Enrofloxacin treatment of gram-negative infections.
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Animals↗
Biomedical subjects
R M Batt
Publications and source records attributed to R M Batt.
Five polymorphic canine microsatellites.
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Alleles↗
Diarrhoea and increased intestinal permeability in laboratory beagles associated with proximal small intestinal bacterial overgrowth.
Repeated episodes of diarrhoea were seen in 4 laboratory beagles after experimental renal surgery and feeding a modified diet. Small intestinal bacterial overgrowth (SIBO) was suspected by exclusion of other causes and measurement of plasma folate. SIBO was confirmed by quantitative duodenal bacteriology. Beagles with SIBO can show no clinical signs, experimental stress and dietary change may have been reasons why these 4 beagles exhibited clinical signs with SIBO. Despite normal gut histology an increase in gut permeability was found using sugar absorption tests. This increased permeability had the potential to cause variations in drug absorption during experimental studies.
Animals↗
A novel HPLC method for the simultaneous quantification of monosaccharides and disaccharides used in tests of intestinal function and permeability.
The quantification of monosaccharides and disaccharides used as probes in intestinal function and permeability tests can be technically demanding, detracting from the value of this approach to the indirect assessment of intestinal damage. In this study, a procedure is described for the simultaneous quantification of rhamnose, lactulose, 3-O-methyl-D-glucose and xylose in urine by HPLC using an anion exchange column with pulsed amperometric detection. This method is relatively fast and simple to perform, requiring no pre-treatment of urine samples or post-column derivatization. Accuracy and precision of determinations are illustrated by analytical recoveries (mean percentage +/- S.D., CV., n = 30) for multiple batch analyses of a diluted urine sample containing 20 mg/l of rhamnose (100 +/- 6.8, 6.2%), lactulose (100 +/- 6.1, 5.5%), 3-O-methyl-D-glucose (98 +/- 5.9, 5.5%) and xylose (104 +/- 7.1, 6.5%). Linearity of standard curves indicated that the lower limit for accurate quantification was 0.1 mg/l for all four sugars. Urinary recoveries following oral administration of these sugars to control dogs were determined as a baseline for the investigation of intestinal damage in this species and comparison of chromatograms illustrated enhanced permeability in dogs with gluten-sensitive enteropathy.
3-O-Methylglucose↗
An unexpected bacterial flora in the proximal small intestine of normal cats.
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Animals↗
Exocrine pancreatic insufficiency.
EPI in dogs represents a well-defined condition that can now be diagnosed simply by the analysis of a single serum sample for TLI. A low TLI concentration represents a highly sensitive and specific test for EPI and may also predict the development of disease before the onset of clinical signs. A lack of pancreatic enzymes results in interference with degradation of the major dietary constituents, and there are secondary changes in the small intestine including a decreased synthesis of enterocyte proteins; bacterial overgrowth in the proximal intestine (SIBO); and malabsorption of vitamins, including cobalamin. Management with uncoated pancreatic extract and a low-fat, high-quality protein diet fed in small, divided meals should be effective in most cases. In animals showing a poor response, additional treatment may be necessary with long-term oral antibiotic for SIBO and H2-receptor blockers before a meal to inhibit acid secretion and minimize degradation of pancreatic extract. Diagnosis of the relatively rare cases of EPI in cats is best achieved by analysis of fecal trypsin by the use of specific substrates until a TLI test becomes readily available, and management should follow similar principles to those established for dogs. The major question for the future is the underlying cause of pancreatic acinar atrophy in dogs, particularly the relative importance of genetic and environmental factors. This information may allow detection and elimination of a genetic abnormality by selective breeding or prophylactic treatment that would prevent the development of the disease.
Animals↗
Electron paramagnetic resonance spectroscopy of stable free radicals in the liver compared with ultrastructural and functional damage in a rat model of alcohol- and iron-overload.
