Publications by authors named "Karin Allenspach"

69 Publications

A comparative analysis of two unrelated outbreaks in Latvia and Australia of acquired idiopathic megaesophagus in dogs fed two brands of commercial dry dog foods: 398 cases (2014-2018).

J Am Vet Med Assoc 2021 Jul;259(2):172-183

Case Description: In Latvia in 2014, acquired idiopathic megaesophagus (AIME) was observed in increased numbers of dogs that consumed varieties of 1 brand of dog food. Within 2 years, 253 dogs were affected. In Australia in November 2017, 6 working dogs that consumed 1 diet of another brand of dog food developed AIME. In total, 145 Australian dogs were affected.

Clinical Findings: AIME was diagnosed predominantly in large-breed male dogs (> 25 kg [55 lb]). Regurgitation, weight loss, and occasionally signs consistent with aspiration pneumonia (coughing, dyspnea, or fever) were noted. Most Latvian dogs had mild to severe peripheral polyneuropathies as evidenced by laryngeal paralysis, dysphonia, weakness, and histopathologic findings consistent with distal axonopathy. In Australian dogs, peripheral polyneuropathies were not identified, and histopathologic findings suggested that the innervation of the esophagus and pharynx was disrupted locally, although limited samples were available.

Treatment And Outcome: Investigations in both countries included clinical, epidemiological, neuropathologic, and case-control studies. Strong associations between the dog foods and the presence of AIME were confirmed; however, toxicological analyses did not identify a root cause. In Latvia, the implicated dietary ingredients and formulations were unknown, whereas in Australia, extensive investigations were conducted into the food, its ingredients, the supply chain, and the manufacturing facilities, but a cause was not identified.

Clinical Relevance: A panel of international multidisciplinary experts concluded that the cause of AIME in both outbreaks was likely multifactorial, with the possibility of individualized sensitivities. Without a sentinel group, the outbreak in Australia may not have been recognized for months to years, as happened in Latvia. A better surveillance system for early identification of pet illnesses, including those associated with pet foods, is needed.
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http://dx.doi.org/10.2460/javma.259.2.172DOI Listing
July 2021

Upregulation of signal transducer and activator of transcription 3 in dogs with chronic inflammatory enteropathies.

J Vet Intern Med 2021 May 6;35(3):1288-1296. Epub 2021 May 6.

Internal Medicine, Clinic for Small Animals, Department for Companion Animals and Horses, University of Veterinary Medicine, Vienna, Austria.

Background: In inflammatory bowel disease (IBD) in humans, phosphorylated signal transducer and activator of transcription 3 (pSTAT3) is upregulated in mucosal epithelial cells and correlates with clinical severity.

Hypothesis/objective: To investigate the expression pattern of pSTAT3 in the mucosa of dogs with chronic inflammatory enteropathy (CIE) and explore correlations between its expression and clinical and histopathological severity scoring.

Animals: Twenty-eight canine CIE patients grouped into food-responsive enteropathy (FRE;  9), steroid-responsive enteropathy (SRE;  10), and protein-losing enteropathy (PLE;  9). Ten healthy beagle dogs served as controls (CO).

Methods: Retrospective case control study. Immunohistochemistry was used to detect pSTAT3 in canine duodenal mucosa samples.

Results: Compared to CO, SRE (P < .001) and PLE (P < .001) dogs had significantly higher pSTAT3 expression in the villus epithelium. The SRE group had a significantly higher expression in the villus lamina propria (VLP) compared to controls (P = .009). In the crypt epithelium (CE), all CIE dogs had significantly higher pSTAT3 expression (FRE, P = .002; SRE, P = .003; PLE, P < .001) compared to CO. In the lamina propria crypt region (CLP), dogs with FRE (P = .04) and SRE (P = .03) had significantly upregulated pSTAT3 compared to controls. A positive correlation was found between canine chronic enteropathy clinical activity index (CCECAI) scoring and pSTAT3 expression for both epithelial (rho = .541; P < .001) and crypt regions (rho = .32; P = .02).

Conclusions And Clinical Importance: pSTAT3 is upregulated in CIE in dogs, correlates with clinical severity, and may be helpful as a clinical marker in dogs with CIE.
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http://dx.doi.org/10.1111/jvim.16141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163116PMC
May 2021

Inflammation, negative affect, and amyloid burden in Alzheimer's disease: Insights from the kynurenine pathway.

Brain Behav Immun 2021 07 26;95:216-225. Epub 2021 Mar 26.

Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Depressive symptoms in Alzheimer's disease (AD) predict worse cognitive and functional outcomes. Both AD and major depression inflammatory processes are characterized by shunted tryptophan metabolism away from serotonin (5-HT) and toward the neuroinflammatory kynurenine (Kyn) pathway. The present study assessed associations between Kyn and behavioral, neuroanatomical, neuropathological, and physiological outcomes common to both AD and negative affect across the AD continuum.

Methods: In 58 cognitively normal, 396 mild cognitive impairment, and 112 AD participants from the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI1) cohort, serum markers of 5-HT, tryptophan, and Kyn were measured and their relationships investigated with immunologic markers, affect and functional outcomes, CSF markers of beta-amyloid (Aβ) and tau, and regional gray matter.

Results: A higher Kyn/Tryptophan ratio was linked to many inflammatory markers, as well as lower functional independence and memory scores. A higher Kyn/5-HT ratio showed similar associations, but also strong relationships with negative affect and neuropsychiatric disturbance, executive dysfunction, and global cognitive decline. Further, gray matter atrophy was seen in hippocampus, anterior cingulate, and prefrontal cortices, as well as greater amyloid and total tau deposition. Finally, using moderated-mediation, several pro-inflammatory factors partially mediated Kyn/5-HT and negative affect scores in participants with subclinical Aβ (i.e., Aβ-), whereas such associations were fully mediated by Complement 3 in Aβ+ participants.

Conclusion: These findings suggest that inflammatory signaling cascades may occur during AD, which is associated with increased Kyn metabolism that influences the pathogenesis of negative affect. Aβ and the complement system may be critical contributing factors in this process.
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http://dx.doi.org/10.1016/j.bbi.2021.03.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187283PMC
July 2021

Emerging Roles of Urine-Derived Components for the Management of Bladder Cancer: One Man's Trash Is Another Man's Treasure.

Cancers (Basel) 2021 Jan 23;13(3). Epub 2021 Jan 23.

SMART Translational Medicine, Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA.

