@article{marshall_bhatnagar_bowman_howard_morris_skorich_redding_blikslager_2011, title={Evaluation of the cyclooxygenase selectivity of robenacoxib and its effect on recovery of ischemia-injured jejunal mucosa in horses}, volume={72}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.72.2.226}, DOI={10.2460/ajvr.72.2.226}, abstractNote={AbstractObjective—To determine the cyclooxygenase (COX) selectivity of robenacoxib and its effect on recovery of jejunal mucosa following ischemic injury in horses.
Animals—12 healthy horses.
Procedures—Half the maximal inhibition (EC50) of robenacoxib for COX-1 and COX-2 activity was established in bloods samples from 6 horses via measurement of thromboxane B2 (TXB2) and prostaglandin E2 concentrations, respectively; COX selectivity was subsequently calculated. Six other horses were anesthetized, and ischemia was induced in the jejunum for 2 hours. Control and ischemia-injured mucosa were collected and incubated with Ringer's solution (control treatment), flunixin meglumine (2.7 × 10−5M), or robenacoxib (2.7 × 10−5M). Transepithelial electrical resistance and mannitol flux were measured over a 4-hour recovery period. Bathing solution TXB2 and prostaglandin E metabolite concentrations were measured to assess COX-1 and COX-2 function, respectively.
Results—The mean ± SD EC50 value of robenacoxib for COX-1 and COX-2 was 11.46 ± 4.46μM and 0.19 ± 0.07μM, respectively, resulting in a COX selectivity ratio of 61.01. The transepithelial electrical resistance of ischemia-injured jejunum treated with flunixin meglumine was significantly lower than that of control and robenacoxib-treated tissues. A significant increase in concentrations of prostaglandin E metabolites and TXB2 was detected in control and robenacoxib-treated tissues but not flunixin meglumine—treated tissues.
Conclusions and Clinical Relevance—Robenacoxib selectively inhibited COX-2 and allowed recovery of barrier function in ischemia-injured equine jejunal tissue in vitro.}, number={2}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Marshall, John F and Bhatnagar, Adria S. and Bowman, Susan G. and Howard, Christina M. and Morris, Natalie N. and Skorich, Dinah A. and Redding, Caitlyn D. and Blikslager, Anthony T.}, year={2011}, month={Feb}, pages={226–232} }
 @article{marshall_blikslager_2011, title={The effect of nonsteroidal anti-inflammatory drugs on the equine intestine}, volume={43}, ISSN={0425-1644}, url={http://dx.doi.org/10.1111/j.2042-3306.2011.00398.x}, DOI={10.1111/j.2042-3306.2011.00398.x}, abstractNote={SummaryNonsteroidal anti‐inflammatory drugs (NSAIDs) are commonly used in the management of pain and endotoxaemia associated with colic in the horse. While NSAIDs effectively treat the symptoms of colic, there is evidence to suggest that their administration is associated with adverse gastrointestinal effects including right dorsal colitis and inhibition of mucosal barrier healing. Several studies have examined the pathophysiology of NSAID associated effects on the large and small intestine in an effort to avoid these complications and identify effective alternative medications. Differences in the response of the large and small intestines to injury and NSAID treatment have been identified. Flunixin meglumine has been shown in the small intestine to inhibit barrier function recovery and increase permeability to lipopolysaccharide (LPS). A range of NSAIDs has been examined in the small intestine and experimental evidence suggests that those NSAIDs with cyclooxygenase independent anti‐inflammatory effects or a COX‐2 selective mode of action may offer significant advantages over traditional NSAIDs.}, number={SUPPL.39}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Marshall, J. F. and Blikslager, A. T.}, year={2011}, month={Jul}, pages={140–144} }
