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1.
J Vet Intern Med ; 37(6): 2375-2384, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37772917

RESUMEN

BACKGROUND: Compared to humans, colorectal polyps are relatively rare in dogs. Epidemiological and prognostic data remain accordingly sparse, although they could help veterinary clinicians in the management of these cases. OBJECTIVES: To report the epidemiological data of dogs with colorectal polyps and identify factors associated with recurrence and survival. ANIMALS: Fifty-eight client-owned dogs with colorectal polyps admitted to 7 veterinary hospitals (53 dogs from France, 5 dogs from Spain, and 4 dogs from Portugal) were included. METHODS: Retrospective multicentric cohort study. Medical records and long-term outcome of the dogs were reviewed. When available, histological samples were reassessed by 2 board-certified pathologists according to the revised Vienna classification (RVC). RESULTS: The West Highland White Terrier (WHWT) breed was significantly associated with the presence of colorectal polyps (OR: 20; 95% CI: 7.5-52; P < .001). The overall median time to recurrence was not reached after 2000 days. The overall estimated median survival time was 1640 days. WHWT breed and larger polyps were significantly associated with a shorter time of polyp recurrence after surgical removal (respectively, P = .05 and P = .01). CONCLUSIONS AND CLINICAL IMPORTANCE: The probability of recurrence of colorectal polyps in dogs is low, but increased in WHWTs and larger polyps, which might benefit from routine screening after removal. No effective predictors of polyp recurrence and survival were identified using the RVC.


Asunto(s)
Pólipos del Colon , Enfermedades de los Perros , Humanos , Perros , Animales , Estudios Retrospectivos , Estudios de Cohortes , Pólipos del Colon/cirugía , Pólipos del Colon/veterinaria , Cruzamiento , Certificación , Enfermedades de los Perros/cirugía
2.
Schweiz Arch Tierheilkd ; 164(11): 801-804, 2022 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-36325643

RESUMEN

INTRODUCTION: Reports on bovine colon polyps are rare. The present report demonstrates macro- and microscopically hyperplastic colon polyps of a seven-year-old German Simmental cow. Differential diagnoses (adenoma and adenocarcinoma) and aetiology are discussed. Even in cattle, intestinal polyps should be considered as a cause of intussusception.


INTRODUCTION: Les rapports concernant des polypes du colon chez les bovins sont rares. Le présent rapport fait état de polypes du côlon macro- et microscopiquement hyperplasiques chez une vache Simmental allemande de sept ans. Les diagnostics différentiels (adénome et adénocarcinome) et l'étiologie sont discutés. Même chez les bovins, les polypes intestinaux doivent être considérés comme une cause d'invagination.


Asunto(s)
Adenocarcinoma , Adenoma , Enfermedades de los Bovinos , Pólipos del Colon , Bovinos , Animales , Pólipos del Colon/diagnóstico , Pólipos del Colon/veterinaria , Pólipos del Colon/patología , Hiperplasia/veterinaria , Hiperplasia/patología , Adenoma/diagnóstico , Adenoma/veterinaria , Adenoma/patología , Adenocarcinoma/diagnóstico , Adenocarcinoma/veterinaria , Adenocarcinoma/patología , Colon/patología , Enfermedades de los Bovinos/diagnóstico , Enfermedades de los Bovinos/patología
3.
J Vet Med Sci ; 84(6): 872-876, 2022 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-35527018

RESUMEN

Hyperplastic goblet cells and abundant mucus are significant characteristics of inflammatory colorectal polyps (ICRPs) in miniature dachshunds. In this study, selected mucin gene expressions and goblet cell proportions were evaluated in miniature dachshunds with ICRPs and in healthy dogs. Mucin 2 (MUC2) gene expression was not significantly different among the groups, whereas mucin 5AC (MUC5AC) gene expression was significantly higher in the polypoid lesions than in healthy colonic mucosa. Although the percentage of goblet cells in the upper crypt regions did not significantly differ between the groups, that in the lower crypt regions was significantly decreased in polypoid lesions. In conclusion, increased MUC5AC gene expression and goblet cell proportion changes may be associated with the pathogenesis of ICRPs.


