Nat T. Messer

Effectiveness of administration of phenylbutazone alone or concurrent administration of phenylbutazone and flunixin meglumine to alleviate lameness in horses

OBJECTIVE To determine the effectiveness of administering multiple doses of phenylbutazone alone or a combination of phenylbutazone and flunixin meglumine to alleviate lameness in horses. ANIMALS 29 adult horses with naturally occurring forelimb and hind limb lameness. PROCEDURES Lameness evaluations were performed by use of kinematic evaluation while horses were trotting on a treadmill. Lameness evaluations were performed before and 12 hours after administration of 2 nonsteroidal anti-inflammatory drug (NSAID) treatment regimens. Phenylbutazone paste was administered at approximately 2.2 mg/kg, PO, every 12 hours for 5 days, or phenylbutazone paste was administered at approximately 2.2 mg/kg, PO, every 12 hours for 5 days in combination with flunixin meglumine administered at 1.1 mg/kg, IV, every 12 hours for 5 days. RESULTS Alleviation of lameness was greater after administration of the combination of NSAIDs than after oral administration of phenylbutazone alone. Improvement in horses after a combination of NSAIDs did not completely mask lameness. Five horses did not improve after either NSAID treatment regimen. All posttreatment plasma concentrations of NSAIDs were less than those currently allowed by the United States Equestrian Federation Inc for a single NSAID. One horse administered the combination NSAID regimen died of acute necrotizing colitis during the study. CONCLUSIONS AND CLINICAL RELEVANCE Administration of a combination of NSAIDs at the dosages and intervals used in the study reported here alleviated the lameness condition more effectively than did oral administration of phenylbutazone alone. This may attract use of combinations of NSAIDs to increase performance despite potential toxic adverse effects.

Tissue-specific dysregulation of cortisol metabolism in equine laminitis

REASONS FOR PERFORMING STUDY The role of glucocorticoids (GCs) in the pathogenesis of laminitis is incompletely understood. Local tissue activity of GC is regulated by the steroid converting enzyme, 11beta-hydroxysteroid dehydrogenase-1 (11beta-HSD-1). Changes in integumentary (skin and hoof lamellar) 11beta-HSD activity occurring during laminitis could affect the extent to which GCs are involved in its development. HYPOTHESIS That changes in integumentary 11beta-HSD-1 activity associated with the laminitic condition would lead to elevated local tissue levels of GCs, which could subsequently contribute, through paracrine and autocrine mechanisms, to the further development of laminitis; and that similar changes in 11beta-HSD-1 activity would be evident in both skin and hoof lamellar tissue. METHODS Activity of 11beta-HSD-1 was determined in skin and hoof lamellar tissue specimens obtained from normal and laminitic horses using a radiometric assay. Skin samples were obtained from 10 normal horses and from 10 horses before and after induction of acute laminitis following administration of starch via nasogastric tube. Hoof lamellar samples were obtained from 10 normal horses, 10 horses following induction of acute laminitis and 4 chronically-foundered horses. Bidirectional 11beta-HSD-1 activity was measured in both skin and lamellar tissues. RESULTS 11-ketoreductase activity exceeded 11beta-dehydrogenase activity in both skin and lamellar tissues. Cutaneous activity was higher than lamellar 11beta-HSD-1 activity in all groups. Both ketoreductase and dehydrogenase activity increased in skin and lamellae following experimental induction of acute laminitis, but the increase in ketoreductase activity was substantially greater than that for dehydrogenase in the lamellae. Induction of acute laminitis was attended by increases of 227 and 220% in cutaneous dehydrogenase and ketoreductase activity, respectively, and 173 and 398% in lamellar dehydrogenase and ketoreductase activity, respectively (P<0.05). CONCLUSIONS The 11-ketoreductase moiety of 11beta-HSD-1 plays a role in equine skin and hoof lamellae regarding the regulation of local glucocorticoid activity. Increased 11-ketoreductase activity will lead to increased local tissue GC activity by virtue of conversion of cortisone to cortisol. POTENTIAL RELEVANCE The laminitic condition is attended by integumentary biochemical changes that enhance the local concentration of cortisol, especially in the hoof lamellar interface. Through multiple and diverse actions, increased local GC activity contributes to the pathogenesis and morbidity associated with laminitis. Pharmacological manipulation of 11beta-HSD-1 deserves further investigation regarding the prevention and treatment of laminitis.

