Inhaled pirfenidone solution (AP01) for IPF: a randomised, open-label, dose-response trial.

INTRODUCTION: Oral pirfenidone reduces lung function decline and mortality in patients with idiopathic pulmonary fibrosis (IPF). Systemic exposure can have significant side effects, including nausea, rash, photosensitivity, weight loss and fatigue. Reduced doses may be suboptimal in slowing disease progression. METHODS: This phase 1b, randomised, open-label, dose-response trial at 25 sites in six countries (Australian New Zealand Clinical Trials Registry (ANZCTR) registration number ACTRN12618001838202) assessed safety, tolerability and efficacy of inhaled pirfenidone (AP01) in IPF. Patients diagnosed within 5 years, with forced vital capacity (FVC) 40%-90% predicted, and intolerant, unwilling or ineligible for oral pirfenidone or nintedanib were randomly assigned 1:1 to nebulised AP01 50 mg once per day or 100 mg two times per day for up to 72 weeks. RESULTS: We present results for week 24, the primary endpoint and week 48 for comparability with published trials of antifibrotics. Week 72 data will be reported as a separate analysis pooled with the ongoing open-label extension study. Ninety-one patients (50 mg once per day: n=46, 100 mg two times per day: n=45) were enrolled from May 2019 to April 2020. The most common treatment-related adverse events (frequency, % of patients) were all mild or moderate and included cough (14, 15.4%), rash (11, 12.1%), nausea (8, 8.8%), throat irritation (5, 5.5%), fatigue (4, 4.4%) and taste disorder, dizziness and dyspnoea (three each, 3.3%). Changes in FVC % predicted over 24 and 48 weeks, respectively, were -2.5 (95% CI -5.3 to 0.4, -88 mL) and -4.9 (-7.5 to -2.3,-188 mL) in the 50 mg once per day and 0.6 (-2.2 to 3.4, 10 mL) and -0.4 (-3.2 to 2.3, -34 mL) in the 100 mg two times per day group. DISCUSSION: Side effects commonly associated with oral pirfenidone in other clinical trials were less frequent with AP01. Mean FVC % predicted remained stable in the 100 mg two times per day group. Further study of AP01 is warranted. TRIAL REGISTRATION NUMBER: ACTRN12618001838202 Australian New Zealand Clinical Trials Registry.

Family Physicians' Experiences of Physical Examination.

PURPOSE: The increased availability of reliable diagnostic technologies has stimulated debate about the utility of physical examination in contemporary clinical practice. To reappraise its utility, we explored family physicians' experiences. METHODS: Guided by principles of phenomenology, we conducted in-depth qualitative interviews exploring 16 family physicians' experiences of conducting physical examination: 7 (44%) men and 9 women (56%) whose clinical experience varied widely, from 11 (69%) urban and 5 (31%) rural locations. We recorded the interviews, transcribed them verbatim, and identified initial themes using template analysis. We worked reflexively, critiquing our own and other team members' interpretations, in order to synthesize and write a final interpretation. RESULTS: Participants described 2 facets of physical examination: making diagnoses and estimating prognoses rationally and objectively; and responding subjectively and intuitively to patients' illnesses, which formed relationships between doctor and patient that enacted medical care in the moment. Physical examination allowed physicians to use their own bodies to experience patients' illnesses. Performing physical examination was integral to being a family doctor because it promoted rapport and developed trust. CONCLUSIONS: Physical examination is part of the identity of family physicians. It not only contributes diagnostic information but is a therapeutic intervention in and of itself. Physical examination contributes to relationship-centered care in family practice.

Determinants of pet food purchasing decisions.

