Introduction: Creatine is a nitrogen-containing compound that is found in many supplements that claim to increase muscle mass and there is increasing evidence that creatine supplementation can increase muscle mass in older individuals. Purpose: To evaluate the safety of 12-months creatine supplementation and resistance exercise in older adults by monitoring measures of kidney and liver function, complete blood count, and reports of adverse events. Methods: Older adults (n=70, males 50 years of age or older (39), and post-menopausal females (31) who were not performing resistance exercise were recruited for the study and randomized by computer to creatine (32; 18 males, 14 females) or placebo (38; 21 males, 17 females) groups. Other exclusionary criteria were: presence/history or kidney impairments, consumption of creatine supplement/bone altering drugs, and the presence of fragility fractures. Participants were given creatine or placebo (0.1g/kg/day) consumed before and after resistance training on exercise days and with a meal on non-exercise days. The study used a double-blind, placebo-controlled design. Blood and urine were collected to assess complete blood cell count, liver function indicators (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and Bilirubin), and creatinine clearance (kidney function) at baseline, 4 months, 8 months, and 12 months. A mixed ANOVA was used to determine differences in the kidney and liver measures within and between groups, and chi-square analysis was used to determine if the frequency counts for liver, kidney, and other adverse events were different between groups.

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Background: High serum phosphorus (hPhos) is common in chronic kidney disease (CKD) and increases the risk of metastatic calcification. Guidelines advise patients with hPhos to restrict dietary phoshorus intake to 800-1000mg/day, and compliance with this diet can be challenging. Innovative education may improve compliance. Hypothesis: Intensive dietary education using the Phosphorus Point System Tool© (PPS) will result in lower serum phosphorus levels compared to standard education (SE). Methods: This study compared the effectiveness of the PPS to SE on 1) serum phosphorus, 2) dietary phosphate intake, knowledge and satisfaction in pre-dialysis CKD. Results: The PPS reduced 12 week serum phosphorus by 0.16 mmol/L (95% CI 0.37 to -0.05, p=0.130) when controlling for baseline. Dietary phosphorus and protein intake decreased significantly at week 6 on PPS compared to SE (p= 0.026, p=0.050; respectively). Summary: Although there was a trend indicating the tool may reduce serum phosphorus levels, further research is needed.

Effective early detection and monitoring of patient response to cancer therapy is important for improved patient outcomes, avoiding unnecessary procedures and their associated toxicities, as well as the development of new therapies. Dynamic contrast-enhanced magnetic resonance imaging shows promise as a way to evaluate tumour vasculature and assess the efficacy of new anti-angiogenic drugs. However, unavoidable patient motion can decrease the accuracy of subsequent analyses rendering the data unusable. Motion correction algorithms are challenging to develop for contrast-enhanced data since intensity changes due to contrast-enhancement and patient motion must somehow be differentiated from one another. A novel method is presented that employs a motion-informed intensity correction in order to facilitate the registration of contrast enhanced data. The intensity correction simulates the presence or absence of contrast agent in the image volumes to be registered in an attempt to emulate the level of contrast-enhancement present in a single reference image volume.

Background: High serum phosphorus (hPhos) is common in chronic kidney disease (CKD) and increases the risk of metastatic calcification. Guidelines advise patients with hPhos to restrict dietary phoshorus intake to 800-1000mg/day, and compliance with this diet can be challenging. Innovative education may improve compliance. Hypothesis: Intensive dietary education using the Phosphorus Point System Tool© (PPS) will result in lower serum phosphorus levels compared to standard education (SE). Methods: This study compared the effectiveness of the PPS to SE on 1) serum phosphorus, 2) dietary phosphate intake, knowledge and satisfaction in pre-dialysis CKD. Results: The PPS reduced 12 week serum phosphorus by 0.16 mmol/L (95% CI 0.37 to -0.05, p=0.130) when controlling for baseline. Dietary phosphorus and protein intake decreased significantly at week 6 on PPS compared to SE (p= 0.026, p=0.050; respectively). Summary: Although there was a trend indicating the tool may reduce serum phosphorus levels, further research is needed.

Effective early detection and monitoring of patient response to cancer therapy is important for improved patient outcomes, avoiding unnecessary procedures and their associated toxicities, as well as the development of new therapies. Dynamic contrast-enhanced magnetic resonance imaging shows promise as a way to evaluate tumour vasculature and assess the efficacy of new anti-angiogenic drugs. However, unavoidable patient motion can decrease the accuracy of subsequent analyses rendering the data unusable. Motion correction algorithms are challenging to develop for contrast-enhanced data since intensity changes due to contrast-enhancement and patient motion must somehow be differentiated from one another. A novel method is presented that employs a motion-informed intensity correction in order to facilitate the registration of contrast enhanced data. The intensity correction simulates the presence or absence of contrast agent in the image volumes to be registered in an attempt to emulate the level of contrast-enhancement present in a single reference image volume.

