@article{martin_sarkan_viall_hostetter_epstein_2024, title={Clinicopathologic Parameters of Peritoneal Fluid as Predictors of Gastrointestinal Lesions, Complications, and Outcomes in Equine Colic Patients: A Retrospective Study}, volume={15}, ISSN={2076-2615}, url={http://dx.doi.org/10.3390/ani15010012}, DOI={10.3390/ani15010012}, abstractNote={Neutrophil characteristics in peritoneal fluid (PF) may aid in diagnosing and treating specific colic lesions and complications. The objective of this retrospective study was to evaluate quantitative PF leukocyte values, as well as PF total protein (TP) and lactate, for associations with diagnosis, morbidity, and mortality in horses with acute colic. Three hundred and forty-two horses that presented to one institution between January 2010–2020 for the evaluation of acute colic were included. The PF total nucleated cell count (TNCC), % and total neutrophil counts, total protein (TP), and lactate were analyzed for associations with lesion location and type, the development of postoperative reflux (POR) or systemic inflammatory response syndrome (SIRS), and survival to discharge via Kruskal–Wallis testing. Horses with strangulating lesions had higher PF % neutrophils, neutrophil count, and TNCC compared to non-strangulating lesions. The development of SIRS or POR was associated with higher PF TNCC, total neutrophil count, TP, and lactate. Horses that did not survive to discharge had increased PF % neutrophils, neutrophil count, TP, lactate, and ratio of PF-to-systemic TP than those that survived via univariable analysis. Identified associations between increased PF neutrophils and the development of POR and SIRS warrant further investigation to better understand their role in the pathogenesis of equine colic and potential as targets for therapeutic intervention.}, number={1}, journal={Animals}, publisher={MDPI AG}, author={Martin, Emily and Sarkan, Kate and Viall, Austin and Hostetter, Shannon and Epstein, Kira}, year={2024}, month={Dec}, pages={12} }
 @inproceedings{martin_gordon_schirmer_peroni_2024, place={Phoenix, Arizona}, title={Equine Bone Marrow-Derived Mesenchymal Stem Cell Extracellular Vesicles Enhance Production of Neutrophil-Derived Antibacterial Reactive Oxygen Species in Vitro}, volume={53}, url={https://doi.org/10.1111/vsu.14148}, DOI={10.1111/vsu.14148}, booktitle={Veterinary Surgery}, author={Martin, E.M. and Gordon, J. and Schirmer, J. and Peroni, J.}, year={2024}, pages={O1–O73} }
 @article{brandon_williams_davis_martin_capper_crabtree_2024, title={Evaluation of pharmacokinetics of metoclopramide administered via subcutaneous bolus and intravenous constant rate infusion to adult horses}, volume={53}, ISSN={0161-3499 1532-950X}, url={http://dx.doi.org/10.1111/vsu.14128}, DOI={10.1111/vsu.14128}, abstractNote={Abstract Objective To determine the pharmacokinetics (PK) of metoclopramide administered via intravenous continuous rate infusion (IV CRI) and subcutaneous (SC) bolus and evaluate for gastrointestinal motility and adverse side effects. Study design Experimental study; randomized, crossover design. Animals Six healthy adult horses. Methods Each horse received metoclopramide via IV CRI (0.04 mg/kg/h for 24 h) and SC bolus (0.08 mg/kg once), with ≥1 week washout period between. Plasma was analyzed by UPLC‐MS/MS. Compartmental modeling was used to determine PK parameters for each treatment; nonparametric superposition was used to simulate multiple SC bolus regimens. Gastrointestinal motility and evidence of adverse effects were monitored. Results T max (h) for SC bolus was 0.583 ± 0.204 versus 17.3 ± 6.41 for IV CRI, while C max (ng/mL) was 27.7 ± 6.38 versus 43.6 ± 9.97, respectively. AUC (h × ng/mL) was calculated as 902 ± 189 for 24 h IV CRI versus 244 ± 37.4 simulated for 0.08 mg/kg SC bolus every 8 h. Simulations revealed similar exposure between groups with administration of 0.96 mg/kg/day SC bolus, divided into three, four, or six doses. SC bolus bioavailability was estimated as 110 ± 11.5%. No clear trends in motility alteration were identified. No adverse effects were noted. Conclusion Repeated SC boluses of metoclopramide at 0.08 mg/kg would result in lower total drug exposure and T max than IV CRI administration but would be highly bioavailable. Clinical significance Higher and/or more frequent SC bolus doses are needed to achieve a similar AUC to IV CRI. No adverse effects were noted; however, evaluation of alternative dosing strategies is warranted.