The objective of this study was to identify determinants of pet food purchasing decisions. An online survey was administered via e-mail, newsletters, and social media. A total of 2181 pet owners completed the survey: 1209 dog owners and 972 cat owners; 26% of respondents were animal professionals. Pet food characteristics ranked the highest were health and nutrition, quality, ingredients, and freshness. The veterinary healthcare team was reported to be the primary (43.6%) and most important source of nutrition information for pet owners; Internet sources were the primary information source for 24.6% of respondents. Most pet owners reported giving equal (53.1%) or more priority (43.6%) to buying healthy food for their pets compared with themselves. Results suggest that pet owners face numerous challenges in determining the best diet to feed their pets.

Déterminants des décisions d'achat des aliments pour animaux de compagnie. Cette étude avait pour objectif d'identifier les déterminants des décisions d'achat des aliments pour animaux de compagnie. Un sondage en ligne a été administré par l'entremise de courriels, de bulletins et des médias sociaux. Un total de 2181 propriétaires d'animaux a répondu au sondage : 1209 propriétaires de chiens et 972 propriétaires de chats; 26 % des répondants étaient des professionnels pour animaux. Les caractéristiques des aliments pour animaux qui étaient les plus importantes étaient la santé et la nutrition, la qualité, les ingrédients et la fraîcheur. L'équipe de soins vétérinaires a été mentionnée comme la source primaire (43,6 %) et la plus importante d'information pour les propriétaires d'animaux. Les sources sur Internet représentaient la source primaire pour 24,6 % des répondants. La plupart des propriétaires d'animaux ont signalé qu'ils accordaient une priorité égale (53,1 %) ou une plus grande priorité (43,6 %) à l'achat d'aliments sains pour leurs animaux de compagnie comparativement à eux-mêmes. Les résultats suggèrent que les propriétaires sont confrontés à plusieurs défis en vue de déterminer la meilleure diète pour leurs animaux de compagnie.(Traduit par Isabelle Vallières).

Post-operative Salmonella surgical site infection in a dog.

Following decompressive surgery for degenerative lumbosacral stenosis, a 6-year-old German shepherd dog developed a subcutaneous infection at the surgical site and discospondylitis at the lumbosacral intervertebral disc. Salmonella enterica subsp. enterica, serotype Dublin was recovered from the surgical site. Salmonella of a different serovar was isolated from a sample of the raw meat-based diet that the owner fed the dog.

Infection postopératoire du site chirurgical parSalmonellachez un chien. Après une chirurgie de décompression pour une sténose lombo-sacrée dégénérative, un chien Berger allemand âgé de 6 ans a développé une infection sous-cutanée au site chirurgical et une discospondylite au disque intervertébral lombo-sacré. Salmonella enterica sous-esp. enterica de sérotype Dublin a été isolée du site chirurgical. Une salmonelle d'un sérovar différent a été isolée d'un échantillon de l'alimentation à base de viande crue donnée par le propriétaire au chien.(Traduit par Isabelle Vallières).

The Role of Veterinary Education in Safety Policies for Animal-Assisted Therapy and Activities in Hospitals and Nursing Homes.

Animal-assisted activities (AAA) and animal-assisted therapy (AAT) programs are increasing in popularity, but current programs vary in their safety and health policies. Veterinarians can have an important role in ensuring the safety of both the animals and humans involved, but it is unclear how best to educate veterinary students to serve effectively in this role. Therefore, the goal of this study was to assess the knowledge gaps and perceptions of first-year veterinary students on health and safety aspects of AAA/AAT programs by administering a survey. This information could then guide future educational training in veterinary schools to address the knowledge gaps in this area. Formal education during the veterinary curriculum had not yet been provided to these students on AAA/AAT before the survey. Of 98 first-year veterinary students, 91 completed the survey. When asked about policies on visiting animals, 58% of students responded that nursing homes are required to have a policy and 67% responded that hospitals are required to have one. Three quarters of students reported that veterinarians, animal handlers, and facilities should share the responsibility for ensuring safe human-animal interaction in AAA/AAT programs. Most (82%) of the students responded that all or most national and local therapy animal groups prohibit animals that consume raw meat diets from participating in AAA/AAT programs. The results of this survey will help veterinary schools better identify knowledge gaps that can be addressed in veterinary curricula so future veterinarians will be equipped to provide appropriate public health information regarding AAA/AAT programs.

