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.
Objective—To investigate the effects of dexamethasone or levothyroxine sodium on endotoxin-induced alterations in glucose and insulin dynamics.
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.
Objective—To investigate the effects of insulin-like
growth factor-II (IGF-II) on DNA and glycosaminoglycan
(GAG) synthesis and the expression of matrix-related
genes in equine articular cartilage explants
and chondrocytes, respectively, with and without
interleukin 1-β (IL1-β).
Sample Population—Articular cartilage from 12 adult
Procedure—Articular cartilage was incubated in standard
media with and without equine IL1-β (10 ng/mL)
containing various concentrations of IGF-II for 72
hours. Synthesis of DNA and GAG was determined by
incorporation of thymidine labeled with radioactive
hydrogen (3H) and sulfate labeled with radioactive sulfur
(35S), respectively. Total GAG content of the
explants and spent media was determined by use of
the 1,9-dimethylmethylene blue assay. Northern blots
of RNA from cultured equine articular cartilage chondrocytes
were hybridized with cDNA of major matrix
Results—Insulin-like growth factor-II stimulated DNA
and GAG synthesis at concentrations of 25 and 50
ng/mL, respectively. In cartilage explants conditioned
with IL1-β, IGF-II stimulated DNA and GAG synthesis
at concentrations of 500 and 50 ng/mL, respectively.
Insulin-like growth factor-II had no effect on total GAG
content as determined by the 1,9-dimethylmethylene
blue assay. No specific effects on steady-state levels
of messenger RNAs were observed.
Conclusions and Clinical Relevance—Insulin-like
growth factor-II stimulated DNA and GAG synthesis in
equine adult cartilage and may have potential application
in vivo. (Am J Vet Res 2004;65:238–244)
Objective—To investigate the effects of enrofloxacin
and magnesium deficiency on explants of equine
Sample Population—Articular cartilage explants and
cultured chondrocytes obtained from adult and
Procedure—Full-thickness explants and cultured
chondrocytes were incubated in complete or magnesium-
deficient media containing enrofloxacin at concentrations
of 0, 1, 5, 25, 100, and 500 µg/ml.
Incorporation and release of sulfate 35S over 24 hours
were used to assess glycosaminoglycan (GAG) synthesis
and degradation. An assay that measured binding
of dimethylmethylene blue dye was used to compare
total GAG content between groups. Northern
blots of RNA from cultured chondrocytes were
probed with equine cDNA of aggrecan, type-II collagen,
biglycan, decorin, link protein, matrix metalloproteinases
1, 3, and 13, and tissue inhibitor of metalloproteinase
Results—A dose-dependent suppression of 35S incorporation
was observed. In cartilage of neonates, 35S
incorporation was substantially decreased at
enrofloxacin concentrations of 25 mg/ml. In cartilage
of adult horses, 35S incorporation was decreased only
at enrofloxacin concentrations of ≥ 100 µg/ml.
Magnesium deficiency caused suppression of 35S
incorporation. Enrofloxacin or magnesium deficiency
did not affect GAG degradation or endogenous GAG
content. Specific effects of enrofloxacin on steadystate
mRNA for the various genes were not
Conclusion and Clinical Relevance—Enrofloxacin
may have a detrimental effect on cartilage metabolism
in horses, especially in neonates. (Am J Vet Res
Objective—To generate data on the effects of firocoxib administration to horses with osteoarthritis.
Animals—Client-owned horses with signs of lameness and joint pain associated with osteoarthritis.
Procedures—Firocoxib was administered as an oral paste (0.1 mg/kg, q 24 h) for 14 days. Assessments were performed on day 0 (baseline) and days 7 and 14.
Results—390 of 429 horses from 80 sites in 25 states met the criteria for analysis. Quarter Horse and Thoroughbred were the 2 most commonly represented breeds, comprising half of the study population. Signs of musculoskeletal pain or lameness attributed to osteoarthritis were diagnosed in a single joint in 197 (197/390 [50.5%]) horses and in multiple joints in 193 (193/390 [49.5%]) horses. In those with involvement of a single joint, the tarsus was the most frequently affected joint (79/197 [40.1 %]). Among the 390 horses with complete lameness data, improvement was reported in approximately 80% by day 14. Investigators rated 307 (78.7%) horses as improved, whereas owners or handlers rated 316 (81.0%) horses as improved at the termination of the study. Horses treated with firocoxib paste had significant improvement in lameness scores from baseline values. Improvement was most rapid within the first 7 days after starting treatment and continued, albeit at a slower rate, through treatment day 14.