}, number={6}, journal={Veterinary Surgery}, publisher={Wiley}, author={Brandon, Amy M. and Williams, Jarred M. and Davis, Jen L. and Martin, Emily G. and Capper, Ava M. and Crabtree, Naomi E.}, year={2024}, month={Jun}, pages={1111–1122} }
 @article{hobbs_le sueur_hallowell_martin_sheats_ueda_2024, title={Use of extracorporeal hemoperfusion therapy in an adult horse with <i>Clostridioides difficile</i> colitis and severe systemic inflammatory response syndrome}, volume={38}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/jvim.17154}, DOI={10.1111/jvim.17154}, abstractNote={An 8-year-old American Quarter Horse gelding was treated with extracorporeal hemoperfusion (HP) therapy for treatment of Clostridioides difficile (C. difficile) colitis-induced systemic inflammatory response syndrome (SIRS). The gelding developed C. difficile associated peracute colitis and severe SIRS as evidenced by a positive fecal C. difficile PCR and tachypnea, tachycardia, fever, neutropenia, altered mucous membrane color, and hyperlactatemia. Concurrent acute kidney injury in the horse limited the use of routine anti-inflammatory and anti-lipopolysaccharide treatments, including flunixin meglumine and polymyxin B, because of potential for nephrosis. Extracorporeal HP therapy was performed twice within 48 hours of the onset of severe SIRS during which the horse's physical examination variables stabilized. The horse was euthanized after 4 days because of laminitis. These findings support further investigation of extracorporeal HP therapy as an adjunctive treatment for severe SIRS/sepsis in horses.}, number={5}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Hobbs, Kallie J. and Le Sueur, Andre N. V. and Hallowell, Kimberly and Martin, Emily and Sheats, Mary Katherine and Ueda, Yu}, year={2024}, month={Aug}, pages={2790–2794} }
 @inproceedings{martin_sarkan_macy_viall_hostetter_epstein_2021, title={Clinicopathologic parameters of equine abdominal fluid as predictors of postoperative reflux and survival: a retrospective analysis}, booktitle={Proceedings of the International Veterinary Emergency and Critical Care Symposium}, author={Martin, E.M. and Sarkan, K.E. and Macy, G. and Viall, A.K. and Hostetter, S.J. and Epstein, K.E.}, year={2021}, month={Sep} }
 @article{martin_schirmer_jones_davis_2018, title={Pharmacokinetics and ex vivo anti‐inflammatory effects of oral misoprostol in horses}, volume={51}, ISSN={0425-1644 2042-3306}, url={http://dx.doi.org/10.1111/evj.13024}, DOI={10.1111/evj.13024}, abstractNote={Misoprostol is an E prostanoid (EP) 2, 3 and 4 receptor agonist that is anecdotally used to treat and prevent NSAID-induced GI injury in horses. Misoprostol elicits anti-inflammatory effects in vivo in men and rodents, and inhibits TNFα production in equine leucocytes in vitro.Define the pharmacokinetic parameters of oral misoprostol in horses, and determine the inhibitory effect of oral misoprostol administration on equine leucocyte TNFα production in an ex vivo inflammation model.Pharmacokinetic study, ex vivo experimental study.Six healthy adult horses of mixed breeds were used. In phase one, horses were given 5 μg/kg misoprostol orally, and blood was collected at predetermined times for determination of misoprostol free acid (MFA) by UHPLC-MS/MS. Pharmacokinetic parameters were calculated. In phase two, horses were dosed as in phase one, and blood was collected at