Body Condition Scores and Evaluation of Feeding Habits of Dogs and Cats at a Low Cost Veterinary Clinic and a General Practice.

This study assessed body condition scores (BCS) and feeding habits for dogs and cats. Eighty-six cats and 229 dogs (and their owners) were enrolled from 2 clinics: a low cost clinic (n = 149) and a general practice (n = 166). BCS and body weight were recorded. Owners completed a survey which included animal age, sex, and breed; owner demographics; and feeding practices (e.g., diet, rationale for feeding practices). Owners from the low cost clinic had a significantly lower income (P < 0.001) and education (P < 0.001) compared to those from the general practice. Animals from the low cost clinic were younger (P < 0.001) and dogs were less likely to be neutered (P < 0.001). Overweight prevalence was 55% overall (P = 0.083), with a significantly higher prevalence in the general practice for cats (44% versus 66%; P = 0.046), but not for dogs (58% versus 53%; P = 0.230). Multivariate analysis showed that only neuter status was significantly associated with BCS (P = 0.004). Veterinarians were the most common source of nutritional information, though lack of accurate nutrition knowledge was common among all participants. These findings support the need for enhanced communication about optimal BCS and nutrition regardless of socioeconomic status.

Measuring the Effects of Reading Assistance Dogs on Reading Ability and Attitudes in Elementary Schoolchildren.

Reading Education Assistance Dogs (R.E.A.D.) is a reading program that uses therapy dogs to increase a child's desire and ability to read. However, more data is needed to demonstrate the effectiveness of such programs. A five-week R.E.A.D. program was implemented to assess feasibility and effectiveness. Participants included 18 children entering the 2nd grade (9 assigned to read to dogs and 9 assigned to read without dogs present). Fifteen children completed the study (9 in the Dog Group and 6 in the Control Group; p = 0.058). To detect changes in reading ability and in attitudes toward reading, a Curriculum Based Measurement (CBM) for reading and an Elementary Reading Attitude Survey (ERAS) was given at week 0 and week 5. There were no significant differences over the course of the study in ERAS scores for the Dog Group, but the Control Group had significant reductions in the ERAS academic score (p = 0.04) and a trend for a reduction in the ERAS total score (p = 0.06). There was a numerically larger but not statistically different reduction in CBM in the Control Group compared to the Dog Group (p = 0.16). Further studies are warranted to determine if these trends represent statistically significant effects of the R.E.A.D.

Expression Profiling of Circulating MicroRNAs in Canine Myxomatous Mitral Valve Disease.

MicroRNAs (miRNAs) are small non-coding RNAs that have shown promise as noninvasive biomarkers in cardiac disease. This study was undertaken to investigate the miRNA expression profile in dogs with myxomatous mitral valve disease (MMVD). 277 miRNAs were quantified using RT-qPCR from six normal dogs (American College of Veterinary Internal Medicine Stage A), six dogs with MMVD mild to moderate cardiac enlargement (ACVIM Stage B1/B2) and six dogs with MMVD and congestive heart failure (ACVIM Stage C/D). Eleven miRNAs were differentially expressed (False Discovery Rate < 0.05). Dogs in Stage B1/B2 or C/D had four upregulated miRNAs, including three cfa-let-7/cfa-miR-98 family members, while seven others were downregulated, compared to Stage A. Expression of six of the 11 miRNAs also were significantly different between dogs in Stage C/D and those in Stage B1/B2. The expression changes were greater as disease severity increased. These miRNAs may be candidates for novel biomarkers and may provide insights into genetic regulatory pathways in canine MMVD.

Echocardiographic and electrocardiographic findings in Irish Wolfhounds eating high-pulse or low-pulse diets.