 @article{marshall_bhatnagar_bowman_morris_skorich_redding_blikslager_2011, title={The effects of a novel anti-inflammatory compound (AHI-805) on cyclooxygenase enzymes and the recovery of ischaemia injured equine jejunum ex vivo}, volume={43}, ISSN={0425-1644}, url={http://dx.doi.org/10.1111/j.2042-3306.2011.00401.x}, DOI={10.1111/j.2042-3306.2011.00401.x}, abstractNote={SummaryReasons for performing study:Flunixin meglumine is used for treatment of equine colic despite evidence of inhibited recovery of mucosal barrier function following small intestinal ischaemic injury. This study aimed to characterise an alternative treatment (AHI‐805) for abdominal pain in the horse.Objective:To determine the effect of AHI‐805, an aza‐thia‐benzoazulene derivative, on the cyclooxygenase enzymes and the recovery of mucosal barrier function following ischaemic injury.Methods:Effect of AHI‐805 onin vitroCOX‐1 and COX‐2 activity was determined by measuring coagulation‐induced thromboxane B2(TXB2) and lipopolysaccharide‐stimulated prostaglandin E2concentrations in equine whole blood. Horses (n = 6) were anaesthetised and jejunum subjected to ischaemia for 2 h. Control and ischaemia injured mucosa was placed in Ussing chambers and treated with Ringer's solution containing control treatment (DMSO), flunixin meglumine (27 µmol/l), or AHI‐805 (27 µmol/l). Transepithelial electrical resistance (TER), mucosal‐to‐serosal flux of3H‐mannitol, and bathing solution TXB2and prostaglandin E metabolites (PGEM) were measured over a 4 h recovery period.Results:Treatment with AHI‐805 had no significant effect on TXB2production but significantly inhibited production of PGE2at a concentration of 1 µmol/l or greater. TER of flunixin or AHI‐805 treated ischaemia‐injured jejunum was significantly lower than control treated injured tissue over the recovery period. Mannitol flux and grade of histological damage were significantly increased by ischaemic injury only. There was a significant increase in PGEM and TXB2in control tissues over the 240 min recovery period, but not in flunixin or AHI‐805 treated tissues.Conclusions:Flunixin meglumine and AHI‐805 inhibit recovery of barrier function in ischaemic‐injured equine jejunumin vitrothrough inhibition of the COX enzymes.Potential relevance:The novel compound AHI‐805 may not be suitable for the treatment of equine colic associated with ischaemic injury.}, number={SUPPL.39}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Marshall, J. F. and Bhatnagar, A. S. and Bowman, S. G. and Morris, N. N. and Skorich, D. A. and Redding, C. D. and Blikslager, A. T.}, year={2011}, month={Jul}, pages={106–111} }
 @article{bowman_marshall_blikslager_2010, title={Demographic characteristics of horses donated to the North Carolina State University Equine Health Center, 1996–2008}, volume={236}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.236.12.1334}, DOI={10.2460/javma.236.12.1334}, abstractNote={Abstract
Objective—To determine demographic characteristics of horses donated to the North Carolina State University Equine Health Center (EHC) between 1996 and 2008.
Design—Retrospective cohort study.
Animals—122 horses donated to the EHC between January 1996 and December 2008, and 246 horses offered for donation to the EHC between January 2007 and December 2008.
Procedures—Telephone and medical records were examined. Data were collected in 5 categories: age, sex, breed, reason for donation, and use prior to donation.
Results—From January 1996 through December 2008, 122 horses were donated to the EHC (median, 3 horses/y; range, 0 to 39 horses/y). There were 131 and 115 horses offered for donation during 2007 and 2008, respectively, of which 38 and 23 were accepted. Mean ± SD age of horses offered for donation during 2007 and 2008 was 12.7 ± 6.7 years, with 75 of the 246 (30.5%) horses between 6 and 10 years old. Musculoskeletal disease was the most commonly listed reason horses were offered for donation (115/240 [47.9%]).