1. Electron paramagnetic resonance spectroscopy was used to study free-radical signals in freeze-clamped frozen liver tissue from rats after a 1 year period of dietary supplementation with alcohol, iron, or alcohol and iron. In alcohol-fed, iron-fed and alcohol- and iron-fed animals, mild histological damage was seen on light microscopy and evidence of mitochondrial and nuclear injury was identified by electron microscopy. 2. Subcellular fractionation studies showed an increase in the activity of the peroxisomal marker catalase (P < 0.01) in alcohol-fed rats compared with controls, but a fall of 82% (P < 0.001) in alcohol- and iron-fed animals. The activity of the mitochondrial marker succinate dehydrogenase rose by 7% (not significant) in alcohol-fed animals and by 17% (not significant) in iron-fed animals, but fell by 94% (P < 0.001) in alcohol- and iron-fed animals, suggesting serious impairment of mitochondrial function. 3. Iron overload was substantial in the iron-fed animals and there was an excellent correlation between liver iron concentration and iron-derived signals by electron paramagnetic resonance spectroscopy (P < 0.001). A clear free-radical signal of g = 2.003-2.005 was detected in all liver samples, but there was no significant difference in the magnitude of this signal in any study group. 4. The absence of any increase in the stable free-radical signal, even in the presence of considerable hepatic damage, does not support the hypothesis that free radicals mediate alcoholic liver disease in this animal model, although the results cannot be taken as proof against this hypothesis.
Animals↗
Diarrhoea caused by Escherichia coli.
Since the mid-1940s, Escherichia coli has been recognized as a cause of diarrhoea. Subsequently it has been shown that at least five different pathogenic mechanisms are used to cause disease. Enterotoxigenic E. coli (ETEC) and enteropathogenic E. coli (EPEC) produce a noninflammatory diarrhoea, whereas enteroinvasive E. coli (EIEC), enterohaemorrhagic E. coli (EHEC) and enteroaggregative E. coli (EAggEC) produce an inflammatory diarrhoea. ETEC are a major cause of diarrhoea in infants (up to three episodes per year) and travellers. They produce diarrhoea by attaching to the small intestinal mucosa and elaborate one or both of heat labile and heat stable toxins. EPEC attach firmly to the intestinal mucosa leading to dissolution of the brush border by inducing vesiculation of the microvilli. This process is known as attaching-effacement, and in the jejunum and ileum results in a loss of brush border disaccharidase enzymes and a large area of absorptive surface. EPEC are a major cause of summer diarrhoea in infants and neonatal diarrhoea. EIEC attach to colonic enterocytes, penetrate by an endocytotic mechanism and replicate therein. This results in necrosis and stripping of large areas of colonic mucosa and a dysentery similar to but usually less severe than Shigella dysentery. EHEC produce attaching-effacement to the terminal ileal and colonic mucosa and release the toxins, verocytotoxin (VT) 1 or 2. These kill colonic enterocytes and produce haemorrhagic colitis. In addition, VT can damage vascular endothelial cells, leading to haemolytic uraemic syndrome. The role of EHEC in diarrhoea in children in the tropics is not known. The most recently described group are the EAggEC. They damage and blunt colonic villi by haemorrhagic necrosis, although the precise pathogenic mechanisms are unclear. EAggEC are a major cause of chronic diarrhoea in children. Although certain O-serotypes are associated with the different enteropathic E. coli, serotyping is not sufficiently specific or sensitive for use as a diagnostic tool. Specific diagnosis is expensive and time consuming and depends upon demonstration of the pathogenicity trait, and the pathogenicity gene(s) or their gene product(s). At present, to undertake such testing is not recommended for routine diagnosis but is most useful when surveys of the aetiology of acute and chronic diarrhoea are undertaken.
Diarrhea↗
Sequential study of pancreatic structure and function during development of pancreatic acinar atrophy in a German shepherd dog.
Sequential assessments of pancreatic structure and function were performed on a female German Shepherd Dog bred from parents with exocrine pancreatic insufficiency (EPI), to monitor development of pancreatic acinar atrophy in this breed. Determinations of serum trypsin-like immunoreactivity (TLI), results of N-benzoyl-L-tyrosyl-P-aminobenzoic acid test, fecal soy bean stimulation test (SST), and gross and histologic examinations of the pancreas did not provide evidence of exocrine pancreatic disease up to 13 months of age. However, electron microscopy revealed degenerative abnormalities of acinar cells that were already apparent at 6 weeks and became more extensive with age. Examination of the pancreas at 22 months of age also indicated no gross or histologic abnormalities, but electron microscopy revealed widespread degenerative changes, including dilatation of the rough endoplasmic reticulum and extensive fusion of zymogen granules affecting most of the acinar cells. Serum TLI concentration was markedly reduced at that time, indicative of EPI, but the dog remained healthy and results of the SST were normal. Within 1 month, the dog had developed clinical signs of EPI, and not only serum TLI concentration, but also results of the N-benzoyl-L-tyrosyl-p-aminobenzoic acid test and SST were compatible with severe loss of exocrine pancreatic tissue. This loss was confirmed by gross and histologic examination of the pancreas at 25 months, which revealed typical features of pancreatic acinar atrophy, including scattered and disorganized exocrine cells in the small remnants of pancreatic tissue. These findings indicate that in German Shepherd Dogs, pancreatic acinar atrophy may involve interference with normal intracellular processing of zymogen granules, which precedes progressive and eventual rapid loss of exocrine pancreatic tissue.
