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1.
Zoonoses Public Health ; 69(6): 673-681, 2022 09.
Article in English | MEDLINE | ID: mdl-35546073

ABSTRACT

While previous research on zoonotic transmission of community-acquired Clostridioides difficile infection (CA-CDI) focused on food-producing animals, the present study aimed to investigate whether dogs are carriers of resistant and/or virulent C. difficile strains. Rectal swabs were collected from 323 dogs and 38 C. difficile isolates (11.8%) were obtained. Isolates were characterized by antimicrobial susceptibility testing, whole-genome sequencing (WGS) and a DNA hybridization assay. Multilocus sequence typing (MLST), core genome MLST (cgMLST) and screening for virulence and antimicrobial resistance genes were performed based on WGS. Minimum inhibitory concentrations for erythromycin, clindamycin, tetracycline, vancomycin and metronidazole were determined by E-test. Out of 38 C. difficile isolates, 28 (73.7%) carried genes for toxins. The majority of isolates belonged to MLST sequence types (STs) of clade I and one to clade V. Several isolates belonged to STs previously associated with human CA-CDI. However, cgMLST showed low genetic relatedness between the isolates of this study and C. difficile strains isolated from humans in Austria for which genome sequences were publicly available. Four isolates (10.5%) displayed resistance to three of the tested antimicrobial agents. Isolates exhibited resistance to erythromycin, clindamycin, tetracycline and metronidazole. These phenotypic resistances were supported by the presence of the resistance genes erm(B), cfr(C) and tet(M). All isolates were susceptible to vancomycin. Our results indicate that dogs may carry virulent and antimicrobial-resistant C. difficile strains.


Subject(s)
Anti-Infective Agents , Clostridioides difficile , Clostridium Infections , Dog Diseases , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/pharmacology , Clindamycin/pharmacology , Clostridioides , Clostridioides difficile/genetics , Clostridium Infections/epidemiology , Clostridium Infections/veterinary , Dog Diseases/drug therapy , Dog Diseases/epidemiology , Dogs , Drug Resistance, Bacterial/genetics , Erythromycin , Genotype , Humans , Metronidazole/pharmacology , Microbial Sensitivity Tests/veterinary , Multilocus Sequence Typing/veterinary , Tetracyclines , Vancomycin/pharmacology
2.
J Small Anim Pract ; 61(4): 211-215, 2020 04.
Article in English | MEDLINE | ID: mdl-32065388

ABSTRACT

Chronic diarrhoea is a frequent complaint in canine practice and the diagnostic path is often characterised by numerous diagnostic tests and stepwise empirical treatments, often applied before gastrointestinal endoscopy/mucosal biopsies. These include dietary interventions (novel protein, hydrolysed protein diet), parasiticides and still, in many cases, antibacterials. Indiscriminate use of antibacterial drugs risks detrimental consequences for both the individual patient (antimicrobial resistance, long-term disruption of intestinal bacterial populations, potential worsening of gastrointestinal signs) and the general public. For that reason, in this Perspective essay we advocate use of antibacterials only after histopathologic evaluation of gastrointestinal biopsies or, for those cases in which endoscopy is not possible, after other therapeutic trials, such as diet/pre-probiotics or anti-inflammatory drugs have proven unsuccessful. They should be reserved, after appropriate dietary trials, for those canine chronic diarrhoeic patients with signs of true primary infection (i.e. signs of systemic inflammatory response syndrome or evidence of adherent-invasive bacteria) that justify antibacterial use.


Subject(s)
Dog Diseases/drug therapy , Gastrointestinal Tract , Probiotics , Animals , Anti-Bacterial Agents/therapeutic use , Bacteria , Diarrhea/drug therapy , Diarrhea/veterinary , Dogs
3.
J Vet Intern Med ; 31(4): 1017-1027, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28543991

