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1
Oreffo, R. O. C. "Vitamin A and bone." Thesis, University of Oxford, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376950.
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Naja, Roy Pascal. "The role of Vitamin D metabolic enzymes in bone development and repair /." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=115860.
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The CYP27B1 enzyme that synthesizes 1alpha,25-(OH) 2D, is expressed in chondrocytes, suggesting that local production of 1alpha,25-(OH)2D could play an autocrine or paracrine role in the differentiation of these cells. To test this hypothesis, we have engineered mutant mice that do not express the Cyp27b1 gene in chondrocytes. This led to increased width of the hypertrophic zone of the growth plate at E15.5, increased bone mass in neonatal long bones, and increased expression of the chondrocytic differentiation markers Indian Hedgehog and PTH/PTHrP receptor. VEGF mRNA levels were decreased, accompanied by decreased PECAM-1 immunostaining, suggesting a delay in vascularization. We have also engineered mice overexpressing a Cyp27b1 transgene in chondrocytes. The transgenic mice showed a partial mirror image phenotype compared to the tissue-specific inactivation model. These results support an autocrine/paracrine role of 1alpha,25-(OH) 2D in endochondral ossification and chondrocyte development in vivo.The CYP24A1 enzyme is involved in the catabolic breakdown of 1alpha,25-(OH)2D but also synthesizes the 24R,25-(OH) 2D metabolite. Studies in chicken suggest a role for 24R,25-(OH) 2D in fracture repair. We induced stabilized transverse mid-diaphysial fractures of the tibia in four-month-old wild-type and Cyp24a1-deficient mice. Examination of the callus sections showed delayed hard callus formation in the homozygous mutant animals compared to wild-type littermates. RT-qPCR showed perturbed levels of type X collagen transcripts in mutant mice at 14 and 21 days post-fracture, reflecting the delayed healing. Rescue of the impaired healing by subcutaneous injection of 24R,25-(OH)2D3 normalized the histological appearance of the callus, static histomorphometric index and type X collagen mRNA expression, while 1alpha,25-(OH)2D 3 did not. These results show that Cyp24a1 deficiency delays fracture repair and strongly suggest that vitamin D metabolites hydroxylated at position 24, such as 24R,25-(OH)2D, play an important role in the mechanisms leading to normal fracture healing.
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Anderson, Paul Hamill. "The regulation of Vitamin D metabolism in the kidney and bone." Title page, contents and abstract only, 2002. http://web4.library.adelaide.edu.au/theses/09PH/09pha5486.pdf.
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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.
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Sparks, Patricia Lynne. "The relationship of vitamin D and selected nutrient intakes, sex hormone binding globulin and markers of bone turnover to bone mineral density in exercising and non-exercising postmenopausal women taking or not taking HRT." Diss., The University of Arizona, 2001. http://hdl.handle.net/10150/289711.
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The loss of bone mineral density (BMD) plays a major role in the increased incidence of osteoporosis in aging women and, consequently, strategies to maintain BMD are critical to quality of life for these women. The role of vitamin D in the accrual and maintenance of bone mineral and its relationship to the incidence and severity of osteoporosis is not well understood. By measuring serum and intake levels this study investigates the relationship of vitamin D to baseline BMD and changes in regional and total body BMD over 1 y. The role of sex hormone binding globulin (SHBG) is also investigated. Because SHBG binds with both estrogen, an antiresorptive agent, and testosterone, a bone formation agent, lower serum SHBG concentrations may promote a greater bioavailability of estrogens and androgens, which could decrease resorption, stimulate formation and increase BMD. Women who were 3-10 y postmenopausal, aged 55 ± 5.1 y, and taking or not taking hormone replacement therapy (HRT) were randomized into exercise and non exercise groups: (1) No HRT, no exercise; (2) HRT, no exercise; (3) No HRT, exercise; and (4) HRT, exercise. The number of subjects per group at the end of one year was 25, 19, 27 and 20, respectively. The thrice weekly exercise regimen, consisting mainly of weight lifting and weight bearing activities, lasted for 1 y. Vitamin D deficiency was found in 3% of the subjects, Serum 25(OH)D₃ concentrations had inverse relationships with changes in BMD in the femoral neck (P < 0.05) and trochanter (P = 0.07). When subjects were grouped according to HRT status, BMD at baseline and one 1 y was never positively related to serum 25(OH)D₃ concentrations in HRT users, Subjects having greater than 80 nmol/L 25(OH)D₃ had significantly decreased concentrations of serum osteocalcin and urinary deoxypyrodinoline (Dpd) crosslinks (P < 0.05). Exercise had no effect on serum content of 25(OH)D₃. Serum concentrations of SHBG were not significantly related to BMD at any site, nor did they show a decrease with exercise even when HRT status was taken into account. Significant inverse relationships (P < 0.05) were found between SHBG, sex hormone indices (Estrone/SHBG; Estradiol/SHBG) and bone turnover markers, osteocalcin and Dpd crosslinks/creatinine.
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Clements, M. R. "The physiology economy of vitamin D." Thesis, Imperial College London, 1988. http://hdl.handle.net/10044/1/47002.
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Hall, Judith. "Physiology and pathophysiology of vitamin D metabolism." Thesis, University of Newcastle upon Tyne, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.377459.
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Barron, Mary Anne. "Vitamin K deficiency in paediatric bone marrow transplantation." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0008/MQ40822.pdf.
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Laird, Eamon John. "Vitamin D status and metabolism : implications for bone health." Thesis, Ulster University, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.674922.
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In addition to its established role in bone health, vitamin D (2S(OH)D) may also have a role in modulating immune function and early life development. Despite recent advances, there is a lack of consensus with regards to the optimal vitamin D cut-offs for multiple health outcomes and this uncertainty is further compounded by the wide measurement variability for the vitamin. Consequently, the work described in this thesis aimed to explore these areas of controversy. Using data from ongoing studies at the University of Ulster, a comparison study (n 131), of vitamin D status in the two most widely used methods (liquid chromatography mass spectrometry (LC-MS/MS) and enzyme immunoassay (ELISA)) of measurement was undertaken. Significant variation in definition of status was observed, with overestimation of vitamin D concentrations by ELISA >2S% compared to LC-MS/MS. In a second study, using LC-MS IMS, the vitamin D status and markers of bone health of a sample of older Irish adults (n 1936) form the Trinity, Ulster Department of Agriculture (TUDA) study was assessed. A total of 16% were vitamin D deficient «2Snmolll) and 42% were deemed to be insufficient (2S-S0nmolll). These levels of nonoptimal vitamin D concentrations were coupled with high rates of impaired bone health (31 % classified as osteopenic and 18% osteoporotic from BMD measures). A higher prevalence of impaired bone health and vitamin D inadequacy was observed in females compared to males while individuals who were vitamin D deficient or insufficient were significantly more likely to be osteoporotic than those who were sufficient (>SO nmol/l). These data provide additional evidence to support the recent 10M recommendation of a 2S(OH)D concentration of 50 nmol/l for optimal bone health. In a third study, the association between vitamin D status, immune markers of inflammation and the ratio of pro: anti-cytokines was investigated in a sub-sample of TUDA participants (n 998). Vitamin D was significantly correlated with pro-inflammatory markers and a 25(OH)D concentration >75nmol was associated with an improved inflammatory (profile as determined by the pro:anti cytokine ratio) compared to individuals with a 25(OH)D status <25 or 25-75nmol/l. In a fourth study, vitamin D status was assessed within a sample (n 260) of pregnant women from a sunny equatorial country (5degS) (Seychelles). Maternal vitamin D status was observed to be >75nmol/l through all sample periods of pregnancy and was significantly associated with higher birth weight and length with no apparent upper limit of effect. These results demonstrate the importance of optimal vitamin D status during pregnancy and the need for adequate dietary recommendations in order to achieve this level within far latitude populations that are exposed to low UVB sun light. In conclusion, the results within the current thesis suggest concentrations of vitamin D greater than recently recommended cut-offs for bone health (50nmol/l) are associated with extra-skeletal health benefits. Furthermore, consideration needs to be given to the current vitamin D dietary recommendations within the UK and Ireland in order to address the high level of deficiency observed in the older adult population and to achieve the optimal vitamin D concentration in terms of benefits for bone health, immune function and neonatal health outcomes for the whole population
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Blackwell, Penelope J. "Bone turnover in hyperprolactinaemic states." Thesis, University of Nottingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366417.
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Charras, Guillaume. "Cellular mechano-transduction in bone." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269783.
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Shum, Laura C. "Mitochondrial Metabolism in Bone Physiology and Pathology." Thesis, University of Rochester, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10792056.
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Worldwide, 1 in 3 women and 1 in 5 men over age 50 will experience fractures due to a decline in bone quality. Elucidating the mechanisms for declining bone quality can lead to better therapeutics. A vital, yet overlooked aspect of bone health is the role of mitochondrial metabolism in both bone physiology and pathology. We have found that the ability of stem cells to differentiate into bone forming osteoblasts is sensitive to mitochondrial dysfunction, and therefore preserving mitochondrial function is essential to maintaining bone quality. In human patient samples, we found that osteogenesis following a spinal fusion is correlated with mitochondrial function of bone marrow stem cells. While the decline of bone with aging has been well studied, we were the first to find a concomitant decline in mitochondrial function in bone tissue. The most common mechanism of mitochondrial dysfunction is opening of the mitochondrial permeability transition pore (MPTP), a non-selective proteinaceous pore on the inner mitochondrial membrane, positively regulated by the protein cyclophilin D (CypD). Our CypD knockout mouse model has protected mitochondrial function in bone tissue and no decline in bone quality during aging. While we did show that protecting mitochondrial function is beneficial to age-associated bone loss, our ovariectomy model in the CypD knockout mouse did not show any protection. Thus, age-related and estrogen-related bone loss are likely controlled through different mechanisms. Overall, this work has shown the importance of mitochondrial metabolism in bone health and should be further explored as a new avenue for therapeutic interventions.
