169 research outputs found
Batch effect exerts a bigger influence on the rat urinary metabolome and gut microbiota than uraemia: a cautionary tale
No full textBackground: Rodent models are invaluable for studying biological processes in the context of whole organisms. The reproducibility of such research is based on an assumption of metabolic similarity between experimental animals, controlled for by breeding and housing strategies that minimise genetic and environmental variation. Here, we set out to demonstrate the effect of experimental uraemia on the rat urinary metabolome and gut microbiome but found instead that the effect of vendor shipment batch was larger in both areas than that of uraemia.
Results: Twenty four Wistar rats obtained from the same commercial supplier in two separate shipment batches underwent either subtotal nephrectomy or sham procedures. All animals undergoing subtotal nephrectomy developed an expected uraemic phenotype. The urinary metabolome was studied using 1 H-NMR spectroscopy and found to vary significantly between animals from different batches, with substantial differences in concentrations of a broad range of substances including lactate, acetate, glucose, amino acids, amines and benzoate derivatives. In animals from one batch, there was a complete absence of the microbiome-associated urinary metabolite hippurate, which was present in significant concentrations in animals from the other batch. These differences were so prominent that we would have drawn quite different conclusions about the effect of uraemia on urinary phenotype depending on which batch of animals we had used. Corresponding differences were seen in the gut microbiota between animals in different batches when assessed by the sequencing of 16S rRNA gene amplicons, with higher alpha diversity and different distributions of Proteobacteria subtaxa and short-chain fatty acid producing bacteria in the second batch compared to the first. Whilst we also demonstrated differences in both the urinary metabolome and gut microbiota associated with uraemia, these effects were smaller in size than those associated with shipment batch.
Conclusions: These results challenge the assumption that experimental animals obtained from the same supplier are metabolically comparable, and provide metabolomic evidence that batch-to-batch variations in the microbiome of experimental animals are significant confounders in an experimental study. We discuss strategies for reducing such variability and the need for transparency in research publications about the supply of experimental animals
Oral dysbiosis initiates periodontal disease in experimental kidney disease
No full textBackground and hypothesis: It is presently unclear why there is a high prevalence of periodontal disease in individuals living with chronic kidney disease. Whilst some have argued that periodontal disease causes chronic kidney disease, we hypothesized that alterations in saliva and the oral microenvironment in organisms with kidney disease may initiate periodontal disease by causing dysbiosis of the oral microbiota. Methods: Experimental kidney disease was created using adenine feeding and subtotal nephrectomy in rats, and by adenine feeding in mice. Loss of periodontal bone height was assessed using a dissecting microscope supported by micro-CT, light, confocal and electron microscopy, and immunohistochemistry. Salivary biochemistry was assessed using NMR spectroscopy. The oral microbiome was evaluated using culture-based and molecular methods, and the transmissibility of dysbiosis was assessed using co-caging and microbial transfer experiments into previously germ-free recipient mice. Results: We demonstrate that experimental kidney disease causes a reproducible reduction of alveolar bone height, without gingival inflammation or overt hyperparathyroidism but with evidence of failure of bone formation at the periodontal crest. We show that kidney disease alters the biochemical composition of saliva and induces progressive dysbiosis of the oral microbiota, with microbial samples from animals with kidney disease displaying reduced overall bacterial growth, increased alpha diversity, reduced abundance of key components of the healthy oral microbiota such as Streptococcus and Rothia, and an increase in minor taxa including those from gram-negative phyla Proteobacteria and Bacteroidetes. Co-housing diseased rats with healthy ones ameliorates the periodontal disease phenotype, whilst transfer of oral microbiota from mice with kidney disease causes periodontal disease in germ-free animals with normal kidney function. Conclusions: We advocate that periodontal disease should be regarded as a complication of kidney disease, initiated by oral dysbiosis through mechanisms independent of overt inflammation or hyperparathyroidism.</p
Novel cardioprotective strategies for the uraemic heart
No full textCardiovascular disease is the leading cause of death in patients with underlying chronic kidney disease (CKD). Up to one third of patients presenting with an acute coronary syndrome have CKD stage 3-5. Outcomes following acute myocardial infarction in patients with underlying CKD remain poor. CKD patients are routinely excluded from clinical trials in novel cardioprotective strategies resulting in a paucity of prospective data on which to base guidelines for clinical practice. The aims of this work were to: • Establish and characterise two models of chronic uraemia in rodents: the subtotal nephrectomy model and the adenine diet model. • Determine the effects of underlying chronic uraemia on myocardial ischaemia tolerance. • Examine pharmacological cardioprotective strategies in the context of underlying uraemia using a PARP inhibitor • Investigate the cardioprotective effects of ischaemic conditioning in the context of uraemia. Ischaemic preconditioning and postconditioning protocols were used in both uraemic and non-uraemic animals in a model of acute myocardial infarction. • Preliminary work, using standard molecular biological techniques, was carried out in order to confirm the putative survival pathways responsible for the effect of preconditioning. • Investigate the effect of combining early and late remote ischaemic preconditioning to identify whether summation of these strategies could provide additional tissue protection in a model of acute kidney injury. The results demonstrate that both models develop a uraemic phenotype. Subtotal nephrectomy animals exhibit reduced ischaemia tolerance. PARP inhibition as a pharmacological post conditioning agent was shown to be ineffective at conferring tissue protection, whereas both ischaemic preconditioning and postconditioning were effective cytoprotective strategies in both non-uraemic and uraemic animals. Furthermore, additional benefit was seen when early and late remote preconditioning were summated in a rodent model of acute kidney injury.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Glycaemic Control Impact on Renal Endpoints in Diabetic Patients on Haemodialysis
