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Improved insulin sensitivity and glucose tolerance may be attributable to vitamin D sufficiency. An experimental design was created to investigate the use of phototherapy to increase serum vitamin D levels and improve circulating blood glucose levels in pre-diabetics. Seven participants with a pre-diabetic condition were randomly allocated to either 3 months of phototherapy or no therapy. OGTT, HbA1c, and serum vitamin D levels were assessed before and after treatment. In 2 treatment participants, pre-diabetes status was reduced from combined IFG/IGT to iIFG in one and iIGT in the second, while 1 control participant developed combined IFG/IGT and another, type 2 diabetes. HbA1c values improved in the phototherapy group but not in the controls. Phototherapy also increased serum vitamin D levels in the treatment group but not in the controls. This pilot study suggests that the experimental protocol was effective and it should be implemented in a larger sample size to confirm those trends.

Ultraviolet B (UVB) radiation from the sun is the chief cause of skin cancer and is also involved in the development of Vitamin D in humans. This poses an interesting challenge, especially for people living in locations at mid to high latitudes. Through an integrative research review and controlled testing the amount of UVB humans receive in the landscape has been explored. Two existing computer models along with personal dosimeter badges were used to evaluate how much UVB students at a school in Waterloo, Ontario received under various conditions in February, 2013. Results showed that it is possible to get the equivalent of 1000 I.U. of vitamin D in February in Waterloo under ideal weather conditions, but not in most conditions. With this information, a guide has been created to optimize UVB for outdoor spaces in all seasons that children may use in northern climates. The design guide includes a summary of the geophysical variables that affect how much UVB reaches the earth’s surface and key concepts to understand including the difference between diffuse and direct radiation. This study provides evidence-based research in the area of climate responsive landscape architecture. / Landscape Architecture Canada Foundation

Omega-3 polyunsaturated fatty acids (PUFA) and vitamin D both have anti-cancer effects through common and unique pathways. The hypothesis of this thesis is that the combination of n-3 PUFA with 1,25(OH)2D3 will inhibit breast cancer cell growth in an additive or synergistic manner. A 3X3 factorial design was used to test the combinations of five PUFA treatments (α-linoleic acid (ALA, 18:3n3), eicosapentaenoic acid (EPA, 20:5n3) and docosahexaenoic acid (DHA, 22:6n3), γ-linolenic acid (GLA, 18:3n6) and arachidonic acid (AA, 20:4n6)) with 1,25(OH)2D3 on MCF-7, MDA-MB-231, and MCF-10A cell growth, and determine any potential synergism in combination treatments. MCF-7 and MCF-10A cells responded to PUFA and 1,25(OH)2D3 treatments, but combinations provided no potential synergism. MDA-MB-231 growth was not affected by 1,25(OH)2D3, while combinations treatments involving ALA, EPA, GLA, and AA caused potentially synergistic growth inhibition. This thesis presents the novel observation that PUFA are sensitizing MDA-MB-231 cells to 1,25(OH)2D3 treatment.

Background: Recent research indicates that inadequate vitamin D status may incur increased cancer risk, particularly for breast and colon cancer. Cutaneous generation of vitamin D through direct absorption of summer sunlight is considered the principal source of vitamin D; however, at latitudes above 40ºN, UVB rays are insufficient to permit cutaneous synthesis during winter. Vitamin D can also be obtained from natural and fortified dietary sources and through supplement use, although dietary reference intake values do not seem to compensate for restricted cutaneous synthesis in winter. Objectives: To determine the prevalence of vitamin D insufficiency post-winter and post-summer, to determine the seasonal variation in 25-hydroxyvitamin D (25(OH)D) levels, and to investigate determinants of 25(OH)D concentrations. Methods: A cross-sectional study of vitamin D status post-winter and post-summer was conducted among 49 premenopausal rotating shift nurses at Kingston General Hospital. In each season, vitamin D levels were measured using a radioimmunoassay to quantify serum 25(OH)D from fasting blood samples, and personal, lifestyle, and dietary factors potentially influencing vitamin D levels were assessed from a self-report questionnaire. Nurses were classified as vitamin D sufficient (>30ng/mL) or insufficient (≤30ng/mL). Results: A statistically significant difference was found between mean serum 25(OH)D concentrations post-winter (32.6ng/mL) and post-summer (42.5ng/mL) (p=0.0003). The prevalence of vitamin D insufficiency post-winter was 49% compared to 24% post-summer p=0.02). Tanning bed use was associated with significantly higher winter serum 25(OH)D levels was tanning bed, while controlling for age, BMI, and vitamin D-fortified yogurt consumption (R2=0.41, p=0.007). For summer, predictors of higher serum 25(OH)D levels were supplement use and tanning bed use in the past six months, while controlling for age, BMI, and beef/veal consumption (R2=0.53, p=0.001). Conclusions: Vitamin D insufficiency was prevalent both post-winter and post-summer, but with much higher prevalence post-winter. Controlling for age and BMI, tanning bed use was a determinant of serum 25(OH)D concentrations in both seasons, while fortified yogurt consumption also contributed in winter, and beef/veal consumption and supplement use contributed in summer. These findings support the need to improve vitamin D status among this population, and to increase the dietary reference intake values and supplement recommendations. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2009-09-22 15:35:27.652

Amiodarone (AM) is a potent antidysrhythmic agent which can cause potentially life-threatening pulmonary fibrosis, and N-desethylamiodarone (DEA) is a metabolite of AM that may contribute to the toxicity of AM in vivo. Recent evidence has implicated the involvement of the renin-angiotensin system (RAS) in the initiation and progression of amiodarone-induced pulmonary toxicity. In cultured HPL1A human peripheral lung epithelial cells, we found AM to be converted to DEA minimally (< 2%) after 24 h of incubation, indicating that the HPL1A cell culture model can be used to study the effects of AM and DEA independently. Apoptotic cell death was assessed by annexin-V-FITC (ann-V) staining and by terminal deoxynucleotidyl transferase-mediated 2’-deoxyuridine 5’-triphosphate nick-end labeling (TUNEL), while necrotic cell death was determined by propidium iodide (PI) staining. The percentage of PI positive cells increased over six-fold after 24 h treatment with 20 μM AM (80.8%) compared to control (12.0%), and doubled after 24 h treatment with 3.5 μM DEA (20.4%) compared to control (10.8%). The percentage of ann-V positive cells decreased from 8.26% (control) to 1.56% following 24 h treatment with 10 μM AM and more than doubled after 24 h incubation with 3.5 μM DEA (22.0%) compared to control (9.86%) (p<0.05). Treatment for 24 h with 5.0 μM DEA caused the percentage of TUNEL positive cells to increase from 4.21% (control) to 26.7% (p<0.05). Vitamin E (5 – 20 μM) did not protect against AM or DEA cytotoxicity, as determined by ann-V and PI dual staining. Angiotensin II (100 pM – 1 μM) alone or in combination with AM or DEA did not alter cytotoxicity. Furthermore, the angiotensin converting enzyme inhibitor captopril did not protect against AM or DEA cytotoxicity. In conclusion, in vitro, AM activates primarily necrotic pathways, whereas DEA activates both necrotic and apoptotic pathways, and the RAS does not seem to be involved in AM or DEA cytotoxicity in HPL1A cells. Multiple mechanisms may contribute to the initiation of lung damage observed clinically, due to actions of both AM and its metabolite DEA. Keywords: amiodarone, desethylamiodarone, vitamin E, renin-angiotensin system / Thesis (Master, Pharmacology & Toxicology) -- Queen's University, 2009-11-26 13:57:09.65