Search Results

You are looking at 41 - 50 of 71 items for

  • Author or Editor: Jack Snyder x
  • Refine by Access: All Content x
Clear All Modify Search

Abstract

Objective—To determine expression of cyclooxygenase (COX) genes 1 and 2 (also called prostaglandin-endoperoxide synthases 1 and 2) and stability of housekeeping gene expression during low-flow ischemia and reperfusion in the jejunum of horses.

Animals—5 healthy adult horses.

Procedures—Horses were anesthetized, and two 30-cm segments of jejunum were surgically exteriorized. Blood flow was maintained at baseline (untreated) values in 1 (control) segment and was decreased to 20% of baseline (low-flow ischemia) for 75 minutes, followed by 75 minutes of reperfusion, in the other (experimental) segment. Biopsy samples were collected from experimental segments at baseline (T0), after 75 minutes of ischemia (T1), and after 75 minutes of reperfusion (T2); samples were collected from control segments at T0 and T2. Horses were euthanized 24 hours after induction of ischemia (T3), and additional samples were collected. Samples were evaluated histologically. Total RNA was extracted; expression of COX genes and stability of 8 housekeeping genes were determined via quantitative real-time PCR assays.

Results—COX-1 and COX-2 genes were constitutively expressed in baseline samples. Low-flow ischemia resulted in significant upregulation of COX-2 gene expression at each subsequent time point, compared with baseline values. The most stably expressed reference genes were β-actin and hypoxanthine phosphoribosyltransferase, whereas glyceraldehyde 3-phosphate dehydrogenase and β-2 microglobulin were the least stably expressed.

Conclusions and Clinical Relevance—Low-flow ischemia resulted in upregulation of COX-2 gene expression in the jejunum of horses. Housekeeping genes traditionally used as internal standards may not be stable in this tissue during arterial low-flow ischemia and reperfusion.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To assess gene expressions of cyclooxygenase-1 and -2 in oral, glandular gastric, and urinary bladder mucosae and determine the effect of oral administration of phenylbutazone on those gene expressions in horses.

Animals—12 healthy horses.

Procedures—Horses were allocated to receive phenylbutazone or placebo (6 horses/group); 1 placebo-treated horse with a cystic calculus was subsequently removed from the study, and those data were not analyzed. In each horse, the stomach and urinary bladder were evaluated for ulceration via endoscopy before and after experimental treatment. Oral, glandular gastric, and urinary bladder mucosa biopsy specimens were collected by use of a skin punch biopsy instrument (oral) or transendoscopically (stomach and bladder) before and after administration of phenylbutazone (4.4 mg/kg, PO, q 12 h) in corn syrup or placebo (corn syrup alone) for 7 days. Cyclooxygenase-1 and -2 gene expressions were determined (via quantitative PCR techniques) in specimens collected before and after the 7-day treatment period and compared within and between groups. Prior to commencement of treatment, biopsy specimens from 7 horses were used to compare gene expressions among tissues.

Results—The cyclooxygenase-1 gene was expressed in all tissues collected. The cyclooxygenase-2 gene was expressed in the glandular gastric and bladder mucosae but not in the oral mucosa. Cyclooxygenase gene expressions were unaffected by phenylbutazone administration.

Conclusions and Clinical Relevance—Cyclooxygenase-2 was constitutively expressed in glandular gastric and bladder mucosae but not in the oral mucosa of healthy horses. Oral administration of phenylbutazone at the maximum recommended dosage daily for 7 days did not affect cyclooxygenase-1 or -2 gene expression.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the pharmacokinetics, pharmacodynamics, and safety of zoledronic acid in horses.

Animals—8 healthy horses.

Procedures—A single dose of zoledronic acid (0.057 mg/kg, IV) was administered during a 30-minute period. Venous blood was collected at several time points. Zoledronic acid concentration in plasma was measured by liquid chromatography–tandem mass spectrometry, and pertinent pharmacokinetic parameters were determined. Plasma was analyzed for total calcium, BUN, and creatinine concentrations and a marker for bone resorption (C-terminal telopeptides of type I collagen).