Serum markers of lamellar basement membrane degradation and lamellar histopathological changes in horses affected with laminitis

In order better to evaluate the extent to which degradation of the lamellar basement membrane (LBM) by matrix metalloproteinases (MMP) occurs in equine laminitis, we determined the concentration of type IV collagen and laminin in normal and laminitic horses, using specific immunoassays. Blood samples were obtained from both the jugular and the cephalic veins of horses (n = 10) before and after the induction of acute alimentary laminitis by carbohydrate overload. Jugular and cephalic venous blood samples were also obtained from horses affected with naturally occurring laminitis (n = 16) and nonlaminitic controls (n = 8). The serum collagen IV concentration was not changed following the induction of laminitis in the experimental group. Serum collagen IV concentration was increased in jugular venous blood obtained from cases of naturally occurring laminitis (mean +/- s.e. 218.04 +/- 18.59 ng/ml) compared with nonlaminitic controls (157.50 +/- 10.93 ng/ml) (P<0.05). Serum collagen IV concentration was also increased in jugular venous blood obtained from severely laminitic horses (219.50 +/- 18.18 ng/ml) compared with nonlaminitic controls (157.50 +/- 10.93 ng/ml) (P<0.05). A difference in serum concentration of collagen IV was not identified based on chronicity of naturally occurring laminitis. Serum laminin concentration did not differ between laminitic and nonlaminitic horses. Differences in serum laminin concentration were not identified based on sampling location (jugular or cephalic vein), severity of laminitic pain, or chronicity of spontaneous laminitis. In conclusion, the circulating concentration of collagen IV was increased in horses affected with naturally occurring laminitis. The potential role for serum collagen IV assay for characterisation of equine laminitis warrants further investigation.

Effect of Feeding Deoxynivalenol (Vomitoxin)-Contaminated Barley to Horses

12,13-epoxytrichothec-9-en-8-one) is a naturally occurring trichothecene toxin produced by several Fusarium fungi that parasitize numerous cereal grains. Numerous species of Fusarium have been found to produce DON. The genus Fusarium occurs throughout the world and may affect corn, wheat, barley, oats, rice, and sorghum and complete feed formulations. Cereal grain contamination by DON occurs most frequently when conditions are cool and wet at the time of grain formation and harvest and is associated predominantly with infection in the field rather than as a complication of storage. 7 Although most descriptions of widespread grain contamination by DON have been confined to temperate zones of the world, DON contamination has also been reported to affect grain in subtropical climates. Deoxynivalenol has been given the trivial name vomitoxin because it causes emesis when ingested by swine and dogs. Other clinical effects attributed to the toxic effects of ingested DON include feed refusa1, decreased weight gain, signs of gastrointestinal irritation (e.g., diarrhea, colic, rectal prolapse, hematochezia), thickening of the squamous aspect of the gastric lining of pigs, reproductive problems, skin irritation, cardiotoxicity, and interference with the immune system. 16 The extent to which DON causes clinical signs of toxicosis is proportional to its concentration in contaminated feed. Ingested DON also affects intestinal immunoglobulin synthesis. Specifically, DON stimulates intestinal IgA production in mice, leading to an elevated concentration of circulating IgA, increased polymeric : monomeric IgA ratio, and accumulation of IgA in the renal mesangium. The renal damage that occurs following DON ingestion has been characterized as a possible autoimmune phenomenon consequent to the entrapment of circulating IgA immune complexes in the mesangium. 14 IgA nephropathy, which is the most common form of glomerulonephritis in human beings worldwide, affects men 2-5 times more commonly than it affects women. Although the cause of IgA glomerulonephritis is unknown, similarities between the clinical syndrome in human beings and experimental DON intoxication in laboratory animal species (e.g., IgA dysregulation, renal micropathology, evidence that testosterone may be a cofactor in experimental DON-induced IgA glomerulonephritis) suggest that DON may be important in the pathogenesis of IgA glomerulonephritis in human beings. Glomerulonephritis is a common finding at necropsy and represents an important cause of chronic renal failure in horses. Chronic renal failure is comparatively uncommon in horses, and glomerulonephritis is most frequently recognized

Equine thyroid dysfunction

Hypothyroidism is the most common type of thyroid gland dysfunction reported in horses. Primary, secondary, and tertiary causes of hypothyroidism are discussed. Equine hypothyroidism remains a controversial endocrine disorder because extrathyroidal factors, including the administration of drugs and systemic diseases, affect serum triiodothyronine (T3) and thyroxine (T3) concentrations in horses. Accurate diagnosis of hypothyroidism therefore requires assessment of the hypothalamic-pituitary-thyroid axis. Diagnostic procedures for evaluating thyroid gland function are outlined and results of studies utilizing experimental models are discussed.

The Use of Laboratory Tests in Equine Practice

The use of laboratory tests has become commonplace and a necessity in progressive clinical veterinary practice. The information gained from selecting appropriate laboratory tests is invaluable in making an accurate diagnosis, establishing a prognosis, and monitoring response to therapy. Acquisition of reliable laboratory results depends on a thorough understanding of those factors that may affect laboratory data other than the disease process being investigated. The proper use of laboratory tests gives the clinician an added dimension to clinical practice that is both informative and intellectually rewarding.

Diabetes, insulin resistance, and metabolic syndrome in horses.