ABSTRACT

BACKGROUND: Biochemical indicators for diagnosing liver disease are plasma alanine aminotransferase activity (ALT), alkaline phosphatase activity (ALP), and bile acid concentration (BA). OBJECTIVES: To determine the sensitivity and specificity of ALT, ALP, and BA for detecting primary hepatitis (PH) in clinically healthy Labrador retrievers and investigate whether ALT and ALP can discriminate between dogs with PH and nonspecific reactive hepatitis (RH). ANIMALS: 191 clinically healthy and 51 clinically ill Labrador retrievers with hepatic histopathology. METHODS: Retrospective study. Medical records were reviewed for ALT, ALP, preprandial BA, liver histopathology, and hepatic copper concentrations. RESULTS: In 64% (122/191) of the clinically healthy Labrador retrievers, hepatic histology revealed inflammatory infiltrates. This frequency might be biased because part of them was included as first-line relatives of dogs with copper-associated hepatitis. Sensitivity of ALT, ALP, and BA in this population for detecting acute hepatitis was 45, 15, and 15%, respectively. For chronic hepatitis, sensitivity was 71, 35, and 13%, respectively. Specificity of ALT, ALP, and BA was >90% for AH, CH, and RH. When increased liver enzymes were present, median ALT was significantly higher in PH cases (312 U/L, range 38-1,369) compared to RH cases (91 U/L, range 39-139) (P < .001). There was no difference in ALP between dogs with a PH and a RH (P = .361). CONCLUSIONS AND CLINICAL IMPORTANCE: Histopathologic abnormalities in the liver were present in the majority of apparent clinically healthy Labrador retrievers. The sensitivity of ALT, ALP, and BA for detecting acute and chronic hepatitis in this population was low. More sensitive biomarkers are needed for early detection of liver disease in apparent clinically healthy dogs.


Subject(s)
Alanine Transaminase/blood , Alkaline Phosphatase/blood , Bile Acids and Salts/blood , Dog Diseases/blood , Hepatitis, Animal/blood , Animals , Biomarkers/blood , Case-Control Studies , Chemical and Drug Induced Liver Injury/blood , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/veterinary , Copper/toxicity , Dog Diseases/diagnosis , Dog Diseases/pathology , Dogs , Female , Hepatitis, Animal/chemically induced , Hepatitis, Animal/diagnosis , Hepatitis, Animal/pathology , Liver/pathology , Male , Sensitivity and Specificity
4.
Vet Comp Oncol ; 15(3): 692-705, 2017 Sep.
Article in English | MEDLINE | ID: mdl-27549077

ABSTRACT

Gastric carcinoma (GC) is the most common neoplasm in the stomach of dogs. Although incidence in the general population is reported to be low, breed-specific GC has a high incidence. Median age at presentation ranges from 8 to approximately 10 years. The disease is mostly located in the lesser curvature and antropyloric region of the stomach. Unfortunately, diagnosis is usually made when the disease is at an advanced stage and, therefore, prognosis is poor. Due to similarities in clinical presentation, diagnosis, histology and prognosis, canine GC may serve as a valuable model for human GC. Extensive pedigrees of canine gastric carcinoma cases could reveal insights for human gastric carcinoma. Putative species differences include the role of Helicobacter in pathogenesis, the wide array of genetic data and screening available for humans, and treatment protocols that are available for human GC.


Subject(s)
Dog Diseases/diagnosis , Stomach Neoplasms/diagnosis , Animals , Disease Models, Animal , Dog Diseases/pathology , Dogs , Humans , Prognosis , Risk Factors , Stomach/pathology , Stomach Neoplasms/pathology , Stomach Neoplasms/veterinary
5.
Vet J ; 218: 1-6, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27938702

ABSTRACT

Hereditary hepatic copper accumulation in Labrador retrievers leads to hepatitis with fibrosis and eventually cirrhosis. The development of a non-invasive blood-based biomarker for copper status in dogs could be helpful in identifying dogs at risk and to monitor copper concentrations during treatment. In this study, two cellular copper metabolism proteins, Cu/Zn superoxide dismutase (SOD1) and its chaperone (copper chaperone for SOD1, CCS) were measured in erythrocytes and tested for association with hepatic copper concentrations in 15 Labrador retrievers with normal or increased hepatic copper concentrations. Antibodies against CCS and SOD1 were applicable for use in canine specimens. This was demonstrated by the loss of immune-reactive bands for CCS and SOD1 in siRNA treated canine bile duct epithelial cells. Erythrocyte CCS and CCS/SOD1 ratios were decreased 2.37 (P <0.001) and 3.29 (P <0.001) fold in the high copper group compared to the normal copper group. Erythrocyte CCS and CCS/SOD1 ratio are potential new biomarkers for hepatic copper concentrations in Labrador retrievers and could facilitate early diagnosis and treatment monitoring for copper-associated hepatitis in dogs.


Subject(s)
Copper/blood , Dogs/metabolism , Erythrocytes/metabolism , Liver/metabolism , Molecular Chaperones/blood , Superoxide Dismutase-1/metabolism , Animals , Biomarkers/blood , Copper/metabolism , Female , Liver/enzymology , Male , Molecular Chaperones/metabolism
6.
J Vet Intern Med ; 30(6): 1816-1823, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27859748

