Primarily synthesised via cutaneous exposure to solar ultraviolet B (UVB) radiation, serum vitamin D concentrations, measured as 25-hydroxyvitamin D (25(OH)D), fluctuate according to solar availability. Seasonal variations in vitamin D are common in areas of high or low latitude determined by the distance from the sun. Seasonal variations in blood pressure, immune markers and some diseases including influenza, have also been reported. However, the contributions of UVB light or vitamin D on the immune markers have not been fully determined. Against this background, the purpose of this research was to investigate the effects of UVB light therapy and dietary vitamin D supplementation on markers of immune function. The D SIRe1 study aimed to assess whether dietary-derived 25(OH)D could have similar effects on immune function as light-derived 25(OH)D. The study was an 8-week comparative intervention trial in healthy adults randomised to receive either 3 times weekly UVB radiation (equivalent to doses received during a Grampian-summer) for 4 weeks; or oral vitamin D3 (1000 IU a day for 8 weeks). Total 25(OH)D was measured by dual tandem mass spectrometry of serum samples following removal of protein and de-lipidation, whilst regulatory T cells (Tregs), known for maintaining immune system homeostasis, by flow cytometry. The study showed similar short-term effects between oral vitamin D and UVB exposure on measured outcomes. However, study interpretation was limited by the lack of a placebo group, yet, to our knowledge, this was the first study to directly compare dose-matched UVB therapy and vitamin D supplementation in healthy participants. Using similar laboratory techniques, the D-SIRe2 study, a placebo-controlled trial, assessed short-term (12 weeks) and long-term (43 weeks) effects of vitamin D supplementation on immune markers. Commencing in spring (March) and finishing in winter (January) 2015/2016, the study showed seasonal fluctuations in most immune markers. The fluctuations did not change according to variations in 25(OH)D concentrations nor were they correlated with solar UVB doses, with the exception of T cell proliferative responses, which were positively correlated with daily solar UVB doses. An interesting finding from this study was the prevention of increases in pro-inflammatory IFN-γ cytokine concentrations in the spring and summer time in the vitamin D3 supplemental group versus placebo. IFN-γ concentrations were raised from 7940 pg/mL at baseline in March, to roughly 12400 pg/mL at week 4 and to 13909 pg/mL at week 12 in the placebo group. The concentrations were roughly 1.3 times the mean concentrations measured in the vitamin D group at the timepoints following baseline concentrations of 10678 pg/mL, and 10013 pg/mL and 10233 pg/mL at weeks 4 and 12, respectively. The interactions between solar light or seasonal effects and oral vitamin D supplementation, as well as their individual and combined effects on immune function, are yet to be fully determined. Moreover, the metabolic and physiological implications of seasonal variation in serum 25(OH)D concentration and markers of immune function are currently unknown, requiring further investigation.

INTRODUCTION: The incidence of pediatric nephrolithiasis (kidney stones) has been increasing over the past several years. While environmental factors, such as poor fluid intake, high-salt diet, and obesity, can play a role, underlying metabolic factors account for at least one-third of cases of nephrolithiasis. Nephrolithiasis and related disorders, such as nephrocalcinosis and hypercalciuria, can lead to long-term kidney problems, including renal scarring, acute and chronic kidney disease, decreased renal function, or end-stage renal disease. The best treatment is prevention and is best guided by knowing the underlying cause. The majority of kidney stones are primarily comprised of calcium, and abnormal calcium metabolism and regulation can lead to nephrolithiasis, nephrocalcinosis, and hypercalciuria. Vitamin D is an important factor in calcium regulation in the body. The physiologically active form of vitamin D is 1α,25-dihydroxyvitamin D (1,25(OH)2D), which increases serum calcium by stimulating intestinal absorption of calcium, increasing renal calcium reabsorption, and mobilizing calcium from bone. Excess 1,25(OH)2D has been shown to be associated with hyperabsorption of calcium in the intestine, nephrolithiasis, hypercalcemia, and hypercalciuria. Production of 1,25(OH)2D requires hydroxylation of 25-hydroxyvitamin D by the kidney enzyme 1α-hydroxylase, which is regulated in turn by serum calcium, parathyroid hormone (PTH), and by 1,25(OH)2D itself. Tight control of 1,25(OH)2D levels is maintained in part by the breakdown of 1,25(OH)2D by the enzyme 24-hydroxylase, which is encoded by the gene CYP24A1. In the past few years, CYP24A1 mutations leading to decreased activity of 24-hydroxylase have been implicated in some cases of idiopathic infantile hypercalcemia as well as nephrolithiasis, nephrocalcinosis, and hypercalciuria. The prevalence of 24-hydroxylase deficiency is not known, and the spectrum of its clinical manifestations is not yet fully understood. Our study aims to describe the clinical characteristics of patients