Equine maxillary cheek teeth infundibulae are frequently affected by developmental and acquired disorders, but the imaging, gross, and histological features of normal and abnormal infundibulae remain ...incompletely understood.
To perform MicroCT, gross examination, and histology on sectioned teeth and compare the imaging and anatomical findings.
original study.
Eight maxillary cheek teeth of different ages and with varying grades of unilateral (
= 5) or bilateral (
= 3) occlusal infundibular caries were extracted from equine heads obtained from an abattoir. The teeth were imaged by MicroCT, then transversely sectioned and grossly and histologically examined, with the imaging and gross and histological anatomical findings examined and compared.
Fifteen infundibulae, including two without occlusal caries had subocclusal cemental hypoplasia or caries. One infundibulum without occlusal caries had no subocclusal cemental defects. Histologically, hypoplastic cemental areas consisted of irregularly-shaped, wide central channels, with multiple, large, cylindrical side-branches that extended peripherally to a variable extent. Cementum with extensive, wide, empty channels, and cementum with a more irregular moth-eaten appearance had dark or eroded gross appearance and a low HU on CT. Some infundibulae had cement-free areas that only contained fragments of collagen-like material, especially at their apical aspects (apical cemental hypoplasia). Carious subocclusal areas had connections with the occlusal surface and had disrupted cemental architecture, including of their central vascular channel that, along with their side branches, contained degraded food, and cemental debris.
No clinical histories or accurate ages were available for these eight teeth.
Hypoplastic cemental lesions, including at central linear and apical sites, histologically contain areas with multiple wide-branched, cylindrical channels or even areas of total cement hypoplasia visible on gross sections When such cemental defects contact the occlusal surface due to normal wear, food impaction, and caries can ensue.
Cardiomyopathy associated with abnormal trabecular bands of tissue traversing one or both ventricles is reported rarely in cats. The case of a 9-year-old cat which presented in congestive heart ...failure is reported. Multiple cardiac abnormalities were found, including a large trabecular tissue bridge which bisected the left ventricle. Other findings included arrhythmia, thrombocytopaenia and raised serum creatine kinase. The cat was euthanased due to clinical deterioration. Necropsy findings included increased cardiac weight, the division of the left ventricle by a large trabecular band composed of connective tissue and cardiac myofibres consistent with a moderator band, nodular thickening of the mitral valve, left atrial dilation, and fibroplasia/fibrosis of the left ventricular myocardium associated with widespread myofibre necrosis due to infarction. Pathological findings in this case differ from previous reports of ventricular transverse bridging tissue in cats with cardiac disease.
There is currently a global shortage of veterinary pathologists in all sectors of the discipline, and recruitment of toxicological pathologists is a particular problem for the pharmaceutical ...industry. Efforts to encourage veterinarians to consider alternative career paths to general practice must start at the undergraduate level, with provision of structured career guidance and strong role models from pathology and research disciplines. It is also imperative that both the importance of biomedical research and the role of animal models be clearly understood by both university staff and undergraduates. Traditionally, much post-graduate training in toxicological pathology is done “on the job” in the United Kingdom, but completion of a residency and/or PhD program is recognized as a good foundation for a career in industry and for successful completion of professional pathology examinations. New models of residency training in veterinary pathology must be considered in the United Kingdom to enable a more tailored approach to training toward specific career goals. A modular approach to residency training would allow core skills to be maintained, while additional training would target specific training requirements in toxicological pathology. Exposure to laboratory-animal pathology, toxicology, research methodology, and management skills would all be of benefit as an introduction to a career in toxicological pathology. However, long-term funding for UK residencies remains a problem that must be resolved if future recruitment needs in veterinary pathology are to be met.
Lawsonia intracellularis is an obligate intracellular bacterial pathogen that causes proliferative enteropathy (PE) in pigs. L. intracellularis infection causes extensive intestinal crypt cell ...proliferation and inhibits secretory and absorptive cell differentiation. However, the affected host upstream cellular pathways leading to PE are still unknown. beta-catenin/Wnt signalling is essential in maintaining intestinal stem cell (ISC) proliferation and self-renewal capacity, while Notch signalling governs differentiation of secretory and absorptive lineage specification. Therefore, in this report we used immunofluorescence (IF) and quantitative reverse transcriptase PCR (RTqPCR) to examine beta-catenin/Wnt and Notch-1 signalling levels in uninfected and L. intracellularis infected pig ileums at 3, 7, 14, 21 and 28 days post challenge (dpc). We found that while the significant increase in Ki67.sup.+ nuclei in crypts at the peak of L. intracellularis infection suggested enhanced cell proliferation, the expression of c-MYC and ASCL2, promoters of cell growth and ISC proliferation respectively, was down-regulated. Peak infection also coincided with enhanced cytosolic and membrane-associated beta-catenin staining and induction of AXIN2 and SOX9 transcripts, both encoding negative regulators of beta-catenin/Wnt signalling and suggesting a potential alteration to beta-catenin/Wnt signalling levels, with differential regulation of the expression of its target genes. We found that induction of HES1 and OLFM4 and the down-regulation of ATOH1 transcript levels was consistent with the increased Notch-1 signalling in crypts at the peak of infection. Interestingly, the significant down-regulation of ATOH1 transcript levels coincided with the depletion of MUC2 expression at 14 dpc, consistent with the role of ATOH1 in promoting goblet cell maturation. The lack of significant change to LGR5 transcript levels at the peak of infection suggested that the crypt hyperplasia was not due to the expansion of ISC population. Overall, simultaneous induction of Notch-1 signalling and the attenuation of beta-catenin/Wnt pathway appear to be associated with the inhibition of goblet cell maturation and enhanced crypt cell proliferation at the peak of L. intracellularis infection. Moreover, the apparent differential regulation of apoptosis between crypt and lumen cells together with the strong induction of Notch-1 signalling and the enhanced SOX9 expression along crypts 14 dpc suggest an expansion of actively dividing transit amplifying and/or absorptive progenitor cells and provide a potential basis for understanding the development and maintenance of PE.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Intestinal adenocarcinoma in a Shetland ewe Crilly, James Patrick; Smith, Sionagh H; Sargison, Neil Donald
Veterinary record case reports,
January 2014, Letnik:
2, Številka:
1
Journal Article
Recenzirano
A seven-year-old Shetland ewe presented with a history of chronic weight loss, abdominal distension and intermittent abdominal discomfort. Serum protein levels and abdominal ultrasonographic findings ...were suggestive of intestinal adenocarcinoma, and the diagnosis was confirmed on postmortem examination.