Asunto(s)
Pólipos del Colon , Enfermedades de los Perros , Animales , Pólipos del Colon/genética , Pólipos del Colon/metabolismo , Pólipos del Colon/veterinaria , Enfermedades de los Perros/patología , Perros , Expresión Génica , Células Caliciformes/metabolismo , Mucosa Intestinal/metabolismo , Mucina 2/genética , Mucina 2/metabolismo
4.
J Vet Med Sci ; 82(10): 1445-1449, 2020 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-32759576

RESUMEN

Inflammatory colorectal polyps (ICRPs) in miniature dachshunds (MDs) are speculated to be a breed-specific inflammatory bowel disease (IBD). Leucine-rich alpha-2 glycoprotein (LRG) has been identified as a novel biomarker of human IBD. The aim of this study was to examine LRG gene expression in the polypoid lesions of ICRPs. Polypoid lesion specimens were collected from 24 MDs with ICRPs. Nonpolypoid colonic mucosa was collected from 18 MDs with ICRPs and 10 controls. The gene expression of LRG, interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and IL-22 was examined. The expression of LRG gene was significantly increased in the polypoid lesions of ICRPs and correlated with that of the four cytokines. In conclusion, the LRG gene was expressed within the polypoid lesions of ICRPs and might be associated with local cytokine expression.


Asunto(s)
Pólipos del Colon , Enfermedades de los Perros , Animales , Pólipos del Colon/genética , Pólipos del Colon/veterinaria , Perros , Expresión Génica , Glicoproteínas/genética , Leucina
5.
Am J Vet Res ; 81(7): 572-580, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32584177

RESUMEN

OBJECTIVE: To investigate the activities of gelatinases (matrix metalloproteinase [MMP]-2 and MMP-9) and serine proteases in the colorectal mucosa of Miniature Dachshunds (MDs) with inflammatory colorectal polyps (ICRPs). ANIMALS: 15 MDs with ICRPs and 5 dogs with non-ICRP-related large bowel diarrhea (controls). PROCEDURES: Zymographic methods were used to evaluate the activities of MMP-2, MMP-9, latent forms of MMP-2 and MMP-9 (pro-MMP-2 and pro-MMP-9), and serine proteases in inflamed and noninflamed tissue samples from MDs with ICRPs and in noninflamed tissue samples from control dogs. The associations of serine protease activities with MMP-2 or MMP-9 activity were also analyzed. RESULTS: Activities of pro-MMP-2 and pro-MMP-9 were detected in most tissue samples, regardless of the tissue type, whereas activities of MMP-2 and MMP-9 were not detected in control tissue samples. In the inflamed tissue samples from MDs with ICRPs, the activities of MMP-2, pro-MMP-9, and MMP-9 were significantly higher than those in the noninflamed tissue samples from those dogs. Serine protease activities were significantly higher in the inflamed and noninflamed tissue samples from MDs with ICRP, compared with findings for control tissue samples. A weak correlation was detected between serine protease activities and MMP-9 activity. CONCLUSIONS AND CLINICAL RELEVANCE: Study results suggested that gelatinase and serine protease activities are upregulated in the colorectal mucosa of MDs with ICRPs, possibly contributing to the pathogenesis of this disease through the functions of these enzymes in degradation of extracellular matrix and promotion of inflammatory cell migration and inflammatory responses.


Asunto(s)
Pólipos del Colon/veterinaria , Neoplasias Colorrectales/veterinaria , Enfermedades de los Perros , Animales , Perros , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 9 de la Matriz , Serina Proteasas
6.
J Vet Med Sci ; 82(4): 437-440, 2020 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-32062634

RESUMEN

Inflammatory colorectal polyps (ICRPs) are frequently observed in miniature dachshunds in Japan and treated by prednisolone and immunosuppressive drugs such as cyclosporine and leflunomide. The purpose of this retrospective study was to compare the treatment efficacy, such as response rate, response interval, recurrence rate, and adverse events between cyclosporine and leflunomide. While the response rates were significantly higher in dogs treated with leflunomide, no significant differences were observed in the response interval or recurrence rate. Two of the 11 dogs treated with leflunomide showed hematological or gastrointestinal adverse events, while no dog treated with cyclosporine showed any adverse events. A case-controlled prospective study to compare the treatment efficacy of leflunomide with that of cyclosporine should be conducted.


Asunto(s)
Pólipos del Colon/veterinaria , Ciclosporina/uso terapéutico , Inmunosupresores/uso terapéutico , Leflunamida/uso terapéutico , Animales , Pólipos del Colon/tratamiento farmacológico , Enfermedades de los Perros/tratamiento farmacológico , Perros , Femenino , Inmunosupresores/efectos adversos , Japón , Leflunamida/efectos adversos , Masculino , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento
7.
Vet Immunol Immunopathol ; 218: 109938, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31518913

