Effect of clodronate on gene expression in the peripheral blood of horses.

There are two FDA-approved bisphosphonate products, clodronate (Osphos®) and tiludronate (Tildren®), for use in horses. It is hypothesized that bisphosphonates can produce analgesic effects and prevent proper healing of microcracks in bone. Therefore, bisphosphonate use is banned in racehorses.

Pharmacokinetics and metabolism of lidocaine HCl 2% with epinephrine in horses following a palmar digital nerve block.

Background: Lidocaine is a local anesthetic that is sometimes administered in combination with epinephrine. The addition of epinephrine increases the time lidocaine remains at the site of administration, thus prolonging the duration of effect. Due to their potential to prevent the visual detection of lameness, the administration of local anesthetics is strictly regulated in performance and racehorses.

() -associated disease, epiploic foramen entrapment, and gastric rupture in a Thoroughbred racehorse: case report and literature review.

Epiploic foramen entrapment (EFE) is a common cause of small intestinal colic in horses and may lead to intestinal strangulation. Strangulating intestinal obstruction impairs the gastrointestinal outflow and can lead to secondary gastric rupture and endotoxemia. can cause enterotyphlocolitis with colic in horses of all ages, and the process is commonly referred to as -associated disease (CDAD).

Clodronate detection and effects on markers of bone resorption are prolonged following a single administration to horses.

Background: Clodronate is a potent antiresorptive agent labelled for use in horses over 4 years of age, for the treatment of navicular syndrome. Concerns regarding the extra-label use of clodronate in equine athletes, such as racehorses, have been raised as inhibition of osteoclast activity by clodronate has been postulated to interfere with normal bone healing, which is imperative to the repair of microfractures. The paucity of data describing the long-term pharmacokinetics of clodronate and effects on biomarkers of bone resorption necessitates further study.

An exercise-inducible metabolite that suppresses feeding and obesity.

Exercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases. However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear. Here we show that exercise stimulates the production of N-lactoyl-phenylalanine (Lac-Phe), a blood-borne signalling metabolite that suppresses feeding and obesity.

Transcriptomic Markers of Recombinant Human Erythropoietin Micro-Dosing in Thoroughbred Horses.

Recombinant human erythropoietin (rHuEPO) is a well-known performance enhancing drug in human athletes, and there is anecdotal evidence of it being used in horse racing for the same purpose. rHuEPO, like endogenous EPO, increases arterial oxygen content and thus aerobic power. Micro-doping, or injecting smaller doses over a longer period of time, has become an important concern in both human and equine athletics since it is more difficult to detect.

Detection and residence time of bisphosphonates in bone of horses.

Bisphosphonates are potent anti-resorptive agents that have the potential to adversely affect bone healing in equine athletes, and normal bone adaption in young racehorses. A concern exists that bisphosphonate inhibition of normal bone metabolism could lead to increased bone fractures during high-intensity exercise. We found only a single report describing concentrations of tiludronate in the bone of horses, and no studies describing clodronate.

Detection of Methylphenidate in Equine Hair Using Liquid Chromatography-High-Resolution Mass Spectrometry.

Methylphenidate is a powerful central nervous system stimulant with a high potential for abuse in horse racing. The detection of methylphenidate use is of interest to horse racing authorities for both prior to and during competition. The use of hair as an alternative sampling matrix for equine anti-doping has increased as the number of detectable compounds has expanded.

Detection and confirmation of zilpaterol in equine hair using liquid chromatography-mass spectrometry.

Zilpaterol is a β -adrenergic agonist and a repartitioning agent that has a high potential for abuse in equine performance athletes. Analysis of zilpaterol in hair is an alternative sampling matrix that extends detection time periods beyond those found in urine or blood samples. Our laboratory has been screening for zilpaterol in hair for many years and recently detected and confirmed its presence in official samples.

Pharmacokinetics of transdermal flunixin meglumine and effects on biomarkers of inflammation in horses.

