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Topic:Anti-inflammatory
Anti-inflammatory agents are substances used to reduce inflammation in horses, often employed in the management of various equine conditions. These agents can be categorized into non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, among others. NSAIDs, such as phenylbutazone and flunixin meglumine, work by inhibiting cyclooxygenase enzymes, which play a role in the inflammatory process. Corticosteroids, like dexamethasone, modulate the immune response and reduce inflammation through their effects on gene expression. The use of anti-inflammatory agents is common in equine veterinary practice to alleviate pain and improve the quality of life in horses suffering from musculoskeletal disorders, colic, and other inflammatory conditions. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacology, efficacy, and safety of anti-inflammatory agents in equine medicine.
Distribution of CCR3 mRNA expression in horse tissues. CCL11 (also known as eotaxin) is a very potent and selective mediator of eosinophil migration which exerts its effects through its receptor, CCR3. In this study we report the cloning of an equine CCR3 cDNA sequence and investigation of the localization of CCR3 mRNA expression in horse tissues. Equine CCR3 displayed high levels of sequence identity with CCR3 sequences in other species. RT-PCR analysis revealed the expression of CCR3 in colon, lung and spleen of normal horses. In situ hybridisation experiments indicated that expression of CCR3 mRNA in colon was predominantly in eosinophils and t...
Use of accelerating solvent extraction for detecting non-steroidal anti-inflammatory drugs in horse feces. Feces are a possible medium to be used for horse doping control. Efficient methods for detecting drugs in feces collected from various animals are routinely applied in institutes of food safety in Belgium. We have already tested whether they are applicable to horse feces. In this report, accelerated solvent extraction (ASE), an efficient method for extracting compounds from solid material, has been tested. ASE has been used to replace the diethyl ether liquid-liquid extraction step present in the method initially set up. This technique has been optimized for detecting several non-steroidal ant...
The effect of aerosolized and intravenously administered clenbuterol and aerosolized fluticasone propionate on horses challenged with Aspergillus fumigatus antigen. Beta-agonists have been shown to display anti-inflammatory properties in several experimental models. The aim of this study was to investigate the anti-inflammatory properties of clenbuterol (CB), administered either intravenously or by aerosol, in comparison with fluticasone propionate (FP) in recurrent airway obstruction (RAO)-susceptible horses. Eight horses, of which five were known to be susceptible to RAO, underwent an inhalation challenge with Aspergillus fumigatus (AF) antigen and were treated with CB intravenously, CB by aerosol, or FP by aerosol. Twenty-four hours after the challenge...
Comparative pharmacokinetics of meloxicam in clinically normal horses and donkeys. To determine the disposition of a bolus of meloxicam (administered IV) in horses and donkeys (Equus asinus) and compare the relative pharmacokinetic variables between the species. Methods: 5 clinically normal horses and 5 clinically normal donkeys. Methods: Blood samples were collected before and after IV administration of a bolus of meloxicam (0.6 mg/kg). Serum meloxicam concentrations were determined in triplicate via high-performance liquid chromatography. The serum concentration-time curve for each horse and donkey was analyzed separately to estimate standard noncompartmental pharmacokinet...
The anti-inflammatory effects of IV administered clenbuterol in horses with recurrent airway obstruction. Cyclic AMP elevating agents have been shown to exhibit anti-inflammatory properties in addition to functions such as bronchodilation. The aim of this study was to investigate this dual action of clenbuterol (CB; Ventipulmin) on horses affected with recurrent airway obstruction (RAO). Seven RAO susceptible horses received inhalation challenges with aerosolised lipopolysaccharide (LPS), hay dust suspension (HDS) and Aspergillus fumigatus antigen (AF) with and without prior treatment with intravenous CB. Data showed that CB exerted significant beneficial effects on lung function, total cell count...
Effect of beclomethasone dipropionate and dexamethasone isonicotinate on lung function, bronchoalveolar lavage fluid cytology, and transcription factor expression in airways of horses with recurrent airway obstruction. Glucocorticoid (GC) therapy is recognized to be effective for the treatment of recurrent airway obstruction (RAO) in horses. Anti-inflammatory properties of GC are thought to be mediated by suppression of inflammatory gene expression via inhibition of transcription factors such as nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). The purpose of this study was to evaluate the effect of low-dose inhaled beclomethasone dipropionate and injectable dexamethasone 21-isonicotinate on clinical signs, pulmonary function, airway cytology, and activity of NF-kappaB and AP-1 in bronchial c...