Results—Zoledronic acid was safely administered IV during a 30-minute period, and no adverse effects were observed. Plasma concentrations of zoledronic acid were consistent with a 2-compartment mammillary model. Plasma concentrations of zoledronic acid were detected for up to 8 hours after administration. Mean total calcium concentrations in plasma were less than the reference range 7 days after zoledronic acid administration. A marker for bone remodeling decreased in concentration after zoledronic acid administration and remained low for the 1-year duration of the study. No changes in BUN and creatinine concentrations were observed after zoledronic acid administration.

Conclusions and Clinical Relevance—Zoledronic acid was safely administered in healthy horses. Zoledronic acid is reported as the strongest bisphosphonate presently available, and studies evaluating potential benefits of zoledronic acid in horses with orthopedic conditions are warranted.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the response to neostigmine of the contractile activity of the jejunum and pelvic flexure and the effects of a continuous rate infusion (CRI) of neostigmine in horses.

Animals—7 adult horses and tissue from 12 adult horses.

Procedures—A CRI of neostigmine (0.008 mg/kg/h) or placebo was administered to 6 horses in a crossover study design. Gastric emptying was evaluated by the acetaminophen test. The frequency of defecation and urination and the consistency and weight of feces were recorded throughout the experiment. The effect of neostigmine on smooth muscle contractile activity was evaluated in tissues from the jejunum and pelvic flexure. The effect of neostigmine and acetylcholine after incubation with muscarinic receptor antagonists (atropine and DAU 5884) and an acetylcholinesterase inhibitor (edrophonium) was also investigated in vitro.

Results—No difference was observed between neostigmine and placebo for time to reach peak plasma acetaminophen concentration and absorption rate constant. A CRI of neostigmine increased fecal production and frequency of urination. Neostigmine induced a dose-dependent increase of contractile amplitude in jejunum and pelvic flexure muscle strips. Incubation of muscle strips with atropine and DAU 5884 inhibited the response to acetylcholine and neostigmine. Incubation of smooth muscle strips from the jejunum with edrophonium increased the response to acetylcholine and had no effect on the response to neostigmine in vitro.

Conclusions and Clinical Relevance—A CRI of neostigmine increased fecal production and urination frequency in horses. A CRI of neostigmine did not decrease gastric emptying. Neostigmine stimulated contractile activity of jejunum and pelvic flexure smooth muscle strips in vitro.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effect of ranitidine on gastric emptying in horses.

Animals—11 adult horses.

Procedures—In vitro, isolated muscle strips from the pyloric antrum and duodenum of 5 horses were suspended in baths and attached to isometric force transducers. Once stable spontaneous contractions were observed, ranitidine or diluent was added at cumulative increasing concentrations. Isometric stress responses were compared. In vivo, 6 horses were assigned to a group in a prospective randomized crossover study design with a wash-out period of 2 weeks between trials. Ranitidine (2.2 mg/kg) or saline (0.9% NaCl) solution was administered IV, and 15 minutes later, acetaminophen (20 mg/kg), diluted in 400 mL of water, was administered via nasogastric tube to evaluate the liquid phase of gastric emptying. Serum acetaminophen concentration was measured at several time points for 3 hours by use of liquid chromatography tandem mass spectrometry. Frequency of defecation was recorded during the 3 hours of the study.

Results—Ranitidine increased the contractile activity of the pyloric antrum smooth muscle at a concentration of 10−4 M. No significant effect of ranitidine on plasma kinetics of acetaminophen was identified. Frequency of defecation did not differ between groups.

Conclusions and Clinical Relevance—Ranitidine did increase gastric motility in vitro, but no effect on liquid phase gastric emptying was identified in healthy horses by use of the acetaminophen absorption model. Results do not support the use of ranitidine to promote gastric emptying.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the pharmacokinetics and effects of the morphine antagonist N-methylnaltrexone (MNTX) on gastrointestinal tract function in horses when administered alone and in combination with morphine.

Animals—5 healthy adult horses.