ABSTRACT

BACKGROUND: Current biochemical indicators cannot discriminate between parenchymal, biliary, vascular, and neoplastic hepatobiliary diseases. MicroRNAs are promising new biomarkers for hepatobiliary disease in humans and dogs. OBJECTIVE: To measure serum concentrations of an established group of microRNAs in dogs and to investigate their concentrations in various types of hepatobiliary diseases. ANIMALS: Forty-six client-owned dogs with an established diagnosis of hepatobiliary disease and stored serum samples and eleven client-owned healthy control Labrador Retrievers. METHODS: Retrospective study. Medical records of dogs with parenchymal, biliary, vascular, or neoplastic hepatobiliary diseases and control dogs were reviewed. Concentrations of miR-21, miR-122, miR-126, miR-148a, miR-200c, and miR-222 were quantified in serum by real-time polymerase chain reaction. RESULTS: No different microRNA concentrations were found in the adenoma and congenital portosystemic shunt groups. In all other diseases, miR-122 concentrations were elevated with the highest concentration in the mucocele group (267-fold, CI: 40-1,768, P < .001). In dogs with biliary diseases, miR-21 and miR-222 were only increased in dogs with mucoceles (26-fold, CI: 5-141, P = .005 and 13-fold, CI: 2-70, P = .025, respectively). Uniquely increased microRNAs were found in the hepatocellular carcinoma group (miR-200c, 35-fold increase, CI: 3-382, P = .035) and the chronic hepatitis group (miR-126, 22-fold increase, CI: 5-91, P = .002). CONCLUSIONS AND CLINICAL IMPORTANCE: A microRNA panel consisting of miR-21, miR-122, miR-126, miR-200c, and miR-222 can distinguish between parenchymal, biliary, and neoplastic hepatobiliary diseases. Serum microRNA profiling is a promising new tool that might be a valuable addition to conventional diagnostics to help diagnose various hepatobiliary diseases in dogs.


Subject(s)
Bile Duct Diseases/veterinary , Dog Diseases/blood , Liver Diseases/veterinary , MicroRNAs/blood , Animals , Bile Duct Diseases/blood , Bile Duct Diseases/diagnosis , Biomarkers/blood , Dog Diseases/diagnosis , Dogs , Female , Liver Diseases/blood , Liver Diseases/diagnosis , Male , Retrospective Studies
7.
Vet J ; 211: 75-81, 2016 May.
Article in English | MEDLINE | ID: mdl-27021912

ABSTRACT

Common parenchymal liver diseases in dogs include reactive hepatopathies and primary hepatitis (acute or chronic). In chronic hepatitis, there is usually a long subclinical phase. Specific clinical signs become overt only when liver damage is severe and in this phase, treatment is usually less effective. Limited data are available regarding the sensitivity of liver enzyme activity or biomarkers for early detection of subclinical hepatitis. Hepatocyte-derived microRNAs (HDmiRs) were recently identified as promising biomarkers for hepatocellular injury in multiple species. Here, the potential of the HDmiRs miR-122 and miR-148a as sensitive diagnostic biomarkers for hepatocellular injury in Labrador retrievers was investigated. Samples from 66 Labrador retrievers with histologically normal livers, high hepatic copper, and with various forms of liver injury were evaluated for serum alanine aminotransferase (ALT) activity and microRNA values. Median values of HDmiR-122 were 34.6 times higher in dogs with liver injury and high ALT than in normal dogs (95% confidence intervals [CI], 13-95; P <0.001). HDmiR-122 values were significantly increased in dogs with liver injury and normal ALT (4.2 times; 95% CI, 2-12; P <0.01) and in dogs with high hepatic copper concentrations and unremarkable histopathology (2.9 times; 95% CI, 1.1-8.0; P <0.05). Logistic regression analyses demonstrated that miR-122 and miR-148a were both predictors of hepatocellular injury. The sensitivity of miR-122 was 84% (95% CI, 73-93%), making it superior to ALT (55%; 95% CI, 41-68%) for the detection of hepatocellular injury in Labrador retrievers (P <0.001). This study demonstrated that serum HDmiR, particularly miR-122, is a highly sensitive marker for the detection of hepatocellular injury in Labrador retrievers and is a promising new biomarker that may be used for early detection of subclinical hepatitis in dogs.


Subject(s)
Alanine Transaminase/blood , Chemical and Drug Induced Liver Injury/veterinary , Copper/toxicity , Dog Diseases/diagnosis , Hepatitis, Animal/diagnosis , MicroRNAs/blood , Animals , Biomarkers/blood , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/etiology , Dog Diseases/etiology , Dogs , Female , Hepatitis, Animal/etiology , Hepatocytes/metabolism , Male
8.
J Vet Intern Med ; 28(6): 1684-91, 2014.
Article in English | MEDLINE | ID: mdl-25269796