Lawsonia intracellularis is an obligate intracellular bacterial pathogen that causes proliferative enteropathy (PE) in pigs. L. intracellularis infection causes extensive intestinal crypt cell ...proliferation and inhibits secretory and absorptive cell differentiation. However, the affected host upstream cellular pathways leading to PE are still unknown. Beta-catenin/Wnt signalling is essential in maintaining intestinal stem cell (ISC) proliferation and self-renewal capacity, while Notch signalling governs differentiation of secretory and absorptive lineage specification. Therefore, in this report we used immunofluorescence (IF) and quantitative reverse transcriptase PCR (RTqPCR) to examine Beta-catenin/Wnt and Notch-1 signalling levels in uninfected and L. intracellularis infected pig ileums at 3, 7, 14, 21 and 28 days post challenge (dpc). We found that while the significant increase in Ki67+ nuclei in crypts at the peak of L. intracellularis infection suggested enhanced cell proliferation, the expression of c-MYC and ASCL2, promoters of cell growth and ISC proliferation respectively, was down-regulated. Peak infection also coincided with enhanced cytosolic and membrane-associated Beta-catenin staining and induction of AXIN2 and SOX9 transcripts, both encoding negative regulators of Beta-catenin/Wnt signalling and suggesting a potential alteration to Beta-catenin/Wnt signalling levels, with differential regulation of the expression of its target genes. We found that induction of HES1 and OLFM4 and the down-regulation of ATOH1 transcript levels was consistent with the increased Notch-1 signalling in crypts at the peak of infection. Interestingly, the significant down-regulation of ATOH1 transcript levels coincided with the depletion of MUC2 expression at 14 dpc, consistent with the role of ATOH1 in promoting goblet cell maturation. The lack of significant change to LGR5 transcript levels at the peak of infection suggested that the crypt hyperplasia was not due to the expansion of ISC population. Overall, simultaneous induction of Notch-1 signalling and the attenuation of Beta-catenin/Wnt pathway appear to be associated with the inhibition of goblet cell maturation and enhanced crypt cell proliferation at the peak of L. intracellularis infection. Moreover, the apparent differential regulation of apoptosis between crypt and lumen cells together with the strong induction of Notch-1 signalling and the enhanced SOX9 expression along crypts 14 dpc suggest an expansion of actively dividing transit amplifying and/or absorptive progenitor cells and provide a potential basis for understanding the development and maintenance of PE.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Methods to protect against radiation-induced lung injury (RILI) will facilitate the development of more effective radio-therapeutic protocols for lung cancer and may provide the means to protect the ...wider population in the event of a deliberate or accidental nuclear or radiological event. We hypothesised that supplementing lipid membranes through nebulization of synthetic lamellar lipids would mitigate RILI. Following pre-treatment with either nebulised lamellar lipids or saline, anaesthetised sheep were prescribed fractionated radiotherapy (30 Gray (Gy) total dose in five 6 Gy fractions at 3-4 days intervals) to a defined unilateral lung volume. Gross pathology in radio-exposed lung 37 days after the first radiation treatment was consistent between treatment groups and consisted of deep red congestion evident on the pleural surface and firmness on palpation. Consistent histopathological features in radio-exposed lung were subpleural, periarteriolar and peribronchial intra-alveolar oedema, alveolar fibrosis, interstitial pneumonia and type II pneumocyte hyperplasia. The synthetic lamellar lipids abrogated radiation-induced alveolar fibrosis and reduced alpha-smooth muscle actin (ASMA) expression in radio-exposed lung compared to saline treated sheep. Administration of synthetic lamellar lipids was also associated with an increased number of cells expressing dendritic cell-lysosomal associated membrane protein throughout the lung.
Abstract Clinically effective gene therapy for Cystic Fibrosis has been a goal for over 20 years. A plasmid vector (pGM169) that generates persistent expression and reduced host inflammatory ...responses in mice has raised prospects for translation to the clinic. The UK CF Gene Therapy Consortium is currently evaluating long-term repeated delivery of pGM169 complexed with the cationic lipid GL67A in a large Multidose Trial. This regulatory-compliant evaluation of aerosol administration of nine doses of pGM169/GL67A at monthly intervals, to the sheep lung, was performed in preparation for the Multidose Trial. All sheep tolerated treatment well with no adverse effects on haematology, serum chemistry, lung function or histopathology. Acute responses were observed in relation to bronchoalveolar cellularity comprising increased neutrophils and macrophage numbers 1 day post-delivery but these increases were transient and returned to baseline. Importantly there was no cumulative inflammatory effect or lung remodelling with successive doses. Molecular analysis confirmed delivery of pGM169 DNA to the airways and pGM169-specific mRNA was detected in bronchial brushing samples at day 1 following doses 1, 5 and 9. In conclusion, nine doses of pGM169/GL67A were well tolerated with no significant evidence of toxicity that would preclude adoption of a similar strategy in CF patients.
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