with laboratory findings suggestive of 24-hydroxylase deficiency, specifically high-normal or elevated serum 1,25(OH)2D. We aimed to determine the prevalence of elevated 1,25(OH)2D among pediatric patients with nephrolithiasis, and to compare clinical outcomes and biochemical findings in patients with normal versus elevated 1,25(OH)2D. PATIENTS AND METHODS: This study was a retrospective chart review. To determine the prevalence of high-normal (56-75 pg/mL) and high (>75 pg/mL) serum 1,25(OH)2D, we reviewed electronic medical records of patients seen in the Boston Children's Hospital Stone Clinic. We identified 346 patients who were evaluated for nephrolithiasis, were under 18 years of age at the time of presentation, and had at least one measurement of 1,25(OH)2D. Patients were classified based on their highest measured level of 1,25(OH)2D. To determine the clinical characteristics of patients with elevated 1,25(OH)2D, we reviewed clinical records and laboratory data of patients at Boston Children's Hospital with a diagnosis of nephrolithiasis, nephrocalcinosis, or hypercalciuria. We identified 83 patients who met our inclusion criteria: age of onset <18 years, at least one measurement of 1,25(OH)2D, and a pre-treatment urine solute analysis. Data collected included demographic information, diagnoses, family history of kidney disease, treatments, laboratory data, and urine solute analyses. We compared findings in patients with normal 1,25(OH)2D (≤55 pg/mL) versus elevated 1,25(OH)2D (>55 pg/mL). RESULTS: Of 346 children with nephrolithiasis in whom 1,25(OH)2D was measured, 100 (28.9%) had high 1,25(OH)2D, and an additional 120 (34.7%) had high-normal 1,25(OH)2D. To determine the clinical characteristics of elevated 1,25(OH)2D, we analyzed the data of 40 patients with normal 1,25(OH)2D and 43 patients with elevated 1,25(OH)2D who had a history of nephrolithiasis, nephrocalcinosis, or hypercalciuria. Seventy-five children had nephrolithiasis, and 25/37 (67.6%) of children with elevated 1,25(OH)2D had a recurrence of nephrolithiasis, compared to only 9/38 (23.7%) of children with normal 1,25(OH)2D (p < .001). Urine calcium/creatinine ratio did not differ between the two groups. However, linear regression analysis showed an association between 1,25(OH)2D levels and urine calcium/creatinine ratio. Important secondary findings included a younger age of onset, higher serum 25-hydroxyvitamin D, and lower parathyroid hormone levels in patients with elevated 1,25(OH)2D. CONCLUSIONS: Important clinical findings of this study were the increased rate of recurrence and the younger age of onset in patients with elevated 1,25(OH)2D. While we recognize that mutations in CYP24A1 do not account for the majority of cases of elevated 1,25(OH)2D, we do advocate for special consideration for these patients. In the absence of a commercially-available assay for 24-hydroxylase activity, children with nephrolithiasis, nephrocalcinosis, or hypercalciuria and elevated 1,25(OH)2D should be closely monitored for recurrence or worsening of symptoms. Furthermore, we advise caution in the use of vitamin D repletion in at-risk patients.

abstract: ABSTRACT Despite significant advancements in drug therapy, cardiovascular disease (CVD) is still the leading cause of death in the United States. Given this, research has begun to seek out alternative approaches to reduce CVD risk. One of these alternative approaches is Vitamin D supplementation. Current research has shown a link between Vitamin D status and CVD risk in both healthy and diseased populations. Among the possible mechanisms is a positive effect of Vitamin D on vascular endothelial function, which can be measured with noninvasive techniques such as flow-mediated dilation (FMD) of conduit vessels using high-resolution ultrasound. This dissertation is comprised of two studies. The first examines whether Vitamin D supplementation can improve FMD in older adults within a time period (two weeks) associated with peak increases in plasma Vitamin D concentrations after a single-dose supplementation. The second examines the effect of Vitamin D supplementation in people with Rheumatoid Arthritis (RA). The reason for looking at an RA population is that CVD is the leading cause of early mortality in people with RA. In the first study 29 Post-Menopausal Women received either 100,000 IU of Vitamin D3 or a Placebo. Their FMD was measured at baseline and 2 weeks after supplementation. After 2 weeks there was a significant increase in FMD in the Vitamin D group (6.19 + 4.87 % to 10.69 + 5.18 %) as compared to the Placebo group (p=.03). In the second study, 11 older adults with RA were given 100,000 IU of Vitamin D or a Placebo. At baseline and one month later their FMD was examined as well as plasma concentrations of Vitamin D and tumor necrosis factor-alpha; (TNF-alpha;). They also filled out a Quality of Life Questionnaire and underwent a submaximal exercise test on the treadmill for estimation of maximum oxygen uptake (VO2max). There was no significant change in FMD in Vitamin D group as compared to the Placebo group (p=.721). Additionally, there was no significant improvement in either plasma Vitamin D or TNF-alpha; in the Vitamin D group. There was however a significant improvement in predicted VO2max from the submaximal exercise test in the group receiving Vitamin D (p=.003). The results of these studies suggest that a single 100,000 IU dose of Vitamin D can enhance FMD within two week in older adults, but that a similar dose may not be sufficient to increase FMD or plasma Vitamin D levels in older adults with RA. A more aggressive supplementation regimen may be required in this patient population. / Dissertation/Thesis / Ph.D. Exercise and Wellness 2012