RESUMEN

Inflammatory colorectal polyp (ICRP) is an emerging disease in Miniature Dachshunds (MDs). Animals with this disease exhibit multiple polyps with severe neutrophil infiltration that respond to immunosuppressive therapy. Macrophages in polypoid lesions have been described to play an important role in neutrophil infiltration in the lesion by producing IL-8. In contrast, IL-10, an anti-inflammatory cytokine, was also reported to be upregulated in polypoid lesions, but its significance in the pathogenesis of ICRP has not been clarified. Regulatory T cells (Tregs) are the main source of IL-10 production and contribute to the maintenance of intestinal homeostasis. Therefore, the objective of this research was to compare the distribution of Tregs in polypoid lesions of ICRPs and the association between the distribution and expression of pro- or anti-inflammatory cytokines. Tissue biopsy specimens of polypoid lesions were collected from 28 MDs with ICRP. Those of macroscopically non-polypoid colonic mucosa from 24 MDs with ICRPs and 21 control dogs were further included as controls. Real-time quantitative polymerase chain reaction was used to quantify gene expression of IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-17, IL-22, IFN-γ, TNF-α, TGF-ß, and forkhead box protein P3 (Foxp3) in each tissue sample. The numbers of Foxp3-positive cells (Tregs) and ionized calcium binding adapter molecule 1 (Iba-1)-positive cells (macrophages) were determined by immunohistochemistry. The gene expression of IL-1ß, IL-6, IL-8, TNF-α, IFN-γ, IL-17, IL-10, TGF-ß, and Foxp3 was significantly upregulated in polypoid lesions relative to control levels. The numbers of Foxp3-positive Tregs and Iba-1-positive macrophages were significantly increased in polypoid lesions compared to those in the non-polypoid colonic mucosa of MDs with ICRPs and control dogs. The upregulation of IL-10 was moderately correlated with the distribution of Tregs in polypoid lesions from MDs with ICRPs. In addition, the relative upregulation of IL-1ß, IL-6, and IL-8 in polypoid lesions, compared to expression in non-polypoid colonic mucosa of MDs with ICRPs, was significantly greater than that of IL-10. These results indicate that increases in Treg numbers and anti-inflammatory cytokines in polypoid lesions comprise reactive changes in response to the inflammation, which warrants further investigation.


Asunto(s)
Pólipos del Colon/veterinaria , Citocinas/inmunología , Perros/inmunología , Inflamación/veterinaria , Linfocitos T Reguladores/inmunología , Animales , Biopsia/veterinaria , Pólipos del Colon/inmunología , Pólipos del Colon/patología , Citocinas/genética , Femenino , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/inmunología , Inflamación/inmunología , Interleucina-10/genética , Interleucina-10/inmunología , Masculino
8.
Vet Pathol ; 55(5): 654-662, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29852840

RESUMEN

Biopsy samples of colorectal polyps were collected and examined from 67 Miniature Dachshund dogs (including 35 cases with an additional biopsy). Histopathologic diagnoses of the initial biopsy samples were "inflammatory polyp" in 52 cases (78%), "adenoma" in 10 cases (15%), and "adenocarcinoma" in 5 cases (8%). Eight of 10 cases (80%) diagnosed as adenoma also had inflammatory polyp lesions in the same specimen. A second biopsy was performed in 25 cases (48%) initially diagnosed with inflammatory polyp. Pathologic diagnoses for the second biopsy were inflammatory polyp in 11 cases (44%), adenoma in 9 cases (36%), and adenocarcinoma in 5 cases (20%). The number of beta-catenin-positive nuclei in epithelial cells was significantly higher in adenoma (46%) and adenocarcinoma (75%) as compared with inflammatory polyp (6%). Normal epithelial cells and hyperplastic goblet cells in inflammatory polyps showed homogeneous positive cytoplasmic immunoreactivity for adenomatous polyposis coli (APC) antigen. However, APC expression was decreased in areas of intense nuclear beta-catenin expression in adenoma and adenocarcinoma lesions. Foci of cytokeratin 5/6-positive squamous cell-like neoplastic cells showed intense beta-catenin nuclear expression that was similar to squamous morules described in human colorectal tumors. The results of the present study suggest that the inflammatory polyp in Miniature Dachshunds is a progressive disease that may develop into adenoma and/or adenocarcinoma. In addition, immunohistochemical findings suggest that aberrations of APC and beta-catenin expression may be involved in tumor development within the inflammatory polyp lesions.