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Bitton, Ariel. "The role of vitamin D and vitamin D analogues in gene regulation and potentiation of immune response to «Mycobacterium tuberculosis»." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=95188.
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1,25-dihydroxyvitamin D3 (1,25D) is the hormonally active form of vitamin D, a key factor in calcium (Ca2+) homeostasis. 1,25D has also been shown to mediate a number of other physiological mechanisms. Here we pay special attention to the immunoregulatory properties of 1,25D, and its role in stimulating immune responses against pathogenic infection. The innate branch of the immune system is responsible for the rapid, non-specific host response against pathogenic infection. 1,25D induces the expression of antimicrobial peptides, which serve as the vanguards of innate immune response as predicted in vitro by human monocytic (THP-1), as well as intestinal epithelial cell lines (SW480, HT-29). Furthermore, antimicrobial peptides regulate a number of immune responses such as wound healing and cytokine induction. Butyrate is a histone deacetlyase inhibitor (HDI), and a natural constituent of the gut, which is known to possess significant gene regulatory properties, including the induction of antimicrobial peptide expression. The purpose of this study is to investigate how therapy, combining 1,25D with the underlying gene regulation activity of butyrate, may function in stimulating immune responses against infection, particularly with regard to Mycobacteria tuberculosis. Given the potential that either butyrate or 1,25D alone promotes the production of antimicrobial peptides, this combination therapy shows promise in developing a novel approach to treat infection by enhancing antimicrobial gene expression. By modifying the side chain of 1,25D to possess HDI-like properties, it may be possible to develop bifunctional vitamin D analogues with enhanced therapeutic value to be used against mycobacterial infection.1,25-dihydroxyvitamin D3 (1,25D) est la forme active de l'hormone vitamine D, un facteur clé dans l'homéostasie du calcium (Ca2 +). 1,25D est aussi un facteur clé dans plusieurs autres mécanismes physiologiques. Dans cette étude, nous sommes particulièrement intéressés par les propriétés immuno-régulatrices de 1,25D et son rôle dans la stimulation de réactions immunitaires contre les infections pathogènes. La branche innée du système immunitaire produit la réaction immédiate non-spécifique de l'hôte contre l'infection pathogène. 1,25D provoque l'expression de peptides antimicrobiens qui constituent l'avant-garde de la réaction immunitaire innée dans les cellules monocytes humaines (THP-1), ainsi que les cellules épithéliales intestinales (SW480, HT-29). En outre, les peptides antimicrobiens régissent un nombre important de réactions immunitaires telles que la cicatrisation de plaies et la production de cytokines. Butyrate est un inhibiteur d'histone déacetylase (IDH) et une substance naturelle de l'intestin, connu pour posséder d'importantes propriétés régulatrices de gènes y compris l'expression de peptides antimicrobiens. Le but de cette étude est d'examiner comment un traitement combinant 1,25D avec l'activité régulatrice génétique sous-jacente de butyrate peut agir comme stimulant de réactions immunitaires contre des infections, en particulier en ce qui concerne la bactérie Mycobacterium tuberculosis. Étant donné le potentiel individuel que le butyrate ou la 1,25D possède à favoriser la production de peptides antimicrobiens, cette conjugaison de thérapies pourrait aider au développement d'une nouvelle approche pour traiter les infections en renforçant l'expression des gènes antimicrobiens. En modifiant la chaîne latérale de 1,25D de sorte qu'elle possède des propriétés similaires à l'IDH, il serait possible de développer des analogues bi-fonctionnels de la vitamine D ayant une valeur thérapeutiq
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Wakley, Glenn Keith. "Space flight and bone." Thesis, University of Bristol, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.246296.
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Bannerman, Alistair L. "Imaging the development of a bone-to-bone ligament construct." Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/6425/.
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Ligament injuries are commonplace, with poor native healing leaving injury sites exposed to instability and further damage. A number of surgical methods have been established for reconstruction using a range of materials, but these have a high failure rate and a number of undesirable side-effects. Much recent work has been focused on the development of tissue engineered ligament grafts. One of the major challenges for this is the formation of an effective ligament-bone interface. In native tissue a multi-phase interface enables smooth transfer of forces between the mechanically mismatched bone and ligament tissue, however this has proved hard to replicate. Previous work has developed a bone-bone ligament construct model intended to emulate the native interface through formation of a mineralised region by soluble cement anchors. Development and optimisation of the model has seen an increasing mechanical strength, but the mechanisms involved are poorly understood. This study investigates the development of the ligament construct through the use of multiple complimentary imaging techniques to provide information on the biological, chemical, and topological development of the construct as it forms from initially homogeneous and separate materials to a complex non-homogeneous system.
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New, Susan A. "An epidemiological investigation into the influence of nutritional factors on bone mineral density and bone metabolism." Thesis, University of Aberdeen, 1995. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU602275.
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A food frequency questionnaire (FFQ) was developed for a study investigating dietary influences on bone mineral density (BMD) and bone metabolism (BM). The percentage contribution of food groups to nutrients of interest were identified from 20 7d weighed records (WR) and incorporated to form a 98 food item FFQ. The FFQ was validated against a further 20 7d WR, and the short (6 weeks) and long-term (1 year) reproducibility tested. Mean nutrient intakes by 7d WR and FFQ, and initial and repeat FFQ were similar and cross-classification showed few women to be grossly misclassified. Information was also collected on past intakes of milk and fruit, weight, height, smoking, social class and physical activity. The effect of dietary intake on BMD was investigated in 994 healthy premenopausal women aged 45-49 years. BMD was measured using dual energy X-ray absorptiometry at the lumbar spine (LS) and hip (femoral neck [FN], trochanter [FT], Wards [FW]). Nutrient intakes were adjusted for energy intake by calculating the residual from regression analysis. Positive relationships were found between BMD and intakes of Mg, K, Zn and vitamin C, remaining significant after adjustment for confounding variables. LS BMD was lower in women who reported a low intake of milk and fruit in their childhood and early adulthood. The influence of dietary intake on BM was assessed in 62 healthy peri-menopausal women aged 45-55 years. Bone resorption was determined by urinary excretion of pyridinoline (Pyd) and deoxypyridinoline (Dpd) using reversed-phase HPLC, and bone formation by serum osteocalcin (OC) using an ELISA. Energy adjusted intakes of K, Mg, carotene and vitamin C were negatively associated with Pyd and Dpd concentrations, remaining significant after appropriate adjustment including menopausal status. OC was positively associated with energy intake and weight. Twenty-six women were measured after one year, but no relationships were found between changes in bone mass and baseline bone metabolism markers or dietary intake. Results suggest there is a higher bone mass and lower bone resorption in women with high intakes of K, Mg, carotene and vitamin C, independent of confounding factors. Positive effects on acid-base balance, Mg deficiency or the role of vitamin C in collagen liydroxylation may provide some explanations for these findings.
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Johansson, Sara. "Vitamin A and Osteoporosis : Experimental and Clinical Studies." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4677.
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Snellman, Greta. "Boning up on Vitamin D : Observational Studies on Bone and Health." Doctoral thesis, Uppsala universitet, Ortopedi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-159873.
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The primary function of vitamin D in humans is to maintain sufficient circulating calcium concentrations. Low vitamin D levels could result in excessive calcium resorption from bone. Vitamin deficiency may therefore decrease bone mineral density (BMD), resulting in an increased risk of fracture. This thesis sought to determine the association between vitamin D intake and bone health and to estimate circulating levels of vitamin D optimal for bone health without increasing the risk for non-bone disease. Furthermore, the thesis assessed the difference in performance between common serum vitamin D assays and the genetic influence of vitamin D status. In prospective population-based cohorts, blood concentrations <40 nmol/L (lowest 5%) increased the risk of fracture in elderly men. Low levels were further associated with a slight decrease in lumbar spine BMD. Both high (>98 nmol/L) and low (<46 nmol/L) vitamin D levels were associated with higher cancer and overall mortality. In another cohort, also of older men and women, no association was found between vitamin D levels and fracture. Low vitamin D levels were weakly associated with decreased total body BMD in men but not in women. Dietary intake of vitamin D over a 20-year period in more than 60,000 Swedish women was not associated with osteoporosis or fracture, regardless of calcium intake. During summer, dietary vitamin D intake and other life style habits are of minor importance for the variation in vitamin D levels relative to sun exposure and genes. In summer time, genes explain about half of the variation in vitamin D levels, but none of the variance in winter time. The variability between vitamin D assays was substantial. Three assays classified 8, 22 and 43% of the same study population as vitamin D insufficient if <50 nmol/L was set as the insufficiency level. Based on the results in this thesis, low 25(OH)D levels and low dietary vitamin D intake are not a major cause of fractures in community-dwelling elderly Swedish women and men. Differences in assay performance and potential negative health outcomes of high 25(OH)D levels need to be considered.