Made available in DSpace on 2014-06-11T19:33:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2001-12-14Bitstream added on 2014-06-13T18:45:02Z : No. of bitstreams: 1 selaimen_crp_dr_arafo.pdf: 295719 bytes, checksum: 63e6e9d608d36175f2e5f4abcc90be71 (MD5) / Foi realizada uma investigação na resposta histológica do periodonto de sustentação de 30 ratos da raça Wistar submetidos a condições nutricionais com ou sem deficiência de cálcio e vitamina D. Os primeiros molares inferiores direitos dos ratos receberam dispositivos ortodônticos (colocados entre o primeiro molar inferior e o incisivo central do mesmo lado, na mandíbula), constituídos de molas de níquel-titânio que liberam em torno de 50g de força durante os períodos de 1, 7 e 14 dias. Os molares do lado esquerdo não receberam aparelho. Os ratos do grupo experimental foram submetidos à dieta deficiente em cálcio e vitamina D, durante os 30 dias que precederam a instalação do dispositivo ortodôntico, assim como durante os dias do experimento. Sob as mesmas condições ortodônticas, os ratos do grupo controle receberam uma dieta equilibrada. Os resultados evidenciaram que a resposta morfológica não foi alterada na seqüência dos seus eventos, mostrando significantes diferenças na estrutura do ligamento periodontal e do osso alveolar, os quais se exacerbaram nos períodos mais longos (7 e 14 dias). O estudo mostrou, ainda, que a estrutura do cemento não foi influenciada pela deficiência de cálcio e vitamina D. O fenômeno de aposição óssea parece ser aquele que discriminou as maiores diferenças entre os grupos controle e experimental. Para todos os grupos e períodos, a inflamação esteve sempre presente. / Orthodontic tooth movement is dependent on bone remodeling. Physiologic potential for bone remodeling is dependent on a balanced Calcium and vitamin D diet. Imbalances of these components are common among children and adolescents today. To evaluate the influences of the deficient diet periodontal tissues was studied. 30 Wistar rats received a NiTi orthodontic coil spring producing 50 gr. of force to moving the lower first right molar against the lower incisor during 1, 7 and 14 days. The lower first left molar was free os appliance. Fifteen specimens who served as controls were fed with a standardized balanced diet while the experimental group had a deficient calcium and vitamin D diet. The histopathologic evaluation on the stained sections with H&E and trycromic of Masson showed that Ca and Vitamin D had a marked influence on the bone turnover surrounding the molar, subject to orthodontic movement. The findings show a significant reduction of formative bone on the interradicular bone crest. There were no differences in resting and resortion bone surfaces but the cement exhibited less resorptive areas in the experimental group. In the left side alveolar bone was substtituided by inflamatory cells. This study indicated that a compromised bone remodeling occurs during orthodontic treatment when there is a diet restriction in calcium and Vitamin D.

abstract: Vitamin D deficiency has been previously associated with a higher Alzheimer’s disease (AD) risk, a condition marked by dependent living and severe cognitive impairment. AD is histologically defined by the presence of brain amyloid beta (Aβ) plaques and neurofibrillary tangles. Ways to enhance Aβ clearance have been examined in order to sustain cognition and delay AD onset. In vitro and in vivo studies suggest that vitamin D might enhance brain Aβ transportation to the periphery by up-regulating P-glycoprotein production. The purpose of this study was to examine the effect of vitamin D supplementation on plasma Aβ in an older population. This study was a parallel-arm, double-blinded, randomized control trial. Participants consumed either a vitamin D supplement or placebo once a week for eight weeks (n=23). Only vitamin D insufficient (serum total 25-OH, D < 30 ng/mL) people were included in the study, and all participants were considered to be cognitively normal (MMSE scores > 27). Serum total 25-OH, D and plasma Aβ1-40 measurements were recorded before and after the eight-week trial. The plasma Aβ1-40 change was compared between the vitamin D group and control group. The vitamin D group experienced a 45% greater change in plasma Aβ1-40 than the control group. The effect size was 0.228 when controlling for baseline plasma Aβ1-40 (p=0.045), 0.197 when controlling for baseline plasma Aβ1-40 and baseline physical activity (p=0.085), and 0.179 when controlling for baseline plasma Aβ1-40, baseline physical activity, and age (p=0.116). In conclusion, vitamin D supplementation might increase brain Aβ clearance in humans, but physical activity and age also appear to modulate Aβ metabolism. / Dissertation/Thesis / Masters Thesis Nutrition 2015