Procedures—Horses were treated with MNTX (1 mg/kg, IV), and serial blood samples were collected for determination of drug pharmacokinetics. For evaluation of effects on the gastrointestinal tract when administered alone, MNTX was administered at a dosage of 0.75 mg/kg, IV, twice daily for 4 days. For evaluation of effects when administered concurrently with morphine, MNTX (0.75 mg/kg, IV, q 12 hours) and morphine (0.5 mg/kg, IV, q 12 hours) were administered for 6 days. Gastrointestinal variables evaluated were defecation frequency, weight of feces produced, fecal moisture content, intestinal transit time, and borborygmus scores.

Results—The time-concentration data for MNTX disposition best fit a 2-compartment model with a steady-state volume of distribution of 244.6 ± 21.8 mL/kg, t1/2 of 47.04 ± 11.65 minutes, and clearance of 11.43 ± 1.06 mL/min/kg. Adverse effects were not observed at doses ≤ 1 mg/kg. Administration of MNTX increased daily fecal weight. When administered concurrently with morphine, MNTX partially prevented the effects of morphine on the gastrointestinal tract by increasing defecation frequency, fecal weight, fecal moisture content, and borborygmus score, and by preventing increases in intestinal transit time.

Conclusions and Clinical Relevance—Because MNTX does not cross the blood-brain barrier, administration of the drug should not alter the analgesic effects of opioids and may attenuate the adverse gastrointestinal effects associated with use of opioids in horses.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of an external nasal dilator strip on cytologic characteristics of bronchoalveolar lavage (BAL) fluid in racing Thoroughbreds.

Design—Clinical trial.

Animals—23 Thoroughbred racehorses in active training.

Procedure—Each horse raced on 2 occasions: once while wearing an external nasal dilator strip and once while not. Bronchoalveolar lavage was performed 12 to 18 hours after each race, and BAL fluid was analyzed for RBC and leukocyte counts and hemosiderin content.

Results—Mean ± SEM count of RBCs in BAL fluid when horses raced without the nasal dilator strip (84.6 ± 27.5 cells/µL) was not significantly different from count when they raced with it (41.7 ± 12.2 cells/µL). Horses were grouped as having mild or severe bleeding on the basis of RBC count in BAL fluid after horses raced without the nasal dilator strip. Mean count when horses with severe bleeding raced without the nasal dilator strip (271.0 ± 63.7 cells/µL) was significantly higher than mean count when these horses raced with the strip (93.8 ± 37.6 cells/µL). Mean count of lymphocytes in BAL fluid was significantly lower after horses raced with the external nasal dilator strip.

Conclusions and Clinical Relevance—Results suggest that use of an external nasal dilator strip in Thoroughbred racehorses may decrease pulmonary bleeding, particularly in horses with severe exerciseinduced pulmonary hemorrhage. ( J Am Vet Med Assoc 2004;224:558–561)

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objectives

To evaluate the role of nitric oxide (NO), vasoactive intestinal peptide (VIP), and a transmitter acting through an apamin-sensitive mechanism in mediating inhibitory transmission in the equine jejunal circular muscle, and to determine the distribution of VIP-and NO-producing nerve fibers in the myenteric plexus and circular muscle.

Procedure

Circular muscle strips were suspended in tissue baths containing an oxygenated modified Krebs solution and attached to isometric force transducers. Responses to electrical field stimulation (EFS), tetrodotoxin, the NO antagonists l-N-nitro-arginine-methyl-ester (L-NAME) and N-nitro-l-arginine, apamin, VIP, authentic NO, and the NO donar sodium nitroprusside were tested. Immunostaining for VIP-like and NADPH diaphorase histochemical staining were performed on paraformaldehyde-fixed tissue.

Results

Subpopulations of myenteric neurons and nerve fibers in the circular muscle were positive for NADPH diaphorase and VIP-like staining. EFS caused a frequency-dependent inhibition of contractile activity. Tetrodotoxin prevented the EFS-induced inhibition of contractions. L-NAME (200 μM) and apamin 0.3 μM) significantly (P < 0.01) reduced EFS-stimulated inhibition of contractile activity at most frequencies tested. The effects of L-NAME and apamin were additive. In their combined presence, EFS induced excitation instead of inhibition (196.7% increase at 5 Hz, n = 28, P < 0.01). Inhibition of contractile activity by EFS was mimicked by sodium nitroprusside. Authentic NO (3-6 μM) abolished contractile activity. VIP induced a dose-dependent inhibition of contractile activity (89.1 ± 6.3% reduction at approximately 0.3 μM, n = 16). Antagonism of NO synthesis did not alter the response to VIP.