ABSTRACT

BACKGROUND: Cyclooxygenase-2 (COX-2) is a key enzyme in the synthesis of pro-inflammatory prostaglandins and 5-lipoxygenase (5-LO) is the major source of leukotrienes. Their role in IBD has been demonstrated in humans and animal models, but not in dogs with chronic enteropathies (CCE). HYPOTHESIS: COX-2 and 5-LO are upregulated in dogs with CCE. ANIMALS: Fifteen healthy control dogs (HCD), 10 dogs with inflammatory bowel disease (IBD), and 15 dogs with food-responsive diarrhea (FRD). METHODS: Prospective study. mRNA expression of COX-2, 5-LO, IL-1b, IL-4, IL-6, TNF, IL-10 and TFG-ß was evaluated by quantitative real-time RT-PCR in duodenal and colonic biopsies before and after treatment. RESULTS: COX-2 expression in the colon was significantly higher in IBD and FRD before and after treatment (all P < .01). IL-1b was higher in FRD in the duodenum after treatment (P = .021). TGF-ß expression was significantly higher in the duodenum of HCD compared to FRD/IBD before treatment (both P < .001) and IBD after treatment (P = .012). There were no significant differences among groups and within groups before and after treatment for IL-4, IL-6, TNF, and IL-10. There was a significant correlation between COX-2 and IL-1b in duodenum and colon before treatment in FRD and IBD, whereas 5-LO correlated better with IL-6 and TNF. IL-10 and TGF-ß usually were correlated. CONCLUSIONS AND CLINICAL IMPORTANCE: COX-2 is upregulated in IBD and FRD, whereas IL-1b and TGF-ß seem to be important pro- and anti-inflammatory cytokines, respectively. The use of dual COX/5-LO inhibitors could be an interesting alternative in the treatment of CCE.


Subject(s)
Arachidonate 5-Lipoxygenase/metabolism , Cyclooxygenase 2/metabolism , Diarrhea/veterinary , Dog Diseases/enzymology , Inflammatory Bowel Diseases/veterinary , Animals , Arachidonate 5-Lipoxygenase/physiology , Case-Control Studies , Chronic Disease , Colon/chemistry , Colon/enzymology , Cyclooxygenase 2/physiology , Diarrhea/enzymology , Dogs , Duodenum/chemistry , Duodenum/enzymology , Female , Inflammatory Bowel Diseases/enzymology , Interleukin-10/analysis , Interleukin-1beta/analysis , Interleukin-4/analysis , Male , Prospective Studies , Real-Time Polymerase Chain Reaction , Transforming Growth Factor beta/analysis , Tumor Necrosis Factor-alpha/analysis
9.
Schweiz Arch Tierheilkd ; 156(4): 179-83, 2014 Apr.
Article in German | MEDLINE | ID: mdl-24686818

ABSTRACT

This case report describes 3 kittens with suspected doramectin toxicity. In a litter of 7 kittens treated with doramectin, 3 developed neurological symptoms. One kitten showed mild apathy and tremors, while a second one additionally presented behavioral changes and seizures that had to be treated with diazepam. Both kittens recovered completely. A third kitten was presented to us in coma 3 days following treatment with doramectin. Subsequently, this kitten developed behavioral changes such as aggression, hyperesthesia, tremors, and seizures and died 36 hours after presentation. Histopathologic examination of the brain showed cytotoxic edema and polioencephalomalacia. The doramectin dosage of the deceased kitten was 380 µg/kg.


Subject(s)
Antiparasitic Agents/poisoning , Cat Diseases/chemically induced , Ivermectin/analogs & derivatives , Aggression/drug effects , Animals , Anthelmintics/poisoning , Behavior, Animal/drug effects , Cats , Fatal Outcome , Hyperesthesia/chemically induced , Hyperesthesia/veterinary , Ivermectin/poisoning , Seizures/chemically induced , Seizures/veterinary
10.
Vet J ; 199(1): 188-90, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24268477

ABSTRACT

This study aimed to examine the aetiology of acute diarrhoea and the relapse rate in 100 client-owned dogs presented to a first-opinion clinic. History, physical examination, faecal testing and owner questionnaire data were collected at initial presentation (T0) and at either the time of relapse or at a recheck performed within 3 months. All dogs received treatment according to their clinical signs. Of 96 dogs that completed the study, 37 (38.5%) relapsed during the study period, 21 (21.9%) relapsed within 3 months, and 16 others (16.6%) at 3 months to 1 year after initial examination. Dogs that had undergone a change in housing location within 1 month prior to presentation and dogs <1 year old were significantly more likely to have positive parasitological analyses (P=0.02 and P=0.001, respectively). Pica was a risk factor for relapse (P=0.0002).