BACKGROUND: Apparently healthy dogs of various breeds eating nontraditional, high-pulse diets can have larger left ventricular diameter, lower systolic function, and more ventricular premature complexes (VPCs) compared with dogs eating traditional, low-pulse diets. It is unknown whether Irish Wolfhounds eating high-pulse diets have similar cardiac abnormalities. HYPOTHESIS/OBJECTIVES: To compare electrocardiographic and echocardiographic findings between Irish Wolfhounds eating high- or low-pulse diets. ANIMALS: Ninety-seven Irish Wolfhounds. METHODS: Retrospective study of Irish Wolfhounds that had echocardiography performed at dog shows between October 2018 and May 2021. Demographic information, echocardiographic measurements, cardiac rhythm (1-minute lead II rhythm strip), and main diet were recorded retrospectively. Diets were classified as high-pulse or low-pulse based on the presence and location of pulses (peas, lentils, chickpeas, or dry beans) on the ingredient list. RESULTS: Thirty-five of 97 Irish Wolfhounds (36%) were eating high-pulse diets and 62 of 97 (64%) were eating low-pulse diets. There were no significant differences between diet groups in echocardiographic measurements. A significantly higher percentage of dogs in the high-pulse diet group (6/35 [17%]) had VPCs compared with those in the low-pulse diet group (1/62 [2%]; effect size = 0.15 [95% confidence interval: 0.004-0.31]; P = .005). CONCLUSIONS AND CLINICAL IMPORTANCE: In this retrospective study of apparently healthy Irish Wolfhounds, high-pulse diets were associated with a higher prevalence of VPCs which could represent early cardiac abnormalities.

Myeloma-induced alloreactive T cells arising in myeloma-infiltrated bones include double-positive CD8+CD4+ T cells: evidence from myeloma-bearing mouse model.

The graft-versus-myeloma (GVM) effect represents a powerful form of immune attack exerted by alloreactive T cells against multiple myeloma cells, which leads to clinical responses in multiple myeloma transplant recipients. Whether myeloma cells are themselves able to induce alloreactive T cells capable of the GVM effect is not defined. Using adoptive transfer of T naive cells into myeloma-bearing mice (established by transplantation of human RPMI8226-TGL myeloma cells into CD122(+) cell-depleted NOD/SCID hosts), we found that myeloma cells induced alloreactive T cells that suppressed myeloma growth and prolonged survival of T cell recipients. Myeloma-induced alloreactive T cells arising in the myeloma-infiltrated bones exerted cytotoxic activity against resident myeloma cells, but limited activity against control myeloma cells obtained from myeloma-bearing mice that did not receive T naive cells. These myeloma-induced alloreactive T cells were derived through multiple CD8(+) T cell divisions and enriched in double-positive (DP) T cells coexpressing the CD8αα and CD4 coreceptors. MHC class I expression on myeloma cells and contact with T cells were required for CD8(+) T cell divisions and DP-T cell development. DP-T cells present in myeloma-infiltrated bones contained a higher proportion of cells expressing cytotoxic mediators IFN-γ and/or perforin compared with single-positive CD8(+) T cells, acquired the capacity to degranulate as measured by CD107 expression, and contributed to an elevated perforin level seen in the myeloma-infiltrated bones. These observations suggest that myeloma-induced alloreactive T cells arising in myeloma-infiltrated bones are enriched with DP-T cells equipped with cytotoxic effector functions that are likely to be involved in the GVM effect.

Status of selected nutrients in obese dogs undergoing caloric restriction.