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Outila, Terhi. "The effect of vitamin D status on calcium and bone metabolism." Helsinki : University of Helsinki, 2001. http://ethesis.helsinki.fi/julkaisut/maa/skemi/vk/outila/.
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Högström, Magnus. "Vitamins, fatty acids, physical activity and peak bone mass." Doctoral thesis, Umeå universitet, Kirurgisk och perioperativ vetenskap, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1451.
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Osteoporosis is a disease characterized by low bone mineral density, deteriorated bone microstructure and increased fracture risk. About 50% of all women and 25% of all men will have an osteoporotic fracture. Given that there is no effective cure in established osteoporosis, prevention is of high importance. Bone mineral density (BMD) is accumulated during childhood and adolescence with a peak at about 20 years of age. Peak BMD has been suggested to explain at least half of the variation in BMD up to old age. Thus, to increase peak BMD could decrease the risk of later fractures. The purpose of the present thesis was to investigate the influence of physical activity, vitamins A and D, and fatty acids on peak bone mass in men. The influence of physical activity on bone accrual was studied in two cohorts. In the first cohort 46 ice hockey players, 18 badminton players and 27 controls, all 17 years of age at baseline, were followed for four years. During the follow up the badminton players gained more bone mass at the hip compared to both the ice hockey players and controls. In the second cohort the associations between physical activity and BMD were investigated in 62 female and 62 male young medical students. The estimated high impact activity per week was associated with bone mass at all sites in the male medical students (r=0.27-0.53, p<0.05). In the female cohort different estimates of physical activity were not related to bone mass at any site. In both males and females correlations between bone mass and body constitution parameters were observed. Levels of vitamin D3, vitamin D2, retinol, retinol-binding-protein-4 (RBP-4) and fatty acids were measured in 78 young men with a mean age of 22.6 years. BMD at various sites were measured using Dual-Energy X-ray absorptiometry. Levels of vitamin D3 showed a significant positive association with all BMD sites and also lean body mass (r=0.23-0.35, p<0.05). Levels of vitamin D2, however, showed a significant negative correlation with BMD of the total body (r=-0.28, p=0.01) and spine (r=-0.27, p=0.02). There was also a significant negative relationship between levels of vitamin D3 and D2 (r=-0.31, p=0.006). Concentrations of n-3 (omega-3) fatty acids showed a positive association with BMD at the total body (r=0.27, p=0.02) and spine BMD (r=0.25, p=0.02). There was also a positive association between levels of n-3 fatty acids and changes in BMD of the spine between 16 and 22 years of age (r=0.26, p=0.02). The significant associations found seemed to be related mostly to the concentration of the n-3 fatty acid docosahexaenoic acid. Levels of retinol and RBP-4 were not related to BMD but to levels of osteocalcin, which is a marker of bone formation. This association disappeared when adjusting for the influence of abdominal fat mass. In summary, the present thesis suggests that many modifiable factors may influence the accumulation of peak bone mass in males, such as physical activity, vitamins, and fatty acids. Further studies are needed to investigate whether optimizing these factors in youth may decrease the risk of osteoporosis later in life.
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Romero, Rodney Gray. "The histology of bone and its piezoelectric characteristics." Thesis, Kingston University, 1986. http://eprints.kingston.ac.uk/20508/.
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An investigation into the effects of micro electric currents on the material of bone is presented along with a review of the ideas and concepts associated with bone’s response to load and the alleged piezoelectric phenomena. A comparison is made between the structure of bone, its strength and stress generated potential. Evidence is forwarded to show that micro currents may influence the behaviour of bone material and it is demonstrated that these effects may be understood through reference to the limiting molar conductivities of the ions in the material and the solutions used.
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Finch, Sarah L. "Postnatal vitamin D supplementation normalizes neonatal bone mass following maternal dietary vitamin D deficiency in the guinea pig." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=100246.
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Since vitamin D deficiency is common at birth, the objective of this study was to test if postnatal vitamin D supplementation would normalize bone mineralization. Forty guinea pigs were randomized to receive a diet with or without vitamin D3 during pregnancy. Newborn pups were randomized to receive 10 IU of vitamin D3 or a placebo daily until d28. Measurements at birth and d28 included whole body and regional bone mass, osteocalcin and deoxypyridinoline, plus biomechanical testing of excised tibias and femurs. Offspring from deficient sows had lower body weight, whole body and tibia bone mineral content (BMC) and lower osteocalcin and biomechanical integrity. By d28 this group had lower whole body bone density and femur BMC, unless supplemented. Interactions with gender showed males continued to have low 25(OH)D despite supplementation. Therefore, neonates born to sows with dietary vitamin D deficiency require supplemental vitamin D to support normal bone mineral accretion.
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Ball, Lindsay Clare. "Cystic fibrosis and vitamin D supplementation." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2010. https://www.mhsl.uab.edu/dt/2010m/ball.pdf.
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Allsopp, Richard Patrick. "The role of the vascular endothelium in bone formation." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.386827.
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Orr, J. F. "Experimental measurement of stresses in bone and joint replacements." Thesis, Queen's University Belfast, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.373559.
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Dobson, Katharine Rebecca. "Studies into the effects of androgens on bone formation." Thesis, University of Sheffield, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301007.
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El, Fakhri Nagla. "Effect of vitamin D supplementation on bone status, glucose homeostasis and immune function in children with vitamin D deficiency." Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7555/.
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Background: Between 1961-1971 vitamin D deficiency was recognized as a public health issue in the UK, because of the lack of effective sunlight and the population mix [1, 2]. In recent years, health care professionals have cited evidence suggesting a re-emergence of the vitamin D deficiency linked to a number of health consequences as a concern [3-6]. Evidence from observational studies has linked low vitamin D status with impairment in glucose homeostasis and immune dysfunction [7-9]. However, interventional studies, particularly those focused on paediatric populations, have been limited and inconsistent. There is a need for detailed studies, to clarify the therapeutic benefits of vitamin D in these important clinical areas. Objective: The aims of this PhD thesis were two-fold. Firstly, to perform preliminary work assessing the association between vitamin D deficiency and bone status, glucose homeostasis and immune function, and to explore any changes in these parameters following short term vitamin D3 replacement therapy. Secondly, to assess the effectiveness of an electronic surveillance system (ScotPSU) as a tool to determine the current incidence of hospital-based presentation of childhood vitamin D deficiency in Scotland. Methods: Active surveillance was performed for a period of two years as a part of an electronic web-based surveillance programme performed by the Scottish Paediatric Surveillance Unit (ScotPSU). The validity of the system was assessed by identifying cases with profound vitamin D deficiency (in Glasgow and Edinburgh) from the regional laboratory. All clinical details were checked against those identified using the surveillance system. Thirty-seven children aged 3 months to 10 years, who had been diagnosed with vitamin D deficiency, were recruited for the bone, glucose and immunity studies over a period of 24 months. Twenty-five samples were analysed for the glucose and bone studies; of these, 18 samples were further analysed for immune study. Treatment consisted of six weeks taking 5000 IU units cholecalciferol orally once a day. At baseline and after completion of treatment, 25 hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), alkaline phosphatase (ALP), collagen type 1 cross-linked C-telopeptide (CTX), osteocalcin (OCN), calcium, phosphate, insulin, glucose, homeostasis model assessment index, estimated insulin resistance (HOMA IR), glycated hemoglobin (HbA1c), sex hormone binding globulin (SHBG), lipids profiles, T helper 1 (Th1) cytokines (interleukin-2 ( IL-2), tumor necrosis factors-alpha (TNF-α), interferon-gamma (INF-γ)), T helper 2 (Th2) cytokines (interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6)), T helper 17 (Th17) cytokine (interleukin-17 (IL-17)), Regulatory T (Treg) cytokine (interleukin-10 (IL-10)) and chemokines/cytokines, linked with Th1/Th2 subset balance and/or differentiation (interleukin-8 (IL-8), interleukin-12 (IL-12), eosinophil chemotactic protein ( EOTAXIN), macrophage inflammatory proteins-1beta (MIP-1β), interferon-gamma-induced protein-10 (IP-10), regulated on activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein-1(MCP-1)) were measured. Leukoocyte subset analysis was performed for T cells, B cells and T regulatory cells and a luminex assay was used to measure the cytokiens. Results: Between September 2009 and August 2011, 163 cases of vitamin D deficiency were brought to the attention of the ScotPSU, and the majority of cases (n = 82) were reported in Glasgow. The cross-validation checking in Glasgow and Edinburgh over a one-year period revealed only 3 (11%) cases of clearly symptomatic vitamin D deficiency, which had been missed by the ScotPSU survey in Glasgow. While 16 (67%) symptomatic cases had failed to be reported through the ScotPSU survey in Edinburgh. For the 23 children who are included in bone and glucose studies, 22 (96%) children had basal serum 25(OH)D in the deficiency range (< 50 nmol/l) and one (4%) child had serum 25(OH)D in the insufficiency range (51-75 nmol/l). Following vitamin D3 treatment, 2 (9%) children had final serum 25(OH)D lower than 50 nmol/l, 6 (26%) children had final serum 25(OH)D between >50-75 nmol/l, 12 (52%) children reached a final serum 25(OH)D >75-150 nmol/l and finally 3 (13%) exceeded the normal reference range with a final 25(OH)D >150 nmol/l. Markers for remodelling ALP and PTH had significantly decreased (p = 0.001 and <0.0001 for ALP and PTH respectively). In 17 patients for whom insulin and HOMA IR data were available and enrolled in glucose study, significant improvements in insulin resistance (p = 0.04) with a trend toward a reduction in serum insulin (p = 0.05) was observed. Of those 14 children who had their cytokines profile data analysed and enrolled in the immunity study, insulin and HOMA IR data were missed in one child. A significant increase in the main Th2 secreted cytokine IL-4 (p = 0.001) and a tendency for significant increases in other Th2 secreted cytokines IL-5 (p = 0.05) and IL-6 (p = 0.05) was observed following vitamin D3 supplementation. Conclusion: An electronic surveillance system can provide data for studying the epidemiology of vitamin D deficiency. However, it may underestimate the number of positive cases. Improving vitamin D status in vitamin D deficient otherwise healthy children significantly improved their vitamin D deficient status, and was associated with an improvement in bone profile, improvements in insulin resistance and an alteration in main Th2 secreting cytokines.