Subject(s)
Diarrhea/pathology , Dog Diseases/pathology , Animals , Dogs , Female , Follow-Up Studies , Male
11.
J Vet Intern Med ; 26(2): 269-74, 2012.
Article in English | MEDLINE | ID: mdl-22268894

ABSTRACT

BACKGROUND: Inflammatory bowel disease (IBD) and food-responsive diarrhea (FRD) are chronic enteropathies of dogs (CCE) that currently can only be differentiated by their response to treatment after exclusion of other diseases. In humans, increased urinary concentrations of leukotriene E4 (LTE4) have been associated with active IBD. OBJECTIVES: To evaluate urinary LTE4 concentrations in dogs with IBD, FRD, and healthy controls, and to assess correlation of urinary LTE4 concentrations with the canine IBD activity index (CIBDAI) scores. ANIMALS: Eighteen dogs with IBD, 19 dogs with FRD, and 23 healthy control dogs. METHODS: In this prospective study, urine was collected and CIBDAI scores were calculated in client-owned dogs with IBD and those with FRD. Quantification of LTE4 in urine was performed by liquid chromatography-tandem mass spectrometry and corrected to creatinine. RESULTS: Urinary LTE4 concentrations were highest in dogs with IBD (median 85.2 pg/mg creatinine [10th-90th percentiles 10.9-372.6]) followed by those with FRD (median 31.2 pg/mg creatinine [10th-90th percentiles 6.2-114.5]) and control dogs (median 21.1 pg/mg creatinine [10th-90th percentiles 9.1-86.5]). Urinary LTE4 concentrations were higher in dogs with IBD than in control dogs (P = .011), but no significant difference between IBD and FRD was found. No correlation was found between urinary LTE4 concentrations and CIBDAI. CONCLUSIONS AND CLINICAL IMPORTANCE: The higher urinary LTE4 concentrations in dogs with IBD suggest that cysteinyl leukotriene pathway activation might be a component of the inflammatory process in canine IBD. Furthermore, urinary LTE4 concentrations are of potential use as a marker of inflammation in dogs with CCE.


Subject(s)
Dog Diseases/urine , Inflammatory Bowel Diseases/veterinary , Leukotriene E4/urine , Animals , Biomarkers/urine , Creatinine/urine , Dog Diseases/immunology , Dogs , Female , Inflammatory Bowel Diseases/immunology , Inflammatory Bowel Diseases/urine , Male , Prospective Studies , ROC Curve , Sensitivity and Specificity , Statistics, Nonparametric
12.
J Anim Sci ; 88(7): 2255-64, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20228237

ABSTRACT

In this study, the hypothesis was tested that the size of gastrointestinal tract (GIT) mucosal components and rates of epithelial cell proliferation and apoptosis change with increasing age. The aims were to quantitatively examine GIT histomorphology and to determine mucosal epithelial cell proliferation and apoptosis rates in neonatal (<48 h old) and adult (8 to 11.5 yr old) dogs. Morphometrical analyses were performed by light microscopy with a video-based, computer-linked system. Cell proliferation and apoptosis of the GIT epithelium were evaluated by counting the number of Ki-67 and caspase-3-positive cells, respectively, using immunohistochemical methods. Thickness of mucosal, glandular, subglandular, submucosal and muscular layers, crypt depths, villus heights, and villus widths were consistently greater (P < 0.05 to P < 0.001), whereas villus height/crypt depth ratios were smaller (P < 0.001) in adult than in neonatal dogs. The number of Ki-67-positive cells in stomach, small intestine, and colon crypts, but not in villi, was consistently greater (P < 0.01) in neonatal than in adult dogs. In contrast, the number of caspase-3-positive cells in crypts of the stomach, small intestine, and colon and in villi was not significantly influenced by age. In conclusion, canine GIT mucosal morphology and epithelial cell proliferation rates, but not apoptosis rates, change markedly from birth until adulthood is reached.


Subject(s)
Animals, Newborn/anatomy & histology , Apoptosis/physiology , Epithelial Cells/physiology , Gastrointestinal Tract/anatomy & histology , Aging/physiology , Animals , Animals, Newborn/growth & development , Cell Proliferation , Dogs/anatomy & histology , Dogs/growth & development , Female , Gastric Mucosa/anatomy & histology , Gastric Mucosa/growth & development , Gastrointestinal Tract/cytology , Gastrointestinal Tract/growth & development , Intestinal Mucosa/anatomy & histology , Intestinal Mucosa/growth & development , Male
13.
Vet Immunol Immunopathol ; 135(1-2): 158-163, 2010 May 15.
Article in English | MEDLINE | ID: mdl-20034678