Asunto(s)
Adenocarcinoma/veterinaria , Adenoma/veterinaria , Pólipos del Colon/veterinaria , Neoplasias Colorrectales/veterinaria , Enfermedades de los Perros/patología , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Adenoma/diagnóstico , Adenoma/patología , Animales , Biopsia/veterinaria , Transformación Celular Neoplásica , Pólipos del Colon/diagnóstico , Pólipos del Colon/patología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Enfermedades de los Perros/diagnóstico , Perros , Técnica del Anticuerpo Fluorescente/veterinaria , Estudios Prospectivos , beta Catenina/metabolismo
9.
J Am Anim Hosp Assoc ; 54(3): 161-166, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29558217

RESUMEN

Inflammatory colorectal polyps (ICRP), which are more commonly recognized in miniature dachshunds, are thought to represent an immune-mediated disease. This retrospective case series describes six miniature dachshunds with refractory ICRP, who were treated with chlorambucil (CLB) combined with firocoxib or prednisolone. Improvement in clinical manifestations was seen in five of the six dogs by the end of the study period; four were treated with CLB/firocoxib and one with CLB/prednisolone. One dog had nonregenerative anemia after 23 mo of treatment with CLB, but whether there was a causative relationship was unclear. No severe adverse events were observed during treatment in the remaining five dogs. CLB in combination with firocoxib or prednisolone appears to be an effective alternative treatment for ICRP in dogs. Further studies are needed to confirm the effectiveness and long-term complications of CLB treatment for ICRP in dogs.


Asunto(s)
Pólipos del Colon/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , 4-Butirolactona/análogos & derivados , 4-Butirolactona/uso terapéutico , Animales , Clorambucilo/uso terapéutico , Pólipos del Colon/tratamiento farmacológico , Perros , Quimioterapia Combinada/veterinaria , Prednisolona/uso terapéutico , Estudios Retrospectivos , Sulfonas/uso terapéutico
10.
Benef Microbes ; 9(2): 247-255, 2018 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-29022381

RESUMEN

Spermine (SPM) and its precursor putrescine (PUT), regulated by ornithine decarboxylase (ODC) and diamino-oxidase (DAO), are polyamines required for cell growth and proliferation. Only a few studies have investigated the anti-inflammatory and tumour inhibitory properties of probiotics on mucosal polyamine levels. We investigated the effects of a high concentration multistrain probiotic for human use on colonic polyamine biosynthesis in dogs. Histological sections (inflammatory bowel disease, n=10; polyposis, n=5) were assessed after receiving 112 to 225×109 lyophilised bacteria daily for 60 days at baseline (T0) and 30 days after treatment end (T90). Histology scores, expression of PUT, SPM, ODC and DAO, and a clinical activity index (CIBDAI) were compared at T0 and T90. In polyps, cellular proliferation (Ki-67 expression), and apoptosis (caspase-3 protein expression) were also evaluated. After treatment, in inflammatory bowel disease significant decreases were observed for CIBDAI (P=0.006) and histology scores (P<0.001); PUT, SPM and ODC expression increased (P<0.01). In polyps, a significant decrease in polyamine levels, ODC activity, and Ki-67, and a significant increase in caspase-3 positivity and DAO expression (P=0.005) was noted. Our results suggest potential anti-proliferative and anti-inflammatory effects of the probiotic mixture in polyps and inflammation, associated with reduced mucosal infiltration and up-regulation of PUT, SPM, and ODC levels.


Asunto(s)
Fenómenos Fisiológicos Bacterianos , Pólipos del Colon/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/veterinaria , Probióticos/uso terapéutico , Amina Oxidasa (conteniendo Cobre)/genética , Amina Oxidasa (conteniendo Cobre)/metabolismo , Animales , Caspasa 3/genética , Caspasa 3/metabolismo , Colon/metabolismo , Colon/patología , Pólipos del Colon/tratamiento farmacológico , Pólipos del Colon/microbiología , Pólipos del Colon/patología , Enfermedades de los Perros/microbiología , Enfermedades de los Perros/patología , Perros , Regulación de la Expresión Génica/efectos de los fármacos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/microbiología , Enfermedades Inflamatorias del Intestino/patología , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Ornitina Descarboxilasa/genética , Ornitina Descarboxilasa/metabolismo , Putrescina/biosíntesis , Espermina/biosíntesis , Resultado del Tratamiento
11.
Vet Immunol Immunopathol ; 188: 78-83, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28615131

RESUMEN

Inflammatory colorectal polyps (ICRPs) in miniature dachshunds (MDs) are a possible novel form of breed-specific canine inflammatory bowel disease (IBD). In this pilot study, we investigated the effects of different Toll like receptor (TLR2, TLR4, TLR5 and TLR9) ligands on pro-inflammatory cytokines (IL-1ß, IL-6, IL-8 and TNF-α) gene expression in ex vivo-cultured colorectal samples from four MDs with ICRPs and four healthy MDs. At baseline, no significant difference in the mRNA expression levels of TLRs and pro-inflammatory cytokines was observed between cases and control MDs. After 4-h incubation, the relative ratios of TNF-α mRNA expression in the TLR2- or TLR4-stimulated colorectal samples, and IL-1ß mRNA expression in the TLR9-stimulated colorectal samples form cases showed higher tendency compared with healthy MDs (P<0.05), although statistically not significant. The results of this pilot study using small number of cases indicated that reactivity against TLR2, TLR4 or TLR9 ligand in the production of pro-inflammatory cytokines might be enhanced in the colorectal mucosa of ICRPs. Further research is needed to perform the functional analysis of TLRs in the sole cell population using intestinal epithelial primary culture and the mononuclear cells isolated from colonic mucosa.