Flunixin meglumine is a highly efficacious nonsteroidal anti-inflammatory drug commonly used in equine medicine and especially in performance horses. Recently, a new transdermal flunixin meglumine product has been approved for use in cattle. Although not currently approved for use in the horse, the convenience of this product may prove appealing for use in horses, warranting study.

Sudden death caused by spinal cord injury associated with vertebral fractures and fetlock failure in a Thoroughbred racehorse.

The most prevalent causes of death in racehorses are musculoskeletal injuries, causing ~83% of deaths within the racing industry in California and elsewhere. The vast majority of these injuries have preexisting lesions that predispose to fatal injury. A 4-y-old Thoroughbred colt suffered an acute suspensory apparatus failure, including biaxial proximal sesamoid bone fractures of the right front fetlock, causing loss of support of the fetlock joint and consequent fall with fractures of the cervical and sacral spine.

Expression of select mRNA in Thoroughbreds with catastrophic racing injuries.

Background: The ability to identify horses at risk for catastrophic injuries continues to be a pressing issue for the racing industry, especially given recent events in North America.

Objectives: Since most catastrophic injuries occur in areas of existing pathology and this pathology is likely to elicit an inflammatory response, it was hypothesised that analysis of messenger RNA (mRNA) expression would detect significant changes in select genes in horses at risk for a catastrophic injury.

Study Design: Prospective cohort study.

Characteristics of complete tibial fractures in California racehorses.

Background: Tibial fractures cause ~3% of racehorse deaths. Pre-existing stress fractures have been associated with multiple racing and training fractures, but not complete tibial fractures.

Objectives: To describe racehorse tibial fractures and compare signalment and exercise histories of affected and control racehorses.

Identification and characterization of the enzymes responsible for the metabolism of the non-steroidal anti-inflammatory drugs, flunixin meglumine and phenylbutazone, in horses.

The in vivo metabolism and pharmacokinetics of flunixin meglumine and phenylbutazone have been extensively characterized; however, there are no published reports describing the in vitro metabolism, specifically the enzymes responsible for the biotransformation of these compounds in horses. Due to their widespread use and, therefore, increased potential for drug-drug interactions and widespread differences in drug disposition, this study aims to build on the limited current knowledge regarding P450-mediated metabolism in horses. Drugs were incubated with equine liver microsomes and a panel of recombinant equine P450s.

Physiologic effects of furosemide in combination with water restriction when administered at 4 and 24 hours prior to high-intensity treadmill training.

Although controversial, due to its reported effectiveness in attenuating bleeding associated with exercise-induced pulmonary hemorrhage (EIPH), furosemide is currently a permitted race day medication in most North American racing jurisdictions. The objective of this study was to assess the efficacy of furosemide in reducing the presence and severity of EIPH when administered 24 hr prior to strenuous treadmill exercise. Eight exercised Thoroughbred horses received saline or 250 mg of furosemide either 4 or 24 hr prior to high-speed treadmill exercise in a balanced 3-way cross-over design.

Serum concentrations, pharmacokinetic/pharmacodynamic modeling, and effects of dexamethasone on inflammatory mediators following intravenous and oral administration to exercised horses.

Corticosteroids are potent anti-inflammatory drugs and as such are commonly administered to performance and racehorses. The objectives of the current study were to describe blood and urine concentrations and the pharmacokinetics and effects on cortisol and inflammatory mediator concentrations, following intravenous and oral administration to 12 exercised horses. Horses received an intravenous administration of 40 mg of dexamethasone sodium phosphate and 20 mg of dexamethasone tablets with a 4 week washout in between administrations.

Pharmacokinetics and anti-inflammatory effects of flunixin meglumine as a sole agent and in combination with phenylbutazone in exercised Thoroughbred horses.