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Drury, Donna. "Vitamin D and K status and bone health in pediatric cystic fibrosis patients." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101116.
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The objective of this study was to investigate the extent to which vitamin D and K are associated with bone health in pediatric cystic fibrosis (CF) patients. We hypothesized that: (1) the prevalence of vitamin D and K deficiencies would be high despite routine vitamin therapy, (2) bone health would be reduced and (3) vitamin K and D status would be associated with bone health.Our results showed poor bone mineral mass in these CF children despite mild disease and good nutritional status. Neither vitamin K nor D was a predictor of bone health but weight and height Z-scores, fat-free mass, physical activity and lung function were all consistent predictors.
These results indicate that nutritional status as well as physical activity are key determinants of bone health in CF children and offer a unique opportunity in the prevention of CF-related bone disease. Further vitamin intervention research needs to be done in this population.
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Tomlinson, James M. "The Jocic reaction and the synthesis of Vitamin E." Thesis, University of Warwick, 2018. http://wrap.warwick.ac.uk/110296/.
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This thesis begins with an introduction to Vitamin E and the Jocic reaction. Chapter 1 provides a review of the biological activity of vitamin E and related compounds and the synthesis, both racemic and asymmetric, of vitamin E compounds. Also discussed in this chapter is the Jocic reaction and the synthesis of trichloromethyl alcohol compounds. Chapter 2 describes the asymmetric total syntheses of both α- and β-tocopherol, where an intramolecular Jocic reaction was used to provide a high enantiomeric excess. Difficulties encountered during the synthesis, and how these were overcome, are detailed. Chapter 3 describes the novel use of hydride as a nucleophile in the Jocic reaction with tertiary polychloromethyl alcohols. This one-carbon homologation procedure was improved by the use of dichloro- rather than trichloromethyl alcohols. The scope of the reaction, mechanisms and stereochemical implications are discussed.
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Kaovorakarn, Evelyn Amber. "The Effects of Vitamin C on Bone Development in Children and Adolescents." Thesis, The University of Arizona, 2015. http://hdl.handle.net/10150/579423.
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Background: Numerous studies have focused on the contribution of calcium and vitamin D to bone growth and mass accumulation, but not many focused on other nutrients such as vitamin for promoting bone growth and mineralization. Objectives: 1) To determine whether dietary intakes of Vitamin C positively supports bone growth and increases the bone mineral density in both boys and girls. 2) To determine the effectiveness of fruits and vegetables for improving bone mineral density in adolescents. Search Methods: The search strategies included a search on PubMed.gov for studies from year 2000 to present that focused on the correlation between the vitamin C or fruits and vegetable intakes and the bone development.
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Hamill, Matthew. "HIV, body composition, bone and vitamin D status in South African women." Thesis, University of Cambridge, 2013. https://www.repository.cam.ac.uk/handle/1810/270410.
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Cross sectional and observational data suggest that HIV-positive individuals and those receiving antiretroviral (ARV) therapy are prone to higher rates of osteoporosis and osteopaenia than HIV-negative individuals. Likewise, HIV-positive individuals often have low vitamin D status. Evidence is emerging more generally of a strong association between HIV infection and poor bone health. There is also evidence that treatment with ARV therapy (ART) and suboptimal vitamin D status may exacerbate this problem (Brown et al, 2006a, 2010). But, to date, causal relationships have not been fully established. This thesis explores the interactions between these separate factors and provides novel data about the effects of HIV infection and its treatment, on bone health in a particular group of black, South African women. Bone loss and poor vitamin D status in the context of HIV infection are important global health issues because these conditions may affect millions of individuals. If HIVassociated bone loss is causally associated with an increased risk of bone fracture then it is possible that there will be an epidemic of HIV-associated fractures in coming decades, particularly in the developing world, including Africa. Study data have so far often been limited by several factors, including cross-sectional design, absence of control groups, a preponderance of attention to bone outcomes in males and in Caucasians, and a lack of good quality data in Africans living in Africa. Th is study aimed to -assess the magnitude of HIV- and ART-associated changes in areal bone mineral density (aBMD), size-adjusted bone mineral content (SA-BMC) and vitamin D status in adult, premenopausal women living in Johannesburg, South Africa. Ninetyeight HIV-negative (Negative reference: Nref) and 149 HIV-positive women were enrolled to allow for comparison between groups. The HIV-positive women were recruited into those eligible to start ART (Positive low CD4 : Plow, n=75) and those unlikely to require ART (Positive preserved CD4 : Ppres, n=74) during a 12-month followup period. The design was longitudinal with visits at 0, 6 and 12 months for measurement of body composition, bone measures and dietary assessment. Blood and urine samples were collected for the evaluation of relevant musculoskeletal analytes, including 25(0H)D at each time point. Most women ( > 80%) who received ART during the course of the study received South African standard first-line therapy consisting of lamivudine, tenofovir and efavirenz. A post hoe analysis of possible effects of ART was performed by retrospectively dividing HIV-positive women into ART-unexposed (n=66) and ART-exposed (n=74). At baseline there was a high prevalence of overweight with 65%, 65% and 44% with BMI > 25 kg/m2 in Nref, Ppres and Plow respectively. Plow had lower weight, BMI, fat mass, lean mass, waist and hip circumferences than the other groups. Nref and Ppres were not different from each other. There were no differences in aBMD or SA-BMC 1 between groups at baseline and no significant differences in vitamin D status between the groups. The mean ±SD serum 25(0H)D concentrations were 59.7 ±16.5, 59.2 ±16.5 and 61.6 ±22.3 nmol/1 in Nref, Ppres and Plow respectively. Plow had significantly lower serum albumin concentration (p < 0.0001) and higher serum phosphate concentration (p < 0.0001). The magnitude of differences in serum phosphate was: Ppres-Nref = 12. 7 ±2.9%; Plow-Nref = 20.3 ±2.9% and Plow-Ppres = 7.6 ±3.1% (p < 0.001). Tubular maximum Reabsorption of Phosphate/Glomerular Filtration Rate (TmP/GFR) was 11.2 ±3.2% and 27.4 ±3.2% respectively greater in Ppres and Plow than Nref (p < 0.0001), and higher in the Plow compared to Ppres 16.2 ±3.4%, (p=0.0002). Serum alkaline phosphatase and urine phosphate to creatinine ratio were not significantly different (p > 0.05). At the 12-month follow-up, Plow subjects remained lighter than their Nref and Ppres counterparts. However, there was a 3.9 ±0.9% increase in mean weight in the Plow group over 12 months (p < 0.001), which represented 10.2 ±0.8% (p < 0.001) increase in fat, rather than lean, mass accumulation. There were significant mean decreases in aBMD and SA-BMC in Plow subjects, and those exposed to ART of the order of 2-3% at total hip, femoral neck and lumbar spine. There were no significant differences in mean vitamin D status between the groups and no significant changes, the mean 25(0H)D concentrations were 63.3 ±17.7, 66.0 ±18.4 and 61.1 ±20.1 nmol/1 in Nref, Ppres and Plow respectively. Serum albumin concentrations had risen by a mean of 9.1 ±1.1% in the Plow group to reach comparable concentrations with the other groups. Alkaline phosphatase activity had significantly risen in the Plow group compared with the other groups (p < 0.001). Serum phosphate concentration remained higher in Plow than the other groups, though the mean value had not increased. Serum phosphate had significantly increased in Nref from baseline to 12 months 7.0 ±2.3% (p=0.05) and non-significantly in Ppres 5.2 ±2.4%. TmP/GFR had declined from baseline by 11.2 ±3.6% in Plow and non-significantly increased in Nref and Ppres (6.4 ±3.3% and 3.8 ±3.5% respectively). These data suggest that HIV infection in South African women is associated with differences in body composition but not with differences in bone measures or vitamin D status. However, being in the Plow group, and ART exposure, was associated with a significant decrease in mean aBMD and SA-BMC, of the order of 2-3%, over 12 months of observation at the hip, femoral neck and lumbar spine. These decreases, in young women, exceed those seen in early menopause, which is of the order of 1-2% annual decrease. The decreases were evident despite the fact that HIV-positive women exposed to ART had increases in fat mass, weight and serum albumin and alkaline phosphatase over time. In this group serum phosphate concentration and TmP/GFR decreased after the introduction of ART, suggesting an effect of ART on renal phosphate handling. ART exposure was not associated with change in vitamin D status. In the post hoe analysis the biochemical results in ART-unexposed compared to ARTexposed was very similar to that in Ppres compared with Plow. Further studies to assess skeletal effects over a longer time in HIV-positive, ARTexposed and na"ive women are warranted. Studies are also required in post-menopausal women, children and men. Given the high prevalence of overweight and obesity recorded in the study population, there may also be a need for interventions to reduce cardiometabolic disease risk in this population.