Urinary bladder cancer (UBC) is the most common malignancy of the urinary tract in humans, with an estimated global prevalence of 1.1 million cases over 5 years. Because of its high rates of recurrence and resistance to chemotherapy, UBC is one of the most expensive cancers to treat, resulting in significant health care costs. The development of innovative molecular and cellular tools is necessary to refine patient stratification and help predict response to treatment. Urine is an underused resource of biological components shed from bladder tumors, such as exfoliated cells and extracellular vesicles, that could serve as molecular fingerprints and provide valuable biological insights into tumor phenotype and mechanisms of resistance to chemotherapy. Additionally, characterization of urine-derived extracellular vesicles and cells could be used as reliable biomarkers for prediction of response to neoadjuvant therapy.
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http://dx.doi.org/10.3390/cancers13030422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865365PMC
January 2021

Colonic mucosal and cytobrush sample cytokine mRNA expression in canine inflammatory bowel disease and their correlation with disease activity, endoscopic and histopathologic score.

PLoS One 2021 20;16(1):e0245713. Epub 2021 Jan 20.

Companion Animal Clinic (Medicine Unit), School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Canine inflammatory bowel disease (IBD) is a group of chronic gastrointestinal disorders, the pathogenesis of which remains elusive, but it possibly involves the interaction of the intestinal immune system with luminal microbiota and food-derived antigens. Mucosal cytokines profiles in canine IBD have been investigated mainly in small intestinal disease, while data on cytokine profiles in large intestinal IBD are limited. The objective of this study was to measure colonic mucosal and cytobrush sample messenger (m)RNA expression of interleukin (IL)-1β, IL-2, IL-12p40, IL-23p19, tumor necrosis factor-alpha (TNF-α) and chemokine C-C motif ligand (CCL28) in dogs with IBD and healthy controls using quantitative real-time polymerase chain reaction (PCR), and assess their correlation with clinical disease activity, endoscopic and histopathologic score. Dogs with IBD had a significantly increased mRNA expression of IL-1β, IL-23p19 and CCL28 in the colonic mucosa, compared to healthy controls. None of the selected cytokines had significantly different mRNA expression in the colonic cytobrush samples between the two groups or between the colonic mucosa and cytobrush samples of dogs with IBD. Finally, there was a statistically significant correlation of clinical disease activity with endoscopic activity score and fibrosis and atrophy of the colonic mucosa in dogs with large intestinal IBD. IL-1β, IL-23p19 and CCL28 could play a role in the pathogenesis of canine large intestinal IBD. Colonic cytokine expression does not correlate with clinical disease activity and/or endoscopic score. However, clinical signs reflect the severity of endoscopic lesions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245713PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817028PMC
June 2021

An initial genome-wide investigation of protein-losing enteropathy in Gordon setters: Exploratory observations.

Can J Vet Res 2021 Jan;85(1):51-60

Department of Veterinary Clinical Sciences (Donnini, Jergens, Allenspach), College of Veterinary Medicine, 1809 South Riverside Drive, Iowa State University, Ames, Iowa 50010, USA; Department of Animal Science (Walugembe, Rothschild), College of Agriculture and Life Sciences, 2255 H. Kildee Hall, Iowa State University, Ames, Iowa 20011, USA.

The objective of this preliminary study was to identify genomic regions that may predispose Gordon setters from the United Kingdom to familial protein-losing enteropathy (PLE) at a young age. A total of 106 related Gordon setters was used, including 6 affected dogs from an affected litter, 6 case controls from the same litter, 10 related/affected dogs, and 84 related/unaffected dogs. Genomic DNA was collected from each Gordon setter and extracted from buccal mucosal swabs. Genotyping of affected and unaffected dogs was carried out using the Canine Illumina HD SNP array and data generated were analyzed with PLINK software, using fixation index (Fst) and runs of homozygosity (ROH) methods. Pairwise Fst analyses between the affected and unaffected Gordon setter dogs identified various regions of differentiation on chromosomes 10, 18, 21, and 23 that contained several important genes. These regions revealed 5 candidate genes, including , and , that are associated with human inflammatory bowel disease (IBD) and could potentially be associated with PLE in Gordon setters. Run of homozygosity (ROH) analyses revealed additional unique regions on chromosomes 15 and 17. These regions contained genes , and that could also be potential candidates for PLE in Gordon setters. The biological functions of the identified genes provided initial insights into the pathophysiology of PLE. Further large-scale studies are warranted to investigate the possible causality of these genomic regions and any possible genetic markers that could be used in predicting susceptibility to PLE syndrome.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747665PMC
January 2021

Genetic Factors of Alzheimer's Disease Modulate How Diet is Associated with Long-Term Cognitive Trajectories: A UK Biobank Study.

J Alzheimers Dis 2020 ;78(3):1245-1257

Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA.

Background: Fluid intelligence (FI) involves abstract problem-solving without prior knowledge. Greater age-related FI decline increases Alzheimer's disease (AD) risk, and recent studies suggest that certain dietary regimens may influence rates of decline. However, it is uncertain how long-term food consumption affects FI among adults with or without familial history of AD (FH) or APOE4 (ɛ4).

Objective: Observe how the total diet is associated with long-term cognition among mid- to late-life populations at-risk and not-at-risk for AD.

Methods: Among 1,787 mid-to-late-aged adult UK Biobank participants, 10-year FI trajectories were modeled and regressed onto the total diet based on self-reported intake of 49 whole foods from a Food Frequency Questionnaire (FFQ).

Results: Daily cheese intake strongly predicted better FIT scores over time (FH-: β= 0.207, p < 0.001; ɛ4-: β= 0.073, p = 0.008; ɛ4+: β= 0.162, p = 0.001). Alcohol of any type daily also appeared beneficial (ɛ4+: β= 0.101, p = 0.022) and red wine was sometimes additionally protective (FH+: β= 0.100, p = 0.014; ɛ4-: β= 0.59, p = 0.039). Consuming lamb weekly was associated with improved outcomes (FH-: β= 0.066, p = 0.008; ɛ4+: β= 0.097, p = 0.044). Among at risk groups, added salt correlated with decreased performance (FH+: β= -0.114, p = 0.004; ɛ4+: β= -0.121, p = 0.009).

Conclusion: Modifying meal plans may help minimize cognitive decline. We observed that added salt may put at-risk individuals at greater risk, but did not observe similar interactions among FH- and AD- individuals. Observations further suggest in risk status-dependent manners that adding cheese and red wine to the diet daily, and lamb on a weekly basis, may also improve long-term cognitive outcomes.
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http://dx.doi.org/10.3233/JAD-201058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895545PMC
January 2020

Canine Protein Losing Enteropathies and Systemic Complications.

Vet Clin North Am Small Anim Pract 2021 Jan 29;51(1):111-122. Epub 2020 Oct 29.

Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, 1809 South Riverside Drive, Ames, IA 50010, USA.

