses after intravenous glucose. The design was an assessor-blind cross-over study. Nine horses were assigned to intravenous vatinoxan (0.2 mg/kg; VAT) or saline (SAL). Horses were administered an intravenous glucose bolus (...
Munsterman AS, Dias Moreira AS, Kottwitz J.To evaluate the effects of detomidine on equine intestinal slow-wave activity and frequency distribution measured by electrointestinography (EIG). Methods: Prospective, experimental study. Methods: University teaching hospital. Methods: A convenience sample of twelve 7- to 21-year-old clinically normal horses. Methods: Horses were randomly assigned to saline control (four horses) or detomidine treatment (eight). After obtaining a 30-min baseline EIG, a saline or detomidine bolus was administered, followed by a constant rate infusion, and another EIG was recorded. Ultrasonographic examinations ...
Usuga A, Vergara AK, Tobón MC, Vargas S, Rojano B, Restrepo G.Maintaining sperm energy homeostasis in vitro is very important to improve the efficacy of stallion sperm preservation. Equine spermatozoa preferentially utilize oxidative phosphorylation over glycolysis to generate ATP. Metformin and rosiglitazone are antidiabetic compounds that enhances metabolic flexibility and glucose utilization. The aim of this study was to evaluate metformin and rosiglitazone supplementation of the freezing medium on quality and oxidative status of thawed stallion semen. A total of 15 ejaculates from five horses were collected and supplemented before freezing with metfo...
Bacon EK, Donnelly CG, Finno CJ, Haase B, Velie BD.Multimodal analgesic administration is a promising strategy for mitigating side effects typically associated with analgesia; nevertheless, variation in analgesic effectiveness still poses a considerable safety concern for both horses and veterinarians. Pharmacogenomic studies have started delving into genetic influences on varying drug effectiveness and related side effects. However, current findings have narrow implications and are limited in their ability to individualize analgesic dosages in horses. Hydromorphone and detomidine were administered to a cohort of 48 horses at standardized time...
Kazama T, Hector RC, Hess AM, Rezende ML.To determine the cardiopulmonary effects of oral trazodone before isoflurane anesthesia in systemically healthy horses. Unassigned: 12 horses donated for euthanasia (from August 2022 through June 2023) due to conditions unrelated to the cardiovascular system were included in this prospective, randomized, controlled trial. Horses were assigned to receive oral trazodone (6 mg/kg; n = 7) or corn syrup (n = 5) 1 hour before xylazine (1 mg/kg, IV) sedation, ketamine (2.2 mg/kg, IV) and propofol (0.7 mg/kg, IV) induction, and anesthetic maintenance with inhaled isoflurane (target 1.6% expired) for 7...
Obrochta B, Tapio H, Raekallio M, Gracia Calvo LA, Pöyhönen RR, Hagman K, Jantunen N, Karikoski N.Sedation in horses is typically achieved using alpha-2 adrenoceptor agonists, although their use is associated with multiple side effects. A peripheral alpha-2 adrenoceptor antagonist, vatinoxan, can alleviate many of these. Objective: To evaluate the effects of vatinoxan infusion on gastrointestinal motility, sedation, and antinociception in horses sedated with detomidine infusion. Methods: Randomised, blinded cross-over in vivo experiments. Methods: Eight horses were given two 4-h infusions: detomidine (0.01 mg/kg + 0.015 mg/kg/h IV) (DET) and a combination of detomidine and vatinoxa...
Kintz P, Baudry M, Gheddar L.Trazodone, a medicine registered for human, is a serotonin agonist-antagonist. At low dose, the drug is sedative due to its antagonist properties. At high dose, it is an agonist with anxiolytic and antidepressant actions. Trazodone can be administered to the horse to reduce anxiety. However, according to the anti-doping rules for horses, the presence of trazodone in blood or urine is considered as a violation which will produce a suspension of both the athlete and the horse as the drug is listed banned on the International Federation of Horseracing Authorities prohibited substances list. As a ...
Gorenberg EB, Slack J, Stefanovski D, Theiss D, Hopster K.Dobutamine is a first-line therapy for hypotension in anaesthetised horses, but the effects on haemodynamic parameters in standing and anaesthetised horses are not well studied. Objective: To investigate the effects of dobutamine in escalating dosages on haemodynamic performance in awake and anaesthetised horses. Methods: Randomised cross-over experimental study. Methods: Six healthy adult horses were enrolled, including both standing and isoflurane-anaesthetised experiments with 1-week washout. Heart rate, mean arterial pressure (MAP), central venous pressure, pulmonary arterial pressure, and...
