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1.
Morphologic changes in the small intestine were investigated during development of naturally acquired wheat-sensitive enteropathy in Irish Setters. To distinguish underlying morphologic abnormalities from nonspecific effects of intestinal damage, progeny of affected dogs reared on a normal wheat-containing diet were compared with their own littermates reared on a cereal-free diet and with age-matched clinically normal Irish Setters fed the same wheat-containing diet. Peroral jejunal biopsy specimens were taken sequentially between 4 months and 1 year of age. At 4 months of age, there were no differences in villus height, comparing the 3 groups, but increased numbers of intraepithelial lymphocytes and goblet cells were already present in biopsy specimens from the affected Irish Setters fed wheat. Dietary wheat resulted in a progressive reduction in villus height in the jejunum of affected Irish Setters from 6 months onward. Underlying morphologic abnormalities were not found, and the characteristic morphologic changes of this enteropathy were secondary to the presence of dietary wheat. However, development of partial villus atrophy was preceded by increased numbers of intraepithelial lymphocytes and goblet cells.  相似文献   

2.
Intestinal permeability was assessed in Irish setters with gluten-sensitive enteropathy by oral administration of an isotonic solution of cellobiose and mannitol, and measurement of their urinary excretion ratio. The cellobiose/mannitol ratio was increased in affected Irish setters fed a wheat-containing diet compared both with littermates reared on a cereal-free diet, with no evidence of jejunal damage, and clinically healthy Irish setters. The ratio fell following six weeks on a gluten-free diet to be comparable with control values, and subsequently increased after six weeks gluten challenge. The results indicate that the cellobiose/mannitol test may be useful for the detection of mucosal damage and for monitoring the response to therapy.  相似文献   

3.
This study examined whether increased intestinal permeability in Irish setters with gluten-sensitive enteropathy was associated with altered immune responses to ingested antigens, and whether a humoral immune response to gluten is involved in the pathogenesis of the condition. Affected setters reared on a wheat-containing diet were compared with littermates reared on a cereal-free diet and age-matched control setters. Measurement of serum immunoglobulins revealed increased serum IgA concentrations in affected dogs. Antibody responses to a variety of dietary antigens were measured by elisa. Antibody levels to ovalbumin, collagen I and II and soya were not significantly different from normal dogs. Anti-gliadin antibody concentrations were lower in affected dogs than controls, and correlated with immune complex formation as assessed by CIq binding. The study suggested a modified immune response in dogs with increased intestinal permeability, although there was no major systemic antibody response to dietary antigens.  相似文献   

4.
The pathogenesis of a wheat-sensitive enteropathy was explored in a litter bred from two Irish setters with a naturally occurring enteropathy. Jejunal biopsies from all eight progeny exhibited morphological changes comparable to those in the parents, while biochemical abnormalities appeared to be related to age. In biopsies obtained from the first group of four dogs at eight months, the activities of alkaline phosphatase and of leucyl-2-naphthylamidase were almost undetectable while disaccharidases were unaltered. In contrast, analytical subcellular fractionation of biopsies obtained from the second group of four dogs at nine months showed that specific activities now reflected a major deficiency of brush border alkaline phosphatase, and normal brush border leucyl-2-naphthylamidase accompanied by elevated soluble activity. Further studies are indicated to determine whether these findings represent an age-related abnormality affecting specific microvillus membrane proteins.  相似文献   

5.
OBJECTIVE: To establish a model for inheritance of gluten-sensitive enteropathy (GSE) in Irish Setters. ANIMALS: 44 dogs of a 6-generation family of Irish Setters with GSE and 7 healthy Irish Setters. PROCEDURE: Phenotype of each dog was determined after oral administration of gluten in the weaning diet, using morphometric evaluation of jejunal biopsies (all generations) and measurement of small intestinal permeability by use of a lactulose-rhamnose permeation test (generations 1, 2, and 3). Overall probability for each of 4 genetic models of inheritance (autosomal recessive, autosomal dominant, sex-linked recessive, and sex-linked dominant) accounting for segregation of partial villus atrophy within the entire family was calculated. RESULTS: The autosomal recessive model was most tenable and was 56,250 times more likely to account for segregation of partial villus atrophy than the autosomal dominant model, assuming disease prevalence of 0.8%. Both sex-linked models were untenable. These conclusions were robust to the error attached to estimation of disease prevalence. High intestinal permeability without morphometric jejunal abnormalities in 4 of 20 dogs in the 3 youngest generations suggested heterogeneity of lesions associated with GSE. CONCLUSIONS: Genetic transmission of GSE is under the control of a single major autosomal recessive locus.  相似文献   