Canine protein-losing enteropathies occur commonly in small animal practice, and their management is often challenging with a long-term survival rate of only about 50%. Recent studies have investigated prognostic factors that may determine outcome in individual cases. In particular, systemic complications such as hypercoagulability, vitamin D3 deficiency, and tryptophan deficiency may play an important role and should be investigated in severely affected cases in order to maximize outcome.
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http://dx.doi.org/10.1016/j.cvsm.2020.09.010DOI Listing
January 2021

Treatment With Hydrolyzed Diet Supplemented With Prebiotics and Glycosaminoglycans Alters Lipid Metabolism in Canine Inflammatory Bowel Disease.

Front Vet Sci 2020 30;7:451. Epub 2020 Jul 30.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.

Canine inflammatory bowel disease (IBD) is a chronic, immunologically mediated intestinal disorder, resulting from the complex interaction of genetic, environmental and immune factors. Hydrolyzed diets are used in dogs with food-responsive diarrhea (FRD) to reduce adverse responses to immunostimulatory proteins. Prebiotics (PRBs) and glycosaminoglycans (GAGs) have previously been demonstrated to show anti-inflammatory activity in the intestinal mucosa. Notably, hydrolyzed diets combined with the administration of PRBs and GAGs offer a promising approach for the treatment of canine IBD. Our aim was to investigate the effects of hydrolyzed diet and GAG+PRB co-treatment on the serum metabolomic profile of IBD dogs. Dogs with IBD randomly received either hydrolyzed diet supplemented with GAGs and PRBs (treatment 1) or hydrolyzed diet alone (treatment 2) for 10 weeks. A targeted metabolomics approach using mass spectrometry was performed to quantify changes in the serum metabolome before and after treatment and between treatment 1 and 2. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), hierarchical cluster analysis (HCA) and univariate statistics were used to identify differences between the treatment groups. PCA, PLS-DA, and HCA showed a clear clustering of IBD dogs before and after hydrolyzed diet, indicating that the treatment impacted the serum metabolome. Univariate analysis revealed that most of the altered metabolites were involved in lipid metabolism. The most impacted lipid classes were components of cell membranes, including glycerophospholipids, sphingolipids, and di- and triglycerides. In addition, changes in serum metabolites after GAG+PRB co-treatment suggested a possible additional beneficial effect on the lipid metabolism in IBD dogs. In conclusion, the present study showed a significant increase in metabolites that protect gut cell membrane integrity in response to hydrolyzed diet alone or in combination with GAG+PRB co-treatment. Administration of such treatment over 70 days improved selected serum biomarkers of canine IBD, possibly indicating improved intestinal membrane integrity.
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http://dx.doi.org/10.3389/fvets.2020.00451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406657PMC
July 2020

Walking in the Light: How History of Physical Activity, Sunlight, and Vitamin D Account for Body Fat-A UK Biobank Study.

Obesity (Silver Spring) 2020 08 22;28(8):1428-1437. Epub 2020 Jun 22.

Department of Food Science and Human Nutrition, Iowa State University, Ames, Iowa, USA.

Objective: The high prevalence of vitamin D deficiency and obesity drives the need for successful strategies that elevate vitamin D levels, prevent adipogenesis, and stimulate lipolysis. This study provides a theoretical model to evaluate how physical activity (PA) and sunlight exposure influence serum vitamin D levels and regional adiposity. This study hypothesized a posteriori that sunlight is associated with undifferentiated visceral adiposity by increasing the ratio of brown to white adipose tissue.

Methods: Using 10-year longitudinal data, accelerometry, a sun-exposure questionnaire, and regional adiposity quantified by dual-energy x-ray absorptiometry imaging, a structural-equation mediation model of growth curves was constructed with a data-driven methodology.

Results: Sunlight and PA conjointly increased serum vitamin D. Changes in vitamin D levels partially mediated how sunlight and PA impacted adiposity in visceral and subcutaneous regions within a subjective PA model. In an objective PA model, vitamin D was a mediator for subcutaneous regions only. Interestingly, sunlight was associated with less adiposity in subcutaneous regions but greater adiposity in visceral regions.

Conclusions: Sunlight and PA may increase vitamin D levels. For the first time, this study characterizes a positive association between sunlight and visceral adiposity. Further investigation and experimentation are necessary to clarify the physiological role of sunlight exposure on adipose tissue.
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http://dx.doi.org/10.1002/oby.22852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501143PMC
August 2020

Recapitulation of the accessible interface of biopsy-derived canine intestinal organoids to study epithelial-luminal interactions.

PLoS One 2020 17;15(4):e0231423. Epub 2020 Apr 17.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, United States of America.

Recent advances in canine intestinal organoids have expanded the option for building a better in vitro model to investigate translational science of intestinal physiology and pathology between humans and animals. However, the three-dimensional geometry and the enclosed lumen of canine intestinal organoids considerably hinder the access to the apical side of epithelium for investigating the nutrient and drug absorption, host-microbiome crosstalk, and pharmaceutical toxicity testing. Thus, the creation of a polarized epithelial interface accessible from apical or basolateral side is critical. Here, we demonstrated the generation of an intestinal epithelial monolayer using canine biopsy-derived colonic organoids (colonoids). We optimized the culture condition to form an intact monolayer of the canine colonic epithelium on a nanoporous membrane insert using the canine colonoids over 14 days. Transmission and scanning electron microscopy revealed a physiological brush border interface covered by the microvilli with glycocalyx, as well as the presence of mucin granules, tight junctions, and desmosomes. The population of stem cells as well as differentiated lineage-dependent epithelial cells were verified by immunofluorescence staining and RNA in situ hybridization. The polarized expression of P-glycoprotein efflux pump was confirmed at the apical membrane. Also, the epithelial monolayer formed tight- and adherence-junctional barrier within 4 days, where the transepithelial electrical resistance and apparent permeability were inversely correlated. Hence, we verified the stable creation, maintenance, differentiation, and physiological function of a canine intestinal epithelial barrier, which can be useful for pharmaceutical and biomedical researches.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231423PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164685PMC
July 2020

Colonic mucosal and serum expression of microRNAs in canine large intestinal inflammatory bowel disease.

BMC Vet Res 2020 Feb 22;16(1):69. Epub 2020 Feb 22.

Departments of Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, USA.

Background: Canine inflammatory bowel disease (IBD) is a group of chronic gastrointestinal (GI) disorders of still largely unknown etiology. Canine IBD diagnosis is time-consuming and costly as other diseases with similar signs should be initially excluded. In human IBD microRNA (miR) expression changes have been reported in GI mucosa and blood. Thus, there is a possibility that miRs may provide insight into disease pathogenesis, diagnosis and even treatment of canine IBD. The aim of this study was to determine the colonic mucosal and serum relative expression of a miRs panel in dogs with large intestinal IBD and healthy control dogs.

