Abstract not available

Includes bibliographical references (leaves 226-273.) Investigates the regulation of the expression of CYP27B1, CYP24 and vitamin D receptor (VDR) mRNA, both in the bone and in the kidney, with the aim to determine whether the regulation of the vitamin D metabolism in the bone is independent from that in the kidney. The effects of age, dietary calcium and vitamin D status on the expression of these genes in both the kidney and the bone, as well as on a number of biochemical factors known to regulate the renal metabolism of 1,25D, such as PTH, calcium and 1,25D itself, were examined. CYP27B1 mRNA expression was also studied in histological sections of rat femoral bone.

Includes bibliographical references. Electronic publication; Full text available in PDF format; abstract in HTML format. Investigates the regulation of the expression of CYP27B1, CYP24 and vitamin D receptor (VDR) mRNA, both in the bone and in the kidney, with the aim to determine whether the regulation of the vitamin D metabolism in the bone is independent from that in the kidney. The effects of age, dietary calcium and vitamin D status on the expression of these genes in both the kidney and the bone, as well as on a number of biochemical factors known to regulate the renal metabolism of 1,25D, such as PTH, calcium and 1,25D itself, were examined. CYP27B1 mRNA expression was also studied in histological sections of rat femoral bone. Electronic reproduction.[Australia] :Australian Digital Theses Program,2001.

Bibliography: leaves 119-136.

The activation of 1,25D-dihydroxyvitamin D3 (1,25D) is catalysed by the enzyme 25-hydroxyvitamin D-1ƒhydroxylase (CYP27B1) in the kidney, which is the primary producer of 1,25D in the body. Although the synthesis of 1,25D by CYP27B1 and the catabolism of 1,25D by 25-hydroxyvitamin D-24-hydroxylase (CYP24) also take place in the bone, the significance of the bone cell-specific metabolism of vitamin D remains largely unknown. This thesis investigates the regulation of the expression of CYP27B1, CYP24 and vitamin D receptor (VDR) mRNA, both in the bone and in the kidney, with the aim to determine whether the regulation of the vitamin D metabolism in the bone is independent from that in the kidney. The effects of age, dietary calcium and vitamin D status on the expression these genes in both the kidney and the bone, as well as on a number of biochemical factors known to regulate the renal metabolism of 1,25D, such as PTH, calcium and 1,25D itself, were examined. CYP27B1 mRNA expression was also studied in histological sections of rat femoral bone. Furthermore, CYP27B1, CYP24 and VDR mRNA expression were also identified in specific regions of the rat femur and in a number of bone cell lines, with the aim to identify the bone cell types that have the capacity to metabolise and/or to respond to vitamin D. The age-related decrease in the circulating levels of 1,25D detected in animals ranging in age from 3 weeks to 2 years old, was a direct result of a reduction in the expression of CYP27B1 mRNA and an increase in the expression of CYP24 and VDR mRNA in the kidney. In contrast, the expression of CYP27B1 and CYP24 mRNA in the bone is high from 3 to 15 weeks of age, which is the period of rapid growth and development. The expression of CYP27B1 mRNA in the bone was positively correlated with the circulating levels of calcium throughout aging, which suggests that the 1,25D produced in the bone may be involved in the mineralisation process. The positive correlation found between the expression of CYP27B1 and CYP24 mRNA in the bone was in contrast with the negative correlation found between the expression of these two enzymes in the kidney. This suggests that the 1,25D produced locally in the bone, rather than the 1,25D produced in the kidney, is the primary determinant of the CYP24 activity in the bone. In vitamin D-deplete animals, fed a 0.1% calcium diet (D(-)/LC), the expression of CYP27B1 mRNA was induced and the expression of CYP24 mRNA was suppressed in the kidney. In contrast, both the expression of CYP27B1 and CYP24 mRNA were low in the bones of these D(-)/LC animals. When vitamin D-deplete animals were fed a 1% calcium diet (D(-)/HC), the expression of both CYP27B1 and CYP24 mRNA was high in the bone, which was in direct contrast with the low expression of these genes detected in the kidney. Besides this, a positive correlation was found between the expression of CYP27B1 mRNA in the bone, serum calcium levels and bone mineral volume (BV/TV) in the epiphysis, which supports the findings for the age study that the locally produced 1,25D may be involved in the promotion of bone mineralisation. Although serum PTH levels was positively correlated with the expression of CYP27B1 mRNA in the kidneys of hypocalcaemic animals, there was no such relationship detected between the levels of serum PTH and the expression of CYP27B1 mRNA in the bone. This finding suggests that the regulation of the expression of CYP27B1 mRNA in the bone is different from the regulation found in the kidney. The identification of CYP27B1 mRNA in osteoblasts-like cells, taken together with the associations between serum calcium and CYP27B1 mRNA expression in the previous studies, suggests that 1,25D produced in osteoblasts may play a significant role in the bone mineralisation process. The detection of CYP27B1 mRNA expression in a number of bone marrow cells suggests that locally produced 1,25D may also play a role in the growth and differentiation of hematopoietic cells. / Thesis (Ph.D.)--School of Molecular and Biomedical Science, 2003.