6.
Exogenous creatinine clearance, urinary electrolyte excretions, calcium and phosphorus balance, serum cholesterol concentration, arterial blood pressure, and body weight were evaluated in dogs with chronic renal failure that were fed 2 commercial diets. Nine dogs ranging in age from 1 to 15 years were identified as having mild to moderate chronic renal failure (CRF, exogenous creatinine clearance = 0.5 to 2.13 ml/kg of body weight/min). These dogs and a group of 10 clinically normal controls were fed a diet containing 31% protein for 8 weeks at which time hematologic and biochemical evaluations and clearance studies were performed. All dogs then were fed a phosphorus-restricted diet containing 16% protein and then reevaluated after 8 weeks. The dogs in this study had hematologic and biochemical abnormalities typical of CRF. Urine absolute and fractional excretion of electrolytes was higher in dogs with CRF than in controls and was affected by diet. Serum cholesterol concentration was higher in dogs with CRF and increased in those dogs after feeding the low protein diet. Changes in dietary sodium intake did not affect arterial blood pressure. The phosphorus-restricted diet did not affect serum amino terminal parathyroid hormone concentration in either group. Control dogs lost body weight, whereas dogs with CRF gained weight when fed the low protein diet. We concluded that dogs with mild to moderately severe CRF have the same biochemical abnormalities and response to dietary restriction of protein and phosphorus as has been previously reported in dogs with experimentally induced CRF. Restriction of dietary sodium may not decrease arterial blood pressure in some dogs with CRF.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

7.
Bacterial overgrowth (greater than 10(5) colony-forming units/ml duodenal juice) in the duodenum was demonstrated in 8 of 11 dogs with exocrine pancreatic insufficiency (EPI). In 4 of these 8 dogs, the overgrowth included large numbers (greater than 10(4) colony-forming units/ml) of obligate anaerobic bacteria and was associated with decreased activities of several brush border marker enzymes and, in 2 dogs, with partial villous atrophy in the jejunum. Changes in the jejunal mucosa of the remaining dogs (with either no overgrowth or overgrowth of aerobic bacteria alone) were characterized by increased activities of some brush border disaccharides and of lysosomal hydrolases. One dog was euthanatized without treatment, at the owner's request. The response of 4 of the remaining 10 dogs treated with enzyme replacement alone was poor or suboptimal, and all of these 4 dogs had bacterial overgrowth. One of these dogs had an excellent clinical response when also given oxytetracycline orally for 14 days, but the other 3 dogs did not improve further in response to the same treatment. It was concluded that bacterial overgrowth in the duodenum is common in dogs with EPI and that, when such overgrowth includes large numbers of obligate anaerobes, there may be associated biochemical and morphologic abnormalities in jejunal mucosa. Functional disturbances related to abnormal intestinal microflora may be responsible for the failure of some dogs with EPI to respond fully to oral pancreatic enzyme supplementation without antibiotic therapy.  相似文献   

8.
OBJECTIVE: To determine the frequency of the 107G-->C canine leukocyte adhesion deficiency (CLAD) mutation in Irish Setters from the Australian breeding population. METHOD: Genomic DNA was isolated from 87 Irish Setter blood samples and a region of the beta-2 integrin gene (ITGB2), encompassing the mutation, was amplified using real-time Polymerase Chain Reaction (PCR). Two fluorescently labelled probes were hybridised to the fragment, and fluorescence resonance energy transfer (FRET) was used to detect the 107G-->C mutation responsible for CLAD. RESULTS: Three new heterozygotes were identified among 87 healthy Irish Setters from Australia. All originated from a litter sired by a known heterozygote. A total of seven heterozygotes have now been identified in 92 dogs (7.6%), representing over 90% of all major breeding stock in five Australian states. Two of the heterozygotes were recently imported adult dogs and the others were their offspring. CONCLUSIONS: The frequency of the 107C allele in the Australian population of Irish Setters is lower than that in Europe. Selective breeding programs should be adopted to eliminate the mutant allele presently in two breeding lines.  相似文献   