Asunto(s)
Pólipos del Colon/veterinaria , Enfermedades de los Perros/patología , Receptores Toll-Like/inmunología , Animales , Biopsia/veterinaria , Estudios de Casos y Controles , Colon/metabolismo , Colon/patología , Pólipos del Colon/inmunología , Pólipos del Colon/patología , Citocinas/metabolismo , Enfermedades de los Perros/inmunología , Perros , Femenino , Ligandos , Masculino , Proyectos Piloto
12.
J Comp Pathol ; 156(2-3): 183-190, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28089357

RESUMEN

Inflammatory colorectal polyps (ICRPs) are characterized by the formation of multiple or solitary polyps with marked neutrophil infiltration in the colorectal area, and are speculated to be a novel form of breed-specific canine idiopathic inflammatory bowel disease (IBD). In human IBD, toll-like receptor (TLR) 2 and TLR4 have been reported to be involved in the pathogenesis of the disease. The aim of this study was to evaluate the expression of TLR2 and TLR4 mRNA in the colorectal mucosa of dogs with ICRPs by in-situ hybridization using an RNAscope assay. Samples of inflamed colorectal mucosa (n = 5) and non-inflamed mucosa (n = 5) from miniature dachshunds (MDs) with ICRPs and colonic mucosa from healthy beagles (n = 5) were examined. TLR2 and TLR4 hybridization signals were localized to the colorectal epithelium, inflammatory cells and fibroblasts in the inflamed colorectal mucosa of affected dogs. The signals were significantly greater in inflamed colorectal epithelium compared with non-inflamed epithelium of MDs with ICRPs and healthy beagles (P <0.05). These results suggest that increased expression of TLR2 and TLR4 mRNA in the inflamed colorectal mucosa results from not only inflammatory cell infiltration, but also the upregulation of TLR2 and TLR4 mRNA in the colonic epithelium.


Asunto(s)
Pólipos del Colon/veterinaria , Enfermedades de los Perros/metabolismo , Enfermedades Inflamatorias del Intestino/veterinaria , Receptor Toll-Like 2/biosíntesis , Receptor Toll-Like 4/biosíntesis , Animales , Perros , Procesamiento de Imagen Asistido por Computador , Hibridación in Situ , Mucosa Intestinal/metabolismo , ARN Mensajero , Recto , Receptor Toll-Like 2/análisis , Receptor Toll-Like 4/análisis
13.
J Vet Med Sci ; 79(3): 456-463, 2017 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-28090006

RESUMEN

We examine the expression of tight junction and adherence junction proteins in the colorectal mucosa of miniature dachshunds (MDs) with inflammatory colorectal polyps (ICRPs). Colorectal mucosa samples were endoscopically obtained from 8 MDs with ICRPs and 8 control dogs for immunoblotting. Paraffin-embedded tissues of surgically resected inflamed lesions from another 5 MDs with ICRPs and full-thickness colorectal specimens from 5 healthy beagles were obtained for immunohistochemistry. The expression patterns of claudin-1, -2, -3, -4, -5, -7 and -8, E-cadherin and ß-catenin were analyzed in the non-inflamed mucosa and inflamed mucosa of ICRPs and colorectal mucosa of control dogs by immunoblotting. The localization of these proteins in the inflamed lesions was analyzed by immunohistochemistry. The expressions of each of claudin, E-cadherin and ß-catenin were not significantly different between control dogs and non-inflamed colonic mucosa from MDs with ICRPs. In contrast, only E-cadherin and ß-catenin were detected in the inflamed lesions of MDs with ICRPs. By immunohistochemistry, claudin-2, -3, -4, -5 and -7, E-cadherin and ß-catenin were expressed in the colorectal epithelium within the inflamed mucosa, but not in granulation tissue. Distributions of claudin-2, -3, -4, -5, and -7, E-cadherin and ß-catenin in the colonic epithelium were not different between MDs with ICRPs and control dogs. These results indicated that no significant alteration was detected in several tight junction or adherence junction proteins expression in the colorectal epithelium of ICRPs.