<p>Syfte: Syftet med föreliggande uppsats är att mäta och beskriva hälsorelaterad livskvalitet hosnjurtransplanterade patienter, tolv till 24 månader efter transplantationen, i relation till den svenskanormalpopulationen. Vidare kommer korrelationen mellan livskvalitet och demografiska faktorer attundersökas. Metod: 54 patienter som njurtransplanterats för tolv till 24 månader sedan har deltagit i studien.Hälsorelaterad livskvalitet undersöktes med hjälp av SF-36 Hälsoenkät. Resultat: Undersökningsgruppen ansersig vara mer fysiskt begränsade och uppger i större utsträckning att de är begränsade att utföra arbete eller andrafysiska aktiviteter på grund av fysisk ohälsa, jämfört med motsvarande åldersgrupp i normalpopulationen.Dessutom värderar undersökningsgruppen sitt generella hälsotillstånd lägre än jämförelsegruppen. Det finnsingen signifikant skillnad i hälsorelaterad livskvalitet mellan njurtransplanterade kvinnor och män med avseendepå fysisk hälsa. Däremot skattar njurtransplanterade män sitt psykiska välbefinnande högre ännjurtransplanterade kvinnor (m=82,7/m=71,6). Ingen korrelation har kunnat påvisas beträffande ålder ochhälsorelaterad livskvalitet hos den valda patientgruppen. Slutsats: Njurtransplanterade patienter värderar sinhälsorelaterade livskvalitet lägre i flera aspekter än den svenska normalpopulationen. Detta gäller framför alltpatienternas fysiska hälsa. Skillnaderna är inte lika uttalade när det gäller psykisk hälsa.</p>

Clinicians lack appropriate non-invasive methods to be able to predict, diagnose, and reduce the risk of rejection in the years following kidney transplantation. Protocol biopsies and monitoring of serum creatinine levels are the most common methods of monitoring graft function after transplant; however, they have several negative aspects. Use of traditional factors regarding donors and recipients such as Human Leukocyte Antigen (HLA) DNA typing, pre-transplant anti-HLA antibody levels, and basic demographics (age, ethnicity/race, gender), has proved inadequate for post-transplant graft monitoring past the first few years. We propose that by utilizing immunologic factors available to clinicians across the United States, development of a non-invasive model for predicting renal graft outcome will provide a useful tool for post-transplant patient monitoring. We advocate an expanded model which incorporates both the traditional factors, as well as new factors, which have shown promise in predicting kidney outcome and are widely available for testing using commercial kits. These additional factors include major histocompatibility complex class I chain-related gene A (MICA) typing of donor and recipient, degree of matching for killer cell immunoglobulin-like receptors (KIRs) between donor and recipient, detection of MICA antibodies, and soluble CD30 level (sCD30). This proposed graft-function prediction model is the first to include all of these factors. Using multi-center data from adult recipients of standard-criteria deceased-donor (SCD) kidneys, we were able to construct models, containing the traditional factors only, for prediction of outcome at 1 year and 3 years post-transplant. Using single-center data from adult recipients of standard-criteria deceased-donor kidneys, we developed comparison models containing traditional factors only, as well as, expanded models containing the new suggested variables for prediction of outcome post-transplant. These additional variables, when incorporated into the expanded models provided greater positive predictive values, greater negative predictive values, and lower false negative rates for graft outcome at 1 year and at 3 years post-transplant than the models utilizing traditional factors only. Our results indicate that evaluation of sCD30, MICA and KIR as part of routine protocol testing, is helpful to clinicians for predicting risk of kidney graft rejection.