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TOON, NICOLE MARIE. "INTAKES OF CALCIUM AND VITAMIN D AND THEIR RELATIONSHIP TO BONE HEALTH." University of Cincinnati / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1116019728.
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Avenell, Alison. "Nutritional influences on bone metabolism : three studies in postmenopausal women." Thesis, University of Aberdeen, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361777.
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Eleven postmenopausal women made weighed food intakes and urine collections for one week, to determine influences on urinary calcium and deoxypyridinoline excretion. Urinary calcium was influenced by both dietary calcium and dietary fibre. Urinary deoxypyridinoline was increased in women consuming more dietary fibre. The influence of ketosis was examined in five postmenopausal women, who increased urinary hydrogen ion excretion, but had no consistent changes in urinary calcium or deoxypyridinoline excretion. Forty-six postmenopausal women, with body mass index greater than 27kg/m2, were randomised to diet XA (5010kJ, 89g protein, 110g carbohydrate, 17g dietary fibre daily) or diet XK (5010kJ, 62g protein, 186g carbohydrate, 28g dietary fibre daily) for six months later. Calcium intakes fell significantly in both groups and fibre intakes were significantly increased in XK dieters compared to XA. Throughout the year group XA had significantly greater weight loss than XK, at one year XA-6.5kg (SE 1.1) and XK-3.0kg (0.8), p < 0.05. No significant changes in deoxypyridinoline or osteocalcin were found for XA or XK during the six months of dieting. Sex hormone binding globulin and follicle stimulating hormone rose particularly in group XA, suggesting a decline in endogenous oestrogen levels. Bone mineral density changes were compared to 46 normal weight non-dieting controls. Sixteen XK dieters lost 20% of their excess body weight, but returned to their starting weight. Annual changes in lumbar spine bone mineral density, measured by dual energy X-ray absorptiometry, for this group were -4.8% (SE 0.9), controls -2.5% (0.5), 95% confidence interval of difference between groups -0.2 to -4.3%, p = 0.03. For group XA, the annual percentage change in lumbar spine bone mineral density was -3.3% (1.0), incorporating a correction factor for truncal thickness. This was not significantly different from the control group. No significant difference in changes of annual femoral neck bone mineral density was found between XA, XK and the control group.
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Abel, Stefan. "The physiological effect of vitamin B12 deficiency in human blood." Thesis, Stellenbosch : Stellenbosch University, 1990. http://hdl.handle.net/10019.1/69031.
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Thesis (MSc) -- Stellenbosch University, 1990.ENGLISH ABSTRACT: The main aim of this workpiece was to establish the physiological parameters against which a vitamin Bu deficiency could be measured. A comparison between the hematological values of healthy patients and those suffering from pernicious anemia due to vitamin Bu deficiency was done. A specific case of pernicious anemia was used in the comparison of abnormal values to the values of normal healthy patients. The comparison consisted of blood analyses with the help of specified instruments, photomicrographs of bone marrow and blood smears and statistical data. A Coulter Counter Model ZF was used for the hematological analyses of blood, a radio-isotope assay for serum vitamin B u was done and photomicrographs were taken with a NIKON Microflex camera with photomicrographic attachments. The importance of vitamin Bu has been shown in this workpiece. With the use of techniques and certain instruments, the effects of a shortage of vitamin Bu has been shown. Analyses of the blood from normal ,healthy patients was compared to that of patients suffering from pernicious anemia. It was demonstrated that pernicious anemia is characterized by a low erythrocyte count, hematocrit (Het), hemoglobin (Hb) and vitamin Bu levels together with a higher mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV). In severe cases of pernicious anemia these levels are extremely high or low as the case may be. Together with these values, the investigation of pernicious anemic blood and bone marrow smears revealed abnormally large erythrocyte precursors and fewer leucocytes than normal. Abnormally shaped cells, called macrocytes, were seen which was due to the disruption in deoxyribonucleic acid (DNA) synthesis caused by the vitamin Bu deficiency. This study produced a set of hematological reference values. The comparative study between healthy and pernicious anemic patients demonstrated a significant drop in serum vitamin B12 values during pernicious anemia. The hematological effect was illustrated by the Coulter Counter blood analysis results and the microscopic examination revealed the presence of megaloblastic erythrocytes, oval erythrocytes, pear-shaped poikilocytes and polymorphonuclear neutropbils with hypersegmented nuclei in blood smears I during vitamin B12 deficiency. This dianoses can be supported by the presence of megaloblasts and metamyelocytes in pernicious anemic bone marrow.
AFRIKAANSE OPSOMMING: Die hoof doel van hierdie werkstuk was om fisiologiese grense te bepaal waarteen 'n vitamien B12 tekort gemeet kan word. 'n Vergelyking tussen die hematologiese waardes van gesonde persone en die van pasiente met pernisieuse anemie wat ontstaan het as gevolg van 'n vitamien B12 tekort was uitgevoer. Die waardes verkry vanaf 'n spesifieke geval van pernisieuse anemie. was vergelyk met waardes vanaf normale gesonde persone. Hierdie vergelyking het bestaan uit bloed analises, fotomikrograwe van bloed en beenmurg smere en statistiese data. Die hematologiese bloed analises was met behulp van 'n Coulter Teller model ZF uitgevoer. 'n Radio-isotoop bepaling vir serum vitamien B12 was gedoen en fotomikrograwe was met 'n NIKON Microflex kamera geneem. Die belang van 'n vitamien B12 tekort was in hierdie werkstuk gedemonstreer. Die effek van hierdie tekort is deur die gebruik van sekere instrumente en tegnieke aangedui en die resultate hiervan is vergelyk tussen gesonde persone en pasiente met 'n vitamien B12 tekort. Hierdie studie het bevestig dat pernisieuse anemie gekenmerk word deur verlaagde eritrosiet, hematokrit (Het), hemoglobien (Hb) en vitamien B12 vlakke tesame met verhoogde gemene korpuskulere hemoglobien (GKH) en gemene korpuskulere volume (GKV) vlakke. Gedurende ernstige gevalle van pernisieuse anemie kan hierdie waardes uitermatig hoog of laag wees. Benewens hierdie waardes het die ondersoek van bloed en beenmurg gedurende vitamien B12 tekort, abnormale groot eritrosiet voorgangers en 'n verminderde hoeveelheid leukosiete getoon. Abnormale sel vorms was ook sigbaar a.g.v. die onderbreking in DNA sintese wat deur 'n vitamien B12 tekort veroorsaak word. Pernisieuse anemie word verkry wanneer daar 'n vitamien B12 en/of folaat tekort in die dieet is of wanneer hierdie vitamiene nie geabsorbeer kan word nie. Die teenwoordigheid van makrosiete, ovaal eritrosiete, peervormige poikilosiete en polimorfonuklere neutrofiele met hipergesegmenteerde keme in bloedsmere dui op 'n megaloblastiese anemie. Hierdie diagnose kan ondersteun word deur die aanwesigheid van megaloblaste en reuse metamielosiete in die beenmurg. Die bepaling van vitamien B12 en folaat vlakke in die bloed kan as addisionele bewysstukke vir 'n volledige diagnose dien. Gedurende hierdie studie is daar 'n stel hematologiese verwysingswaardes vasgestel. Die vergelykende studie tussen gesonde persone en pasiente met pernisieuse anemie het getoon dat daar 'n beduidende verlaging in serum vitamien B12 waardes gedurende pernisieuse anemie is. Die hematologiese effek was ook duidelik waameembaar in die Coulter teller se bloed analiese en mikroskopiese ondersoeke het die · teenwoordigheid van makrosiete, ovaal eritrosiete, peervormige poikilosiete en polimorfenuklere neutrofiele met hipersegmenteerde keme in bloedsmere aangedui. Hierdie diagnose kan ondersteun word deur die aanwesigheid van megaloblaste en reuse metamielosiete in die beenmurg.
This study was financially aided by a bursary from the CSIR.
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Campbell, Craig. "Bone health in children with cerebral palsy." Thesis, University of Ottawa (Canada), 2006. http://hdl.handle.net/10393/27231.
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Background. Children with cerebral palsy (CP) encounter a number of orthopedic complications as a result of abnormalities in motor function. One of the most significant complications is fragility fractures, occurring in up to 23% of children in prior reports. Despite a growing literature on how to best interpret bone densitometry in children, little research has determined optimal utilization of dual x-ray absorptiometry (DXA) in children with CP in order to characterize the patients' bone health status. This study outlines the use of the mechanostat theory of bone physiology to classify osteopenia and interpret bone complications in this population. The mechanostat theory posits that muscle forces have the greatest impact on bone strength and that low bone mass will result from one of two pathologic circumstances: a primary disorder of abnormally low bone mass despite normal muscle forces, and a secondary disorder of bone mass due to abnormally low muscle forces on bone. The later category, secondary osteopenia, is hypothesized to be the bone health state of most children with CP, due to the motor dysfunction resulting from brain injury in these children. Bone morbidity is expected to be greater in those with osteopenia.