Asunto(s)
Enfermedades de los Perros/metabolismo , Mucosa Intestinal/metabolismo , Pólipos Intestinales/veterinaria , Proteínas de la Membrana/metabolismo , Animales , Cadherinas/metabolismo , Claudinas/metabolismo , Pólipos del Colon/metabolismo , Pólipos del Colon/veterinaria , Conexinas/metabolismo , Perros , Femenino , Pólipos Intestinales/metabolismo , Masculino , Uniones Estrechas/metabolismo , beta Catenina/metabolismo
14.
J Vet Med Sci ; 78(2): 265-9, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26460312

RESUMEN

Inflammatory colorectal polyp (ICRP), common in miniature dachshunds, presents with hematochezia, tenesmus and mucoid feces. Although an 80% response rate has been reported when treated with prednisolone and cyclosporine, effective treatment is needed for the remaining 20% of ICRP dogs. Leflunomide is an immunosuppressive drug reported as effective in several immune-mediated diseases. In the present study, we retrospectively evaluated the efficacy and adverse effects of leflunomide in 15 ICRP dogs that were refractory to treatment with prednisolone and cyclosporine. Treatment efficacy was assessed by endoscopy, clinical symptoms and rectal palpation. Adverse effects were determined by clinical symptoms and blood testing during follow-up. The leflunomide treatment response rate was 93.3%. The median dosage of leflunomide and the median response time were 3 mg/kg (range: 1.7-4.0 mg/kg) and 35 days (range: 20-119 days), respectively. Adverse effects observed included lethargy (3 dogs), anorexia (1 dog), respiratory symptoms (1 dog), leukocytopenia (2 dogs), thrombocytopenia (1 dog), anemia (1 dog) and liver enzyme elevation (8 dogs). Most of the adverse effects improved with symptomatic treatment and leflunomide discontinuation or dosage reduction. In conclusion, leflunomide treatment is effective in ICRP dogs refractory to treatment with prednisolone and cyclosporine. Because several adverse effects were observed, close monitoring is needed during leflunomide treatment follow-up.


Asunto(s)
Pólipos del Colon/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Pólipos Intestinales/veterinaria , Isoxazoles/uso terapéutico , Animales , Perros , Femenino , Inmunosupresores/efectos adversos , Isoxazoles/efectos adversos , Leflunamida , Masculino , Estudios Retrospectivos
15.
Vet Immunol Immunopathol ; 164(3-4): 160-9, 2015 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-25746347

RESUMEN

Inflammatory colorectal polyps (ICRPs) frequently occur in miniature dachshunds (MDs) in Japan, typically form multiple polyps with severe neutrophil infiltration. ICRPs are speculated as a novel, breed-specific canine inflammatory bowel disease. Pattern recognition receptors (PRRs) play an important role in the differentiation of pathogens from commensal bacteria and food antigens, and polymorphisms of various PRRs have been shown to be associated with human and canine IBD. We recently reported that the reactivity of nucleotide-binding oligomerization domain 2 (NOD2), toll-like receptor (TLR) 1/2, TLR2, and TLR2/6 are greater in ICRP-affected MDs than that in controls. Therefore, this study was aimed to investigate single nucleotide polymorphisms (SNPs) of PRRs associated with ICRPs in MDs. Mutational analysis of canine NOD2, TLR1, TLR2, and TLR6 genes was performed with six ICRP-affected MDs, five control MDs, and five healthy beagles. The mutational analysis identified 13 non-synonymous SNPs in NOD2, TLR1, TLR2, and TLR6 genes, of which six SNPs in NOD2 exon 3 were further analyzed in an association study using 63 ICRP-affected MDs, 82 control MDs, and 237 control dogs of various breeds. Four of the SNPs (A1532G, T1573C, C1688G, and G1880A of the NOD2 gene) were in Hardy-Weinberg equilibrium and in complete linkage disequilibrium in MDs, and their minor allele frequencies were significantly lower in ICRP-affected MDs than in control MDs (0.016 vs. 0.140, P=0.0002). The calculated inheritance model was an additive model (odds ratio=0.10, 95% confidence interval=0.02-0.45, P=0.0001), which indicates that the haplotype with minor alleles in these SNPs (A, T, C, and G in A1532G, T1573C, C1688G, and G1880A) possess a protective effect regarding the development of ICRPs. However, these SNPs were not specific for MDs, although the minor allele frequencies of these SNPs in control MDs were significantly lower than in other breed dogs. These results suggest that the identified four SNPs (A1532G, T1573C, C1688G, and G1880A in the NOD2 gene) may play a role in the pathogenesis of ICRPs in MDs. Because the majority of MDs and other breed dogs do not have the protective alleles, their absence may not be a specific cause of ICRPs in MDs but rather contribute to the development of inflammation.