No full textObjective. To identify the number of haemodialysis patients with diabetes in a large NHS Trust, their current glycaemic control, and the impact on other renal specific outcomes. Design. Retrospective, observational, cross-sectional study. Methods. Data was collected from an electronic patient management system. Glycaemic control was assessed from HbA1c results that were then further adjusted for albumin (Alb) and haemoglobin (Hb). Interdialytic weight gains were analysed from weights recorded before and after dialysis, 2 weeks before and after the most recent HbA1c date. Amputations were identified from electronic records. Results. 39% of patients had poor glycaemic control (HbA1c > 8%). Adjusted HbA1c resulted in a greater number of patients with poor control (55%). Significant correlations were found with interdialytic weight gains ( < 0.02, = 0.14), predialysis sodium ( < 0.0001, = −1.9), and predialysis bicarbonate ( < 0.02, = 0.12). Trends were observed with albumin and C-reactive protein. Patients with diabetes had more amputations (24 versus 2). Conclusion. Large number of diabetic patients on haemdialysis have poor glycaemic control. This may lead to higher interdialytic weight gains, larger sodium and bicarbonate shifts, increased number of amputations, and possibly increased inflammation and decreased nutritional status. Comprehensive guidelines and more accurate long-term tests for glycaemic control are needed
Glycaemic Control Impact on Renal Endpoints in Diabetic Patients on Haemodialysis
No full textObjective. To identify the number of haemodialysis patients with diabetes in a large NHS Trust, their current glycaemic control, and the impact on other renal specific outcomes. Design. Retrospective, observational, cross-sectional study. Methods. Data was collected from an electronic patient management system. Glycaemic control was assessed from HbA1c results that were then further adjusted for albumin (Alb) and haemoglobin (Hb). Interdialytic weight gains were analysed from weights recorded before and after dialysis, 2 weeks before and after the most recent HbA1c date. Amputations were identified from electronic records. Results. 39% of patients had poor glycaemic control (HbA1c > 8%). Adjusted HbA1c resulted in a greater number of patients with poor control (55%). Significant correlations were found with interdialytic weight gains (P<0.02, r=0.14), predialysis sodium (P<0.0001, r=-1.9), and predialysis bicarbonate (P<0.02, r=0.12). Trends were observed with albumin and C-reactive protein. Patients with diabetes had more amputations (24 versus 2). Conclusion. Large number of diabetic patients on haemdialysis have poor glycaemic control. This may lead to higher interdialytic weight gains, larger sodium and bicarbonate shifts, increased number of amputations, and possibly increased inflammation and decreased nutritional status. Comprehensive guidelines and more accurate long-term tests for glycaemic control are needed
Developing a model for supervising social work students in groups
No full textMuch is written about group supervision in other health care fields; however less attention is paid to this topic in social work. This lack of scholarly attention became obvious to the author when he attempted to begin supervising students in groups and was unable to reference a suitable model or template of group supervision from which to gain ideas or direction. The author therefore decided to develop his own model of group supervision. The following article gives an account of how the author developed this model by critically appraising the relevant policy and theory from a local and national perspective to inform his practice
Assessing the anti-microbial activity of a copper-free foot bath solution: Preliminary results
No full textDigital dermatitis (DD) is the main reason for the lameness in dairy cows (Reichenbach, Jones & Bewley, 2017). Digital dermatitis is caused by different types of bacteria species and results in lesions, mainly on the heels of the rear feet and it affects the skin and causes inflammation in the feet (Palmer and O’ Connell, 2015). Digital Dermatitis affects 70 to 95% of North American farms (Solano, Barkema, Pickel& Orsel, 2017). Foot bath treatments are most commonly used to prevent DD, because treating each animal individually is labour intensive. Data shows that about 38.9% farmers in small operations and 80.8% in large operations use footbath to control DD (Reichenbach,Jones, & Bewley, 2017). Copper is a staple solution for foot baths (Thompson 2015), but copper can be an environmental hazard (Laven 2006). Copper-free options are available, but these have not been fully evaluated (Thompson 2015).This poster won the Vice Provost and Associate Vice-President, Academic award (2020). Advisor: Dr. Renee Prasad, Department of Agriculture
Developing a model for supervising social work students in groups
No full textMuch is written about group supervision in other health care fields;however less attention is paid to this topic in social work. This lack of scholarlyattention became obvious to the author when he attempted to begin supervisingstudents in groups and was unable to reference a suitable model or template ofgroup supervision from which to gain ideas or direction. The author thereforedecided to develop his own model of group supervision. The following articlegives an account of how the author developed this model by critically appraisingthe relevant policy and theory from a local and national perspective to inform hispractice
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