Results: Compared to healthy control dogs, dogs with large intestinal IBD showed significantly increased relative expression of miR-16, miR-21, miR-122 and miR-147 in the colonic mucosa and serum, while the relative expression of miR-185, miR-192 and miR-223 was significantly decreased. Relative expression of miR-146a was significantly increased only in the serum of dogs with large intestinal IBD. Furthermore, serum miR-192 and miR-223 relative expression correlated to disease activity and endoscopic score, respectively.

Conclusion: Our data suggest the existence of dysregulated miRs expression patterns in canine IBD and support the potential future use of serum miRs as useful noninvasive biomarkers.
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http://dx.doi.org/10.1186/s12917-020-02287-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035774PMC
February 2020

Apparent total tract digestibility, fecal characteristics, and blood parameters of healthy adult dogs fed high-fat diets.

J Anim Sci 2020 Mar;98(3)

Department of Animal Science, Iowa State University, Ames, IA.

Pet foods may be formulated with decreased starch to meet consumer demands for less processed diets. Fats and oils may be added to low-starch diets to meet energy requirements, but little is known about its effects on canine health. The study objective was to evaluate the effects of feeding healthy adult dogs low carbohydrate, high-fat diets on apparent total tract digestibility, fecal characteristics, and overall health status. Eight adult Beagles were enrolled in a replicated 4 × 4 Latin Square design feeding trial. Dogs were randomly assigned to one of four dietary fat level treatments (T) within each period: 32% (T1), 37% (T2), 42% (T3), and 47% (T4) fat on a dry matter basis. Fat levels were adjusted with the inclusion of canola oil added to a commercial diet. Each dog was fed to exceed its energy requirement based on NRC (2006). Blood samples were analyzed for complete blood counts, chemistry profiles, and canine pancreatic lipase immunoreactivity levels. Apparent total tract digestibility improved (P < 0.05) as the fat level increased for dry matter, organic matter, fat, and gross energy. Fecal output decreased as levels of fat increased in the diet (P = 0.002). There was no effect of fat level on stool quality or short-chain fatty acid and ammonia concentrations in fecal samples (P ≥ 0.20). Blood urea nitrogen levels decreased with increased fat level (P = 0.035). No significant differences were seen in canine pancreatic lipase immunoreactivity (P = 0.110). All blood parameters remained within normal reference intervals. In summary, increased dietary fat improved apparent total tract digestibility, did not alter fecal characteristics, and maintained the health status of all dogs.
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http://dx.doi.org/10.1093/jas/skaa043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059695PMC
March 2020

Glucocorticoid and dietary effects on mucosal microbiota in canine inflammatory bowel disease.

PLoS One 2019 30;14(12):e0226780. Epub 2019 Dec 30.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America.

The pathogenesis of canine inflammatory bowel disease (IBD) involves complex interactions between mucosal immunity and the intestinal microbiota. Glucocorticoids are commonly administered to reduce mucosal inflammation and gastrointestinal signs. The study objective was to evaluate the effects of diet and oral prednisone on the spatial distribution of mucosal bacteria in IBD dogs. Eight dogs diagnosed with IBD were treated with immunosuppressive doses of prednisone. The mucosal microbiota from endoscopic biopsies of IBD dogs and healthy controls (HC; n = 15 dogs) was evaluated by fluorescence in situ hybridization (FISH) targeting the 16S rRNA genes of total bacteria and bacterial species relevant in canine/human IBD. Apicaljunction protein (AJP) expression using immunohistochemistry investigated the effect of medical therapy on intestinal barrier integrity. All IBD dogs had a reduction in GI signs following diet and prednisone therapy compared with baseline CIBDAI scores (P < 0.05). The mucosal microbiota of HC and diseased dogs was most abundant in free and adherent mucus. Only Lactobacilli were increased (P < 0.05) in the adherent mucus of IBD dogs compared to HC. The spatial distribution of mucosal bacteria was significantly different (P < 0.05) in IBD dogs following prednisone therapy, with higher numbers of Bifidobacteria and Streptococci detected across all mucosal compartments and increased numbers of Bifidobacterium spp., Faecalibacterium spp., and Streptococcus spp. present within adherent mucus. Differences in intestinal AJPs were detected with expression of occludin increased (P < 0.05) in IBD dogs versus HC. The expressions of occludin and E-cadherin were increased but zonulin decreased (P < 0.05 for each) in IBD dogs following prednisone therapy. In conclusion, the spatial distribution of mucosal bacteria differs between IBD and HC dogs, and in response to diet and glucocorticoid administration. Medical therapy was associated with beneficial changes in microbial community structure and enhanced mucosal epithelial AJP expression.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226780PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936794PMC
April 2020

Ki-67/CD3 ratio in the diagnosis of chronic inflammatory enteropathy in dogs.

J Vet Intern Med 2020 Jan 11;34(1):92-97. Epub 2019 Dec 11.

Department for Companion Animals and Horses, Clinic for Small Animal Internal Medicine, University of Veterinary Medicine, Vienna, Austria.

Background: T cells play a key role in the pathogenesis of chronic inflammatory enteropathy (CIE) in dogs. Cluster of differentiation 3 (CD3) antigen serves as a marker for T cells. In human medicine, Ki-67 is an indicator for cell growth but there are only a few studies in dogs with CIE.

Objective: To investigate Ki-67 in relation to T cells as a marker for CIE in dogs.

Animals: Eleven dogs with CIE and 6 healthy beagle controls (CO).

Methods: Retrospective case-control study. Dogs were clinically assessed by the Canine Chronic Enteropathy Clinical Activity Index (CCECAI). Duodenal mucosal biopsy samples were endoscopically obtained for histopathologic examination by means of the World Small Animal Veterinary Association score. Double-labeled immunofluorescence was used to investigate colocalization of Ki-67 and CD3 in epithelium and lamina propria (LP) of villi and crypts.

Results: Dogs with CIE had significantly higher clinical score (median, 5.0; interquartile range [IQR], 3-7) compared to CO (all 0; P < .001). The Ki-67/CD3 double-positive cells were significantly increased in the LP of the crypt region of CIE dogs (0.63 cells/mm ; IQR, 0-0.54) versus CO (0.08 cells/mm ; IQR, 0-0.26; P = .044). A significant correlation was found between CCECAI and the Ki-67/CD3 ratio in the LP of the crypt region (r = 0.670; P = .012) in dogs with CIE.

Conclusions And Clinical Importance: The Ki-67/CD3 ratio is upregulated in the LP crypt region of dogs with CIE and it correlates with clinical severity. Therefore, Ki-67/CD3 could be a useful tool for detection of CIE.
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http://dx.doi.org/10.1111/jvim.15680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979107PMC
January 2020

Administration of a Synbiotic Containing Does Not Significantly Alter Fecal Microbiota Richness or Diversity in Dogs With and Without Food-Responsive Chronic Enteropathy.