T0, 0.5, 1 and 4 h following misoprostol administration for leucocyte isolation. Leucocytes were stimulated with 100 ng/mL LPS, and TNFα mRNA concentrations were determined via quantitative real-time PCR.About 5 μg/kg oral misoprostol produced a rapid time to maximum concentration (Tmax ) of 23.4 ± 2.4 min, with a maximum concentration (Cmax ) of 0.29 ± 0.07 ng/mL and area under the curve (AUC0-∞ ) of 0.4 ± 0.12 h ng/mL. LPS stimulation of equine leucocytes ex vivo significantly increased TNFα mRNA concentrations, and there was no significant effect of misoprostol even at the Tmax .Only a single dose was used, and sample size was small.Misoprostol is rapidly absorbed following oral administration in horses, and a single 5 μg/kg dose had no significant inhibitory effect on ex vivo LPS-stimulated TNFα mRNA production in leucocytes. Further studies analysing different dosing strategies, including repeat administration or combination with other anti-inflammatory drugs, are warranted.}, number={3}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Martin, E. M. and Schirmer, J. M. and Jones, S. L. and Davis, J. L.}, year={2018}, month={Oct}, pages={415–421} }
 @article{davis_schirmer_medlin_2018, title={Pharmacokinetics, pharmacodynamics and clinical use of trazodone and its active metabolite <i>m‐</i>chlorophenylpiperazine in the horse}, volume={41}, ISSN={0140-7783 1365-2885}, url={http://dx.doi.org/10.1111/jvp.12477}, DOI={10.1111/jvp.12477}, abstractNote={Trazodone is a serotonin receptor antagonist and reuptake inhibitor used extensively as an anxiolytic in human and small animal veterinary medicine. The aims of this study were to determine the pharmacokinetics of oral trazodone in experimental horses and to evaluate the effect of oral trazodone in clinical horses. Six experimental horses were administered trazodone at 7.5 or 10 mg/kg. Plasma concentrations of trazodone and its metabolite (m‐ CPP ) were determined via UPLC ‐ MS / MS . Noncompartmental pharmacokinetic analysis, sedation and ataxia scores were determined. Trazodone was rapidly absorbed after oral administration with a maximum concentration of 2.5–4.1 μg/ml and half‐life of the terminal phase of approximately 7 hr. The metabolite was present at low levels in all horses, representing only 2.5% of the total area under the curve. In experimental horses, concentration‐dependent sedation and ataxia were noted, lasting up to 12 hr. For clinical cases, medical records of horses treated with trazodone for various abnormal behaviours were reviewed and data were summarized. Trazodone was successful in modifying behavioural problems to some degree in 17 of 18 clinical cases. Tolerance and subsequent lack of drug effect occurred in two of 18 clinical cases following 14 or 21 days of use. In both populations of horses, adverse effects attributed to trazodone include oversedation, muscle fasciculations and transient arrhythmias.}, number={3}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Davis, J. L. and Schirmer, J. and Medlin, E.}, year={2018}, month={Jan}, pages={393–401} }
 @article{martin_jones_2017, title={Inhibition of microsomal prostaglandin E-synthase-1 (mPGES-1) selectively suppresses PGE 2 in an in vitro equine inflammation model}, volume={192}, ISSN={0165-2427}, url={http://dx.doi.org/10.1016/j.vetimm.2017.09.008}, DOI={10.1016/j.vetimm.2017.09.008}, abstractNote={Inhibition of prostaglandin E2 (PGE2) production effectively limits inflammation in horses, however nonspecific prostaglandin blockade via cyclooxygenase (COX) inhibition elicits deleterious gastrointestinal side effects in equine patients. Thus, more selective PGE2 targeting therapeutics are needed to treat inflammatory disease in horses. One potential target is microsomal prostaglandin E-synthase-1 (mPGES-1), which is the terminal enzyme downstream of COX-2 in the inducible PGE2 synthesis cascade. This enzyme has yet to be studied in equine leukocytes, which