Background: Flunixin meglumine (FM) and phenylbutazone (PBZ) are potent anti-inflammatory agents and as such their potential to mask injuries that would otherwise keep a horse from training or racing is concerning. A common practice in racetrack medicine in the USA is to administer the two drugs within close proximity (24 hours apart) of each other, raising the concern of pharmacokinetic interactions and enhanced anti-inflammatory effects.

Objectives: Describe the pharmacokinetics and effects of PBZ on the clearance of FM when administered in close proximity as well as effects on inflammatory mediators.

Detection, pharmacokinetics, and selected pharmacodynamic effects of methamphetamine following a single transmucosal and intravenous administration to exercised Thoroughbred horses.

Methamphetamine is a central and peripheral nervous system stimulant. There is only a single study that describes exposure to and disposition of this compound in horses. The potential for abuse and inadvertent exposure in equine athletes along with the limited data available necessitates further study.

Phenylbutazone blood and urine concentrations, pharmacokinetics, and effects on biomarkers of inflammation in horses following intravenous and oral administration of clinical doses.

Phenylbutazone (PBZ) is a potent mon-steroidal anti-inflammatory drug used commonly in performance horses. The objectives of the current study were to describe blood and urine concentrations and the pharmacokinetics of PBZ and its metabolites following intravenous (IV) and oral administration and to describe the duration of pharmacodynamic effect. To that end, 17 horses received an IV administration and 18 horses an oral administration of 2 g of PBZ.

Prospective pre- and post-race evaluation of biochemical, electrophysiologic, and echocardiographic indices in 30 racing thoroughbred horses that received furosemide.

Background: Exercise induced cardiac fatigue (EICF) and cardiac dysrhythmias are well described conditions identified in high-level human athletes that increase in frequency with intensity and duration of exercise. Identification of these conditions requires an understanding of normal pre- and post-race cardiac assessment values. The objectives of this study were to (1) characterize selected indices of cardiac function, electrophysiologic parameters, and biochemical markers of heart dysfunction prior to and immediately after high level racing in Thoroughbred horses receiving furosemide; and (2) create pre- and post-race reference values in order to make recommendations on possible screening practices for this population in the future.

Retrospective study of fatal pneumonia in racehorses.

Respiratory diseases have a major impact on racehorses in training and are often cited as the second most common reason of horses failing to perform. Cases were submitted by the California Horse Racing Board to the California Animal Health and Food Safety laboratory for postmortem examination between January 1, 2005 and December 31, 2014. We determined the demographics of racehorses with fatal pneumonia, characterized the pathologic findings in animals with a postmortem diagnosis of respiratory infection, and determined the most significant pathogens associated with lower respiratory tract disease.

Pharmacokinetics and pharmacodynamics of meldonium in exercised thoroughbred horses.

Although developed as a therapeutic medication, meldonium has found widespread use in human sports and was recently added to the World Anti-Doping Agency's list of prohibited substances. Its reported abuse potential in human sports has led to concern by regulatory authorities about the possible misuse of meldonium in equine athletics. The potential abuse in equine athletes along with the limited data available regarding the pharmacokinetics and pharmacodynamics of meldonium in horses necessitates further study.

Interlaboratory trial for the measurement of total cobalt in equine urine and plasma by ICP-MS.

Cobalt is an essential mineral micronutrient and is regularly present in equine nutritional and feed supplements. Therefore, cobalt is naturally present at low concentrations in biological samples. The administration of cobalt chloride is considered to be blood doping and is thus prohibited.

Diagnostic approach to catastrophic musculoskeletal injuries in racehorses.

Catastrophic musculoskeletal injuries are the most common cause of euthanasia or spontaneous death in racehorses, and the most common cause of jockey falls with potential for serious human injury. Horses are predisposed to the vast majority of these injuries by preexisting lesions that can be prevented by early diagnosis and adequate bone injury management. A thorough examination of the musculoskeletal system in racehorses often determines the cause of these injuries and generates data to develop injury prevention strategies.