Front Vet Sci 2019 30;6:277. Epub 2019 Aug 30.

Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United States.

Canine chronic enteropathies (CE) are a group of intestinal diseases that can be categorized based on treatment response into diet- or food- responsive enteropathy (FRD), antibiotic-responsive enteropathy, steroid-responsive enteropathy, and non-responsive enteropathy. CE can often be associated with intestinal dysbiosis and thus administration of probiotic or synbiotic products may provide a useful tool for the management of some of these patients. (EF) is a probiotic strain included in a commercially available synbiotic for small animals, however its impact on the microbial communities in dogs with FRD has not yet been evaluated. The administration of a synbiotic will lead to a significant difference of the fecal microbial composition and/or diversity in dogs with FRD, and these changes are not attributable to diet change alone. Twelve dogs with FRD fed a hydrolyzed protein diet received either a synbiotic (EF, fructooligosaccharides, gum Arabic) or placebo. Fecal samples were taken before and 6 weeks into treatment. Fecal samples were also acquired from 8 healthy dogs before and 6 weeks after being switched to the same hydrolyzed protein diet as their sole food. Bacterial DNA was extracted from fecal samples and next generation sequencing based on the 16S rRNA genes was performed. Microbial composition and diversity between groups were compared using QIIME. There was a small increase in species diversity in the feces of dogs with FRD treated with synbiotics. However, there were no significant differences in microbial community composition before and after 6 weeks in either the synbiotic or placebo treated dogs with FRD or the healthy dogs. In all groups, large individual variations were observed. No changes in microbial composition were observed in diseased or healthy dogs with diet change alone. However, administration of a synbiotic increased bacterial richness in both groups.
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http://dx.doi.org/10.3389/fvets.2019.00277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735529PMC
August 2019

Enterocolic increase of cannabinoid receptor type 1 and type 2 and clinical improvement after probiotic administration in dogs with chronic signs of colonic dysmotility without mucosal inflammatory changes.

Neurogastroenterol Motil 2020 01 8;32(1):e13717. Epub 2019 Sep 8.

School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy.

Background: Colonic dysmotility in dogs can cause different GI signs. Sometimes, histology of enterocolic biopsies does not reveal inflammatory infiltrates or mucosal lesions that are typically associated with clinical disease activity. It is speculated that, similarly to humans, colonic dysmotility may be anxiety-based, although recent data demonstrate that irritable bowel syndrome (IBS) could result from acute infectious enteritis. Specific Lactobacillus spp. strains administered orally in humans induced the expression of μ-opioid and cannabinoid receptors in mucosal enterocytes, modulating intestinal morphine-like analgesic functions. We investigated the potential association of GI signs caused by colonic dysmotility and mucosal expression of cannabinoid receptors in intestinal epithelial cells and the number of mucosal mast cells.

Methods: Ten to 15 endoscopic biopsies were collected from colonic mucosa of 20 dogs diagnosed with dysmotility disturbances before and after probiotic (Slab51 bacterial blend; Sivoy ) administration (3-month period). Number and distribution of mast cells (MCs), and cannabinoid receptor type 1 (CB1) and type 2 (CB2) were evaluated by immunohistochemistry and PCR. Results were compared to data obtained from five clinically healthy dogs (archive samples).

Key Results: Decreased numbers of MCs (P < .0001) and increased CB1- and CB2-positive epithelial cells (P < .0001) in diseased dogs were positively associated with post-treatment CCECAI scores (P < .0001).

Conclusions And Inferences: Our results suggest that probiotic administration can reduce signs of colonic dysmotility, possibly due to microbiota modulation and epithelial cell receptor-mediated signaling in intestinal mucosa.
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http://dx.doi.org/10.1111/nmo.13717DOI Listing
January 2020

Microbiota-Related Changes in Unconjugated Fecal Bile Acids Are Associated With Naturally Occurring, Insulin-Dependent Diabetes Mellitus in Dogs.

Front Vet Sci 2019 27;6:199. Epub 2019 Jun 27.

Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United States.

Diabetes mellitus (DM) in humans has recently been associated with altered intestinal microbiota. The consequences of intestinal dysbiosis, such as increased intestinal permeability and altered microbial metabolites, are suspected to contribute to the host inflammatory state and peripheral insulin resistance. Human diabetics have been shown to have changes in bile acid (BA) metabolism which may be detrimental to glycemic control. The purpose of this study was to examine BA metabolism in dogs with naturally-occurring, insulin-dependent DM and to relate these findings to changes in the intestinal microbiota. A prospective observational study of adult dogs with a clinical diagnosis of DM ( = 10) and healthy controls (HC, = 10) was performed. The fecal microbiota were analyzed by 16S rRNA gene next-generation (Illumina) sequencing. Concentrations of fecal unconjugated BA (fUBA) were measured using gas chromatography and mass spectrometry. Analysis of bacterial communities showed no significant difference for any of the alpha-diversity measures between DM vs. HC dogs. Principal coordinate analysis based on unweighted Unifrac distance metric failed to show significant clustering between dog groups (ANOSIM: = 0.084; = 0.114). However, linear discriminate analysis effects size (LEfSe) detected differentially abundant bacterial taxa (α = 0.01, LDA score >2.0) on various phylogenetic levels. While was overrepresented in dogs with DM, the proportions of Erysipelotrichia, , and were increased in HC dogs. Dogs with DM had increased concentration of total primary fUBA compared to HC dogs ( = 0.028). The concentrations of cholic acid and the cholic acid percentage of the total fUBA were increased ( = 0.028 and = 0.035, respectively) in the feces of DM dogs relative to HC dogs. The levels of lithocholic acid (both absolute value and percentage of the total fUBA) were decreased ( = 0.043 and < 0.01, respectively) in DM dogs vs. HC dogs. Results indicate that dogs with DM have both intestinal dysbiosis and associated fUBA alterations. The pattern of dysbiosis and altered BA composition is similar to that seen in humans with Type 2 DM. The dog represents a novel large animal model for advancing translational medicine research efforts (e.g., investigating pathogenesis and therapeutics) in DM affecting humans.
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http://dx.doi.org/10.3389/fvets.2019.00199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610424PMC
June 2019

The Gut-Brain Axis in Neurodegenerative Diseases and Relevance of the Canine Model: A Review.

Front Aging Neurosci 2019 18;11:130. Epub 2019 Jun 18.

Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.