Effects of phenylbutazone alone or in combination with flunixin meglumine on blood protein concentrations in horses. To assess effects of treatment with phenylbutazone (PBZ) or a combination of PBZ and flunixin meglumine in horses. Methods: 24 adult horses. Methods: 13 horses received nonsteroidal antiinflammatory drugs (NSAIDs) in a crossover design. Eleven control horses were exposed to similar environmental conditions. Treated horses received PBZ (2.2 mg/kg, PO, q 12 h, for 5 days) and a combination of PBZ and flunixin meglumine (PBZ, 2.2 mg/kg, PO, q 12 h, for 5 days; flunixin meglumine, 1.1 mg/kg, IV, q 12 h, for 5 days). Serum samples were obtained on day 0 (first day of treatment) and day 5, and total...
Severe acute rhabdomyolysis associated with Streptococcus equi infection in four horses. Four Quarter Horses (9 months to 7 years of age) with submandibular lymphadenopathy and firm muscles (palpation of which elicited signs of pain) were evaluated; in general, the horses had a stiff gait, and 3 horses became recumbent. Streptococcus equi was cultured from aspirates of lymph nodes or samples of purulent material collected from the auditory tube diverticula. Once the horses were recumbent, their condition deteriorated rapidly despite aggressive antimicrobial and antiinflammatory treatment, necessitating euthanasia within 24 to 48 hours. One horse did not become recumbent and recove...
Effects of the omega-3 fatty acid, alpha-linolenic acid, on lipopolysaccharide-challenged synovial explants from horses. To determine the effects of pretreatment with alpha-linolenic acid, an omega-3 polyunsaturated fatty acid, on equine synovial explants challenged with lipopolysaccharide (LPS). Methods: 8 mature mixed-breed horses (4 mares and 4 geldings). Methods: Synovial explants were assigned to receive 1 of 7 concentrations of alpha-linolenic acid, ranging from 0 to 300 microg/mL. At each concentration, half of the explants were controls and half were challenged with 0.003 microg of LPS as a model of synovial inflammation. Cell inflammatory response was evaluated by measurement of prostaglandin E2 product...
Chip fractures from the distal lateral trochlear ridge of the talus of a quarter horse gelding: a veterinary medicine clinical report. An eighteen-month old quarter horse gelding was diagnosed with chip fractures from the distal lateral trochlear ridge of the talus. The horse presented with the symptom of persistent synovitis. The diagnosis was based on radiographic evidence. The horse was treated initially with arthroscopic surgery. He was given a non-steroidal anti-inflammatory agent, and a chondroprotective agent to prevent further damage to, and aid in the healing of, the damaged joint.
Elimination of arthritis pain and inflammation for over 2 years with a single 90 min, topical 14% gallium nitrate treatment: case reports and review of actions of gallium III. Arthritis is inflammation in a joint often with joint damage, usually accompanied by pain, swelling and stiffness, resulting from infection, trauma, degenerative changes, metabolic disturbances, autoimmune or other causes. It occurs in various forms, including rheumatoid arthritis, osteoarthritis, bacterial arthritis and gout. Gallium III can inhibit the production of inflammatory cytokines, such as IL-1beta, produced by macrophage-like cells in vitro. A dose-dependent inhibition of IL-1beta and TPA stimulated MMP activity by gallium nitrate at increasing concentrations occurs, demonstrating t...
Treatment strategies for mares with placentitis. Equine placentitis, and resultant preterm labor, are important sources of fetal and neonatal loss. The primary cause of equine placentitis is infection of the placenta with Streptococcus equi subspecies zooepidemicus, which ascends through the caudal reproductive tract. Current treatment protocols for mares affected with placentitis are empirical. This paper reviews treatment approaches for resolving placentitis and preterm labor in both equine and non-equine species. Specific therapies reviewed include antimicrobial, anti-inflammatory, tocolytic, and progestin agents.
Equine endotoxaemia–a state-of-the-art review of therapy. The pathophysiology of endotoxaemia, a leading cause of death in the horse, is beginning to be understood in greater detail. Endotoxin may be absorbed into the systemic circulation in a number of different ways: most commonly the body's normal defense mechanisms are disrupted or bypassed, or the normal clearance mechanisms overwhelmed. Following this wide-spread effects are observed, although the most significant are seen in the cardiovascular system. Fever, arterial hypoxaemia and signs of abdominal pain are also common. With increased understanding of the disease new therapeutic agents have ...