Master of Science / Department of Animal Sciences and Industry / Jim Nelssen / A thorough literature review on feeding vitamin D₃ and 25(OH)D₃ revealed a large amount of research conducted in swine and poultry. In general, increasing vitamin D₃ concentrations or adding 25(OH)D₃ to the maternal diet increases the vitamin D₃ status of the dam and often the progeny as well. Varying results have been reported on the practical and valuable impacts of this elevated status with some topics including improved sow performance, changes in muscle fiber morphometrics, and growth performance to market. The first experiment used a total of 69 sows and the progeny from one group of 22 sows to determine the effects of feeding a combination of vitamin D₃ and 25(OH)D₃ to the sow. Differences in sow productivity and growth performance of progeny due to dietary treatment were not observed (P > 0.05). When pigs were sacrificed at birth, there were no treatment effects for all fiber morphometric measures (P > 0.170), except primary fiber number and the ratio of secondary to primary muscle fibers (P < 0.014). Pigs from the CON and DL fed sows had less primary fibers than pigs from sows fed the DH treatment (P < 0.046), but did not differ from each other (P = 0.732). These results suggest progeny went through a longer prenatal period of primary myogenesis which delayed the onset of secondary myogenesis. Pigs from DL fed sows had a smaller secondary to primary muscle fiber ratio compared to pigs from sows fed the CON treatment (P = 0.016), with pigs from sows fed DL treatment not differing from either (P > 0.057). There were treatment x time interactions for all sow and pig serum metabolites (P < 0.001). Therefore, we chose to compare treatment means within time period. At all time periods, sow serum 25(OH)D₃ concentrations differed for all treatments with the magnitude of difference largest at weaning (P < 0.011). The second and third experiment investigated the impact of adding benzoic acid and an essential oil blend to diets and creep feed. When these additives were included in growing pig diets in a 28-d trial, a main effect of time (P < 0.001) was detected where there was no evidence of difference during the first 3 weeks for ADG and G:F, however both responses decreased during the final week of the experiment (P < 0.001) and average pen BW increased (P < 0.001) for all time points. There was a treatment x time interaction (P = 0.003) for ADFI where during the first 3 weeks, there was no evidence of difference due to dietary treatment, but during the final week of the study, pigs consumed more (P = 0.007) of the control diet (2.38 kg/d control vs. 2.24 kg/d benzoic acid paired and essential oil blend). Fecal samples collected provided no evidence of differences (P > 0.05) in fecal pathogens due to dietary treatment. When these additives were included in the maternal diet and in the creep feed, they did not (P > 0.05) affect sow performance or preweaned piglet performance. Fecal swabbing of pigs the day before weaning showed they did not eat the creep feed and, therefore, no (P > 0.05) improvements in growth performance were observed in the nursery. In conclusion, adding benzoic acid and an essential oil blend to diets and creep feed did not affect growth performance and combining vitamin D₃ and 25(OH)D₃ in the maternal diet improved the vitamin D₃ status of the dam and progeny and increased primary muscle fibers at birth.

Submitted by Irene Nascimento (irene.kessia@ufpe.br) on 2016-10-06T19:45:18Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação SEM ASSINATURAS digital 15 agosto.pdf: 2546414 bytes, checksum: 1e36b1b598390d7b76a91504316b19ff (MD5) / Made available in DSpace on 2016-10-06T19:45:18Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação SEM ASSINATURAS digital 15 agosto.pdf: 2546414 bytes, checksum: 1e36b1b598390d7b76a91504316b19ff (MD5) Previous issue date: 2016-05-31 / Avaliar associação de deficiência de vitamina D com risco cardiovascular e risco de insuficiência cardíaca em idosos atendidos em ambulatório de cardiologia. Estudo de corte transversal com abordagem analítica. Foram coletados dados de prontuários de pacientes com idade a partir dos 60 anos, no Núcleo de Atenção ao Idoso e no ambulatório de cardiologia, do Hospital das Clínicas da UFPE do período de agosto a novembro de 2015. As variáveis dependentes (Sheffield e o risco de insuficiência cardíaca avaliado pelo questionário ABC), e a independente, a deficiência de vitamina D. A idade, sexo, escolaridade, etnia, hipertensão, diabetes mellitus, hipotireoidismo, insuficiência renal, demência, acidente vascular cerebral, dislipidemia, depressão, tabagismo, etilismo, obesidade, andropausa, arritmia cardíaca foram consideradas intervenientes. Na análise dos dados, para testar a associação entre as variáveis foram empregados o teste Qui-quadrado de Pearson e o teste exato de Fisher. Na análise logística multivariada admitiu-se ponto de corte p-valor≤ 0,20, fornecido pela análise bivariada. No modelo de regressão logística foi utilizado o método stepwise. Para análise da significância das variáveis foi feita utilizando-se o teste Wald e para a associação entre o risco cardiovascular e o de insuficiência cardíaca foi utilizado o teste Qui-quadrado. Dentre os 137 idosos, mulheres (75,9%), sobrepeso (48,2%) ou obesidade (30,6%); aumento do índice cintura/quadril (88,3%) e dislipidemia (94,2%). Identificou-se 91,2% hipertensos; 35,0% com doença coronariana definida ou possível e 27,7% com arritmia cardíaca ou hipertrofia de ventrículo esquerdo. 