Identifying appropriate animal models is critical in developing translatable and systems for therapeutic drug development and investigating disease pathophysiology. These animal models should have direct biological and translational relevance to the underlying disease they are supposed to mimic. Aging dogs not only naturally develop a cognitive decline in many aspects including learning and memory deficits, but they also exhibit human-like individual variability in the aging process. Neurodegenerative processes that can be observed in both human and canine brains include the progressive accumulation of β-amyloid (Aβ) found as diffuse plaques in the prefrontal cortex (PFC), including the , as well as the hippocampus and the cerebral vasculature. Tau pathology, a marker of neurodegeneration and dementia progression, was also found in canine hippocampal synapses. Various epidemiological data show that human patients with neurodegenerative diseases have concurrent intestinal lesions, and histopathological changes in the gastrointestinal (GI) tract occurs decades before neurodegenerative changes. Gut microbiome alterations have also been reported in many neurodegenerative diseases including Alzheimer's (AD) and Parkinson's diseases, as well as inflammatory central nervous system (CNS) diseases. Interestingly, the dog gut microbiome more closely resembles human gut microbiome in composition and functional overlap compared to rodent models. This article reviews the physiology of the gut-brain axis (GBA) and its involvement with neurodegenerative diseases in humans. Additionally, we outline the advantages and weaknesses of current and models and discuss future research directions investigating major human neurodegenerative diseases such as AD and Parkinson's diseases using dogs.
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http://dx.doi.org/10.3389/fnagi.2019.00130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591269PMC
June 2019

Indoleamine-pyrrole 2,3-dioxygenase-1 (IDO-1) mRNA is over-expressed in the duodenal mucosa and is negatively correlated with serum tryptophan concentrations in dogs with protein-losing enteropathy.

PLoS One 2019 10;14(6):e0218218. Epub 2019 Jun 10.

College of Veterinary Medicine, Iowa State University, Ames, IA, United States of America.

Introduction: Dogs with protein-losing enteropathy (PLE) have decreased serum tryptophan concentrations, which may contribute to disease pathogenesis. Indoleamine-pyrrole 2,3-dioxygenase-1 (IDO-1) expression is associated with low serum tryptophan concentrations and is increased in the gastrointestinal tract of humans with inflammatory bowel disease (IBD). Therefore, the objective of our study was to determine if the mRNA expression of IDO-1 is increased in the duodenal mucosa of dogs with PLE as compared to dogs with chronic enteropathy (CE) and healthy dogs, and whether this expression is correlated with changes in serum tryptophan concentration.

Methods: Our study was a retrospective study using archived paraffin-embedded duodenal biopsy specimens from 8 healthy Beagle dogs from the Iowa State University Canine Service Colony and 18 and 6 client-owned dogs diagnosed with CE and PLE, respectively at the Bristol Veterinary School. A novel RNA in situ hybridization (ISH) technology, RNAscope, was used to identify IDO-1 mRNA mucosal expression in duodenal tissues. An IDO-1 specific probe was hybridized onto 10 duodenal biopsy sections from each dog whereby RNAscope signal (mRNA expression) was quantified by a single operator using light microscopy.

Results: Dogs with PLE had significantly higher mRNA expression of IDO-1 in the duodenal mucosa compared to healthy dogs (mucosal percentage IDO-1 positive: P = 0.0093, (mean ± S.D) control: 19.36 ± 7.08, PLE: 34.12 ± 5.98, average fold difference: 1.76 and mucosal IDO-1 H-score: P = 0.0356, (mean ± S.D) control: 45.26 ± 19.33, PLE: 84.37 ± 19.86, average fold difference: 1.86). The duodenal mucosal mRNA expression of IDO-1 was negatively correlated with serum tryptophan concentrations in dogs with PLE (mucosal IDO-1 H-score: Spearman's rank correlation coefficient = -0.94, P = 0.0048).

Conclusions: In conclusion, our study suggests that decreased serum tryptophan concentrations in dogs with PLE is associated with increased intestinal IDO-1 expression. Further studies are needed to determine potential inflammatory pathways responsible for increased expression of IDO-1 in the intestinal tract of dogs with PLE.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218218PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557522PMC
February 2020

Interleukin-13 and interleukin-33 mRNA are underexpressed in the duodenal mucosa of German Shepherd dogs with chronic enteropathy.

J Vet Intern Med 2019 Jul 6;33(4):1660-1668. Epub 2019 Jun 6.

College of Veterinary Medicine, Iowa State University, Ames, Iowa.

Background: A recent genome-wide association study in German Shepherd dogs (GSDs) with chronic enteropathy (CE) has identified polymorphisms in the Th2 cytokine genes.

Hypothesis/objective: To determine if the expression of the Th2 cytokines, interleukin-13 (IL-13) and interleukin-33 (IL-33), is altered in the duodenal mucosa of GSDs with CE compared to non-GSDs with CE and healthy dogs.

Animals: Twenty client-owned dogs diagnosed with CE (10 GSDs and 10 non-GSDs) at the Bristol Veterinary School and 8 healthy Beagle dogs from the Iowa State University Service Colony.

Methods: Retrospective study using archived paraffin-embedded duodenal biopsy samples. A novel RNA in situ hybridization technology (RNAscope) was used to hybridize IL-13 and IL-33 mRNA probes onto at least 10 sections from duodenal biopsy samples for each dog. RNAscope signals were visualized using a microscope and semi-quantitative assessment was performed by a single operator.

Results: Based on duodenal villus, subvillus, epithelial, and lamina propria average expression scores, GSDs with CE had significantly lower IL-13 and IL-33 mRNA expression compared to non-GSDs with CE (IL-13, P < .04; IL-33, P < .02) and healthy Beagle dogs (IL-13, P < .02; IL-33, P < .004).

Conclusions And Clinical Importance: Similar to human patients with ulcerative colitis, a subtype of human inflammatory bowel disease, these data indicate that Th2 cytokines may be involved in the pathogenesis of CE in GSDs.
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http://dx.doi.org/10.1111/jvim.15544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639532PMC
July 2019

Derivation of adult canine intestinal organoids for translational research in gastroenterology.

BMC Biol 2019 04 11;17(1):33. Epub 2019 Apr 11.

Departments of Veterinary Clinical Sciences, Iowa State University, Ames, IA, USA.

Background: Large animal models, such as the dog, are increasingly being used for studying diseases including gastrointestinal (GI) disorders. Dogs share similar environmental, genomic, anatomical, and intestinal physiologic features with humans. To bridge the gap between commonly used animal models, such as rodents, and humans, and expand the translational potential of the dog model, we developed a three-dimensional (3D) canine GI organoid (enteroid and colonoid) system. Organoids have recently gained interest in translational research as this model system better recapitulates the physiological and molecular features of the tissue environment in comparison with two-dimensional cultures.

