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Abstract

Objective—To investigate the effects of dexamethasone or levothyroxine sodium on endotoxin-induced alterations in glucose and insulin dynamics.

Animals—24 horses.

Procedures—Horses were randomly allocated to 3 treatment groups and received 48 mg of levothyroxine mixed with 200 g of oats, 20 mg of dexamethasone plus oats, or oats alone (control) for 15 days, followed by IV infusion of lipopolysaccharide (20 ng/kg) while individually housed in stalls. Frequently sampled IV glucose tolerance tests were performed prior to pretreatment, after pretreatment, and 20 hours after lipopolysaccharide administration. Area under the curve for plasma glucose and serum insulin concentrations was calculated, and minimal model analyses were performed.

Results—Significant treatment-by-time effects were detected for insulin sensitivity (SI) and area under the curve for glucose and insulin in the 15-day pretreatment period. Insulin sensitivity significantly decreased over time in all treatment groups, with the largest decrease detected in the dexamethasone group. Administration of lipopolysaccharide further decreased mean SI by 71% and 63% in the dexamethasone and control groups, respectively, but did not affect horses in the levothyroxine group. Mean SI was the lowest in the dexamethasone group, but percentage reduction was the same for dexamethasone and control groups.

Conclusions and Clinical Relevance—Insulin sensitivity decreased during the pretreatment period in all 3 groups, indicating that hospitalization affected glucose and insulin dynamics. Dexamethasone significantly lowered SI, and endotoxemia further exacerbated insulin resistance. In contrast, there was no additional effect of endotoxemia on SI in horses pretreated with levothyroxine, suggesting that this treatment prevented endotoxemia-induced insulin resistance.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate the effects of sequential anesthesia of the individual compartments of the equine stifle joint on lameness induced by intra-articular deposition of interleukin (IL)-1β.

Animals—6 horses.

Procedures—For each horse, baseline hind limb lameness was first evaluated. A randomly selected compartment of 1 stifle joint was then injected with IL-1β to induce synovitis and lameness; subsequently, the same compartment was anesthetized with 2% mepivacaine hydrochloride, and lameness was reevaluated. Two weeks later, baseline lameness was evaluated, and lameness was similarly induced; thereafter, the 2 synovial compartments of the stifle joint not injected with IL-1β were anesthetized sequentially in random order (ie, first and second blocks); lameness was evaluated after each block. Finally, the IL-1β–treated compartment was anesthetized (third block); lameness was again evaluated. This second experiment was repeated for the contralateral stifle joint 2 weeks later. Throughout the study, lameness was quantified objectively by assessing vertical pelvic movement asymmetry with a wireless, inertial sensor-based system.

Results—Intra-articular deposition of IL-1β induced lameness in all injected limbs. In the first experiment, anesthesia of the compartment injected with IL-1β resulted in a significant decrease in lameness, with vertical pelvic movement asymmetry approaching baseline. In the second experiment, lameness improved significantly after the second and third blocks and was almost completely abolished after all 3 synovial compartments were anesthetized.

Conclusions and Clinical Relevance—In horses, lameness caused by a lesion in 1 compartment of a stifle joint can be improved more by instillation of local anesthetic solution into that compartment than by anesthesia of the other compartments.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate the effects of endotoxin administered IV on glucose and insulin dynamics in horses.

Animals—16 healthy adult mares.

Procedures—Each week of a 2-week randomized crossover study, each horse received an IV injection (duration, 30 minutes) of Escherichia coli O55:B5 lipopolysaccharide (LPS) in 60 mL of sterile saline (0.9% NaCl) solution (20 ng/kg) or sterile saline solution alone (control treatment). Frequently sampled IV glucose tolerance test procedures were performed at 24 hours before (baseline) and 24 and 48 hours after injection; glucose and insulin dynamics were assessed via minimal model analysis.

Results—13 of 16 horses had a clinical response to LPS, which was characterized by mild colic and leukopenia. Before treatment, mean ± SD insulin sensitivity was 2.9 ± 1.9 × 10−4 L·min−1·mU−1; this significantly decreased to 0.9 ± 0.9 × 10−4 L·min−1·mU−1 24 hours after treatment (69% reduction) and was 1.5 ± 0.9 × 10−4 L·min−1·mU−1 48 hours after treatment. At baseline, mean ± SD acute insulin response to glucose was 520 ± 196 mU·min·L−1; this significantly increased to 938 ± 620 mU·min·L−1 (80% increase) and 755 ± 400 mU·min·L−1 (45% increase) at 24 and 48 hours after LPS treatment, respectively.

Conclusions and Clinical Relevance—Compared with baseline values, insulin sensitivity was decreased for 24 hours after IV injection of LPS, and affected horses had a compensatory pancreatic response. These disturbances in glucose and insulin dynamics may contribute to development of laminitis in horses.

Full access
in American Journal of Veterinary Research