Asunto(s)
Pólipos del Colon/veterinaria , Enfermedades de los Perros/genética , Proteína Adaptadora de Señalización NOD2/genética , Polimorfismo de Nucleótido Simple , Secuencia de Aminoácidos , Animales , Clonación Molecular , Pólipos del Colon/genética , Perros , Frecuencia de los Genes , Datos de Secuencia Molecular , FN-kappa B/fisiología
16.
J Vet Med Sci ; 77(4): 439-47, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25650150

RESUMEN

Inflammatory colorectal polyps (ICRPs) frequently occur in miniature dachshunds (MDs) in Japan. MDs with ICRPs develop multiple polyps with severe neutrophil infiltration that respond to immunosuppressive therapy. Therefore, ICRPs are thought to constitute a novel, breed-specific form of canine inflammatory bowel disease (IBD). Pattern recognition receptors (PRRs) play a key role in the distinction of pathogens from commensal bacteria and food antigens. Dysfunction resulting from genetic disorders of PRRs have been linked to human and canine IBD. Therefore, we analyzed the reactivity of PRRs in MDs with ICRPs. Twenty-six MDs with ICRPs and 16 control MDs were recruited. Peripheral blood-derived monocytes were obtained from each dog and then stimulated with PRR ligands for 6 and 24 hr; subsequently, messenger RNA (mRNA) expression levels and protein secretion of IL-1ß were quantified using quantitative real-time PCR and ELISA, respectively. The levels of IL-1ß mRNA and protein secretion after stimulation with a nucleotide-binding oligomerization domain 2 (NOD2) ligand were significantly greater in monocytes from ICRP-affected MDs than in those from control MDs. In addition, IL-1ß protein secretion induced by toll-like receptor (TLR) 1/2, TLR2 and TLR2/6 stimulation was also significantly greater in ICRP-affected MDs. These results suggest that reactivity against NOD2, TLR1/2, TLR2 and TLR2/6 signals is enhanced in ICRP-affected MDs and may play a role in the pathogenesis of ICRPs in MDs. Additional studies of the genetic background of these PRRs should be performed.


Asunto(s)
Pólipos del Colon/veterinaria , Enfermedades de los Perros/metabolismo , Inflamación/veterinaria , Receptores de Reconocimiento de Patrones/metabolismo , Animales , Pólipos del Colon/metabolismo , Enfermedades de los Perros/patología , Perros , Femenino , Regulación de la Expresión Génica , Predisposición Genética a la Enfermedad , Inflamación/metabolismo , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Reconocimiento de Patrones/genética
17.
Vet J ; 203(2): 256-8, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25576139

RESUMEN

This study explored the hypothesis that inflammatory colorectal polyps (ICRPs) in miniature Dachshunds are more likely to occur ventrally in the colorectum. Angle-fixed colonoscopic images were collected from 11 miniature Dachshunds with ICRPs and randomly rotated. Macroscopic severity at 12 divided angles was scored by four veterinarians blinded to the rotation angle. Mean prevalence and severity scores of ICRPs were significantly higher ventrally than dorsally (P < 0.01).


Asunto(s)
Pólipos del Colon/veterinaria , Enfermedades de los Perros/epidemiología , Animales , Pólipos del Colon/epidemiología , Pólipos del Colon/etiología , Pólipos del Colon/inmunología , Enfermedades de los Perros/etiología , Enfermedades de los Perros/inmunología , Perros , Femenino , Mucosa Intestinal/patología , Masculino , Especificidad de la Especie , Tokio/epidemiología
18.
J Am Vet Med Assoc ; 244(12): 1435-40, 2014 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-24871067

RESUMEN

CASE DESCRIPTION: An 11-year-old castrated male mixed-breed dog was examined for a 3-month history of hematochezia and tenesmus. Abdominal ultrasonography and rectal examination prior to referral had revealed a colorectal polyp, diagnosed as a benign colorectal polypoid adenoma after histologic examination of tissue samples. The patient was referred for treatment. CLINICAL FINDINGS: A 2-cm-diameter sessile polypoid mass was located approximately 6 cm orad to the anus in the right dorsolateral region of the descending colon just caudal to the pubis. There was no evidence of metastasis on thoracic radiography or abdominal ultrasonography. Results of a CBC and serum biochemical analysis were within reference limits. TREATMENT AND OUTCOME: Endoscopic mucosal resection (EMR) and snare electrocautery were used to resect the mass and a definitive histopathologic diagnosis of a sessile colorectal polypoid adenoma was made. A 9.9-mm gastroduodenoscope was used during colonoscopy to inspect the mass. To aid in EMR, a 25-gauge endoscopic injection needle was used to infuse sterile saline (0.9% NaCl) solution under the base of the polyp, into the submucosa to elevate the mucosa from the muscularis layer beneath the polyp prior to polypectomy. This was necessary because of the sessile, rather than pedunculated, base of the mass. The entire polyp was successfully removed with endoscopic guidance. The clinical signs of hematochezia and tenesmus resolved immediately, and serial rectal examinations were performed over the following 36 months with no palpable evidence of recurrence. CLINICAL RELEVANCE: The patient described in the present report underwent successful colonic EMR and snare polypectomy with no known evidence of mass recurrence during the following 36 months, suggesting that this minimally invasive procedure may be a valuable treatment option for sessile polyps. The advantage of this technique was that elevation of the mucosa via injection of saline solution improved visibility of the polyp and helped to separate the polyp base from the deeper submucosal colorectal tissue, making complete resection possible.