Aging↗
Pancreatic function following partial pancreatectomy and anastomosis of the pancreatic duct to the stomach or duodenum in dogs.
The effects of pancreatic duct anastomosis to stomach (stomach group) or duodenum (duodenal group) on pancreatic function were examined in dogs following two thirds pancreatectomy. Normal fasting blood glucose concentrations were maintained in both groups despite significant reductions in glucose tolerance in the stomach group, and reductions in fasting insulin and insulin peak response in both groups. Pancreatic exocrine function was significantly decreased in both groups, though plasma p-aminobenzoic acid (PABA) concentrations were generally higher in the duodenal group. A correlation was found between plasma trypsin-like immunoreactivity (TLI) and pancreatic weight. These results indicate that anastomosis of the pancreas to bowel can be undertaken with minimal postoperative complications and that the site of the anastomosis influences pancreatic function. They suggest that preservation of more than one third of the pancreas is required for optimal function. The complementary information provided by the PABA and TLI tests suggests their dual application will be clinically useful for the detection and characterisation of naturally occurring pancreatic diseases.
4-Aminobenzoic Acid↗
Immune responses to dietary antigens in gluten-sensitive enteropathy of Irish setters.
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 C1q 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.
Animals↗
The large plasmids found in enterohemorrhagic and enteropathogenic Escherichia coli constitute a related series of transfer-defective Inc F-IIA replicons.
Forty-six of 52 (88.5%) enterohemorrhagic Escherichia coli (EHEC) strains screened carried a "common" plasmid of about 90 kb which encoded sequences homologous to the Inc F-IIA replicon. A similarly high incidence of Inc F-IIA plasmid-containing strains was observed in other groups of diarrheagenic E. coli, but not in random environmental coliform isolates. Enteropathogenic E. coli (EPEC) contain plasmids of similar properties and share a 23-kb DNA fragment with plasmids from EHEC. The common region encodes the F-IIA replication region and sequences homologous to the transfer operon of the Inc F-II plasmid R1. Sequence homology varied between plasmids isolated from different EHEC/EPEC strains with > 80% showing homology to the regions encoding the rep and par genes. Only 5% of plasmids from EHEC strains had intact sequences homologous to the DNA between these two regions, including the oriT site. Some plasmids with an apparently intact tra operon still failed to plaque F-pilus-specific phages. This is consistent with observations that the large plasmids of EHEC and EPEC are phenotypically nonconjugative. These results suggest that the large plasmids of EHEC/EPEC constitute a family of transfer-deficient Inc F-IIA plasmids with varying degrees of deletion in tra function. The evolutionary ramifications of this finding are considered.
DNA Probes↗
Novel invasion determinant of enteropathogenic Escherichia coli plasmid pLV501 encodes the ability to invade intestinal epithelial cells and HEp-2 cells.