65% dos idosos tinham deficiência de vitamina D, com maiores riscos: sexo masculino (OR: 3,94; IC 95%=1,41-11,04; p=0,006), faixa etária ≤70 anos (OR:2,06; IC 95% =1,01-4,20; p=0,04); tabagistas (OR: 5,0; IC95% =2,02-12,34; p=0,000); obesos (OR: 8,19; IC95%=2,71-24,78; p=0,000); diabéticos (OR: 3,39; IC 95%=1,50-7,64; p=0,002), com pontuação compatível com demência (OR: 4,79; IC 95% =1,56-14,66; p= 0,003); depressão (OR: 2,679; IC 95% =1,155-6,214; p=0,02), arritmia cardíaca (OR: 2,54; IC 95%=1,05-6,11; p=0,034), doença coronariana (OR:15,34; IC 95%=4,43-53,03; p=0,000); hipertrofia ventricular esquerda ou redução da fração de ejeção ventricular esquerda (OR: 33,44; IC95%= 4.41-253,37; p=0,000). 56,9% dos idosos apresentaram risco aumentado de insuficiência cardíaca e 67,2% tinham alto risco cardiovascular. Houve associação entre ambos os riscos (p<0,001). O risco de insuficiência cardíaca esteve associado significativamente à deficiência de vitamina D (OR:4,53; IC95%=1,94-10,59; p=0,000); sexo masculino (OR: 15,32; IC 95%=3,39-69,20; p=0,000); obesidade (OR: 4,17; IC95%=1,36-12,81; p= 0,012); arritmia cardíaca (OR 3,69; IC 95% = 1,23-11,11; p=0,020). O risco cardiovascular foi fortemente associado com deficiência de vitamina D (OR: 4,53; IC95% = 1,94-10,59; p=0,000); baixa escolaridade (OR: 1,91;IC 95%=0,81-4,48; p=0,134); depressão (OR:3,22;IC95%=1,14-9,09; p=0,027) e obesidade (OR: 3,03;IC95%=0,98-9,37;p=0,054). Houve alta prevalência de deficiência de vitamina D nos idosos e forte associação entre deficiência de vitamina D e aumento dos riscos cardiovascular e de insuficiência cardíaca nesta população. / To assess vitamin D deficiency associated with cardiovascular risk and risk of heart failure in elderly patients in outpatient cardiology clinics. Cross-sectional study with analytical approach. Data were obtained from files of patients older than 60, in the Care Center for Aged People and in the Cardiology Ambulatory of the Clinic Hospital of the Federal University of Pernambuco, the period from August to November 2015. The dependent variables (Sheffield and risk of heart failure as appraised by the ABC questionnaire), while the independent variable is the vitamin D deficiency. Age, gender, level of education, ethnic group, hypertension, diabetes mellitus, hypothyroidism, renal failure, dementia, stroke, dyslipidemia, cardiac arrhythmia, depression, smoking, alcoholism, obesity, andropause were intervening variables. In the data analysis, to test the association between variables were used the chi-square test of Pearson and Fisher's exact test. In multivariate logistic analysis was admitted to p-point valor≤ 0.20 cut, provided by bivariate analysis. In the logistic regression model was used the stepwise method. To analyze the significance of the variables was made using the Wald test and the association between cardiovascular risk and heart failure was performed using Chi-square test. Of the 137 elderly women (75.9%), overweight (48.2%) or obese (30.6%); increasing the index waist / hip (88.3%) and lipids (94.2%). It was identified 91.2% hypertensive; 35.0% with definite or possible coronary artery disease and 27.7% with cardiac arrhythmia or left ventricular hypertrophy. 65% of the elderly were deficient in vitamin D, with higher risks: males (OR: 3.94; 95% CI = 1.41 to 11.04, p = 0.006), age ≤70 years (OR: 2.06; 95 % = from 1.01 to 4.20; p = 0.05); smokers (OR: 5.0; 95% CI = 2.02 to 12.34, p = 0.000); obese (OR: 8.19, 95% CI 2.71 to 24.78; p = 0.000); diabetes (OR: 3.39; 95% CI = 1.50 to 7.64; p = 0.003), with scores compatible with dementia (OR: 4.79; 95% CI = 1.56 to 14.66; p = 0.003); depression (OR: 2.679; 95% CI = 1.155 to 6.214; p = 0.02), cardiac arrhythmia (OR: 2.54; 95% CI = 1.05 to 6.11; p = 0.045), coronary heart disease ( OR: 15.34; 95% CI = 4.43 to 53.03, p = 0.000); left ventricular hypertrophy or reduced left ventricular ejection fraction (OR: 33.44; 95% CI = 4.41-253,37; p = 0.000). The sample revealed 56,9% of the aged with increased risk of heart failure and 67,2% with high cardiovascular risk. Association between both risks became clear (p < 0.001). The risk of heart failure was significantly associated with vitamin D deficiency (OR 12.19, 95% CI 4.23 - 35.16; p = 0.000); male (OR: 15.32; 95% CI = 3.39 - 69.20, p = 0.000); obese (OR: 4.17, 95% CI 1.36- 12.81; p = 0.012); cardiac arrhythmia (OR 3.69, 95% CI = 1.23 to 11.11, p = 0.020). Cardiovascular risk was strongly associated with vitamin D deficiency (OR: 4.53, 95% CI 1.94 - 10.59; p = 0.000); low educational level (OR: 1.91; 95% CI = 0.81- 4.48; p = 0.134); depression (OR: 3.22; 95% CI = 1.14 - 9.09; p = 0.027) and obesity (OR: 3.03; 95% CI = 0.98 - 9.37; p = 0.054). There was a high prevalence of vitamin D deficiency in the elderly and strong association between vitamin D deficiency and increased cardiovascular risk and heart failure in this population.