9.
Canine leukocyte adhesion deficiency (CLAD) is a primary immunodeficiency disease characterized by recurrent bacterial infections in the presence of marked leukocytosis. The disease was 1st described in the mid-1980s in a cross-breed Irish Setter Dog in the United States. It results from a defective beta-2 subunit of heterodimeric leukocyte adhesion proteins. The causative mutation for CLAD in Irish Setter Dogs from Europe has been identified as a missense mutation at base pair position 107 in the beta-2 integrin subunit gene (ITGB2) that results in an amino acid change from cysteine to serine at amino acid 36 (Cys36Ser) in the beta-2 integrin subunit protein. In the current work, the originally described dog with CLAD has been genetically tested and shown to have the same mutation as the European Irish Setters. This suggests that the mutation has been in the Irish Setter population for many generations spanning more than 2 decades. A related breed, the Irish Red and White Setter, has a history of interbreeding with Irish Setters and shares a common ancestry with the Irish Setter breed. DNA from Irish Red and White Setters residing in the United States was screened either by sequencing or by the newly developed restriction enzyme test for the Irish Setter Cys36Ser CLAD mutation. Seven of 54 dogs tested (13%) were found to be carriers of the Irish Setter CLAD mutation. Five of these were directly related to a sire from the UK, demonstrating the importation of an allele from another continent and establishing the need for genetic testing in this breed in the United States.  相似文献   

10.
The small intestine of healthy adult Beagles was examined to determine whether subclinical abnormalities might exist that would be relevant to the use of Beagles in pharmacologic studies. Duodenal juice was obtained for qualitative and quantitative bacteriologic examinations; jejunal mucosa was taken for morphologic and biochemical investigation, and intestinal permeability was assessed by quantification of 24-hour urinary excretion of 51Cr-labeled EDTA after its oral administration. Comparisons were made with findings in healthy adult dogs of other breeds that served as controls. Small intestinal bacterial overgrowth was found in 14 of the 21 Beagles examined, and represented a mixed flora that included obligate anaerobic bacteria in 8 dogs and exclusively aerobic bacteria in 6 dogs. Intestinal permeability (percentage urinary recovery of 51Cr-labeled EDTA; mean +/- SEM) was considerably higher (P < 0.01) in Beagles with anaerobic overgrowth (37.6 +/- 3.2%) or aerobic overgrowth (30.5 +/- 4.8%), compared with Beagles with no overgrowth (17.3 +/- 1.6%) and with controls (11.1 +/- 1.0%). In Beagles, significant (r = 0.54, P = 0.03) correlation was observed between 24-hour urinary recovery of 51Cr-labeled EDTA and bacterial numbers in duodenal juice. Morphologic changes in jejunal mucosa were minimal, and specific activities of brush border enzymes were not significantly decreased, apart from aminopeptidase N, but activities of lysosomal and endoplasmic reticular marker enzymes were higher in the 3 groups of Beagles with anaerobic, aerobic, or no overgrowth, compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

11.
The effects of age and dietary change on the structure and function of piglet small intestine were investigated in gnotobiotic pigs. The small intestinal mucosa was damaged when gnotobiotic pigs were weaned on to a pelleted meal diet; villus height, crypt cell production rate, and activities of brush border enzymes were reduced. Small intestinal damage was associated with reduced weight gain over a three week period; diarrhoea was not observed. The continuous consumption of meal appeared to perpetuate the intestinal damage for three weeks, although evidence of intestinal repair, as indicated by an increased crypt cell production rate, was present three weeks after weaning. Antibodies to soya antigen were detected in serum after weaning and the intestinal damage could have been caused by antibody-mediated immune reactions to soya proteins. Villi of milk fed gnotobiotic pigs shortened significantly with age.  相似文献   

12.
OBJECTIVE: To determine whether the rcd-1 mutation causing progressive retinal atrophy (PRA) in Irish Setters is in the Australian breeding population. METHOD: DNA samples were tested for the mutation using the Polymerase Chain Reaction and specific primer nucleotides to amplify the phosphodiesterase gene followed by restriction enzyme cleavage and fragment size determination. RESULTS: No mutant alleles were found in 38 Irish Setters, representing over 80% of all major breeding stock in five Australian states. CONCLUSIONS: It is likely that the Australian population of Irish Setters is free of the rcd-1 form of PRA.  相似文献   

13.
Intestinal permeability in dogs with small intestinal disease was measured by quantitation of 24-hour urinary excretion of 51Cr-labeled EDTA following intragastric administration. Permeability was high in dogs with a variety of naturally acquired small intestinal diseases including wheat-sensitive enteropathy of Irish Setters, small intestinal bacterial over-growth, and giardiasis, and permeability was decreased after successful treatment. These findings indicate that the assessment of intestinal permeability may be a useful technique for detecting small intestinal disease and for monitoring the efficacy of treatment in dogs.  相似文献   