play a pivotal role in equine inflammatory disease. The objective of this study was to determine if mPGES-1 is a PGE2-selective anti-inflammatory target in equine leukocytes. To evaluate this objective, leukocyte-rich plasma (LRP) was isolated from equine whole blood collected via jugular venipuncture of six healthy adult horses of mixed breeds and genders. LRP was primed with granulocyte-monocyte colony-stimulating factor (GM-CSF) and stimulated with lipopolysaccharide (LPS) in the presence or absence of an mPGES-1 inhibitor (MF63), a COX-2 inhibitor (NS-398), or a nonselective COX inhibitor (indomethacin). Following treatment, mPGES-1 and COX-2 mRNA and protein levels were measured via qPCR and western blot, respectively, and PGE2, thromboxane (TXA2) and prostacyclin (PGI2) levels were measured in cellular supernatants via ELISA. This study revealed that LPS significantly increased mPGES-1 mRNA, but not protein levels in equine LRP as measured by qPCR and western blot, respectively. In contrast, COX-2 mRNA and protein were coordinately induced by LPS. Importantly, treatment of LPS-stimulated leukocytes with indomethacin and NS-398 significantly reduced extracellular concentrations of multiple prostanoids (PGE2, TXA2 and PGI2), while the mPGES-1 inhibitor MF63 selectively inhibited PGE2 production only. mPGES-1 inhibition also preserved higher basal levels of PGE2 production when compared to either COX inhibitor, which might be beneficial in a clinical setting. In conclusion, this work identifies mPGES-1 as a key regulator of PGE2 production and a PGE2-selective target in equine leukocytes. This study demonstrates that mPGES-1 is a potentially safer and effective therapeutic target for treatment of equine inflammatory disease when compared to traditional non-steroidal anti-inflammatory drugs.}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Martin, Emily M. and Jones, Samuel L.}, year={2017}, month={Oct}, pages={33–40} }
 @article{martin_till_sheats_jones_2017, title={Misoprostol Inhibits Equine Neutrophil Adhesion, Migration, and Respiratory Burst in an In Vitro Model of Inflammation}, volume={4}, ISSN={2297-1769}, url={http://dx.doi.org/10.3389/fvets.2017.00159}, DOI={10.3389/fvets.2017.00159}, abstractNote={In many equine inflammatory disease states, neutrophil activities, such as adhesion, migration, and reactive oxygen species (ROS) production become dysregulated. Dysregulated neutrophil activation causes tissue damage in horses with asthma, colitis, laminitis, and gastric glandular disease. Non-steroidal anti-inflammatory drugs do not adequately inhibit neutrophil inflammatory functions and can lead to dangerous adverse effects. Therefore, novel therapies that target mechanisms of neutrophil-mediated tissue damage are needed. One potential neutrophil-targeting therapeutic is the PGE1 analog, misoprostol. Misoprostol is a gastroprotectant that induces intracellular formation of the secondary messenger molecule cyclic AMP (cAMP), which has been shown to have anti-inflammatory effects on neutrophils. Misoprostol is currently used in horses to treat NSAID-induced gastrointestinal injury; however, its effects on equine neutrophils have not been determined. We hypothesized that treatment of equine neutrophils with misoprostol would inhibit equine neutrophil adhesion, migration, and ROS production, in vitro. We tested this hypothesis using isolated equine peripheral blood neutrophils collected from 12 healthy adult teaching/research horses of mixed breed and gender. The effect of misoprostol treatment on adhesion, migration, and respiratory burst of equine neutrophils was evaluated via fluorescence-based adhesion and chemotaxis assays, and luminol-enhanced chemiluminescence, respectively. Neutrophils were pretreated with varying concentrations of misoprostol, vehicle, or appropriate functional inhibitory controls prior to stimulation with LTB4, CXCL8, PAF, lipopolysaccharide (LPS) or