Oyaneder L, Lagos N, Dörner C.The present study was conducted to evaluate the safety and the long-lasting anesthetic properties of Neosaxitoxin (NeoSTX) when injected into the intercoccygeal space in standing horses. A group of eighteen (n = 18) healthy client-owned mature crossbreed horses were enrolled in this study. Caudal epidural injection was ascertained by two methods, the "hanging drop" technique and radiographs. Horses were allocated into three groups (n = 6) each group receiving different dosages of NeoSTX. To assess the onset of action and duration of anesthesia, six horses received 20 μg in 2 mL, six 20Â...
Yu Y, Wang J, Ruan L, Chen L, Khan MZ, You A, Wang C, Li L, Ren H, Wang T, Liu W.Equid alphaherpesvirus type 8 (EHV-8) is a contagious pathogen that causes reproductive disorders, respiratory diseases, and viral encephalitis in equids, resulting in significant economic losses for the global horse and donkey industries. Currently, there are no approved antiviral drugs or vaccines available for EHV-8 control. In this study, we investigated the antiviral efficacy of celastrol against EHV-8 both in vitro and in vivo. Our results demonstrated that celastrol significantly inhibited EHV-8 infection in Rabbit kidney (RK-13) and equine dermal cells (NBL-6) in a dose-dependent manne...
Kemp KL, Yuen NKY, Skinner JE, Bertin FR.Phenylbutazone is prescribed to manage pain caused by hyperinsulinemia-associated laminitis. Phenylbutazone reduces glucose and insulin concentrations in horses with insulin dysregulation (ID) but the underlying mechanism of action is unknown. Objective: Investigate the effect of phenylbutazone on tissue insulin sensitivity in horses. It is hypothesized that the reduced glucose and insulin concentrations in horses with ID receiving phenylbutazone are mediated by a higher tissue insulin sensitivity. Methods: Fifteen light breed horses, including seven with ID. Methods: Randomized cross-over stu...
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...
Li VL, He Y, Contrepois K, Liu H, Kim JT, Wiggenhorn AL, Tanzo JT, Tung AS, Lyu X, Zushin PH, Jansen RS, Michael B, Loh KY, Yang AC, Carl CS....Exercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases1-5. However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear6. Here we show that exercise stimulates the production of N-lactoyl-phenylalanine (Lac-Phe), a blood-borne signalling metabolite that suppresses feeding and obesity. The biosynthesis of Lac-Phe from lactate and phenylalanine occurs in CNDP2+ cells, including macrophages, monocytes and other immune and epithelial cells localized to diverse organs. In diet-induced obese mice,...
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...
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 ...
Schnellmann C, Gerber V, Rossano A, Jaquier V, Panchaud Y, Doherr MG, Thomann A, Straub R, Perreten V.Because of the frequency of multiple antibiotic resistance, Staphylococcus species often represent a challenge in incisional infections of horses undergoing colic surgery. To investigate the evolution of antibiotic resistance patterns before and after preventative peri- and postoperative penicillin treatment, staphylococci were isolated from skin and wound samples at different times during hospitalization. Most staphylococci were normal skin commensals and belonged to the common coagulase-negative group. In some cases they turned out to be opportunistic pathogens present in wound infections. M...
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...
Schmoldt A, Benthe HF, Haberland G, Jallon JM, Risler Y, Iwatsubo M, Karuzina II, Bachmanova GI, Kuznetsova GP, Izotov MV, Archakov AI, Kröger H....It has been found that NADPH-dependent hydroxylation of dimethylaniline, aniline, p- and o-nitroanisol and lipid peroxidation is inhibited by the tyrosine-copper (II) complex (low molecular weight analog of superoxide dismutase), which is indicative of a possibility of superoxide radicals formation in these reactions. The inhibition of the above-mentioned reactions with Tyr2-Cu2+ is less pronounced or absent, if cumole hydroperoxide is used as cosubstrate instead of NADPH. Differences in the Tyr2-Cu2+ complex effects on the cumule hydroperoxide-dependent xenobiotics hydroxylation and lipid per...