Orientador: Sergio Roberto Peres Line / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-15T00:52:49Z (GMT). No. of bitstreams: 1 Ramenzoni_LizaLima_D.pdf: 1680205 bytes, checksum: 6080ff087e6c9a65c1f6a082b0ad1d36 (MD5) Previous issue date: 2009 / Resumo: O gene PAX9, pertencente à família Pax, é amplamente expresso em vários tecidos craniofaciais durante o desenvolvimento. Sabe-se que mutações neste gene em humanos causam fenótipo de oligodontia, afetando os dentes molares e segundos pré-molares. Grande variedade de agentes fisiológicos e farmacológicos externos podem ter impacto relevante na regulação da atividade transcricional de genes modulando fatores de transcrição. A presente tese focaliza o estudo da região 5'do gene PAX9 humano e tem como objetivo analisar a influência da dexametasona, ácido retinóico e ergocalciferol (vitamina D2) na atividade transcricional de sua região promotora, utilizando construções em vetor plasmideano que dirige a transcrição do gene da luciferase de vagalume (Photinus pyralis, pGL3 basic vector). Para ensaios de transcrição, foram amplificados através de ensaios com transcriptase reversa, transcritos do gene PAX9 de células mamárias de adenocarcinoma MCF-7 e células odontoblastóides de camundongo MDPC23. Estes transcritos foram quantificados através de PCR quantitativo. Fragmentos da região promotora do gene PAX9 humano de 1198pb (-1106 - +92), 843pb (-751- +92) e 691bp (-1106 - +92 com deleção de 507pb nos sítios -645 e -138) foram recombinados com vetor de expressão pGL3Basic e denominados PAX9-pGL3B1, PAX9-pGL3B2 e PAX9-pGL3B3, respectivamente. As contruções foram transfectadas em cultura de células mamárias de adenocarcinoma MCF-7 e células odontoblastóides de camundongo MDPC23. Todas as placas de cultura foram submetidas à ação de três drogas: dexametasona (DEX), ácido retinóico (RE) e ergocalciferol (VITD2). Após lise das células, os níveis relativos de expressão da proteína luciferase foram analisados com o uso do kit Dual-Glo Luciferase em luminômetro. Os resultados referentes às células mamárias de adenocarcinoma MCF-7 mostraram que: 1) Altas concentrações de ácido retinóico aumentaram a síntese de RNA mensageiro transcrito. 2) Fragmentos do promotor PAX9 de 1198pb (PAX9-pGL3B1) e 843pb (PAX9-pGL3B2) foram ativados na presença de ácido retinóico mas suas transcrições desestimuladas na presença da dexametasona e ergocalciferol. 3) A atividade da luciferase na construção PAX9-pGL3B2 foi mais fraca que outras duas construções, indicando que a sequência -1106 and -751 ou 355pb era importante para a atividade transcricional. 4) Fragmento do promotor clivado nos sítios -645 e -138 com deleção de 507pb (PAX9-pGL3B3) foi ativado negativamente somente na presença do ergocaciferol, enquanto que com a dexametasona e ácido retinóico o mesmo não foi afetado. Quanto às células odontoblastóides de camundongo MDPC23, os resultados mostraram que: 1) Todas as concentrações de ergocalciferol influenciaram positivamente a síntese de RNA mensageiro transcrito. 2) A atividade promotora das construções PAX9-pGL3B1 e PAX9-pGL3B2 foi aumentada com baixa concentração de dexametasona e ergocaciferol enquanto que alta concentração diminuiu esta atividade. 3) Na construção PAX9-pGL3B3, todas concentrações de ergocaciferol influenciaram a transcrição do promotor negativamente, enquanto que com a dexametasona e ácido retinóico, a mesma não foi afetada. Concluímos que as drogas dexametasona, ácido retinóico e ergocalciferol podem modular a expressão do gene PAX9. A região de 507pb deletada do promotor do gene PAX9 humano pode conter sítios de ligação para receptores do ácido retinóico e dexametasona. / Abstract: PAX9, member of the family homeobox, has important functions in embryogenesis and it is widely expressed in various craniofacial tissues during development. PAX9 mutations in human families cause autosomal dominant oligodontia, characterized by the absence of permanent molars and pre-molars. A great variety of physiological or pharmacological environmental factors may have impact on downstream signaling cascades and transcriptional regulation of gene modulating transcription factors. This work focused on the analysis on the 5'-flanking region of the PAX9 gene studying the influence of retinoic acid, dexamethasone and vitamin D on the expression of PAX9 by expression constructs that carry the reporter gene luciferase (Photinus pyralis, pGL3 basic vector). In the present study, we have PCR amplified cDNAs encoding mouse Pax9 from Mouse Odontoblast Cell-Like-23 (MDPC23) and PAX9 from Human breast adenocarcinoma (MCF-7) and quantified by Quantitative PCR. We examined the transcriptional activity of human PAX9 promoter from constructions: 1) PAX9-pGL3B1 construct clone PAX9 gene promoter 1198bp from -1106 upstream to +92 downstream of translation start site (ATG). 