Conclusion

NO, VIP, and a substance acting through an apamin-sensitive mechanism appear to comediate inhibitory transmission in the equine jejunal circular muscle.

Clinical Relevance

These findings may suggest new therapeutic targets for motility disorders, such as agents that inhibit the synthesis or actions of NO. (Am J Vet Res 1996;57:1206-1213)

Free access
in American Journal of Veterinary Research

Objective

To determine whether peritoneal fluid pH, glucose concentration, and lactate dehydrogenase activity can be used to differentiate horses with septic peritonitis from those with nonseptic peritonitis.

Design

Prospective study.

Animals

46 horses, including 10 healthy horses, 15 horses with septic peritonitis, and 21 horses with nonseptic peritonitis.

Procedure

Peritoneal fluid and blood samples were analyzed for pH, glucose concentration, and lactate dehydrogenase activity. Complete blood cell counts were performed, and peritoneal fluid samples were submitted for bacterial culture.

Results

Horses with septic peritonitis had significantly lower peritoneal fluid pH and glucose concentrations than horses with nonseptic peritonitis and healthy horses. Compared with other tests, serum-to-peritoneal fluid glucose concentration differences > 50 mg/dl had the highest diagnostic use for detection of septic peritonitis. Peritoneal fluid pH < 7.3, glucose concentration < 30 mg/dl, and fibrinogen concentration > 200 mg/dl were also highly indicative of septic peritonitis.

Clinical Implications

Peritoneal fluid pH and glucose concentration can be used to assist in the identification of horses with septic peritonitis. These measurements can provide an early indication of sepsis, especially if cytologic evaluation of peritoneal fluid is unavailable or results are equivocal and peritoneal fluid bacterial culture results are pending. (J Am Vet Med Assoc 1999;214: 1032–1036)

Free access
in Journal of the American Veterinary Medical Association

Objective

To identify breed, age, sex, physical findings, history, and outcome of treatment in horses and other equids with enterolithiasis.

Design

Retrospective study.

Animals

900 equids with enterolithiasis.

Procedure

Medical records from equids with enterolithiasis admitted between 1973 and 1996 were reviewed. Data on signalment, history, physical examination and clinicopathologic findings, surgical findings, and outcome were compiled from records and from telephone interviews with owners. Sex and breed predilections were determined by comparison of the study population with the general hospital population of equids during the same time period.

Results

Equids with enterolithiasis represented 15.1% of patients admitted for treatment of colic, and 27.5% of patients undergoing celiotomy for treatment of colic. Arabian and Arabian crosses, Morgans, American Saddlebreds, and donkeys were significantly overrepresented, and Thoroughbreds, Standardbreds, warmbloods, and stallions were significantly underrepresented in the study population, compared with the hospital population. The mean age of equids with enterolithiasis was 11.4 years. The most common historic findings were signs of intermittent colic (33.3%) and passage of enteroliths in the feces (13.5%). Physical examination findings were similar to those found in equids with other forms of nonstrangulating large colon obstructive disease. Fifteen percent (131) developed gastrointestinal tract rupture caused by an enterolith that necessitated euthanasia. Short-term and 1-year survival rates for equids undergoing celiotomy for treatment of enterolithiasis and recovering from anesthesia were excellent (96.2 and 92.5%, respectively), and postoperative complications were uncommon. Recurrence of enterolithiasis was identified in 7.7% of the study population.

Clinical Implications

Results indicated that short-term and 1-year survival rates for equids undergoing surgery for enterolithiasis are excellent. Identification of signalment, history, and management factors may help identify equids with a high risk for development of enterolithiasis. (J Am Vet Med Assoc 1999;214;233–237)

Free access
in Journal of the American Veterinary Medical Association