Asunto(s)
Adenoma/veterinaria , Pólipos del Colon/veterinaria , Neoplasias Colorrectales/veterinaria , Enfermedades de los Perros/cirugía , Endoscopía Gastrointestinal/veterinaria , Mucosa Intestinal/cirugía , Adenoma/clasificación , Adenoma/cirugía , Animales , Pólipos del Colon/cirugía , Neoplasias Colorrectales/cirugía , Perros , Masculino
19.
Vet Immunol Immunopathol ; 156(1-2): 32-42, 2013 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-24148828

RESUMEN

Inflammatory colorectal polyps (ICRPs) in miniature dachshunds were recently recognized as a major cause of large bowel diarrhea in this dog breed in Japan. ICRPs are characterized by the formation of multiple small polyps and/or space-occupying large polyps in the colorectal area and are thought to be a novel form of inflammatory bowel disease (IBD). To explore key mediators in the pathogenesis of ICRPs, we analyzed several pro-inflammatory cytokine (IL-1ß, IL-6, TNF-α, IL-8, IL-12p35, IL-12/23p40, and IL-23p19) mRNA expressions in colorectal polyps in ICRP dogs by quantitative PCR. Among these cytokines, IL-8 mRNA expression was markedly up-regulated in large polyps. To examine IL-8 protein expression, we analyzed IL-8 protein level and its location in colorectal mucosal specimens of ICRP dogs by ELISA and immunofluorescence microscopy. IL-8 protein was significantly increased in large polyps and serum in dogs with ICRPs compared to controls. By immunofluorescence microscopy, IL-8 was only localized in macrophages, but not in mucosal epithelial cells or neutrophils. IL-8-positive macrophages were significantly increased in large polyps compared to controls. These results suggest that IL-8 is produced mainly by macrophages and may induce neutrophil infiltration in the colorectal area of ICRP dogs.


Asunto(s)
Enfermedades de los Perros/inmunología , Enfermedades Inflamatorias del Intestino/veterinaria , Interleucina-8/genética , Mucosa Intestinal/inmunología , Pólipos Intestinales/veterinaria , Animales , Pólipos del Colon/inmunología , Pólipos del Colon/veterinaria , Perros , Femenino , Enfermedades Inflamatorias del Intestino/inmunología , Interleucina-8/sangre , Pólipos Intestinales/inmunología , Masculino , ARN Mensajero/análisis , Enfermedades del Recto/inmunología , Enfermedades del Recto/veterinaria
20.
J Vet Med Sci ; 75(4): 535-8, 2013 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-23154450

RESUMEN

Two miniature dachshunds, a 7-year-old neutered male and an 8-year-old male, presented with chronic hematochezia and tenesmus. A solitary pedunculated or multiple diffuse colorectal polyps were identified by colonoscopy and resected by polypectomy. Inflammatory colorectal polyps (ICRPs) were diagnosed according to histopathological findings. Both cases were treated with immunosuppressive therapy, and the clinical signs were resolved, although the colorectal polyps remained to some extent. Several months after the initial diagnosis, both cases presented with recurrence of hematochezia and enlargement of the polyps. A second colonoscopic polypectomy was performed, and adenoma was diagnosed histopathologically in both cases. ICRPs are a nonneoplastic disease, but their long-term prognosis is unknown. Careful follow-up seems to be important, and repetitive biopsy is recommended when growth of polyps is identified in miniature dachshunds with ICRPs.


Asunto(s)
Pólipos Adenomatosos/veterinaria , Pólipos del Colon/veterinaria , Neoplasias Colorrectales/veterinaria , Enfermedades de los Perros/patología , Pólipos Adenomatosos/tratamiento farmacológico , Pólipos Adenomatosos/patología , Pólipos Adenomatosos/cirugía , Animales , Pólipos del Colon/tratamiento farmacológico , Pólipos del Colon/patología , Pólipos del Colon/cirugía , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/cirugía , Perros , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/veterinaria
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