Influence of vedaprofen (Quadrisol) on quality and freezability of stallion semen. The objective of this study was to evaluate the effect of the non-steroidal anti-inflammatory drug (NSAID) vedaprofen (Quadrisol) on quality and freezability of stallion semen. Experiments were performed using 22 Franches Montagnes stallions from the National Stud in Avenches (Switzerland) randomly divided into a control and test group. Vedaprofen was given orally to all stallions of the test group at the recommended therapeutic dose (initial dose of 2mg/kg followed by 1mg/kg body weight every 12h) for 14 days. Control animals received the same amount of carrier substance. During treatment, bl...
COX-1 and COX-2 inhibition in horse blood by phenylbutazone, flunixin, carprofen and meloxicam: an in vitro analysis. 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...
Pharmacokinetics and synovial fluid concentrations of flurbiprofen enantiomers in horses: chiral inversion. Flurbirpofen (FBP), a member of the 2-aryl propionate nonsteroidal anti-inflammatory drug class, has potent anti-inflammatory and analgesic properties. The commercial preparation is a racemic mixture of the R(-) and S(+) enantiomers of FBP. In this study, R(-) and S(+) FBP were used to investigate the metabolic chiral inversion. Each enantiomer was administered separately (0.25 mg/kg) and in a racemic mixture (0.5 mg/kg) intravenously to horses. Plasma and synovial concentration of each enantiomer was determined and the disposition of each was analyzed. After intravenous administration of R(-)...
Modulation of articular chondrocyte activity by pirfenidone. Pirfenidone is under investigation as an anti-inflammatory and anti-fibrotic agent in several organs including lung. Since important features of arthritic conditions include inflammation and long-term damage to articular cartilage, we have investigated whether PD can suppress chondrocyte responses to bacterial lipopolysaccharide (LPS) and interleukin 1 (IL-1); modulators that induce a cascade of inflammatory responses that lead to articular joint tissue damage. PD (0 - 5microM) showed no effect on cell number or viability when incubated with high density primary equine chondrocyte cultures for...
Effects of cyclooxygenase inhibitors flunixin and deracoxib on permeability of ischaemic-injured equine jejunum. Recent studies have shown that flunixin prevented recovery of equine jejunum post ischaemia. However, the use of a purported cyclooxygenase (COX)-2 preferential inhibitor, etodolac, also prevented recovery. These findings may have implications for the use of nonsteroidal anti-inflammatory drugs in colic patients. Objective: To compare the effects of deracoxib, a highly selective canine COX-2 inhibitor, with flunixin on in vitro recovery of ischaemic-injured equine jejunum. Methods: Six horses underwent 2 h jejunal ischaemia, after which mucosa was mounted in Ussing chambers and recovered for 2...
Expression of the cyclooxygenase isoforms in the prodromal stage of black walnut-induced laminitis in horses. To compare the levels of mRNA expression of cycooxygenase (COX)-1 and COX-2 in the digital laminae of normal horses and horses in the developmental stages of laminitis experimentally induced by administration of black walnut extract (BWE). Methods: Samples of mRNA extracted from the digital laminae of 5 control horses and 5 horses at the onset of leukopenia after administration of BWE. Methods: Specimens of laminae were collected from anesthetized horses prior to euthanasia. Expression of COX-1 and COX-2 mRNA in laminae of control and affected horses was evaluated via real-time quantitative po...
Pharmacodynamics and pharmacokinetics of nonsteroidal anti-inflammatory drugs in species of veterinary interest. This review summarises selected aspects of the pharmacokinetics (PK) and pharmacodynamics (PD) of nonsteroidal anti-inflammatory drugs (NSAIDs). It is not intended to be comprehensive, in that it covers neither minor species nor several important aspects of NSAID PD. The limited objective of the review is to summarise those aspects of NSAID PK and PD, which are important to an understanding of PK-PD integration and PK-PD modelling (the subject of the next review in this issue). The general features of NSAID PK are: usually good bioavailability from oral, intramuscular and subcutaneous administ...
Pharmacokinetics of meloxicam in plasma and urine of horses. To determine pharmacokinetic parameters for meloxicam, a nonsteroidal anti-inflammatory drug, in horses. Methods: 8 healthy horses. Methods: In the first phase of the study, horses were administered meloxicam once in accordance with a 2 x 2 crossover design (IV or PO drug administration; horses fed or not fed). The second phase used a multiple-dose regimen (daily oral administration of meloxicam for 14 days), with meloxicam administered at the recommended dosage (0.6 mg/kg). Plasma and urine concentrations of meloxicam were measured by use of validated methods with a limit of quantification of...