Conclusions and Clinical Relevance—Firocoxib significantly improved lameness scores throughout the 14-day period with few adverse effects. Firocoxib can be a safe cyclooxygenase-2–specific NSAID for the treatment of musculoskeletal pain and lameness associated with osteoarthritis.
Objective—To ascertain whether laminitis can be induced via administration of oligofructose (OF) at doses of 5.0 and 7.5 g/kg in horses and to assess glucose and insulin dynamics before and after treatment.
Animals—19 adult horses.
Procedures—Horses were fed OF (1.0 g/kg) mixed with oats for 6 days. Oligofructose at doses of 5.0 and 7.5 g/kg was then mixed with 4 L of water and administered (0 hours) to 8 (group A) and 4 (group B) horses, respectively, via nasogastric intubation; 8 horses received water alone. One horse in group A that did not develop laminitis was subsequently treated again and included in group B. Before and at intervals after treatment, resting plasma glucose and serum insulin concentrations were measured and frequently sampled IV glucose tolerance tests were performed. Area under the glucose curve (AUCg) and area under the insulin curve (AUCi) were calculated, and minimal model analyses were performed.
Results—3 of 8 horses in group A and all 4 horses in group B developed laminitis. Significant treatment-time effects were detected for resting plasma glucose concentrations and AUCg. Among horses in group A, mean AUCg values at 24 and 48 hours were 34% and 32% higher, respectively, than the mean value at 24 hours. Treatment groups did not differ significantly with respect to resting serum insulin concentration, AUCi, or minimal model analysis results.
Conclusions and Clinical Relevance—In horses, laminitis can be induced and glucose dynamics altered via nasogastric administration of 5.0 g of OF/kg. An alteration in insulin dynamics was not detected following treatment with OF.
OBJECTIVE To develop a risk prediction model for factors associated with an SeM-specific antibody titer ≥ 3,200 in horses after naturally occurring outbreaks of Streptococcus equi subsp equi infection and to validate this model.
DESIGN Case-control study.
ANIMALS 245 horses: 57 horses involved in strangles outbreaks (case horses) and 188 healthy horses (control horses).
PROCEDURES Serum samples were obtained from the 57 cases over a 27.5-month period after the start of outbreaks; serum samples were obtained once from the 188 controls. A Bayesian mixed-effects logistic regression model was used to assess potential risk factors associated with an antibody titer ≥ 3,200 in the case horses. A cutoff probability for an SeM-specific titer ≥ 3,200 was determined, and the model was externally validated in the control horses. Only variables with a 95% credibility interval that did not overlap with a value of 1 were considered significant.
RESULTS 9 of 57 (6%) case horses had at least 1 titer ≥ 3,200, and 7 of 188 (3.7%) of control horses had a titer ≥ 3,200. The following variables were found to be significantly associated with a titer ≥ 3,200 in cases: farm size > 20 horses (OR, 0.11), history of clinically evident disease (OR, 7.92), and male sex (OR, 0.11). The model had 100% sensitivity but only 24% specificity when applied to the 188 control horses (area under the receiver operating characteristic curve = 0.62.)
CONCLUSIONS AND CLINICAL RELEVANCE Although the Bayesian mixed-effects logistic regression model developed in this study did not perform well, it may prove useful as an initial screening tool prior to vaccination. We suggest that SeM-specific antibody titer be measured prior to vaccination when our model predicts a titer ≥ 3,200.
Objective—To compare results (ie, return to racing
and earnings per race start) of surgical versus nonsurgical
management of sagittal slab fractures of the
third carpal bone in racehorses.
Animals—32 racehorses (19 Thoroughbreds, 11
Standardbreds, and 2 Arabians).