Goodrich LR, Nixon AJ.The medical treatment of osteoarthritis (OA) in the horse is one of the most utilized therapeutic regimens in the equine practice. It is important to understand the anatomy of synovial joints and the pathophysiology of the disease process to treat OA adequately. Once a thorough understanding of the disease process is comprehended the proper combination of systemic nonsteroidal anti-inflammatory drugs (NSAIDs), intraarticular steroids, viscosupplementation and chondroprotectants can be used to treat the disease and inhibit further progression of degenerative changes to the cartilage surface. Th...
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...
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.
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...
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 ...
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...
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...
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...
Dowling BA, Dart AJ, Hodgson DR, Smith RK.The superficial digital flexor tendon (SDFT) is an elastic structure that during maximal exercise appears to operate close to its functional limits. The biomechanical and biochemical responses to exercise, injury, and healing are still poorly understood but ongoing research is providing valuable new information which is addressed in this review. It appears that the SDFT matures early, after which time it has limited ability to adapt to stress and undergoes progressive degeneration. Focal hypocellularity, collagen fibril degeneration, selective fibril loading and alterations in the noncollageno...
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...
Haugaard MM, Hesselkilde EZ, Pehrson S, Carstensen H, Flethøj M, Præstegaard KF, Sørensen US, Diness JG, Grunnet M, Buhl R, Jespersen T.Small-conductance calcium-activated potassium (SK) channels have been found to play an important role in atrial repolarization and atrial fibrillation (AF). Objective: The purpose of this study was to investigate the existence and functional role of SK channels in the equine heart. Methods: Cardiac biopsies were analyzed to investigate the expression level of the most prominent cardiac ion channels, with special focus on SK channels, in the equine heart. Subcellular distribution of SK isoform 2 (SK2) was assessed by immunohistochemistry and confocal microscopy. The electrophysiologic and anti-...
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...
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 ...
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...
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...
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...
DrugCentral monitors new drug approvals and standardizes drug information. The current update contains 285 drugs (131 for human use). New additions include: (i) the integration of veterinary drugs (154 for animal use only), (ii) the addition of 66 documented off-label uses and iii) the identification of adverse drug events from pharmacovigilance data for pediatric and geriatric patients. Additional enhancements include chemical substructure searching using SMILES and 'Target Cards' based on UniProt accession codes. Statistics of interests include the following: (i) 60% of the covered drugs are...
Higgins AJ, Lees P.Arachidonic acid is a polyunsaturated fatty acid covalently bound in esterified form in the cell membranes of most body cells. Following irritation or injury, arachidonic acid is released and oxygenated by enzyme systems leading to the formation of an important group of inflammatory mediators, the eicosanoids. It is now recognised that eicosanoid release is fundamental to the inflammatory process. For example, the prostaglandins and other prostanoids, products of the cyclooxygenase enzyme pathway, have potent inflammatory properties and prostaglandin E2 is readily detectable in equine acute in...
Beretta C, Garavaglia G, Cavalli M.We report on the inhibitory activity of the NSAIDs meloxicam, carprofen, phenylbutazone and flunixin, on blood cyclooxygenases in the horse using in vitro enzyme-linked assays. As expected, comparison of IC50 indicated that meloxicam and carprofen are more selective inhibitors of COX-2 than phenylbutazone and flunixin; meloxicam was the most advantageous for horses of four NSAIDs examined. However at IC80, phenylbutazone (+134.4%) and flunixin (+29.7%) had greater COX-2 selectivity than at IC50, and meloxicam (-41.2%) and carprofen (-12.9%) had lower COX-2 selectivity than at IC50. We therefor...
Brideau C, Van Staden C, Chan CC.To determine potency and selectivity of nonsteroidal anti-inflammatory drugs (NSAID) and cyclooxygenase- (COX-) specific inhibitors in whole blood from horses, dogs, and cats. Methods: Blood samples from 30 healthy horses, 48 healthy dogs, and 9 healthy cats. Methods: Activities of COX-1 and COX-2 were determined by measuring coagulation-induced thromboxane and lipopolysaccharide-induced prostaglandin E2 concentrations, respectively, in whole blood with and without the addition of various concentrations of phenylbutazone, flunixin meglumine, ketoprofen, diclofenac, indomethacin, meloxicam, car...