immune complex (IC). This study revealed that misoprostol pretreatment significantly inhibited LTB4-induced adhesion, LTB4-, CXCL8-, and PAF-induced chemotaxis, and LPS-, IC-, and PMA-induced ROS production in a concentration-dependent manner. This data indicate that misoprostol-targeting of E-prostanoid (EP) receptors potently inhibits equine neutrophil effector functions in vitro. Additional studies are indicated to further elucidate the role of EP receptors in regulating neutrophil function. Overall, our results suggest misoprostol may hold promise as a novel anti-inflammatory therapeutic in the horse.}, journal={Frontiers in Veterinary Science}, publisher={Frontiers Media SA}, author={Martin, Emily Medlin and Till, Rebecca Louise and Sheats, Mary Katherine and Jones, Samuel L.}, year={2017}, month={Sep} }
 @article{martin_messenger_sheats_jones_2017, title={Misoprostol Inhibits Lipopolysaccharide-Induced Pro-inflammatory Cytokine Production by Equine Leukocytes}, volume={4}, ISSN={2297-1769}, url={http://dx.doi.org/10.3389/fvets.2017.00160}, DOI={10.3389/fvets.2017.00160}, abstractNote={Pro-inflammatory cytokines including tumor necrosis factor α (TNFα), IL-1β, IL-6, and IL-8 are potent immune mediators that exacerbate multiple equine diseases such as sepsis and laminitis. Unfortunately, safe and effective cytokine-targeting therapies are lacking in horses; therefore, novel mechanisms of inhibiting cytokine production are critically needed. One potential mechanism for inhibiting cytokine synthesis is elevation of intracellular cyclic AMP (cAMP). In human leukocytes, intracellular cAMP production is induced by activation of E-prostanoid (EP) receptors 2 and 4. These receptors can be targeted by the EP2/4 agonist and prostaglandin E}, journal={Frontiers in Veterinary Science}, publisher={Frontiers Media SA}, author={Martin, Emily Medlin and Messenger, Kristen M. and Sheats, Mary Katherine and Jones, Samuel L.}, year={2017}, month={Sep} }
 @article{pratt-phillips_medlin_2013, title={Value of faculty-provided materials in an introductory equine science course}, volume={33}, ISSN={0737-0806}, url={http://dx.doi.org/10.1016/j.jevs.2013.03.161}, DOI={10.1016/j.jevs.2013.03.161}, abstractNote={Online prerequisite review (OPR) tutorials were designed and implemented to reinforce foundational scientific material in order to protect in-class time, foster self-directed learning, and ensure all students have similar baseline knowledge.Twenty-one tutorials covering undergraduate prerequisite material were developed by faculty and organized into six core modules, comprising basic biology, chemistry, and physiology topics. A quiz on this material was given on the first day of each course. This score was correlated with the final exam score at course completion. Additional student and faculty feedback was collected through surveys.2372 quiz-exam pairings were collected over three consecutive fall semesters. A one point increase in the quiz score was associated with a 3.6 point (95% confidence interval 3.1–4.0) higher exam score, as well as a greater probability of passing the exam (P<0.0001). Furthermore, simple linear regression revealed a positive correlation between quiz and exam scores (P<0.0001). Three full years of student survey data revealed an overwhelmingly positive perception of the OPR tutorials, and surveyed faculty reported better use of class time and improved student competency and participation.Implementation of OPR tutorials may give faculty more efficient use of class time, and their associated quizzes serve as an early indicator for students at-risk of not passing who are candidates for early interventions. Furthermore, the OPR tutorial design gives it great transferability to biomedical post-graduate programs.}, number={5}, journal={Journal of Equine Veterinary Science}, publisher={Elsevier BV}, author={Pratt-Phillips, S.E. and Medlin, E.G.}, year={2013}, month={May}, pages={393} }