BACKGROUND: The purpose of this study was to test the hypothesis that dog plasma concentrations of selected nutrients decrease after undergoing caloric restriction for weight loss. Thirty-one overweight dogs that had successfully lost at least 15% of initial body weight were included in the study. Nutrients that had been previously identified to be at potential risk of deficiency during caloric restriction were measured in plasma (choline, amino acids) and urine (selenium) at the initiation and completion of a standardized weight loss regimen in dogs. RESULTS: Dogs remained healthy throughout the study, and no signs attributable to nutrient deficiency were noted. Percentage weight loss was 28.3% (16.0-40.1%) starting body weight, over a period of 250 days (91-674 days). Median energy intake during the weight loss period was 62 (44 to 74) Kcal/kg(0.75) target weight per day. Choline (P = 0.046) and threonine (P = 0.02) decreased after weight loss. Glycine (P = 0.041), and urinary selenium:creatinine ratio (P = 0.006) both increased after weight loss. There were no other significant differences in plasma nutrient concentrations. CONCLUSIONS: Since concentrations of most measured nutrients did not change significantly, the data are not consistent with widespread nutrient deficiency in dogs undergoing caloric restriction using a diet formulated for weight loss. However, the significance of the decrease in plasma choline concentration requires further assessment.

Nutritional and microbial analysis of bully sticks and survey of opinions about pet treats.

The objectives of this study were to measure the caloric density of bully sticks, to analyze the bully sticks for bacterial contamination, and to assess owner opinions about these and other pet treat products. Mean caloric density was 15 kcal/inch (38 kcal/cm) [range: 9 to 22 kcal/inch (23 to 56 kcal/cm), 2.96 to 3.07 kcal/g]. Of 26 bully sticks that were tested for bacterial contamination 1 (4%) was contaminated with Clostridium difficile, 1 was contaminated with methicillin-resistant Staphylococcus aureus (MRSA), and 1 with a tetracycline resistant Escherichia coli.

Analyse nutritionnelle et microbienne des bâtonnets en peau de buffle et sondage d'opinion à propos des gâteries pour animaux de compagnie. Les objectifs de cette étude consistaient à mesurer la densité calorique des bâtonnets en peau de bovin, à analyser les bâtonnets en peau de bovin pour une contamination bactérienne et à évaluer les opinions des propriétaires à propos de ces gâteries et d'autres gâteries pour animaux de compagnie. La densité calorique moyenne était de 15 kcal/pouce (38 kcal/cm) [écart : de 9 à 22 kcal/pouce (de 23 à 56 kcal/cm), de 2,96 à 3,07 kcal/g]. Parmi les 26 bâtonnets en peau de bovin qui ont été testés pour une contamination bactérienne, 1 (4 %) était contaminé par Clostridium difficile, 1 était contaminé par Staphylococcus aureus résistant à la méthicilline (SARM) et 1 par Escherichia coli résistant à la tétracycline.(Traduit par Isabelle Vallières).

Pit bull-type breeds with dilated cardiomyopathy eating nontraditional diets improve after diet change (2015-2022).

OBJECTIVE: To compare signalment, clinical signs, diet, echocardiographic findings, and outcome for pit bull-type breeds diagnosed between 2015 and 2022 with dilated cardiomyopathy (DCM) or with DCM diagnosed by a cardiologist but that did not meet all study echocardiographic criteria (DCM-C). ANIMALS: 91 dogs with DCM and 11 dogs with DCM-C. PROCEDURES: Data were collected on clinical findings, echocardiographic measurements, and diet at the time of diagnosis (for 76/91 dogs); echocardiographic changes; and survival. RESULTS: For dogs with diet information available for time of diagnosis, 64/76 (84%) dogs were eating nontraditional commercial diets, while 12/76 (16%) were eating traditional commercial diets. There were few differences between diet groups at baseline, with congestive heart failure and arrhythmias common in both groups. Thirty-four dogs with known baseline diet and diet change status had follow-up echocardiograms between 60 and 1,076 days later (traditional diet, n = 7; nontraditional diet that changed diets, 27; and nontraditional diet group without diet change, 0). Dogs in the nontraditional diet group that changed diets had a significantly greater decrease in normalized left ventricular diameter (diastolic, P = .02; systolic, P = .048) and the left atrium-to-aorta ratio (P = .002) and a significantly greater increase in fractional shortening (P = .02) compared to dogs eating traditional diets. Dogs eating nontraditional diets with diet change (n = 45; P < .001) and dogs eating traditional diets (12; P < .001) had a significantly longer survival time compared to dogs eating nontraditional diets without diet change (4). Dogs with DCM-C also had significant echocardiographic improvements after diet change. CLINICAL RELEVANCE: Congestive heart failure and arrhythmias were common in pit bull-type breeds with DCM. Those eating nontraditional diets that changed diets had significant improvements in echocardiographic measurements after diet change.