Thesis (M.Sc.)--Memorial University of Newfoundland, 2004. / Bibliography: leaves 147-168.

This thesis describes and evaluates an optical method utilizing ultra violet (UV) absorbance for on-line monitoring of haemodialysis treatment. Increased efficiency of haemodialysis treatment is considered to correlate to decreased morbidity and mortality when urea clearance (Kt/V) is elevated. However, further improvements have not been achieved at a higher Kt/V. The mortally rate in the haemodialysis population is still high (27% in Sweden). Urea as the clinical marker is under discussion, partly due to urea being non-toxic, but also that the uraemic syndrom is the result of a cumulative retention of innumerable involved compounds. On-line monitoring systems based on urea determination for improved dialysis efficiency have been suggested and developed in different settings over the last two decades, but have not achieved worldwide utilisation as routine clinical equipment. This thesis demonstrates that the UV-technique utilising 280, 285 and 297 nm is capable of estimating dialysis efficiency in therms of Kt/V, nutritional status in terms of protein catabolic rate (PCR), with the same characteristics as existing methods. One novel finding using UV-absorbance with high sampling rates is the on-line visualisation of the clearance process for following variations in clearance caused by clinical events and disturbances as well as during and after adjustments. The fact that the UV-absorbance technique does not measure urea directly but has high correlation to several other both UV-absorbing and not-absorbing solutes makes it suitable to reflect a more overall solute retention process. Finally, a new efficiency parameter based on the calculation of the area under UV- curve (clearance curve), is suggested to reflect the total removal of some solutes. In summary the UV-technique has the potential to be an additional tool to evaluate improvements of dialysis efficiency, which may result in decreased morbidity, longer life span and enhanced quality of life for the haemodialysis patients.

Diabetic nephropathy is a chronic kidney disease and one of the more severe complications from diabetes mellitus type 2. The glomerular and tubular dysfunctions usually lead to end stage renal disease and the treatments of these patients (dialysis, kidney transplants) are a huge economic burden for the society. Due to an epidemiologic increase of type 2 diabetes, conventional diagnostic markers like creatinine and albumin are not sufficient, since they are only able to identify already existing kidney damage. With targeted metabolomics, the analysis of small molecules produced from metabolism, this project aimed at finding novel and more sensitive metabolic biomarkers from several different classes of metabolites. The different assays were performed with flow injection analysis, high performance liquid chromatography, gas chromatography and mass spectrometry, and with principal component analysis and discriminant analysis, up-and down-regulated metabolites could be identified and their respective biochemical pathways, if possible, explained. In diabetics significantly elevated concentrations of very long chain fatty acids (impaired peroxisomal β-oxidation), urinary sugars and acylcarnitines in plasma could be recognized. Markers indicating kidney damage included significantly increased plasma concentrations of asymmetric dimethylarginine (inhibition of nitric oxide synthase resulting in decreased endothelial functionality) and histamine (indication of uremic pruritus). Oxidative stress was also found to be a potential prognostic marker as indicated by the raised methionine-sulfoxide to methionine ratio in nephrotic patients. To summarize, this project succeeded in identifying metabolic biomarkers both for diabetes type 2 and nephropathy, which in the future might become important tools in slowing down progression or diagnosing these diseases.