@article{wooten_lascelles_cook_law_blikslager_2010, title={Evaluation of the relationship between lesions in the gastroduodenal region and cyclooxygenase expression in clinically normal dogs}, volume={71}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.71.6.630}, DOI={10.2460/ajvr.71.6.630}, abstractNote={Abstract
Objective—To determine whether clinically normal dogs have lesions in the pylorus and duodenum and to examine the expression of cyclooxygenase (COX) isoforms in the pylorus and duodenum of these dogs.
Animals—27 clinically normal dogs.
Procedures—Physical examination was performed on clinically normal dogs from animal shelters and research projects; the dogs were then euthanized. After the dogs were euthanized, the pylorus and duodenum were photographed and scored for gross appearance of lesions. Samples were obtained for histologic evaluation and determination of COX expression via western blot analyses. Tissues from the pylorus and duodenum were categorized as normal, inflamed, or eroded on the basis of histologic analysis. Each histologic category of tissue was then evaluated to determine the correlation with gross appearance and COX expression.
Results—Of the 27 dogs, 5 had unremarkable histologic findings in the pylorus and duodenum. Inflammation was found in the pylorus of 10 dogs and in the duodenum of 5 dogs. Epithelial erosion was detected in the pylorus of 1 dog and in the duodenum of 3 dogs. Gross appearance was not significantly correlated with histologic appearance. Expression of COX-1 was not upregulated by inflammation, whereas COX-2 expression was increased by inflammation or erosion.
Conclusions and Clinical Relevance—Dogs that appear to be clinically normal may have underlying gastroduodenal lesions associated with upregulation of COX-2. Because of the inability to determine this during routine physical examination, practitioners should be aware of this potential situation when prescribing COX inhibitors.}, number={6}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Wooten, Jenna G. and Lascelles, B. Duncan X. and Cook, Vanessa L. and Law, J. Mac and Blikslager, Anthony T.}, year={2010}, month={Jun}, pages={630–635} }
 @article{cook_jones shults_mcdowell_campbell_davis_marshall_blikslager_2009, title={Anti-inflammatory effects of intravenously administered lidocaine hydrochloride on ischemia-injured jejunum in horses}, volume={70}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.70.10.1259}, DOI={10.2460/ajvr.70.10.1259}, abstractNote={Abstract
Objective—To investigate effects of lidocaine hydrochloride administered IV on mucosal inflammation in ischemia-injured jejunum of horses treated with flunixin meglumine.
Animals—24 horses.
Procedures—Horses received saline (0.9% NaCl) solution (SS; 1 mL/50 kg, IV [1 dose]), flunixin meglumine (1 mg/kg, IV, q 12 h), lidocaine (bolus [1.3 mg/kg] and constant rate infusion [0.05 mg/kg/min], IV, during and after recovery from surgery), or both flunixin and lidocaine (n = 6/group). During surgery, blood flow was occluded for 2 hours in 2 sections of jejunum in each horse. Uninjured and ischemia-injured jejunal specimens were collected after the ischemic period and after euthanasia 18 hours later for histologic assessment and determination of cyclooxygenase (COX) expression (via western blot procedures). Plasma samples collected prior to (baseline) and 8 hours after the ischemic period were analyzed for prostanoid concentrations.
Results—Immediately after the ischemic period, COX-2 expression in horses treated with lidocaine alone was significantly less than expression in horses treated with SS or flunixin alone. Eighteen hours after the ischemic period, mucosal neutrophil counts in horses treated with flunixin alone were significantly higher than counts in other treatment groups. Compared with baseline plasma concentrations, postischemia prostaglandin E2 metabolite and thromboxane B2 concentrations increased in horses treated with SS and in horses treated with SS or lidocaine alone, respectively.
Conclusions and Clinical Relevance—In horses with ischemia-injured jejunum, lidocaine administered IV reduced plasma prostaglandin E2 metabolite concentration and mucosal COX-2 expression. Coadministration of lidocaine with flunixin ameliorated the flunixin-induced increase in mucosal neutrophil counts.}, number={10}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Cook, Vanessa L. and Jones Shults, Jennifer and McDowell, Marsha R. and Campbell, Nigel B. and Davis, Jennifer L. and Marshall, John F. and Blikslager, Anthony T.}, year={2009}, month={Oct}, pages={1259–1268} }
 @article{cook_meyer_campbell_blikslager_2009, title={Effect of firocoxib or flunixin meglumine on recovery of ischemic-injured equine jejunum}, volume={70}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.70.8.992}, DOI={10.2460/ajvr.70.8.992}, abstractNote={Abstract
Objective—To determine whether treatment of horses with firocoxib affects recovery of ischemic-injured jejunum, while providing effective analgesia.