Pharmacokinetic-pharmacodynamic relationships and dose response to meloxicam in horses with induced arthritis in the right carpal joint. To determine pharmacokinetic-pharmacodynamic (PK-PD) relationships and dose effects for meloxicam in horses and to propose a suitable dosage for use in clinical studies. Methods: 6 adult horses. Methods: The study was conducted by use of a randomized, Latin-square design. Arthritis was induced in the right carpal joint of each horse by administration of Freund's complete adjuvant. Various dosages of meloxicam (0, 0.25, 0.5, 1.0, and 2.0 mg/kg, IV) were then administered. Validated endpoints including stride length and overall clinical lameness score (scale of 0 to 20) were used to assess the e...
Preferential and non-selective cyclooxygenase inhibitors reduce inflammation during lipopolysaccharide-induced synovitis. Synovitis in horses is frequently treated by administration of non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase isoforms (COX-1 and COX-2). Constitutively expressed COX-1 is involved in physiologic functions such as maintenance of gastric mucosal integrity, whereas COX-2 is up-regulated at sites of inflammation. Thus, COX-2 inhibitors reduce inflammation with reduced gastrointestinal side effects as compared to non-selective COX inhibitors. The objective of the present study was to compare the anti-inflammatory effects of the preferential COX-2 inhibitor etodolac wi...
Effects of flunixin meglumine or etodolac treatment on mucosal recovery of equine jejunum after ischemia. To examine the effects of flunixin meglumine and etodolac treatment on recovery of ischemic-injured equine jejunal mucosa after 18 hours of reperfusion. Methods: 24 horses. Methods: Jejunum was exposed to 2 hours of ischemia during anesthesia. Horses received saline (0.9% NaCl) solution (12 mL, i.v., q 12 h), flunixin meglumine (1.1 mg/kg, i.v., q 12 h), or etodolac (23 mg/kg, i.v., q 12 h). Tissue specimens were obtained from ischemic-injured and nonischemic jejunum immediately after ischemia and 18 hours after recovery from ischemia. Transepithelial electric resistance (TER) and transepithel...
Effect of topical application of diclofenac liposomal suspension on experimentally induced subcutaneous inflammation in horses. To determine whether 1% diclofenac liposomal suspension (DLS) ointment would be absorbed transdermally and attenuate experimentally induced subcutaneous inflammation in horses. Methods: 7 healthy adult horses. Methods: Inflammation was produced by injecting 1% sterile carrageenan into subcutaneously implanted tissue cages 8 hours before (time -8) and at the time of application of test ointment. A crossover design was used. Horses received 1 of 2 treatments (topically administered control or DLS ointments) during 48 hours of carrageenan-induced subcutaneous inflammation. A single application of...
Treatment of peritonitis. In summary, peritonitis in the horse is a potentially life-threatening disease that must be treated promptly and aggressively. Therapy should be aimed at reducing systemic shock and hypovolemia, correction of the primary cause, antibiotic and anti-inflammatory therapy, and abdominal drainage and lavage. The prognosis depends on the ability to diagnose and treat the underlying cause and prevent the development of complications. Mortality rates can be as high as 59.7%, with horses developing postoperative peritonitis having a 56% mortality rate. Long-term complications like adhesion formation or...
Treatment of acute and chronic gastrointestinal inflammation. Treating inflammation in the equine gastrointestinal tract remains a challenge. Our most potent anti-inflammatory drugs, COX inhibitors and glucocorticoids, have unwanted effects on the gastrointestinal tract and host defense that often limit their use. Newer strategies targeting specific cells and molecules that regulate a subset of the events occurring during inflammation are rapidly becoming available and should allow clinicians to reduce the detrimental effects of inflammation without inhibiting the beneficial aspects.
Equine recurrent airway obstruction: pathogenesis, diagnosis, and patient management. Recurrent airway obstruction is a condition that affects some older horses maintained in confinement. Clinical signs range from exercise intolerance with occasional cough to dyspnea at rest. Bronchoalveolar lavage cytology is characterized by neutrophilic leukocytosis (15%-85%) and is recommended for making the diagnosis in horses with mild to moderate disease. Environmental management combined with periodic bronchodilator and antiinflammatory corticosteroid therapy yields the best prognosis for disease remission.
In vitro investigation of the effects of cyclooxygenase-2 inhibitors on contractile activity of the equine dorsal and ventral colon. To evaluate the effect of 2 cyclooxygenase (COX)-2 inhibitors on contractile activity of the circular smooth muscle layer of the equine dorsal and ventral colon. Methods: Samples of the dorsal and ventral colon obtained from 10 healthy horses. Methods: Full-thickness tissue samples were collected from the dorsal colon in the area of the diaphragmatic flexure and the ventral colon in the area of the sternal flexure. Samples were cut into strips oriented along the fibers of the circular muscle layer and mounted in a tissue bath system for determination of contractile strength. Incremental amount...