14.
The genetic immunodeficiency disease canine leukocyte adhesion deficiency (CLAD) was originally described in juvenile Irish Setters with severe, recurrent bacterial infections. CLAD was subsequently shown to result from a mutation in the leukocyte integrin CD18 subunit which prevents leukocyte surface expression of the CD11/CD18 complex. We describe the development of a mixed-breed CLAD colony with clinical features that closely parallel those described in Irish Setters. We demonstrate that the early identification of CLAD heterozygotes and CLAD-affected dogs by a combination of flow cytometry and DNA sequencing allows the CLAD-affected animals to receive life-saving antibiotic therapy. The distinct clinical phenotype in CLAD, the ability to detect CD18 on the leukocyte surface by flow cytometry, and the history of the canine model in marrow transplantation, enable CLAD to serve as an attractive large-animal model for the investigation of novel hematopoietic stem cell and gene therapy strategies.  相似文献   

15.
After twenty weeks of continuous dosing with Trichostrongylus colubriformis larvae substantial, but declining, numbers of worms had persisted in most of the lambs examined, although there were wide inter-individual variations. Mucosal lesions were found in the proximal small intestines of all the infected animals, their severity being directly related to worm burden. Representative brush border enzyme activities analysed in intestinal mucosal extracts from the same lambs showed differing responses. Alkaline phosphatase and glycyl-L-leucine dipeptidase were significantly depleted, whereas maltase activity was only marginally reduced, and leucine aminopeptidase activity was normal. Mucosal acetylcholinesterase activity was significantly elevated in the parasitised animals and, interestingly in view of the postulated role of this enzyme in nematode pathogenicity, the level of activity was directly correlated with individual worm burdens. Intestinal trypsin and chymotrypsin activities were unaffected and the level of superoxide dismutase, an enzyme associated with the inflammatory response, was normal. There were also no consistent changes in the mucosal activities of several enzymes including lactic dehydrogenase, creatine phosphokinase, aldolase, and glutamic oxaloacetate transaminase, whose leakage from damaged or necrotic tissues has been well defined in terms of the concomitant increase in their activity in the circulation. Lambs treated orally with fenbendazole five and/or ten weeks before slaughter either in the presence or absence of continued larval intake, had negligible worm burdens, and showed little evidence of intestinal damage at post mortem. Brush border enzyme levels, with the exception of alkaline phosphatase and, in two cases dipeptidase, were normal in these animals. The activity of alkaline phosphatase was approximately double that in the continuously infected, untreated lambs, but remained markedly lower than in the uninfected controls. The activities of the other enzymes studied, including acetylcholinesterase, were within the control range. In summary, in chronic trichostrongylosis even relatively low nematode burdens were associated with marked pathological and biochemical damage in the intestine with both lesion severity and mucosal acetylcholinesterase activity being directly related to worm numbers. Although morphological integrity was completely restored after anthelmintic treatment, the persistent low activity of brush border alkaline phosphatase coupled with the enzymological findings in untreated, infected animals suggests that recovery of the full functional capability of the intestinal mucosa may take longer.  相似文献   

16.
Twenty-five dogs with insulin-secreting neoplasms of the pancreas were studied. The diagnosis in each case was determined by histologic evaluation of pancreatic tissue obtained at surgery. The breed distribution revealed that German Shepherd Dogs, Irish Setters, and Collies were most commonly represented. Physical examination, complete blood counts, serum biochemical analysis, and urinalysis were of little diagnostic value, aside from the finding of hypoglycemia in 21 of 25 dogs. Radiographs of the thorax and abdomen were noncontributory to the ultimate diagnosis. Prior to surgery, fasting immunoreactive insulin concentrations and blood glucose concentrations were studied. Insulin:glucose ratios, glucose:insulin ratios, and amended insulin:glucose ratios were determined from the insulin and glucose concentrations in a single blood sample in each of 28 trials. In addition, glucagon tolerance tests were performed on 12 dogs. The amended insulin:glucose ratios proved to be the most reliable for diagnosis. Pancreatic masses were evident at surgery in 23 of 25 dogs; the remaining 2 dogs had microscopic evidence of an islet cell tumor. Nineteen of the islet cell tumors were carcinomas and 6 were simply described as "islet cell tumors." The mean life expectancy after surgery was 12.3 months. Treatment for malignant islet cell tumours included frequent feeding glucocorticoids, and diazoxide.  相似文献   