Animals—18 horses.
Procedures—Horses (n = 6 horses/group) received saline (0.9% NaCl) solution (1 mL/50 kg, IV), flunixin meglumine (1.1 mg/kg, IV, q 12 h), or firocoxib (0.09 mg/kg, IV, q 24 h) before 2 hours of jejunal ischemia. Horses were monitored via pain scores and received butorphanol for analgesia. After 18 hours, ischemic-injured and control mucosa were placed in Ussing chambers for measurement of transepithelial resistance and permeability to lipopolysaccharide. Histomorphometry was used to determine denuded villus surface area. Western blots for cyclooxygenase (COX)-1 and COX-2 were performed. Plasma thromboxane B2 and prostaglandin E2 metabolite (PGEM) concentrations were determined.
Results—Pain scores did not significantly increase after surgery in horses receiving flunixin meglumine or firocoxib. Transepithelial resistance of ischemic-injured jejunum from horses treated with flunixin meglumine was significantly lower than in saline- or firocoxib-treated horses. Lipopolysaccharide permeability across ischemic-injured mucosa was significantly increased in horses treated with flunixin meglumine. Treatment did not affect epithelial restitution. Cyclooxygenase-1 was constitutively expressed and COX-2 was upregulated after 2 hours of ischemia. Thromboxane B2 concentration decreased with flunixin meglumine treatment but increased with firocoxib or saline treatment. Flunixin meglumine and firocoxib prevented an increase in PGEM concentration after surgery.
Conclusions and Clinical Relevance—Flunixin meglumine retarded mucosal recovery in ischemic-injured jejunum, whereas firocoxib did not. Flunixin meglumine and firocoxib were effective visceral analgesics. Firocoxib may be advantageous in horses recovering from ischemic intestinal injury.}, number={8}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Cook, Vanessa L. and Meyer, Colleen T. and Campbell, Nigel B. and Blikslager, Anthony T.}, year={2009}, month={Aug}, pages={992–1000} }
 @article{cook_neuder_blikslager_jones_2009, title={The effect of lidocaine on in vitro adhesion and migration of equine neutrophils}, volume={129}, ISSN={0165-2427}, url={http://dx.doi.org/10.1016/j.vetimm.2008.12.017}, DOI={10.1016/j.vetimm.2008.12.017}, abstractNote={The effect of lidocaine on in vitro migration and adhesion of equine neutrophils was evaluated. Neutrophils were isolated from equine whole blood using a Percoll-gradient centrifugation protocol. Purified neutrophils were incubated with lidocaine at concentrations from 0.1 to 1000 μg/ml for 30 min at 37 °C, after calcein loading. Neutrophil integrin-mediated adhesion in response to stimulation with 100 nM LTB4, 100 nM PAF, or 100 ng/ml IL-8, or integrin-mediated migration in response to stimulation with 100 nM LTB4, 150 nM PAF, or 100 ng/ml IL-8 was assessed. Statistical significance was set at P < 0.05. Neutrophil adhesion was significantly increased in response to all three stimulants. IL-8-stimulated adhesion was significantly increased when neutrophils were incubated with 1 mg/ml lidocaine, compared to lower lidocaine concentrations. LTB4-stimulated adhesion was significantly increased when neutrophils were incubated with 1 mg/ml lidocaine compared to that at 5 μg/ml lidocaine. Migration was significantly increased in response to IL-8. IL-8 and LTB4 stimulated migration was significantly increased when neutrophils were incubated with 1 mg/ml lidocaine, compared to lower lidocaine concentrations. In conclusion, lidocaine did not inhibit neutrophil migration or adhesion in vitro at therapeutic concentrations, and increased migration and adhesion at higher concentrations.}, number={1-2}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Cook, Vanessa L. and Neuder, Laura E. and Blikslager, Anthony T. and Jones, Samuel L.}, year={2009}, month={May}, pages={137–142} }
 @article{sheats_cook_jones_blikslager_pease_2009, title={Use of ultrasound to evaluate outcome following colic surgery for equine large colon volvulus}, volume={42}, ISSN={0425-1644 2042-3306}, url={http://dx.doi.org/10.2746/042516409X456040}, DOI={10.2746/042516409X456040}, abstractNote={SummaryReasons for performing study:The post operative response of the large colon wall after a surgically corrected large colon volvulus (LCV) has not been investigated.Objectives:To use transabdominal ultrasound to monitor the post operative change in large colon wall thickness following surgical correction of LCV.Hypothesis:A prolonged period to colon wall involution is correlated with an increased rate of post operative morbidity and mortality.Methods:A prospective clinical study including horses that presented to the North Carolina State University Veterinary Teaching Hospital for colic between September 2006 and