Methods. Single, community-based, rehabilitation centre, cross sectional study of 53 subjects with CP age 2-15 years of age. Subjects underwent a baseline interview, examination, x-ray, laboratory and DXA bone densitometry. Calculations of z-score values for total body bone mineral content and muscle mass were made based on published normal children. The z-scores determined the classification of osteopenia with -2 defined as abnormally low bone mineral content or muscle mass.
Results. The subjects (51% females) had a mean age of 9 years (s.d.=3.8, range=2.5-15.8). All types and severity of CP were represented in the sample. Normal DXA bone parameters were seen in 24 children, with 11 children classified as having primary osteopenia, five having secondary osteopenia and three with both primary and secondary (mixed). Three children had fragility fractures. Using the classification proposed herein, the fractures occurred only in children defined as having osteopenia. Having at least one bone complication and joint subluxation were more prevalent in the osteopenic subjects compared to non-osteopenic subjects (Chi square, p<0.05). Using z-scores for bone mineral content as an outcome variable, only one CP specific factor, the Gross Motor Function Classification System, was an important independent variable (beta=-0.48, R2=0.18, p<0.05). The final model also included age (beta=0.52, R2=0.34, p<0.05) and gender (beta=-0.36, R2=0.12, p<0.05), showing lower z-scores in males and those of younger age. Use of anti-convulsants, type of CP, family history, calcium and vitamin D intake did not contribute to the model. Measures of pain or quality of life, although worse in osteopenic subjects, were not significantly related to reductions in bone mineral content, when severity of CP was controlled.
Conclusions. Using the mechanostat theory to interpret bone density DXA measurements is a more physiologic way to interpret bone health in children and appears foundationally sound in this sample of children with CP. In the reported subjects orthopedic complications were more common in those with osteopenia, and fragility fractures were accurately classified in functional terms according to whether the osteopenia resulted from a primary or secondary bone defects.
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McIntyre, Christopher William. "Studies into the effects of non-calcaemic vitamin D sterols on bone cells." Thesis, Queen Mary, University of London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391629.
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Kanan, Raed Mohammad. "Molecular genetics and biochemistry of vitamin D binding proteins in metabolic bone disease." Thesis, University of Newcastle Upon Tyne, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287811.
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Lubczańska, Maria A. "The human vascular vitamin D hormonal system : expression and regulation." Thesis, University of Warwick, 2013. http://wrap.warwick.ac.uk/58451/.
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Background: Patients suffering from chronic kidney disease (CKD) are at high risk of cardiovascular related premature death. In addition, traditional strategies for preventing cardiovascular disease (CVD) in patients with normal kidney function are less successful in patients with CKD. Vascular calcification (VC) and cardiac hypertrophy are common consequences. Recent evidence suggests that activation of the vitamin D receptor (VDR) is protective and is associated with significantly better survival in end stage renal disease (ESRD). Vascular smooth muscle cells (VSMCs) play a key role in the process of CKDrelated arteriopathy and are capable of phenotype transformation into chondro/osteoblast-like cells, which promotes the deleterious vascular effects, including calcification. Although the kidney is the main site of 1,25(OH)2D synthesis, some other non-renal tissues also express, VDR, 25-hydroxyvitamin D 1α-hydroxyalse (1α-OHase) an enzyme responsible for the synthesis of 1,25(OH)2D, and 1,25(OH)2D 24- hydroxylase (24-OHase), an enzyme responsible for the catabolism of 1,25(OH)2D. Extra-renal 1,25(OH)2D can affect a multitude of pathways in an autocrine/paracrine way, without the involvement of the endocrine system. Aims: This project aimed to investigate the role of autocrine vitamin D signalling in human VSMCs using both arterial tissue from ESRD and non-ESRD patients and primary cultures of human aortic smooth muscle cells (HAoSMCs). Specific aims were to characterise the expression and functionality of vitamin D system in vasculature as well as to examine the effect of classical regulators of the endocrine vitamin D system – 1,25(OH)2D3, calcium, phosphate, TNF-α and other interleukins, as well as novel factors such as FGF-23 and Klotho, on the local vitamin D metabolism in arteries. Results: We have demonstrated the presence of VDR, 1-OHase and 24-OHase in human kidney, artery and HAoSMCs. To our knowledge, we are the first to demonstrate the presence of 24-OHase in arteries. Our data suggested diminished expression of VDR mRNA and protein, with significantly decreased levels of 1α- OHase protein expression in CKD patients. Further crucial finding was the apparent increase of 24-OHase protein in CKD arteries suggested higher local vitamin D catabolism in CKD. In order to establish which factors regulate expression of 1α- OHase, 24-OHase and VDR in HAoSMCs, further studies were undertaken. Results confirmed that treatment with high calcium, phosphate, TNF-α, INF-γ, IL-6, IL-17A, FGF-23 or Klotho modulated VDR protein expression, which had further effect on expression of 1α-OHase and 24-OHase mRNA and protein. Conclusions: The results suggest that altered mineral and inflammatory environment, characteristic to CKD may favour local 1,25(OH)2D3 catabolism, potentially driving transdifferentiation of VSMCs, leading to VC. Vascular VDR activation, in particular through local metabolic activation, is crucial for vascular health, especially, under stress conditions. Local inducers and inhibitors of vascular vitamin D system have been determined, however further examination is required for potential application in future treatment of CKD related VC.
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Hoeger, Glenn Charles 1962. "Vitamin E turnover in cultured pulmonary alveolar macrophages." Thesis, The University of Arizona, 1992. http://hdl.handle.net/10150/278219.
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Vitamin E (α-TH), the primary lipid soluble antioxidant, can protect tissues from oxidative insult. Oxidant-producing pulmonary alveolar macrophages (PAM), may depend on α-TH to prevent oxidative damage. α-TH levels in cultured PAM declined rapidly during the first 12-18 hours in culture. Approximately 60% of the decrease was detected as unoxidized alpha-TH released to RPMI 1640 (containing 5% fetal bovine serum (FBS)) culture medium. α-TH was not detected in serum-free Ham's F12 medium. PAM appeared to reabsorb α-TH from the medium. PAM activation with phorbol myristate acetate (PMA) did not affect cellular α-TH depletion. However, the amount of α-TH detected in the medium of PMA treated cultures was only 50% of that detected in medium from untreated controls. Inhibition of superoxide production with iodoacetate had no effect on cellular depletion kinetics, however medium α-TH levels were still 50% of controls. Inhibition of nitric oxide, synthesis appeared to have no effect on α-TH status.
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Westfall, Carola Hammer 1953. "Bone mineral content of femur, lumbar vertebrae, and radius in eumenorrheic female athletes." Thesis, The University of Arizona, 1988. http://hdl.handle.net/10150/276757.
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This study compared bone mineral index (BMI, gm/cm²) of the femur, spine, and radius, measured by photon absorptiometry in various groups of eumenorrheic female athletes. The sample included body builders (11), swimmers (13), runners (5 collegiate, 11 recreational), and inactive controls (18) averaging 25 years of age, ranging from 17 to 38 years. Lumbar vertebral BMI for body builders (1.40 gm/cm²) was significantly (p ≤ 0.05) greater than controls (1.25 gm/cm²). The body builders' femoral neck BMI (1.09 gm/cm²) was significantly greater than swimmers (0.97 gm/cm², recreational runners and controls (0.95 gm/cm²). Years of exercise history and calcium consumption were not significant predictors of BMI. Correlation coefficients between fat-free body and all BMI sites were significant and more closely related to bone mineral than other variables (weight, height, weight/height²). Correlation coefficients for proximal and distal radius BMI and femoral and spine BMI were significant, the distal radius having higher association.
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Ellis, Tiffany A. "Comparison of bone density in female vollyball players and age-matched non-athletes." Virtual Press, 2005. http://www.oregonpdf.org.
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Bawazeer, Nahla M. "Vitamin B12 and folate status during pregnancy among Saudi population." Thesis, University of Warwick, 2011. http://wrap.warwick.ac.uk/49940/.
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T2DM is a growing health problem worldwide. It is now increasingly being diagnosed earlier in life. The factors involved in such an epidemic are complex. The intrauterine environment has long been known as an important contributor to many diseases including metabolic disorders such as T2DM. Recently, there is emerging evidence for maternal micronutrients affecting vital developmental processes in utero which can adversely “programme” the offspring to develop metabolic disorders in later life. Thus, “gene-diet” interaction during foetal development is likely to be a significant contributor to the epidemic of T2DM. In particular, the intrauterine imbalance between the two related vitamins, vitamin B12 and folate, affect DNA methylation and in turn programme the foetus for the whole life. Evidence from mandatory folic acid fortification studies suggests that in the presence of adequate folate, neural tube defects due to vitamin B12 insufficiency have tripled. In India, children born to mothers with “high folate and low vitamin B12” had higher adiposity and insulin resistance. Therefore, micronutrient status during pregnancy is likely to have a significant impact on the metabolic risk of the offspring. This thesis examines whether vitamin B12 insufficiency is prevalent in pregnancy, especially in a non-vegetarian population across the world as well as the Saudi pregnant population. As estimated intake is an accepted measure for micronutrient levels, we also examined the relationship between estimated vitamin B12 and folate intake with actual levels in the blood. We have found that vitamin B12 insufficiency was not uncommon during pregnancy across the world even in the non-vegetarian population and is also common in the Saudi population. Surprisingly, vitamin B12 insufficiency was observed in 50% of the tested population even in the presence of adequate vitamin B12 intake. In addition, we have also shown for the first time in the Saudi population that maternal BMI is inversely related to vitamin B12 levels, particularly in pregnancy. Even though we have shown a similar (or worse) picture in mothers with gestational diabetes, this study needs to be replicated, as our numbers are too small. Prospective studies linking the role of vitamin B12 insufficiency especially in the presence of high folate on birth outcomes in the Saudi population as well as intervention studies investigating the role of vitamin B12 supplementation in women of childbearing age and in pregnancy are urgently needed.