2) PAX9-pGL3B2 construct clone PAX9 gene promoter 843bp from -751 upstream of translation start site (ATG) to +92 downstream of translation start site (ATG). 3) PAX9-pGLB3 construct clone PAX9 gene promoter 691bp from -1106 upstream of translation start site (ATG) to +92 downstream of translation start site (ATG) using deletion of 507bp in restriction sites (-645 and -138) of ApaI enzyme. These constructions were transfected into Mouse Odontoblast Cell-Like-23 (MDPC23) and PAX9 from Human breast adenocarcinoma (MCF-7). Cell cultures were all submitted to selective regulation of tree drugs: dexamethasone (DEX), retinoic acid (RE) and ergocalciferol (VITD2). Relative luciferase expression units were obtained by dual luciferase assay kit. The results in Human breast adenocarcinoma (MCF-7) showed that retinoic acid and dexamethasone influenced negatively the expression of PAX9 promoter. PAX9-pGL3B1 and PAX9-pGL3B2 promoter was inhibited under the treatment of dexamethasone and ergocalciferol. Retinoic acid and dexamethasone did not altered PAX9-pGL3B3 (-1106 to +92, 507bp deleted with ApaI digest) behavior. Luciferase activity in plasmid PAX9-pGL3B2 was always weaker than the other two constructions indicating that sequence present between -1106 and -751 or 355bb were important for the transcriptional activity of PAX9 promoter. The results in Mouse Odontoblast Cell-Like-23 (MDPC23) showed that it PAX9-pGL3B1 and PAX9-pGL3B2 promoter activity was increased by the treatment of lower concentration of dexamethasone and ergocalciferol, whereas higher concentration of the same drugs decreased this activity. The effect of the retinoic acid in the luciferase activity of PAX9-pGL3B1 has the same pattern but for the PAX9-pGL3B2, all concentrations increased the promoter activity. For the PAX9-pGL3B3 construction, concentrations of ergocalciferol had a statistically significance decreasing the activity of the promoter and no effect of the activity was observed in the dexamethasone and retinoic acid treatment. In conclusion, dexamethasone, retinoic acid and ergocalciferol may bind to PAX9 gene promoter and up or down-regulate PAX9 transcriptional activity. A 507bp region (-645 and -138) within PAX9 promoter may harbor biding sites for dexamethasone and retinoic acid since none of concentrations of these reagents influenced changes in promoter activity. / Doutorado / Histologia e Embriologia / Doutor em Biologia Buco-Dental

Orientador: Jose Eduardo Tanus dos Santos / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-12T08:46:01Z (GMT). No. of bitstreams: 1 Rezende_VaniaBraghinide_M.pdf: 3064536 bytes, checksum: de50c064d7a27c30aff305d7d7bbaa05 (MD5) Previous issue date: 2007 / Resumo: O receptor da vitamina D (VDR) possui um importante papel na toxicidade do chumbo (Pb). Poucos trabalhos avaliaram o efeito dos polimorfismos VDR sobre as concentrações circulantes do metal em populações expostas ambientalmente. Além disso, nenhum estudo avaliou o efeito da combinação desses polimorfismos (haplótipos) sobre os mesmos parâmetros. A análise de haplótipos (combinação de marcadores genéticos dentro de uma determinada região no cromossomo) tem demonstrado ser uma melhor ferramenta em comparação com a análise de polimorfismos (SNPs) vistos isoladamente. Nesse estudo, avaliamos o efeito dos haplótipos estimados a partir dos polimorfismos BsmI , ApaI e FokI do VDR sobre os níveis de Pb-S (chumbo no sangue), Pb-P (chumbo no plasma) e na fração %Pb-P/Pb-S (chumbo no plasma/chumbo no sangue) em 150 voluntários expostos ambientalmente ao chumbo (65 homens e 85 mulheres; idade: 18 a 57 anos). Os genótipos para todos os polimorfismos do VDR foram determinados por PCR seguido por digestão com enzimas de restrição (RFLP). Pb-P e Pb-S foram determinados por espectrometria de massas com plasma indutivamente acoplado (ICP-MS) e espectrometria de absorção