Procedure—Medical records and radiographs were
reviewed to obtain information regarding signalment
and treatment. Follow-up information was obtained
from race records. Robust regression analysis was
performed to evaluate earnings per start in horses
that raced at least once before and after injury.
Results—22 (69%) horses raced at least once after
treatment of the fracture. All 7 horses treated by
means of interfragmentary compression raced after
treatment, and horses that underwent interfragmentary
compression had significantly higher earnings
per start after the injury than did horses treated without
surgery. Eight of 9 horses treated by means of
arthroscopic debridement of the damaged cartilage
and bone raced after treatment, but only 7 of 16 horses
treated without surgery (ie, stall rest) were able to
return to racing after treatment.
Conclusions and Clinical Relevance—Results suggest
that racehorses with sagittal slab fractures of the
third carpal bone have a favorable prognosis for return
to racing after treatment. Horses treated surgically
were more likely to race after treatment than were
horses treated without surgery. (J Am Vet Med Assoc
Objective—To measure plasma ACTH, D-melanocyte–stimulating hormone (D-MSH), and insulin concentrations during various photoperiods between February and October in horses and ponies with and without pituitary pars intermedia dysfunction (PPID).
Animals—13 clinically normal (control) ponies, 14 clinically normal (control) horses, 7 ponies with PPID, and 8 horses with PPID.
Procedures—Blood samples were collected from February through October during 8 photoperiods: 1, February 13 through March 2; 2, April 4 through 6; 3, June 19 through 22; 4, August 6 through 7; 5, August 14 through 17; 6, September 4 through 6; 7, September 26 through 28; and 8, October 16 through 18. Plasma ACTH, D-MSH, and insulin concentrations at each photoperiod were compared among groups.
Results—Log ACTH concentration was increased during photoperiod 4 through 8, compared with photoperiod 1 through 3, in all groups. In photoperiod 3 through 7, log ACTH concentrations were higher in horses and ponies with PPID, compared with values for control horses and ponies. D-Melanocyte–stimulating hormone (log and raw value) concentration was higher in photoperiod 2 through 8, compared with photoperiod 1, in control horses and ponies. In horses and ponies with PPID, log D-MSH concentration was higher in photoperiod 3 through 8, and D-MSH concentration was higher in photoperiod 4 through 8, compared with photoperiod 1. In control horses and ponies, plasma insulin concentration was lower in photoperiod 3 than in photoperiod 1.
Conclusions and Clinical Relevance—Plasma D-MSH and ACTH concentrations increased as daylight decreased from summer solstice (maximum daylight hours) to 12 hours of daylight.
Objective—To determine the effects of long-term oral administration of levothyroxine sodium (L-T4) on glucose dynamics in adult euthyroid horses.
Animals—6 healthy adult mares.
Procedures—Horses received L-T4 (48 mg/d) orally for 48 weeks. Frequently sampled IV glucose tolerance test procedures were performed on 3 occasions (24-hour intervals) before and at 16, 32, and 48 weeks during the treatment period. Data were assessed via minimal model analysis. The repeatability of measurements was evaluated.
Results—During treatment, body weight decreased significantly from the pretreatment value; mean ± SD weight was 49 ± 14 kg, 43 ± 7 kg, and 25 ± 18 kg less than the pretreatment value at weeks 16, 32, and 48, respectively. Compared with pretreatment findings, 1.8-, 2.4-, and 1.9-fold increases in mean insulin sensitivity (SI) were detected at weeks 16, 32, and 48, respectively; SI was negatively correlated with body weight (r = −0.42; P < 0.001). During treatment, glucose effectiveness increased and the acute insulin response to glucose decreased. Overall mean within-horse coefficients of variation were 5% and 29% for plasma glucose and serum insulin concentrations, respectively, and 33%, 26%, and 23% for SI, glucose effectiveness, and the acute insulin response to glucose, respectively.
Conclusions and Clinical Relevance—Long-term administration of L-T4 was associated with weight loss and increased SI in adult euthyroid horses, although other factors may have confounded results. Levothyroxine sodium may be useful for the treatment of obesity and insulin resistance in horses, but further studies are required.