An Escherichia coli K-12 transformant carrying 96.5-kb plasmid pLV501 from enteropathogenic E. coli (EPEC) strain K798 is able to produce the same characteristic attaching-effacing lesions in a rabbit ileal biopsy explant model as its parent strain. Cloned EcoRI-SalI DNA restriction fragments from this plasmid failed to reproduce the attaching-effacing lesions, but one recombinant plasmid, pLV527, containing 4.5 kb of pLV501 DNA, conferred on E. coli DH1 transformants the ability to invade enterocytes in the rabbit explant model. DH1(pLV527) was also able to adhere to and invade HEp-2 cells. The relative invasive ability of DH1(pLV527) was quantified by recovery of internalized bacteria following gentamicin treatment of infected HEp-2 monolayers. DH1(pLV527) was 1,000-fold more invasive than DH1 carrying pBR322 or a recombinant plasmid which had no physiological effect on ileal biopsy explants but was less invasive than an enteroinvasive E. coli strain or a transformant carrying the cloned invasion genes of Shigella flexneri. Invasion by DH1(pLV501) could also be detected but occurred at a level 30 times lower than that by DH1(pLV527). Colony-hybridization of the pLV527 insert against a panel of 49 EPEC and related strains revealed that only 11 contained pLV527-hybridizing sequences; thus, the invasion determinant is not an essential component of the attachment-effacement pathogenic mechanism. One pLV527-hybridizing strain displayed both attachment-effacement and invasiveness in the rabbit ileal biopsy explant model. No significant hybridization was observed to non-EPEC invasive pathogenic enteric bacteria, indicating that the invasion determinant encoded on pLV527 is distinct from those used by these organisms.
Animals↗
Dietary modulation of gluten sensitivity in a naturally occurring enteropathy of Irish setter dogs.
Gluten sensitivity in a naturally occurring enteropathy of Irish setter dogs, and the effects of excluding dietary cereal from birth on the subsequent response to gluten challenge were investigated. Peroral jejunal biopsy specimens were obtained at 1 year of age for morphometric and biochemical examinations, and intestinal permeability was assessed using 51Cr-ethylenediaminetetraacetic acid. Affected setters, reared on a normal wheat containing diet, exhibited partial villus atrophy, intraepithelial lymphocyte infiltration, reduced brush border alkaline phosphatase activity, and increased intestinal permeability. Gluten sensitivity was shown by introduction of a gluten free diet, which resulted in resolution of morphological and biochemical abnormalities and decreased intestinal permeability, and subsequent gluten challenge, which resulted in relapse. In contrast, littermates reared exclusively on a cereal free diet showed minimal changes when challenged with gluten, apart from intraepithelial lymphocyte infiltration. These findings document a gluten sensitive enteropathy in Irish setters and indicate that exclusion of dietary cereal from birth may modify subsequent expression of the disease.
Alkaline Phosphatase↗
Effects of enteropathogenic Escherichia coli on microvillar membrane proteins during organ culture of rabbit intestinal mucosa.
This study examines the effects of an enteropathogenic Escherichia coli on microvillar membrane proteins during organ culture of rabbit ileal explants. Explants maintained with enteropathogenic E coli showed brush border effacement affecting approximately 50% of enterocytes, and where enteropathogenic E coli were closely adherent to the enterocyte surface microvilli were apparently being shed as vesicles. The microvillar membrane enzymes alkaline phosphatase, aminopeptidase N and alpha-glucosidase were released into the culture medium during organ culture, and this process was significantly enhanced by enteropathogenic E coli. This increased loss of microvillar membrane enzymes into the culture medium was associated with decreased tissue activities of microvillar membrane enzymes in enteropathogenic E coli infected ileal explants compared with control. For aminopeptidase N in particular, however, total enzyme activities in the tissue plus culture medium were increased comparing enteropathogenic E coli with control, suggesting that there might be an increase in the rate of synthesis of certain microvillar membrane proteins. Reorientating sucrose density gradient centrifugation of culture medium showed that alkaline phosphatase, aminopeptidase N and alpha-glucosidase were predominantly associated with particles of peak modal density 1.19 g/ml in both groups, confirming that enteropathogenic E coli accelerate release of microvillar membrane enzymes as vesicles. Analytical fractionation of ileal explants showed that enteropathogenic E coli resulted in a loss of microvillar membrane enzyme activities from the main brush border peak of modal density 1.21 g/ml present in controls. The density of the remaining smaller and lighter peak increased from 1.19 g/ml to 1.23 g/ml after homogenisation in digitonin, confirming association of these proteins with cholesterol containing membranes and not endoplasmic reticulum. These findings suggest that enteropathogenic E. coli accelerate the normal shedding of microvillar membrane proteins as vesicles, and may stimulate a compensatory increase in microvillar membrane protein synthesis.
Alkaline Phosphatase↗
Small intestinal bacterial overgrowth and enhanced intestinal permeability in healthy beagles.
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)
Animals↗
Antibody responses to BSA in dogs: a source of error in diagnostic immunoassays.
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Animals↗