March, 2008, had surgically diagnosed and corrected LCV (at least 360°) without resection and recovered from anaesthesia. Ultrasound of the ventral large colon was performed at the time of anaesthetic recovery and every 6–8 h until the colon wall returned to normal thickness (≤5 mm). Outcome was evaluated using a one‐way ANOVA to compare average time to colon wall involution between: 1) survivors and nonsurvivors; and 2) horses that developed multiple organ dysfunction syndrome (MODS) during the post operative period and those that recovered without evidence of MODS.Results:Sixteen horses that recovered without evidence of MODS had a significantly shorter period to colon wall involution (≤5 mm) compared to those diagnosed with MODS (mean ± s.e. 19.6 h ± 2.5 and 39.7 h ± 6.7 respectively, P = 0.006). There was no significant difference in mean period to colon wall involution between survivors and nonsurvivors (26.2 ± 4.9 and 33.2 ± 7.8 h, respectively).Conclusions:A shorter time to colon wall involution was associated with decreased post operative morbidity in horses presented for surgical correction of large colon volvulus without resection.Potential relevance:Ultrasonographic monitoring of colon wall involution after surgical correction of LCV may aid in identifying those cases at risk of MODS. Further investigation of colon wall involution time using a larger number of horses is warranted.}, number={1}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Sheats, M. K. and Cook, V. L. and Jones, S. L. and Blikslager, A. T. and Pease, A. P.}, year={2009}, month={Dec}, pages={47–52} }
 @article{cook_shults_mcdowell_campbell_davis_blikslager_2008, title={Attenuation of ischaemic injury in the equine jejunum by administration of systemic lidocaine}, volume={40}, DOI={10.2746/04251640SX293574}, number={4}, journal={Equine Veterinary Journal}, author={Cook, V. L. and Shults, J. J. and McDowell, M. and Campbell, N. B. and Davis, J. L. and Blikslager, Anthony}, year={2008}, pages={353–357} }
 @article{cook_blikslager_2008, title={Use of systemically administered lidocaine in horses with gastrointestinal tract disease}, volume={232}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.232.8.1144}, DOI={10.2460/javma.232.8.1144}, number={8}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Cook, Vanessa L. and Blikslager, Anthony T.}, year={2008}, month={Apr}, pages={1144–1148} }
 @article{moeser_klok_ryan_wooten_little_cook_blikslager_2007, title={Stress signaling pathways activated by weaning mediate intestinal dysfunction in the pig}, volume={292}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00197.2006}, DOI={10.1152/ajpgi.00197.2006}, abstractNote={Weaning in the piglet is a stressful event associated with gastrointestinal disorders and increased disease susceptibility. Although stress is thought to play a role in postweaning intestinal disease, the mechanisms by which stress influences intestinal pathophysiology in the weaned pig are not understood. The objectives of these experiments were to investigate the impact of weaning on gastrointestinal health in the pig and to assess the role of stress signaling pathways in this response. Nineteen-day-old pigs were weaned, and mucosal barrier function and ion transport were assessed in jejunal and colonic tissues mounted on Ussing chambers. Weaning caused marked disturbances in intestinal barrier function, as demonstrated by significant ( P < 0.01) reductions in transepithelial electrical resistance and increases in intestinal permeability to [3H]mannitol in both the jejunum and colon compared with intestinal tissues from age-matched, unweaned control pigs. Weaned intestinal tissues exhibited increased intestinal secretory activity, as demonstrated by elevated short-circuit current that was sensitive to treatment with tetrodotoxin and indomethacin, suggesting activation of enteric neural and prostaglandin synthesis pathways in weaned intestinal tissues. Western blot analyses of mucosal homogenates showed increased expression of corticotrophin-releasing factor (CRF) receptor 1 in the jejunum and colon of weaned intestinal tissues. Pretreatment of pigs with the CRF receptor antagonist α-helical CRF(9–41), which was injected intraperitoneally 30 min prior to weaning, abolished the stress-induced mucosal changes. Our results indicate that weaning stress induces mucosal dysfunction mediated by intestinal CRF receptors and activated by enteric nerves and prostanoid pathways.}, number={1}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Moeser, Adam J. and Klok, Carin Vander and Ryan, Kathleen A. and Wooten, Jenna G. and Little, Dianne and Cook, Vanessa L. and Blikslager, Anthony T.}, year={2007}, month={Jan}, pages={G173–G181} }