Untargeted metabolomic profiling of dogs with myxomatous mitral valve disease and congestive heart failure shows metabolic differences associated with the presence of cardiac cachexia.

OBJECTIVE: To determine the effects of cardiac cachexia on the metabolomic profile in dogs with myxomatous mitral valve disease (MMVD). ANIMALS: 3 groups of dogs with MMVD enrolled between November 30, 2018, and April 7, 2022: (1) Dogs with congestive heart failure (CHF) and cachexia (CHF-cachexia group; n = 10); (2) dogs with CHF that had no cachexia (CHF-no cachexia group; n = 10); and (3) dogs with asymptomatic disease (American College of Veterinary Internal Medicine [ACVIM] Stage B2) with no cachexia (B2 group; n = 10). METHODS: Metabolomic profiles were analyzed from serum samples using ultra-high-performance liquid chromatography-tandem mass spectroscopy. Dogs in the 3 groups were compared, with statistical significance defined as P < .05 with a low false discovery rate (q < .10) and nominal statistical significance defined as P < .05 but q > .10. RESULTS: Numerous metabolites were significantly (n = 201) or nominally significantly (n = 345) different between groups. For example, when comparing the CHF-cachexia vs CHF-no cachexia groups, lipids were the predominant metabolite differences, including many medium- and long-chain dicarboxylates and dicarboxylate acylcarnitines. For comparisons of the CHF-cachexia vs B2 groups and the CHF-no cachexia vs B2 groups, amino acids, nucleotides, and cofactors/vitamins were the predominant metabolite differences. CLINICAL RELEVANCE: Some significant metabolite differences were identified between dogs with and without cardiac cachexia.

Comparison of echocardiographic measurements and cardiac biomarkers in healthy dogs eating nontraditional or traditional diets.

BACKGROUND: There has been a recent association between nontraditional diets and development of diet-associated dilated cardiomyopathy (DCM) in dogs. HYPOTHESIS/OBJECTIVES: To compare echocardiographic measurements and cardiac biomarkers between healthy dogs eating nontraditional vs traditional diets. We hypothesized that dogs eating nontraditional diets would have lower measures of systolic myocardial performance compared to dogs eating traditional diets. ANIMALS: Forty-six healthy dogs: 23 eating nontraditional diets and 23 eating traditional diets. METHODS: Prospective, cross-sectional study. Dogs were divided into groups based on diet ingredients. Dogs underwent 2-dimensional (2D), 3-dimensional (3D), and Doppler echocardiographic examinations and analysis of plasma N-terminal prohormone of B-type natriuretic peptide, serum cardiac troponin I, and whole blood and plasma taurine concentrations. RESULTS: Mean 2D ejection fraction (EF) was lower for dogs eating nontraditional diets (48.65 ± 7.42%) vs dogs eating traditional diets (56.65 ± 4.63%; P < .001; mean difference 8.0% [4.0%-12.0%] 95% confidence interval [CI]). Mean 3D EF was lower for dogs eating nontraditional diets (45.38 ± 7.35%) vs dogs eating traditional diets (57.58 ± 4.84%; P < .001; 12.0% [8.0%-16.0%] 95% CI). Mean 2D left ventricular end-systolic volumes, indexed to body weight, were significantly higher in dogs eating nontraditional diets (1.46 ± 0.08 mL/kg) vs dogs eating traditional diets (1.06 ± 0.08 mL/kg; P = .002; 0.4 mL/kg [0.18-0.62 mL/kg] 95% CI). CONCLUSIONS AND CLINICAL IMPORTANCE: Healthy dogs eating nontraditional diets had lower indices of systolic function and larger left ventricular volumes compared to dogs eating traditional diets. Screening of apparently healthy dogs eating nontraditional diets might allow for early detection of diet-associated DCM.