atômica com forno de grafite, respectivamente. Os resultados mostraram que os polimorfismos do VDR estão associados às concentrações de Pb circulantes e que o haplótipo H8, formado pelos alelos a, b e f, está associado com menores concentrações de Pb-S, Pb-P e %Pb-P/Pb-S. Estes achados podem apresentar importantes implicações toxicogenéticas, sendo necessários estudos posteriores para elucidar os mecanismos responsáveis por tais efeitos. / Abstract: The Vitamin D Receptor (VDR) plays an important role in the toxicity of lead (Pb). Genetic factors, i.e polymorphisms, influence blood lead (Pb-B) concentrations in lead exposed subjects. However, only a few research studies have evaluated the effect of VDR polymorphism on the lead concentration in environmentally. Also, no studies have evaluated the combinatorial effect of these polymorphisms on the same parameters. The haplotype analysis (combination of genetic indicators in a certain region of the chromossome) has been shown to be a better tool if compared with the analyses of single polymorphisms. This study aimed at examining the combined effects (haplotype analysis) of three polymorphisms (BsmI , ApaI and FokI) in vitamin D receptor ( VDR) gene on Pb-B and on the concentrations of lead in plasma (Pb-P), which is more relevant to lead toxicity, in 150 environmentally exposed subjects (65 mens and 85 women). Genotypes were determined by RFLP, and Pb-P and Pb-B were determined by inductively coupled plasma mass spectrometry and by graphite furnace atomic absorption spectrometry, respectively. Subjects with the bb (BsmI ) or ff (FokI) genotypes have lower B-Pb than subjects in the other genotype groups. Subjects with the aa (ApaI ) or ff genotypes have lower P-Pb than subjects in the other genotype groups. Lower Pb-P, Pb-B, and %Pb-P/Pb-B levels were found in subjects with the haplotype combining the a, b, and f alleles for the ApaI , BsmI , and FokI polymorphisms, respectively, compared with the other haplotype groups. These findings may have important toxicogenetic implications and their molecular basis needs to be addressed in further studies. / Mestrado / Mestre em Farmacologia

Bakgrund: Man har länge vetat att vitamin D har grundläggande funktioner för vår kropps välbefinnande. Det finns två källor för att ta till oss D-vitamin, via endogen produktion och via födointag. Till en större del får vi vårt D-vitamin-behov genom den endogena processen, men på grund av färre UV-B strålar under vissa säsonger eller geografiska platser så kan denna process bli otillräcklig. Vilket gör oss tvungna att konsumera specifik mat eller kosttillskott för att ej få D-vitaminbrist. Detta har blivit ett stort problem för länder uppe i norr, på grund av att perioden utan tillräckliga mängder UV-B strålning är lång. Vissa länder till exempel Sverige försöker motverka detta genom att berika vissa livsmedel, bland annat mjölk, ost och smör, med D-vitamintillskott. Dock verkar detta mestadels inte vara tillräckligt. Då flera studier har visat ett mönster mellan D-vitaminbrist och lägre sinnesstämning, så har studier angående D-vitamin-påverkan på både kroppens mentala och fysiska tillstånd blivit allt viktigare. Syfte: Syftet med detta arbete är att granska D-vitamins gynnsamma effekt och om den kan klassificeras som läkemedel vid behandling av vinterdepression. Metod: Fem litteraturstudier med fokus på D-vitaminforskning och dess motverkande effekt av seasonal affective disorder (SAD) eller negativ sinnesstämning har granskats. Dessa studier valdes från databaserna; PubMed, Sciencedirect och OneSearch. Resultat: Studierna visade en svag koppling mellan D-vitamin och sinnesstämning. Dock kunde inga konkreta svar uppnås om hur D-vitamin påverkar oss mentalt. På grund av detta kan D-vitamintillskott inte ses eller rekommenderas som medicin för olika former av negativ sinnesstämning eller depression. Diskussion: För få studier har hittills gjorts för att kunna svara på hur D-vitamin påverkar oss mentalt och vilka följder en låg eller förhöjd 25-OH D koncentration har på en persons sinnesstämning. Fler studier behöver göras med både noggrannare och mer varierande metoder och kontroller för att kunna finna ett konkret svar på hur vår D-vitaminhalt är kopplad till vår sinnesstämning. Samt om en höjd nivå kan leda till förebyggandet av SAD, negativ sinnesstämning eller mild depression.