Results: Organoids were derived from tissue of more than 40 healthy dogs and dogs with GI conditions, including inflammatory bowel disease (IBD) and intestinal carcinomas. Adult intestinal stem cells (ISC) were isolated from whole jejunal tissue as well as endoscopically obtained duodenal, ileal, and colonic biopsy samples using an optimized culture protocol. Intestinal organoids were comprehensively characterized using histology, immunohistochemistry, RNA in situ hybridization, and transmission electron microscopy, to determine the extent to which they recapitulated the in vivo tissue characteristics. Physiological relevance of the enteroid system was defined using functional assays such as optical metabolic imaging (OMI), the cystic fibrosis transmembrane conductance regulator (CFTR) function assay, and Exosome-Like Vesicles (EV) uptake assay, as a basis for wider applications of this technology in basic, preclinical and translational GI research. We have furthermore created a collection of cryopreserved organoids to facilitate future research.

Conclusions: We establish the canine GI organoid systems as a model to study naturally occurring intestinal diseases in dogs and humans, and that can be used for toxicology studies, for analysis of host-pathogen interactions, and for other translational applications.
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http://dx.doi.org/10.1186/s12915-019-0652-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460554PMC
April 2019

CAR T Cell Immunotherapy in Human and Veterinary Oncology: Changing the Odds Against Hematological Malignancies.

AAPS J 2019 04 8;21(3):50. Epub 2019 Apr 8.

Department of Medicine, Mayo Clinic Division of Hematology, Rochester, Minnesota, 55905, USA.

The advent of the genome editing era brings forth the promise of adoptive cell transfer using engineered chimeric antigen receptor (CAR) T cells for targeted cancer therapy. CAR T cell immunotherapy is probably one of the most encouraging developments for the treatment of hematological malignancies. In 2017, two CAR T cell therapies were approved by the US Food and Drug Administration: one for the treatment of pediatric acute lymphoblastic leukemia (ALL) and the other for adult patients with advanced lymphomas. However, despite significant progress in the area, CAR T cell therapy is still in its early days and faces significant challenges, including the complexity and costs associated with the technology. B cell lymphoma is the most common hematopoietic cancer in dogs, with an incidence approaching 0.1% and a total of 20-100 cases per 100,000 individuals. It is a widely accepted naturally occurring model for human non-Hodgkin's lymphoma. Current treatment is with combination chemotherapy protocols, which prolong life for less than a year in canines and are associated with severe dose-limiting side effects, such as gastrointestinal and bone marrow toxicity. To date, one canine study generated CAR T cells by transfection of mRNA for CAR domain expression. While this was shown to provide a transient anti-tumor activity, results were modest, indicating that stable, genomic integration of CAR modules is required in order to achieve lasting therapeutic benefit. This commentary summarizes the current state of knowledge on CAR T cell immunotherapy in human medicine and its potential applications in animal health, while discussing the potential of the canine model as a translational system for immuno-oncology research.
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http://dx.doi.org/10.1208/s12248-019-0322-1DOI Listing
April 2019

Correlating Gastrointestinal Histopathologic Changes to Clinical Disease Activity in Dogs With Idiopathic Inflammatory Bowel Disease.

Vet Pathol 2019 05 18;56(3):435-443. Epub 2018 Dec 18.

1 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.

Prior studies have failed to detect a convincing association between histologic lesions of inflammation and clinical activity in dogs with inflammatory bowel disease (IBD). We hypothesized that use of a simplified histopathologic scoring system would improve the consistency of interpretation among pathologists when describing histologic lesions of gastrointestinal inflammation. Our aim was to evaluate the correlation of histopathologic changes to clinical activity in dogs with IBD using this new system. Forty-two dogs with IBD and 19 healthy control dogs were enrolled in this retrospective study. Endoscopic biopsies from the stomach, duodenum, ileum, and colon were independently scored by 8 pathologists. Clinical disease activity was scored using the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) or the Canine Chronic Enteropathy Clinical Activity Index (CCECAI), depending on the individual study center. Summative histopathological scores and clinical activity were calculated for each tissue (stomach, duodenum, ileum, and colon) and each tissue histologic score (inflammatory/morphologic feature). The correlation between CCECAI/CIBDAI and summative histopathologic score was significant ( P < .05) for duodenum ( r = 0.42) and colon ( r = 0.33). In evaluating the relationship between histopathologic scores and clinical activity, significant ( P < .05) correlations were observed for crypt dilation ( r = 0.42), lamina propria (LP) lymphocytes ( r = 0.40), LP neutrophils ( r = 0.45), mucosal fibrosis ( r = 0.47), lacteal dilation ( r = 0.39), and villus stunting ( r = 0.43). Compared to earlier grading schemes, the simplified scoring system shows improved utility in correlating histopathologic features (both summative histology scores and select histologic scores) to IBD clinical activity.
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http://dx.doi.org/10.1177/0300985818813090DOI Listing
May 2019

Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of gastrointestinal stromal tumors of dogs.

J Vet Intern Med 2018 Nov 11;32(6):2045-2053. Epub 2018 Oct 11.

Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa.

Background: Gastrointestinal stromal tumors (GISTs) are uncommon intestinal neoplasms in the dog. Literature regarding adjunctive therapy for GISTs in dogs is sparse. High-risk GISTs in humans respond to tyrosine kinase inhibition in the adjuvant setting.

Objectives: To review cases of toceranib phosphate use in dogs with GISTs and provide initial assessment of possible biological activity. A secondary aim was to evaluate patient and tumor characteristics for possible prognostic value.

Animals: Twenty-seven dogs with confirmed GISTs based on histopathology and immunohistochemistry treated with toceranib.

Methods: Retrospective study in which cases of toceranib use in dogs with GIST were solicited using the American College of Veterinary Internal Medicine Oncology and Small Animal Internal Medicine listservs.

Results: Five of 7 dogs with gross disease experienced clinical benefit (71%; 3 complete responses, 1 partial response, 1 stable disease). These included 2 dogs with durable responses after toceranib discontinuation. Median progression-free interval (PFI) in dogs with gross disease was 110 weeks (range, 36-155 weeks). Median PFI in dogs with microscopic disease was 67 weeks (range, 9-257 weeks). Metastasis at diagnosis (P = 0.04) and high mitotic index (P < 0.001) were associated with shorter PFI in toceranib-treated dogs.

Conclusions And Clinical Importance: Biological activity of toceranib is evident in dogs with gross disease. Metastasis of GIST at diagnosis, as well as high tumor mitotic index, was associated with shorter PFI in toceranib-treated dogs. Larger studies are needed to define postsurgical risk and refine the use of toceranib in dogs with gross and microscopic GIST.
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http://dx.doi.org/10.1111/jvim.15335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271363PMC
November 2018

Changes in duodenal CD163-positive cells in dogs with chronic enteropathy after successful treatment.