ABSTRACT

There is growing evidence that aberrant innate immune responses towards the bacterial flora of the gut play a role in the pathogenesis of canine inflammatory bowel disease (IBD). Toll-like receptors (TLR) play an important role as primary sensors of invading pathogens and have gained significant attention in human IBD as differential expression and polymorphisms of certain TLR have been shown to occur in ulcerative colitis (UC) and Crohn's disease (CD). The aim of the current study was to evaluate the expression of two TLR important for recognition of commensals in the gut. TLR2 and TLR4 mRNA expression in duodenal biopsies from dogs with IBD was measured and correlated with clinical and histological disease severity. Endoscopic duodenal biopsies from 20 clinical cases and 7 healthy control dogs were used to extract mRNA. TLR2 and TLR4 mRNA expression was assessed using quantitative real-time PCR. TLR2 mRNA expression was significantly increased in the IBD dogs compared to controls, whereas TLR4 mRNA expression was similar in IBD and control cases. In addition, TLR2 mRNA expression was mildly correlated with clinical severity of disease, however, there was no correlation between TLR2 expression and histological severity of disease.


Subject(s)
Dog Diseases/immunology , Duodenum/chemistry , Inflammatory Bowel Diseases/veterinary , Toll-Like Receptor 2/analysis , Animals , Biopsy/veterinary , Dogs , Duodenum/immunology , Duodenum/pathology , Female , Gene Expression/genetics , Gene Expression/immunology , Inflammatory Bowel Diseases/immunology , Inflammatory Bowel Diseases/pathology , Male , Reverse Transcriptase Polymerase Chain Reaction/veterinary , Severity of Illness Index , Toll-Like Receptor 2/biosynthesis , Toll-Like Receptor 2/immunology
14.
Domest Anim Endocrinol ; 38(1): 32-7, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19733998

ABSTRACT

Lipids are important for cell function and survival, but abnormal concentrations may lead to various diseases. Cholesterol homeostasis is greatly dependent on the active transport by membrane proteins, whose activities coordinate lipid status with cellular function. Intestinal Niemann-Pick C1-Like 1 protein (NPC1L1) and scavenger receptor B1 (SR-B1) participate in the uptake of extracellular cholesterol, whereas ATP binding cassette A1 (ABCA1) mediates the efflux of excessive intracellular cholesterol. Caveolin-1 binds cholesterol and fatty acids (FA) and participates in cholesterol trafficking. Sterol response element binding protein-2 (SREBP-2) is a sensor that regulates intracellular cholesterol synthesis. Given that cholesterol is a constituent of chylomicrons, whose synthesis is enhanced with an increased FA supply, we tested the hypothesis that feeding polyunsaturated FA (PUFA)-enriched diets in treatment of canine chronic enteropathies alters the mRNA expression of genes involved in cholesterol homeostasis. Using quantitative reverse transcriptase polymerase chain reaction (RT-PCR), we compared the mRNA abundance of NPC1L1, SR-B1, ABCA1, caveolin-1, and SREBP-2 in duodenal mucosal biopsies of dogs with food-responsive diarrhea (FRD; n=14) and inflammatory bowel disease (IBD; n=7) before and after treatment with cholesterol-free PUFA-enriched diets and in healthy controls (n=14). The abundance of caveolin-1, ABCA1, and SREBP-2 were altered by PUFA-enriched diets (P<0.05), whereas that of NPC1L1 and SR-B1 mRNA remained unchanged. The gene expression of caveolin-1, ABCA1, and SREBP-2 was down-regulated (P<0.05) by PUFA-enriched diets in IBD dogs only. Our results suggest that feeding PUFA-enriched diets may alter cholesterol homeostasis in duodenal mucosal cells of dogs suffering from IBD.


Subject(s)
Cholesterol/metabolism , Dietary Fats, Unsaturated/administration & dosage , Dog Diseases/diet therapy , Fatty Acids, Unsaturated/administration & dosage , Inflammatory Bowel Diseases/veterinary , ATP Binding Cassette Transporter 1 , ATP-Binding Cassette Transporters/genetics , Animals , Biopsy/veterinary , Caveolin 1/genetics , Dietary Fats, Unsaturated/metabolism , Dog Diseases/metabolism , Dogs , Fatty Acids, Unsaturated/metabolism , Inflammatory Bowel Diseases/diet therapy , Inflammatory Bowel Diseases/metabolism , Membrane Transport Proteins/genetics , RNA, Messenger/chemistry , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction/veterinary , Scavenger Receptors, Class B/genetics
15.
J Small Anim Pract ; 50(12): 649-54, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19954441