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Khoja, Sawsan Omar. "Nutritional status of vitamin D and dietary intake of key bone health nutrients in Saudi Arabian women : implications for bone health." Thesis, University of Surrey, 2006. http://epubs.surrey.ac.uk/844240/.
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Osteoporosis is a common highly prevalence public health problem affecting both gender in all age stages in worldwide. Little information is known about the bone health and lifestyle characteristics of women living in Middle Eastern countries in general and Saudi Arabia in specific. The complete information and statistical figures of osteoporosis prevalent and vitamin D deficiency among population it has not yet been identified. The strong correlation between dietary intake and bone health has been explored in Western populations but no data are available in Middle Eastern countries. The aims of this study were four fold: (i) to examine the extent of poor bone health in the Saudi population of postmenopausal and premenopausal women; (ii) to investigate the effect of lifestyle factors including physical activity levels and sun-time exposure on bone integrity; (iii) to determine the extent of vitamin D deficiency in the population and the effect of this status on bone mass and calcium/bone metabolism; (iv) to evaluate the dietary quality and quantity in Saudi women and investigate fully the effect of diet on bone health indices. As part of our investigation, a total of 212 Saudi Arabian apparently healthy women were voluntarily participated in this study. A total of 112 postmenopausal and 100 premenopausal women. They were aged 45-60 years and 20-30 years respectively. Bone mineral density (BMD) was determined at the lumbar spine (L2-L4) and femoral neck using dual x-ray absorptiometry (DXA). Calcaneal bone mass was measured by broadband ultrasound attenuation (BUA). All subjects were interviewed concerning their habitual dietary intake, physical activity levels and general lifestyle. Information on dietary intake of each individual was obtained using 3-day estimated food diaries. The amount of food consumed (in grams) for the five food groups was calculated for each subject. Intakes were converted to frequency of consumption (time/d) by dividing food groups by average portion sizes. Using the only existing Food Composition Table for the Middle East, the nutrient values for energy, protein, fat, fibre, calcium, phosphorus, iron, vitamin C, vitamin D and potassium were chosen for the five food groups identified and calculated per 100g. Bone resorption was assessed by measurement of pyridinium crosslinks (PYD) and (DPD) using a second morning urine sample. Bone formation was assessed by bone specific alkaline phosphatase (BSAP) and osteocalcin (OC). Serum 25(OH)D, 1,25(OH)D, PTH, calcium, and phosphorus were measured. Bone health indices indicated a high prevalence of low bone mass in these groups. According to WHO criteria (WHO, 1994), a total of 52% of postmenopausal and 37% of premenopausal women were osteopenic at the lumbar spine. Osteoporotic prevalence was 13% and 2% respectively. Similar results were found for the femoral neck. Physical activity levels were low and exposure to sunlight was low. A significant correlation was found between period of sunlight exposure (min/d) and axial BMD and calcaneal bone mass. The 'quality' of food consumption by Saudi Arabian women does not follow the recommended food guidelines, and the intakes of energy, fibre and potassium in women are lower than those recommended in western population but intakes of phosphorus are somewhat higher. Calcium, vitamin C and iron are around recommended levels. Vitamin D deficiency is highly prevalent in Saudi women, with 78% of women being below the classical threshold of 12ng/ml. A low milk consumption was associated with higher bone resorption in both postmenopausal and premenopausal women which remained significant after adjustment for the key confounding factors of age, weight, height and menopausal status. A low intake of fruit and vegetables and nutrients associated with high fruit and vegetable intake including vitamin C, potassium and estimates of net endogenous acid production were found to be related to poorer indices of bone health. These results are a cause for concern. It indicates that bone health is poor and dietary and lifestyle factors are not favourable to skeletal integrity in Saudi Arabian women.
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Cardy, Susan Mary. "Lactobacillus leichmannii as a probe for the quantitation of vitamin B-12." Thesis, University of Warwick, 1989. http://wrap.warwick.ac.uk/107025/.
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Initial attempts to isolate the gene encoding Vitamin B12 receptor protein (jbtuB) from Lactobacillus leichmannii, resulted in the isolation of the JbtuB gene from E. coli, due to either a cross-over or gene exchange event. Complementation of an E. coli JbtuB mutant was demonstrated and expression analysis, using both in vivo and in vitro systems, revealed the cloned gene to encode a polypeptide with an apparent Mr of 66,400 as determined by PAGE. Nucleotide sequence data confirmed that the cloned gene was identical to the JbtuB gene from E. coli. The initial 2.0 Kb Hindlll genomic DNA fragment from L. leichmannii, which exhibited homology to a synthetic oligonucleotide probe (derived from the btuB gene from E. coli), was re-cloned into an amplifiable high copy number vector in E. coli. The recombinant DNA was found to be stably maintained and had not undergone any physical rearrangements. Nucleotide sequence data revealed three putative open-reading frames, one of which encoded a protein which exhibited a degree of homology to the C-terminus of the Vitamin B., receptor protein (BtuB) from E. coli. The functions of the other two open-reading frames remain to be elucidated. The B. 2 binding protein from L. leichmannii has been isolated and purified. It has an Mr of approximately 21,500 as determined by gel filtration. Polyclonal antibodies were raised to it for use in the identification of the desired gene product from the cloned L. leichmannii genomic fragment. Cross reactivity was found between, the antisera to the B12 binding protein from L. leichmannii and the B12 receptor protein (BtuB) from E. coli. The reverse case was found to be true also. Transformation of L. leichmannii was achieved by electroporation. Vectors pSA3, pC194, pCKl, but not pAM01, transformed the organism to chloramphenicol resistance, albeit at low frequency.
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Zarei, Allahdad. "Comparison of the effects of vitamin D metabolites on osteoblast and osteocyte bone cells." Thesis, University of Oxford, 2015. http://ora.ox.ac.uk/objects/uuid:8d363814-c1e5-4f16-929d-18ac9debde75.
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While the major source of vitamin D is D3 from ultraviolet exposure, some supplements supply D2. The relative potency of vitamin D2 versus vitamin D3 remains controversial. The aims of the current study were, 1. To optimize the in vitro model, including use of cell lines, vitamin D concentrations, and outcome biomarkers. 2. To compare the potency of vitamin D2 and D3 metabolites on mouse and human bone cellular activity. 3. To explore the expression of VDR in osteoarthritic (OA) bone tissues as well as cellular responses to vitamin D2 and D3 metabolites ex-vivo. In mouse 2T3 osteoblasts, at physiological doses, both vitamin D2 and D3 metabolites increased ALP activity and mineralisation and up-regulated osteoblastic signature genes and proteins. At supra-physiological doses D3 metabolites were more potent inhibitors of 2T3 function than D2 metabolites. Although hBMS cell proliferation was inhibited by both 25(OH)D2 and D3, ALP activity was enhanced by both metabolites. However, 25(OH)D3 was a more potent stimulator of ALP and mineralisation of hBMSCs. D2 and D3 equally stimulated expression of CX43 and PHEX markers in osteocytic cell lines. Immunohistochemistry of femoral heads showed much reduced VDR expression in OA osteocytes and osteoclasts, yet both 25(OH)D2 and D3 increased OA-hBMSCs mineralisation more than non-OA-hBMSCs ex-vivo. While vitamin D2 or D3 increased mouse 2T3 osteoblastic activity at physiological doses, OA and non-OA hBMSCs differentiation was more responsive to 25(OH)D3. Key bone cells such as osteocyte and osteoclasts expressed less VDR in OA. For the first time vitamin D2 metabolites have been thoroughly examined and emerged as a potent stimulator of bone cell differentiation, at least in vitro. Vitamin D3 in contrast is confirmed as highly potent in bone cells, but with toxicity at much lower doses than D2.
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Willett, Alexis Maria. "Factors affecting vitamin D status in older adolescents and their relevance to bone health." Thesis, University of Cambridge, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.615157.
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Micklesfield, Lisa Kim. "Exercise and bone mass in mature premenopausal women." Master's thesis, University of Cape Town, 1996. http://hdl.handle.net/11427/26979.
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Akter, Rahima. "Role of lamin A/C in the cellular features of age-related bone loss." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=32525.