Conclusions and Clinical Relevance—Results indicated that unwanted horses donated to the EHC between 1996 and 2008 spanned a wide range of ages and breeds and included both males and females. The most common reason given for unwanted horses offered for donation during 2007 and 2008 was musculoskeletal disease, with degenerative joint disease, lameness of undetermined cause, laminitis, and navicular disease being the most common musculoskeletal conditions.}, number={12}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Bowman, Susan G. and Marshall, John F. and Blikslager, Anthony T.}, year={2010}, month={Jun}, pages={1334–1337} }
 @article{davis_marshall_papich_blikslager_campbell_2011, title={The pharmacokinetics and in vitro cyclooxygenase selectivity of deracoxib in horses}, volume={34}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/j.1365-2885.2010.01185.x}, DOI={10.1111/j.1365-2885.2010.01185.x}, abstractNote={Davis, J. L., Marshall, J. F., Papich, M. G., Blikslager, A. T., Campbell, N. B. The pharmacokinetics and in vitro cyclooxygenase selectivity of deracoxib in horses. J. vet. Pharmacol. Therap.34, 12–16.The purpose of this study was to determine the pharmacokinetics of deracoxib following oral administration to horses. In addition, in vitro equine whole blood cyclooxygenase (COX) selectivity assays were performed. Six healthy adult horses were administered deracoxib (2 mg/kg) orally. Plasma samples were collected prior to drug administration (time 0), and 10, 20, 40 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after administration for analysis with high pressure liquid chromatography using ultraviolet detection. Following PO administration, deracoxib had a long elimination half‐life (t1/2k10) of 12.49 ± 1.84 h. The average maximum plasma concentration (Cmax) was 0.54 μg/mL, and was reached at 6.33 ± 3.44 h. Bioavailability was not determined because of the lack of an IV formulation. Results of in vitro COX selectivity assays showed that deracoxib was selective for COX‐2 with a COX‐1/COX‐2 ratio of 25.67 and 22.06 for the IC50 and IC80, respectively. Dosing simulations showed that concentrations above the IC80 for COX‐2 would be maintained following 2 mg/kg PO q12h, and above the IC50 following 2 mg/kg PO q24h. This study showed that deracoxib is absorbed in the horse after oral administration, and may offer a useful alternative for anti‐inflammatory treatment of various conditions in the horse.}, number={1}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Davis, J. L. and Marshall, J. F. and Papich, M. G. and Blikslager, A. T. and Campbell, N. B.}, year={2011}, month={Jan}, pages={12–16} }
 @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{moorman_marshall_devine_payton_jann_bahr_2009, title={COMPARISON OF FLAT-PANEL DIGITAL TO CONVENTIONAL FILM-SCREEN RADIOGRAPHY IN DETECTION OF EXPERIMENTALLY CREATED LESIONS OF THE EQUINE THIRD METACARPAL BONE}, volume={50}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.2009.01586.x}, abstractNote={Radiographic diagnosis of equine bone disease using digital radiography is prevalent in veterinary practice. However, the diagnostic quality of digital vs. conventional radiography has not been compared systematically. We hypothesized that digital radiography would be superior to film‐screen radiography for detection of subtle lesions of the equine third metacarpal bone. Twenty‐four third metacarpal bones were collected from horses euthanized for reasons other than orthopedic disease. Bones were dissected free of soft tissue and computed tomography was performed to ensure that no osseous abnormalities were present. Subtle osseous lesions were produced in the dorsal cortex of the third metacarpal bones, and the bones were radiographed in a soft tissue phantom using indirect digital and conventional radiography at standard exposures. Digital radiographs were printed onto film. Three Diplomates of the American College of Veterinary Radiology evaluated the radiographs for the presence or absence of a lesion. Receiver operator characteristic curves were constructed, and the area under these curves were compared to assess the ability of the digital and film‐screen radiographic systems to detect lesions. The area under the ROC curves for film‐screen and digital radiography were 0.87 and 0.90, respectively (P=0.59). We concluded that the digital radiographic system was comparable to the film‐screen system for detection of subtle lesions of the equine third metacarpal bone.}, number={6}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Moorman, Valerie J. and Marshall, John F. and Devine, Dustin V. and Payton, Mark and Jann, Henry W. and Bahr, Robert}, year={2009}, pages={577–583} }