Analogous to the situation in human medicine, contemporary practices in horse management, which incorporate lengthy periods of physical inactivity coupled with provision of nutritional rations characterized by inappropriately high sugar and starch, have led to obesity being more commonly recognized by practitioners of equine veterinary practice. In many of these cases, obesity is associated with insulin resistance (IR) and glucose intolerance. An equine metabolic syndrome (MS) has been described that is similar to the human MS in that both IR and aspects of obesity represent cornerstones of its definition. Unlike its human counterpart, Identification of the equine metabolic syndrome (EMS) portends greater risk for development of laminitis, a chronic, crippling affliction of the equine hoof. When severe, laminitis sometimes necessitates euthanasia. Unlike the human condition, the risk of developing type 2 diabetes mellitus and many other chronic conditions, for which the risk is recognized as increased in the face of MS, is less likely in horses. The equine veterinary literature has been replete with reports of scientific investigations regarding the epidemiology, pathophysiology, and treatment of EMS.

Exophthalmia Associated with Paranasal Sinus Osteoma in a Quarterhorse Mare

An 11-year-old Quarterhorse mare developed a paranasal sinus osteoma that extended into the right orbit and led to ipsilateral exophthalmia. Although the tumor was radiographically evident in the paranasal sinuses, ultrasonography was used to demonstrate extension of the tumor into the retrobulbar space, and endoscopy was used to identify its extension into the nasopharynx. Biopsies were obtained using both fine-needle aspiration and paranasal sinus trephination. Despite numerous antemortem diagnostic tests, only postmortem histologic analysis of the mass afforded the diagnosis of osteoma.

Effects of propylthiouracil and bromocryptine on serum concentrations of thyrotrophin and thyroid hormones in normal female horses.

REASONS FOR PERFORMING STUDY There exists a need for better diagnostic tests to characterise thyroid disease in horses. Currently available diagnostic tests fail to differentiate between thyroid gland disorders and thyroid abnormalities resulting from pituitary or hypothalamic problems. OBJECTIVES To evaluate the effects of treatment with propylthiouracil (PTU) and bromocryptine (BROM) on serum concentrations of triiodothyronine (T3), thyroxine (T4), reverse T3 (rT3) and equine thyroid-stimulating hormone (e-TSH, thyrotrophin) in mature horses. METHODS Healthy mature horses were treated using either PTU or BROM for 28 days. The effect of treatment on the thyroid axis was assessed by measuring T3, T4, rT3 and e-TSH before and at +14 and +28 days. The effect of PTU and BROM on the response of T3, T4, rT3 and e-TSH to thyrotrophin-release hormone (TRH) administration was also assessed before and at +14 and +28 days of treatment. RESULTS Treatment with PTU led to a significant reduction in serum concentrations of T3, T4 and rT3 on Day 28 and increase of e-TSH on Day 28 (P < 0.05). Treatment with BROM did not cause any measurable effect on serum concentrations of T3, T4, rT3 or e-TSH. The percentage increment by which serum concentration of T4, T3 and e-TSH increased following stimulation with TRH was decreased by treatment with PTU for 28 days (P < 0.05) but were not affected by treatment with BROM for 28 days. CONCLUSIONS These results suggest that 1) treatment with PTU may be used in horses as a model of primary hypothyroidism; 2) the use of BROM as a model of secondary hypothyroidism in horses is not supported; and 3) e-TSH assay deserves further investigation for the clinical diagnosis of thyroid axis dysfunction in horses. POTENTIAL RELEVANCE Propylthiouracil effectively causes primary hypothyroidism. There is substantial variability between horses with respect to their sensitivity to this substance when administered orally. Further studies pertaining to the characterisation of equine thyroid disorders are warranted and the use of both PTU for the experimental induction of primary hypothyroidism and e-TSH for the diagnostic characterisation of thyroid disorders in horses should be considered.

Clinical assessment of blood glucose homeostasis in horses: comparison of a continuous glucose monitoring system with a combined intravenous glucose and insulin test protocol.

BACKGROUND The combined glucose-insulin test (CGIT) is helpful for evaluating insulin sensitivity. A continuous glucose monitoring system (CGMS) reports changes in interstitial glucose concentrations as they occur in the blood. Use of the CGMS minimizes animal contact and may be useful when performing a CGIT. HYPOTHESIS Results obtained using a CGMS are useful for the evaluation of glucose responses during the evaluation of insulin sensitivity in equids. ANIMALS Seven mature, obese ponies. METHODS Ponies were equipped with CGMS for determination of interstitial glucose concentrations. Glucose (150 mg/kg, i.v.) and insulin (0.1 U/kg, i.v.) were administered and blood glucose concentrations determined at (minutes after time zero) 1, 5, 15, 25, 35, 45, 60, 75, 90, 105, and 120 with a hand-held glucometer. Blood chemistry results were compared with simultaneously obtained results using CGMS. RESULTS Concordance coefficients determined for comparison of blood glucose concentrations determined by a hand-held glucometer and those determined by CGMS after the zero time point were 0.623, 0.764, 0.834, 0.854, and 0.818 (for delays of 0, 5, 10, 15, and 20 minutes, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE Interstitial glucose concentrations obtained by the CGMS compared favorably to blood glucose concentrations. CGMS may be useful for assessment of glucose dynamics in the CGIT.