Innate Immun 2018 10 17;24(7):400-410. Epub 2018 Sep 17.

1 Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Australia.

Chronic enteropathy (CE) in dogs is characterized retrospectively per treatment response as food-responsive enteropathy (FRE), antibiotic-responsive enteropathy (ARE), and immunosuppressant-responsive enteropathy (IRE) - the latter most resembling inflammatory bowel disease in people. The aim of this study was to characterize duodenal macrophages (Mϕ) in CE using immunohistochemistry; with calprotectin (CAL) as a marker of early differentiated Mϕ and CD163 expression as a marker for resident Mϕ in the duodenum before and after treatment. Prior to treatment, dogs with FRE and IRE had a lower CD163/CAL ratio than control dogs (CTRL) in crypts; this increased significantly and normalized compared with CTRL after treatment. Conversely, the CD163/CAL ratio in dogs with ARE was comparable to that in healthy dogs before and after treatment. In summary, these results suggest that Mϕ play a role in the pathogenesis of CE in FRE and IRE, with a decrease in resident Mϕ and an increase in early differentiated Mϕ, but not in ARE dogs. Mϕ normalize after successful treatment.
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http://dx.doi.org/10.1177/1753425918799865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830873PMC
October 2018

Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats.

J Vet Intern Med 2018 Sep 7;32(5):1692-1702. Epub 2018 Aug 7.

College of Veterinary Medicine, Iowa State University.

Background: The gastrointestinal (GI) microbiota in healthy cats is altered in IBD. Little research has been performed to identify whether specific bacterial groups are associated with small cell GI lymphoma (LSA).

Hypothesis: Mucosal bacteria, including Enterobacteriaceae and Fusobacterium spp., are abundant in intestinal biopsies of cats with small cell GI LSA compared to cats with IBD.

Animals: Fourteen cats with IBD and 14 cats with small cell GI LSA.

Methods: Retrospective case control study. A search of the medical records was performed to identify cats diagnosed with IBD and with GI LSA. Bacterial groups identified by FISH in GI biopsies were compared between cohorts and correlated to CD11b and NF-κB expression.

Results: Fusobacterium spp. (median; IQR bacteria/region) were higher in cats with small cell GI LSA in ileal (527; 455.5 - 661.5; P = .046) and colonic (404.5; 328.8 - 455.5; P = .016) adherent mucus, and combined colonic compartments (free mucus, adherent mucus, attaching to epithelium) (8; 0 - 336; P = .017) compared to cats with IBD (ileum: 67; 31.5 - 259; colon: 142.5; 82.3 - 434.5; combined: 3; 0 - 34). Bacteroides spp. were higher in ileal adherent mucus (P = .036) and 3 combined ileal compartments (P = .034) of cats with small cell GI LSA. There were significant correlations between Fusobacterium spp. totals and CD11b cell (P = .009; rs .476) and NF-κB expression (P = .004; rs .523).

Conclusions: The bacterial alterations appreciated might be influential in development of small cell GI LSA, and should drive further studies to elucidate the effects of microbial-mediated inflammation on GI cancer progression.
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http://dx.doi.org/10.1111/jvim.15291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189339PMC
September 2018

Genome-wide association studies of inflammatory bowel disease in German shepherd dogs.

PLoS One 2018 20;13(7):e0200685. Epub 2018 Jul 20.

Department of Pathology and Pathogen Biology, Royal Veterinary College, University of London, North Mymms, United Kingdom.

Canine Inflammatory Bowel Disease (IBD) is considered a multifactorial disease caused by complex interactions between the intestinal immune system, intestinal microbiota and environmental factors in genetically susceptible individuals. Although IBD can affect any breed, German shepherd dogs (GSD) in the UK are at increased risk of developing the disease. Based on previous evidence, the aim of the present study was to identify single nucleotide polymorphisms (SNPs), which may confer genetic susceptibility or resistance to IBD using a genome-wide association study (GWAS). Genomic DNA was extracted from EDTA blood or saliva samples of 96 cases and 98 controls. Genotyping of cases and controls was performed on the Canine Illumina HD SNP array and data generated was analyzed using PLINK. Several SNPs and regions on chromosomes 7,9,11 and 13 were detected to be associated with IBD using different SNP-by-SNP association methods and FST windows approach. Searching one Mb up-and down-stream of the most significant SNPs, as identified by single SNP analysis as well as 200Kb before and after the start and the end position of the associated regions identified by FST windows approach, we identified 63 genes. Using a combination of pathways analysis and a list of genes that have been reported to be involved in human IBD, we identified 16 candidate genes potentially associated with IBD in GSD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0200685PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054420PMC
January 2019

Interleukin-1β expression is increased in the duodenum of dogs with idiopathic inflammatory bowel disease.

Vet Rec 2018 11 9;183(17):536. Epub 2018 May 9.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, USA.

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http://dx.doi.org/10.1136/vr.104495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252374PMC
November 2018

Alterations in serum amino acid concentrations in dogs with protein-losing enteropathy.

J Vet Intern Med 2018 May 31;32(3):1026-1032. Epub 2018 Mar 31.

Bristol Veterinary School, University of Bristol, Langford, Bristol, United Kingdom.

Background: Certain amino acids are decreased in humans with inflammatory bowel disease (IBD) and supplementation with the same amino acids has shown beneficial effects in animal models of IBD. Currently, the amino acid status of dogs with protein-losing enteropathy (PLE) is unknown.

Hypothesis/objective: To determine if serum amino acid concentrations are abnormal in dogs with PLE and correlated with clinical and laboratory variables and outcome.

Animals: Thirty client-owned dogs diagnosed with PLE and 12 apparently healthy dogs seen at Bristol Veterinary School.

Methods: Retrospective study using stored residual serum from fasted dogs with PLE, collected at the time of diagnostic investigation and from apparently healthy dogs. Serum was analyzed for 30 amino acids using an automated high-performance liquid chromatography amino acid analyzer.

Results: Serum tryptophan concentrations were significantly decreased in dogs with PLE (median, 22 nmol/mL; range, 1-80 nmol/mL) compared with apparently healthy control dogs (median, 77.5 nmol/mL; range, 42-135 nmol/mL, P < .001). There were no significant differences in the remaining 29 serum amino acids between dogs with PLE and apparently healthy. Serum tryptophan concentrations were also significantly correlated with serum albumin concentrations in dogs with PLE (P = .001, R = 0.506).

Conclusions And Clinical Importance: Decreased serum tryptophan concentration might play a role in the pathogenesis of canine PLE or be a consequence of the disease.
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http://dx.doi.org/10.1111/jvim.15116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980272PMC
May 2018
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