ABSTRACT

OBJECTIVES: To assess complication rate, risk factors for complications and outcome in dogs with oesophageal and gastric endoscopic foreign body (FB) removal. METHODS: Medical records of 102 dogs undergoing endoscopic removal of oesophageal and/or gastric FBs from March 2001 to November 2006 were retrospectively reviewed. All owners were contacted by telephone to provide follow-up information. RESULTS: West Highland white terriers, Yorkshire terriers and Bernese mountain dogs were over-represented compared to the hospital population. Endoscopy alone was successful in 92/102 dogs (90.2 per cent), whereas gastrotomy (but no oesophagotomy) was required in 10 dogs (9.8 per cent). Complications in 13/102 dogs (12.7 per cent) were perforation (8), oesophageal stricture (1), oesophageal diverticula (1), perioesophageal abscess (1), pneumothorax and pleural effusion (1) and respiratory arrest (1). Six dogs (all weighing <10 kg) had complications resulting in death or euthanasia. Bone FBs, bodyweight of less than 10 kg, and oesophageal or gastric FB in place for more than three days were significant risk factors for complications. Of the dogs available for follow-up (75/96), 92 per cent had no complications after discharge. CLINICAL SIGNIFICANCE: Endoscopic FB removal is associated with a low overall complication rate with bone FBs and bodyweight of less than 10 kg as significant risk factors.


Subject(s)
Dog Diseases/surgery , Esophagoscopy/veterinary , Foreign Bodies/veterinary , Gastroscopy/veterinary , Postoperative Complications/veterinary , Animals , Breeding , Dogs , Esophagoscopy/adverse effects , Esophagus/pathology , Esophagus/surgery , Female , Follow-Up Studies , Foreign Bodies/surgery , Gastroscopy/adverse effects , Male , Postoperative Complications/epidemiology , Retrospective Studies , Risk Factors , Stomach/pathology , Stomach/surgery , Treatment Outcome
16.
J Comp Pathol ; 141(2-3): 195-8, 2009.
Article in English | MEDLINE | ID: mdl-19477462

ABSTRACT

An 8-year-old crossbred dog was presented with a one-month history of progressive weakness, respiratory impairment and abdominal distension. Surgical exploration revealed the presence of a splenic mass that infiltrated the mesentery and was adherent to the stomach and pancreas. The mass was composed of highly cellular areas of spindle-shaped cells arranged in interlacing bundles, streams, whorls and storiform patterns (Antoni A pattern) and less cellular areas with more loosely arranged spindle to oval cells (Antoni B pattern). The majority of neoplastic cells expressed vimentin, S-100 and glial fibrillary acidic protein (GFAP), but did not express desmin, alpha-smooth muscle actin or factor VIII. These morphological and immunohistochemical findings characterized the lesion as a malignant peripheral nerve sheath tumour (PNST). Primary splenic PNST has not been documented previously in the dog.


Subject(s)
Dog Diseases/pathology , Nerve Sheath Neoplasms/veterinary , Splenic Neoplasms/veterinary , Animals , Biomarkers, Tumor/analysis , Dogs , Euthanasia, Animal , Fatal Outcome , Female , Glial Fibrillary Acidic Protein/analysis , Immunohistochemistry/veterinary , Nerve Sheath Neoplasms/chemistry , Nerve Sheath Neoplasms/pathology , Nerve Sheath Neoplasms/surgery , S100 Proteins/analysis , Splenic Neoplasms/chemistry , Splenic Neoplasms/pathology , Splenic Neoplasms/surgery , Vimentin/analysis
17.
Vet J ; 181(2): 178-86, 2009 Aug.
Article in English | MEDLINE | ID: mdl-18397835

ABSTRACT

Lymphocyte stimulation tests (LST) were performed in five dogs sensitised with ovalbumin (OVA) and seven healthy dogs. In addition, all five OVA-sensitised and two control dogs were tested after two in vivo provocations with OVA-containing eye drops. The isolated cells were suspended in culture media containing OVA and were cultured for up to 12 days. Proliferation was measured as reduction in 5,6-carboxylfluorescein diacetate succinimidyl ester (CFSE) intensity by flow cytometry on days 0, 3, 6, 9 and 12. A cell proliferation index (CPI) for each day and the area under the curve (AUC) of the CPI was calculated for each dog. All OVA-sensitised dogs demonstrated increased erythema after conjunctival OVA application. The presence of OVA-specific lymphocytes was demonstrated in 2/5 OVA-sensitised dogs before and 4/5 after in vivo provocation. Using the AUC, the difference between OVA-sensitised and control dogs was significant in all three LST before in vivo provocation (P<0.05) and borderline significant (P=0.053) in 2/3 LST after provocation. The most significant difference in CPI was observed after 9 days of culture (P=0.001). This pilot study indicates that the LST allows detection of rare antigen specific memory T-cells in dogs previously sensitised to, but not concurrently undergoing challenge by a specific antigen.