Comparison of echocardiography, biomarkers and taurine concentrations in cats eating high- or low-pulse diets.

OBJECTIVES: There are ongoing investigations into diet-associated dilated cardiomyopathy in dogs, but there has been minimal investigation into possible diet-associated dilated cardiomyopathy in cats. The objective of this study was to compare cardiac size and function, cardiac biomarkers and taurine concentrations in healthy cats eating high- vs low-pulse diets. We hypothesized that cats eating high-pulse diets would have larger hearts, lower systolic function and higher biomarker concentrations than cats eating low-pulse diets and that there would be no difference in taurine concentrations between the diet groups. METHODS: Echocardiographic measurements, cardiac biomarkers, and plasma and whole-blood taurine concentrations were compared between cats eating high- and low-pulse commercial dry diets in a cross-sectional study. RESULTS: There were no differences between the high- (n = 21) and low-pulse (n = 31) diet groups with regard to age, sex and breed, but more cats in the high-pulse group were overweight or obese (67% vs 39%; P = 0.05). Diet duration was not different in the groups, but the range was wide (6-120 months). No differences were found between the diet groups for key cardiac measurements, biomarker concentrations, or plasma or whole-blood taurine concentrations. However, there were significant negative correlations between diet duration and measures of left ventricular wall thickness in the high-pulse, but not the low-pulse, diet group. CONCLUSIONS AND RELEVANCE: This study did not detect significant associations between high-pulse diets and cardiac size, function and biomarkers, but the secondary observation of significant negative correlations between time on high-pulse diets and left ventricular wall thickness warrants further evaluation.

Expression of pleiotrophin, an important regulator of cell migration, is inhibited in intestinal epithelial cells by treatment with non-steroidal anti-inflammatory drugs.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs for the suppression of inflammation and pain. However, the analgesic properties of NSAIDs are also associated with significant negative side effects, most notably in the gastrointestinal (GI) tract. Increasingly, evidence indicates that the ulcerogenic properties of some NSAIDs are not exclusively the result of inhibition of cyclooxygenase isoforms in the GI tract, and other mechanisms, including inhibition of cell migration and epithelial restitution, are being explored. Recently, microarray analysis was used to identify potential novel targets of NSAID activity in intestinal epithelial cells. Treated cells exhibited significant reductions in the gene expression of pleiotrophin (PTN), a cytokine and growth factor known to participate in angiogenesis and bone growth. This report aimed to confirm the microarray results reported previously, and to measure protein expression of PTN in intestinal epithelial cells. Furthermore, we also examined the effects of exogenous PTN on cell migration in the presence and absence of either NSAIDs with variable ulcerogenic potential or PTN-specific siRNA. Our results demonstrated that indomethacin and NS-398, two NSAIDs with ulcerogenic potential significantly decrease both gene and protein expressions of PTN in IEC-6 cells and protein expression in IEC-6-Cdx2 cells. Additionally, cell migration experiments with PTN siRNA showed that PTN is an important mediator of IEC-6 cell migration, and addition of exogenous PTN partially restores the deficits in cell migration caused by treatment with indomethacin and NS-398. Finally, measurement of PTN protein expression in the GI tract of horses treated with phenylbutazone showed that PTN expression is reduced by NSAIDs in vivo. Our results show that PTN is an important mediator of cell migration in IEC-6 cells, and PTN is a potential target through which NSAIDs may inhibit cell migration, epithelial restitution, and wound healing in the GI tract.