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Lamin A/C, an important component of the nuclear envelope, has been associated with cell differentiation and tissue development. In bone, recent studies have described that altered function of lamin A/C, due to mutations or incorrect processing, is associated with accelerated and severe bone loss. This could be due to alterations in the differentiation of mesenchymal stem cells (MSC) induced by lack of lamin A/C activity. Therefore, considering that decreased osteoblastogenesis and increased adipogenesis are the characteristic changes observed within bone marrow microenvironment that leads to age-related bone loss, we have studied the effect of inhibition of lamin A/C on MSC into either osteoblasts or adipocytes both in vitro and in vivo. For in vitro studies, we identified the effect of pharmacological inhibition of lamin A/C on adipogenesis. Subsequently, we inhibited lamin A/C by using different doses of lamin A/C siRNA in osteogenic and adipogenic differentiating MSCs as well as normal human osteoblasts. To further verify our results, we have used Zmpste24-/- null progeroid mice that lacks mature lamin A/C and studied the bone changes in absence of mature lamin A/C in in vivo. We have found that partial inhibition of lamin A/C decreased osteoblast differention and function without affecting their survival. Furthermore, our animal studies showed that absence of mature lamin A/C induced a reduction in bone mass and bone quality associated with low bone turnover. In contrast, accumulation of prelamin A induced significant levels of adipogenesis within the bone marrow cavity. In summary, our results provide evidence in support of a pivotal role of lamin A/C in the commLamin A/C, un important composant de l'enveloppe nucléaire, a été associé avec la différentiation cellulaire et le développement tissulaire. Dans l'os, des études récentes ont demontrée que l'alteration de lamin A/C, due a des mutations du gène LMNA, est associée avec une perte accélérée et sevère de l'os. Ceci pourrait être dû à une altération de la différentiation des cellules souches mésenchymateuses (CSM) induit par une perte de l'activité de lamin A/C. Par conséquent, en considerant que la diminution de l'ostéoblastogènese et l'augmentation de l'adipogènese sont les changements caractéristiques observés à l'intérieur du micro-environnement de la moelle osseuse qui mènent à une perte osseuse relié à l'âge, nous avons étudié l'effet de l'inhibition de lamin A/C sur la différentiation des cellules souches soit en adipocyte ou en ostéoblast in vitro et in vivo. Pour les études in vitro, nous avons identifiés l'effet de l'inhibition pharmacologique de lamin A/C sur l'adipogènese. Par la suite, nous avons inhibé lamin A/C en utilisant différentes doses de lamin A/C siRNA sur les cellules souches en différentiatiation en ostéoblast et en adipocytes et aussi sur des ostéoblast humaine. Pour confirmer nos résultats précedents, nous avons utilisés un modèle progerique murin Zmste24-/-. Ces souris ne possedent pas la forme mature de lamin A/C. Nous avons etudiés les changements osseux en absence de la forme mature de lamin A/C in vivo. Nous avons trouvé qu'une inhibition partielle de lamin A/C diminue la différentiation et la fonction des ostéoblastes sans affecter leur survie. En outre, nos études sur les souris ont d
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Young, Julia, and n/a. "Bone morphogenetic proteins are involved in controlling mammalian fertility." University of Otago. Department of Biochemistry, 2008. http://adt.otago.ac.nz./public/adt-NZDU20090112.122706.
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Transforming growth factor beta (TGFβ) superfamily members are involved in controlling mammalian fertility. The largest subset of the TGFβ superfamily are the bone morphogenetic proteins (BMP). BMP ligands signal through the type I and II BMP receptors and utilise the Smads1/5/8 phosphorylation cascade to control gene expression in the cell nucleus. Although BMPs act through the same pathway, they have the ability to activate unique sets of genes dependant on the identity of the ligand. In this study, HEK293T cells were challenged with BMP ligands for four hours and gene expression profiles were compared using microarray technology. The genes upregulated in the presence of BMP2, BMP4, BMP6 and BMP7 play roles in cellular proliferation and differentiation. These functions are critical stages in the successful development of an ovarian follicle whilst undergoing folliculogenesis. All of the BMP ligands investigated in this study were also observed to upregulate the expression of a small group of common genes indicating that a shared regulatory pattern occurs within the BMP pathway. Of these genes, Smad6 and Smad7, inhibitor of DNA binding proteins 1-4 (ID 1-4), and msh homeobox homolog 2 (MSX2) were previously known BMP target genes. However, none of the remaining genes upregulated by all BMPs were previously shown to be BMP targets.
The results from the microarray experiment were used as founding data for the in silico mining of novel genes not present on the array that may be differentially expressed in response to these ligands. The expression levels of several of the novel genes identified by in silico mining were then measured in vitro, however the results showed no differential expression in the HEK293T cells.
To apply the knowledge of the microarray studies to the tissue of interest, eight genes were selected for assessment in ovine granulosa cells. Four of the genes upregulated in response to BMP6 in HEK293T cells were also differentially expressed in primary ovine granulosa cell cultures in response to BMP6 addition.
The identification of several sheep breeds with mutations in TGFβ superfamily members has enabled investigations into the roles that specific TGFβ components play in controlling fertility. The highly fertile Booroola sheep has a substitution mutation in the type IB BMP receptor that results in an additive effect on ovulation rate. The Booroola mutation causes precocious maturation of ovarian follicles with fewer granulosa cells surrounding an enlarged oocyte, and carriers of the mutation have higher levels of circulating follicle stimulating hormone (FSH). BMPs have previously been shown to influence the regulation of FSH synthesis and secretion in the pituitary gland. In this study, primary pituitary cells were harvested and cultured from homozygous Booroola ewes and from wildtype ewes to determine if the mutation caused alterations in FSH secretion in vitro. The cells were collected 24 h following induction of luteolysis and cultured for 72 h prior to being challenged for 24 h with bone morphogenetic proteins (BMP2, BMP4, BMP6), growth and differentiation factor-9 (GDF9), transforming growth factor β1 (TGFβ1), activin-A and gonadotropin releasing hormone (GnRH). The levels of FSH and luteinising hormone (LH) were measured by radioimmunoassay and compared to the untreated controls. Primary pituitary cell cultures from Booroola ewes secreted less FSH than wildtype cells in the presence of BMP2, BMP4 and BMP6. These BMPs did not affect the FSH stores within the cells, or the levels of LH released. GDF9 appeared to act in a BMP-like manner by suppressing FSH secretion. The BMPRIB receptor however, was not found to co-localise with gonadotroph cells in either Booroola or wildtype pituitary tissues. These findings imply that the increased sensitivity of Booroola cells to BMP2, BMP4, BMP6, and GDF9 cannot be due to the direct action of the BMPRIB mutant Booroola receptor in the cells that synthesize FSH. The alternative type I BMP receptor to BMPRIB that can act in BMP signal transduction is BMPRIA. This receptor was also not found in gonadotroph cells of wildtype orBooroola ewes This is in contrast to findings in other flocks which have been shown to express BMPRIA in gonadotroph cells.
This study has identified unique sets of differentially regulated genes in response to BMP-2, 4, 6, and 7 as well as TGFβ1 in a human HEK293T cell culture system. Among the differentially expressed genes, a common set of 12 genes were upregulated by all BMP ligands. None of these genes were present in the TGFβ1 set. Selected genes were validated in ovine primary granulosa cell cultures, showing that the human cell culture system functions similarly to cells of biologial relevance in fertility. Within the pituitary gland, BMPs are shown to influence FSH secretion. The presence of the Booroola mutation enhances the BMP effects on gonadotroph cells, however the lack of BMPRIB on gonadotroph cells indicates that the effects are indirect.
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Gambari, Laura <1985>. "Hydrogen Sulfide (H2S) Based Therapeutics for Bone Diseases: Translating Physiology to Treatments." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7535/.
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Much progress has been made in the past decade in elucidating the physiological, pathophysiological and pharmacological role of Hydrogen Sulphide (H2S). Recently a function of H2S virtually in every tissue of the human organism has emerged. However, the H2S-mediated regulation of bone homeostasis has been scarcely investigated. Despite a recent increased interest in the field, many fundamental issues remain indeterminate. The main objective of this study was to increase the basic knowledge on the role of H2S in bone through in vitro and in vivo studies and develop novel therapeutic strategies for bone diseases. Ex vivo experiments revealed that H2S-generating enzymes (Cystathionine-β-synthase, CBS; Cystathionine-γ-lyase, CSE) are expressed in human bone tissues and human bone-derived cells. In vitro experiments evidenced that CBS and CSE expression is a distinctive feature of the transition of mesenchymal stromal cells (h-MSCs) toward mature osteoblast. Furthermore, loss of function experiments on CBS and CSE during osteogenic differentiation of h-MSCs revealed an impaired mineralization ability. In vivo experiments in mice highlighted the role of CBS, CSE and H2S in the maintenance of bone homeostasis and CBS, CSE and H2S were found to be depleted in post-menopausal osteoporosis. Furthermore, our in vitro and in vivo data validated the use of H2S-donors as novel potential candidates for the treatment of bone pathologies. In particular H2S administration prevented and reversed ovariectomy-induced bone loss in mice. Based on these evidences, we firstly developed an H2S-releasing hybrid drug (DM-22) by modifying a clinically relevant anti-resorptive drug in order to improve the therapy of bone loss. DM-22 displayed improved biological properties compared to the parent drug; in particular, it increased the osteogenic differentiation ability of h-MSCs. Secondly, we developed an H2S-releasing scaffold to improve bone regeneration which was permissive for h-MSCs colonization and supported their osteogenic differentiation.
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Sutton, Amelia L. "The Regulation and Function of 1,25-Dihydroxyvitamin D3-Induced Genes in Osteoblasts." Case Western Reserve University School of Graduate Studies / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=case1121820822.
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