Subject(s)
Dog Diseases/immunology , Hypersensitivity/veterinary , Lymphocyte Activation/immunology , Lymphocytes/immunology , Ovalbumin/adverse effects , Animals , Cell Division/drug effects , Dog Diseases/blood , Dogs , Erythema/etiology , Erythema/veterinary , Hypersensitivity/blood , Hypersensitivity/immunology , Lymphocyte Activation/drug effects , Lymphocytes/drug effects , Lymphocytes/pathology , Reference Values
18.
J Vet Intern Med ; 22(3): 553-60, 2008.
Article in English | MEDLINE | ID: mdl-18466244

ABSTRACT

BACKGROUND: Inflammatory bowel disease (IBD) is thought to result from a dysregulated interaction between the host immune system and commensal microflora. Toll-like receptors (TLRs) recognize microbe-associated molecular patterns (MAMPs), but their role in enteropathies in dogs is unknown. HYPOTHESIS: That there is a dysregulation of TLRs recognizing bacterial MAMPs in dogs with IBD. ANIMALS: Sixteen healthy beagles and 12 dogs with steroid-treated (ST) and 23 dogs with food-responsive (FR) diarrhea. METHODS: Prospective, observational study. mRNA expression of canine TLR2, 4, and 9 was evaluated by quantitative real-time RT-PCR in duodenal and colonic biopsies obtained before and after standard therapy. Samples from control dogs were taken at necropsy, with additional biopsies of stomach, jejunum, ileum, and mesenteric lymph node in 6 dogs. RESULTS: There were significant differences (P< or = .017) in expression of TLR2, 4, and 9 between the 6 sampled locations in healthy control dogs (lymph node > small intestine > or = colon). Before therapy, ST expressed more mRNA than control dogs for all 3 receptors (P < .05). There were no significant differences between pretreatment and posttreatment values, even though 32/35 dogs improved clinically. No associations were found when comparing receptor mRNA expression with either histology or clinical activity scores. CONCLUSIONS AND CLINICAL IMPORTANCE: Bacteria-responsive TLR2, 4, and 9 are upregulated in duodenal and colonic mucosa in IBD. This might lead to increased inflammation through interaction with the commensal flora. The absence of significant changes after therapy despite clinical improvement might point toward the existence of a genetic predisposition to IBD as described in human IBD.


Subject(s)
Dog Diseases/metabolism , Intestinal Diseases/veterinary , Toll-Like Receptors/metabolism , Animals , Case-Control Studies , Chronic Disease , Dog Diseases/genetics , Dogs , Female , Food Hypersensitivity/genetics , Food Hypersensitivity/metabolism , Food Hypersensitivity/veterinary , Gastrointestinal Tract/metabolism , Gastrointestinal Tract/pathology , Gene Expression Regulation , Inflammatory Bowel Diseases/genetics , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/veterinary , Intestinal Diseases/genetics , Intestinal Diseases/metabolism , Male , RNA, Messenger/genetics , RNA, Messenger/metabolism , Toll-Like Receptors/genetics , Up-Regulation
19.
J Small Anim Pract ; 48(10): 584-7, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17608665

ABSTRACT

A five-year-old, entire, male dachshund was presented with a five day history of hypersalivation and regurgitation as well as polyuria and polydipsia for several months. Chest radiographs demonstrated megaoesophagus and aspiration pneumonia. Furthermore, hyperadrenocorticism was demonstrated by means of elevations in levels of serum alkaline phosphatase and cholesterol, decreased urinary specific gravity, increased response to adrenocorticotropic hormone stimulation, insufficient suppression of the post-dexamethasone plasma cortisol levels, an increased endogenous adrenocorticotropic hormone concentration and bilaterally enlarged adrenal glands on abdominal ultrasound. The dog became severely dyspnoeic and was euthanased after magnetic resonance imaging was performed. The magnetic resonance imaging and necropsy revealed the sellar region mainly filled with fluid, with only small tissue remnants, a condition defined as empty sella syndrome in human medicine. To the author's knowledge, this is the first dog described with empty sella syndrome and only the second dog described with hyperadrenocorticism secondary to ectopic adrenocorticotropic hormone production. However, the association between empty sella syndrome and hyperadrenocorticism may be no more than incidental.


Subject(s)
Adrenocortical Hyperfunction/veterinary , Dog Diseases/diagnosis , Empty Sella Syndrome/veterinary , Esophageal Achalasia/veterinary , Adrenocortical Hyperfunction/complications , Adrenocortical Hyperfunction/diagnosis , Animals , Diagnosis, Differential , Dog Diseases/blood , Dog Diseases/pathology , Dogs , Empty Sella Syndrome/complications , Empty Sella Syndrome/diagnosis , Esophageal Achalasia/complications , Esophageal Achalasia/diagnosis , Magnetic Resonance Imaging , Male , Pedigree
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