Renal cell carcinoma (RCC) is the commonest urogenital tumor, characterized by increased expression of hypoxia inducible factors (HIFs). During normoxia, HIFα subunits are targeted for proteasomal degradation by the product of the von Hippel Lindau gene (pVHL). In RCC, mutations in the VHL gene allow the HIFα subunits to escape degradation and translocate to the nucleus where they activate transcription of their target genes. Although both HIF1α and HIF2α are upregulated in RCC, it has been suggested that HIF2α plays the dominant role. To further elucidate the function of HIF2α in RCC, we generated a transgenic mouse model that permits temporal stabilization of HIF2α in renal tubular cells. Induction of HIF2α results in the rapid development of renal cysts - a feature observed in RCC. Taken together, these results suggest that HIF2α is a key player in development of RCC and an excellent candidate target for therapy in this disorder.

Hedgehog (HH) signaling controls renal development. Mutations in PTC1, the HH receptor, cause cancer in non-renal tissues. We hypothesized that constitutively active HH signaling is deleterious to renal development in mice with PTC1 deficiency targeted to the metanephric mesenchyme (MM)(Rarb2-Cre;Ptc1 loxP/-, termed Ptc1 mutants). Increased HH signaling in MM of mutant mice was confirmed by qRT-PCR for Ptc1. A decrease in NCAM-positive nephrogenic precursors at E13.5 and WT1-positive glomeruli at E18.5 was found. Increased cortical expression of Foxd1 was observed. At E13.5, a cluster of ectopic cells expressing Raldh2, Ptc2 and Bmp4 accumulated at the presumptive uretero-pelvic junction (UPJ). Magnetic resonance imaging demonstrated an increase in pelvic volume. Constitutive expression of GLI3 repressor via the Gli3Δ699 allele in Ptc1 mutants increased nephron number comparable to wild type mice and decreased pelvic volume compared to Ptc1 mutants. Thus repression of HH activity is required for proper nephrogenesis and patterning of the UPJ.

After a wild-type isolate of Epicoccum purpurascens was exposed to shortwave ultraviolet light, several new strains were recovered which were improved in sporulation, fungicide tolerance, and performance in suppression of white mold caused by Sclerotinia sclerotiorum. The efficacy of E. purpurascens in controlling white mold of snap bean (Phaseolus vulgaris) was assessed in greenhouse and field trials. White mold was significantly reduced in both greenhouse and field trials when 2-4 sprays of E. purpurascens conidial suspensions (in 1% malt extract) were sprayed onto the plant surface during the flowering period. Germination of E. purpurascens conidia on senescent petals was greater than on younger flowers. Addition of malt extract to conidial suspensions improved germination on flowers and increased colonization of emerging flowers. Application of E. purpurascens did not accelerate senescence of bean leaves or affect pod yield of bean in greenhouse trials. Mycoparasitism of S. sclerotiorum by E. purpurascens was found only rarely in in vitro tests and was not observed on flower disks. Production of inhibitory compounds by E. purpurascens was the most important mechanism in suppression of white mold but competition for nutrients also appeared to play a role in biocontrol. The influence of nutrients on conidial germination, growth, sporulation and production of antifungal compounds by E. purpurascens were also investigated.

The generation of macrophages requires the coordinated responses to stimulatory and inhibitory signals that cell receive from their environment. While the up-regulation of macrophage production and survival is essential to fortify the immune system, their down-regulation is also vital to prevent macrophage related diseases and malignancy. Previous studies in goldfish showed that primary kidney macrophages release endogenous growth inducing factors into proliferative phase supernatant, which up-regulate their proliferation and survival. In this thesis, the effect of senescence phase supernatant (collected from goldfish primary kidney macrophage cultures) on goldfish primary kidney macrophages proliferation, survival and its impact on the ability of macrophages to tolerate H2O2 was analyzed. The results showed that the senescence phase supernatant down-regulated the proliferation and survival, and decreased the chemical tolerance of the cells. This indicated that the goldfish primary kidney macrophages promote targeted control of their proliferation and survival by secreting endogenous growth inhibitory factors in the senescence phase supernatant. / Physiology, Cell and Development Biology