17.
The histochemical distribution of selected enzymes were examined in the small intestine of 5 about 3-week-old normal calves fed on whole cow’s milk. Alkaline phosphatase and β-D-galactosidase (= lactase) in the epithelial brush border, and non-specific esterase in the cytoplasm showed a strong reaction in the villi of the anterior small intestine and a marked decrease in the posterior regions. Aminopeptidase in the brush border of the villi showed a reverse distribution, with the strongest reaction in the posterior small intestine. Adenosine-triphosphate-splitting enzyme in the epithelial brush border, acid phosphatase and succinate dehydrogenase in the cytoplasm of the epithelial cells gave a relatively uniform reaction in the villi throughout the small intestine. A fluoride-resistant acid phosphatase was demonstrated in the brush border of the villi in the anterior small intestine. The distribution of enzymes demonstrated in this study was generally compatible with the known absorptive functions of the various parts of the small intestine.  相似文献   

18.
Amino acid profiles and serum albumin and serum total protein concentrations were evaluated in dogs with renal disease. Nine dogs ranging in age from 1 to 15 years were identified as having mild to moderate chronic renal failure (CRF; exogenous creatinine clearance, 0.5 to 2.13 ml/kg of body weight/min). These dogs and a group of 10 clinically normal control dogs were fed a diet containing 31% protein for 8 weeks, at which time serum and urine amino acid assays and clearance studies were performed. All dogs then were fed a diet containing 16% protein for 8 weeks and then reevaluated. Chronic renal failure was associated with mild abnormalities in serum concentrations of amino acids. When fed the higher protein diet, dogs with CRF had lower serum concentrations of glutamine, leucine, proline, and serine and higher serum concentrations of cystathionine and 3-methylhistidine than clinically normal control dogs. When fed the low protein diet, dogs with CRF had lower serum serine concentrations and higher serum concentrations of cystathionine, phenylalanine, and 3-methylhistidine. Urine excretion of amino acids in all dogs on both diets was low, and dogs with CRF had lower renal clearances of 3-methylhistidine than control dogs. There were no significant differences in concentrations of serum albumin and total solids between either group, regardless of diet. We concluded that dogs with mild to moderately severe CRF have mild abnormalities of serum free amino acid concentrations, but renal conservation of essential amino acids is not impaired.  相似文献   

19.
Fourteen racing huskies were matched into pairs then assigned to two diets, a commercial stress diet and an experimental diet. Proportions of protein: fat:carbohydrate on an available energy basis were 23:57:20 in a commercial stress diet and 28:69:3 in an experimental diet. The team participated in the 1979 Iditarod Trail race and was overtaken by an episode of diarrhea. Clinical signs were suggestive of parvovirus infection; high serum titers of parvo antibodies were found after the race. Blood examination showed normal levels of metabolites, electrolytes and enzymes after the race. Erythrocyte counts were depressed significantly during the race, by 15% in dogs fed an experimental diet and by 27% in those fed a commercial stress diet. Erythrocyte parameters have also become depressed during the racing season in middle distance sled dogs fed 28% protein (energy basis) but not 32 or 39%. Depressed red blood cell production has been demonstrated previously in dogs subjected to stress induced experimentally in several ways, and its restoration has been affected by dietary protein. Erythrocyte parameters may be useful indicies of the degree of stress in a dog as well as the adequacy of its protein intake during stress.  相似文献   

20.
OBJECTIVE: To determine effects of protein intake on blood variables, plasma volume, and maximal oxygen uptake (VO2max) in sled dogs undergoing rigorous training. ANIMALS: 32 Alaskan sled dogs, between 2 and 6 years old. PROCEDURE: Dogs were assigned to 1 of 4 groups on the basis of age, sex, and ability. Isocaloric diets containing 18% (diet A), 23% (diet B), 29% (diet C), or 35% (diet D) of energy as protein were assigned randomly to each group and fed 1 month before and during a 12-week training period. Maximal oxygen uptake was measured at 0 (before training) and 12 weeks. Body weight, protein and energy intake, plasma volume, PCV, hemoglobin concentration, and serum biochemical variables were measured at 0, 8, and 12 weeks. RESULTS: Serum biochemical variables, PCV, and hemoglobin concentration remained within reference ranges for all dogs. Dogs fed diet A had a decrease in VO2max and a greater rate of soft tissue injury throughout training, compared with dogs fed the other diets. At 12 weeks, dogs fed diets C and D had greater serum sodium concentration and hemoglobin concentration than did dogs fed diet A. Dogs fed diet D also had more plasma volume at 12 weeks than did dogs of any other group. CONCLUSIONS AND CLINICAL RELEVANCE: Consumption of a diet with 18% dietary protein on an energy basis (3.0 g of protein/kg of body weight) is insufficient to meet the metabolic requirements of sled dogs in training. For intense interval work, a diet with 35% dietary protein as energy (6.0 g of protein/kg) may provide a performance advantage by promoting an increase in plasma volume.  相似文献   

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