Purpose: To determine if there is an association between early childhood caries (ECC) and vitamin D deficiency, as measured via a serum sample. An exploratory goal was to investigate the possibility of measuring vitamin D with a salivary assay. Methods: Serum samples of patients who were scheduled for a dental or otolaryngology procedure under general anesthesia were assessed for 25-hydroxyvitamin D (25(OH)D), parathyroid hormone and calcium. Results: Our analysis indicates that the vitamin D levels of the controls and ECC group were significantly different. There were significant inverse correlations between: 1) PTH levels and vitamin D and 2) decayed, missing, filled teeth (dmft) and vitamin D. Conclusions: A relationship between low serum levels of vitamin D and the prevalence of ECC for children 0 to 6 years of age was observed. The salivary assay was unable to measure vitamin D, but future studies should still explore this non-invasive technique.

There is a paucity of longitudinal data investigating the role of vitamin D in the maintenance of health in ethnic minority groups. Specifically, little is known about the role of vitamin D on muscle strength, how this affected by emigrating from low to high latitudes. This PhD thesis provides insight into the relationship between vitamin D status and muscle strength in healthy adults migrating from sunny climates (45°N to 45°S to the equator) to higher latitude (Aberdeen, 57°N) (first study) and also sunlight behaviours in both low and high latitudes (second study). A total of 71 people of ethnic minority aged 19-42 years took part in the first study with 56% were seen within 3 months of arriving in Aberdeen (newcomers) and the remainder having been resident for any longer period than this (residents). Participants attended visits every 3 months for 15 months. At each visit, fasted blood samples were collected for analysis of serum 25-hydroxyvitamin D [25(OH)D] by dual tandem-mass spectrometry, parathyroid hormone (PTH), carboxy-terminal collagen crosslinks (CTX) and N-terminal propeptide of type I collagen (P1NP) by electrochemiluminescent immunoassay. Maximal voluntary contraction (MVC) was measured using a Takei digital grip dynamometer (both arms) and a Biodex dynamometer (right knee) for isometric knee extension and isokinetic knee extension and flexion. Mean baseline 25(OH)D concentrations were higher in the newcomers (35.2 nmol/L) than the residents (25.0 nmol/L, p<0.01). After adjusting for the season of measurement at baseline, there was a trend for higher vitamin D status only between newcomers arriving in spring (33.5 nmol/L) and residents (26.8 nmol/L, p=0.09), but not between the newcomers arriving in autumn (36.1 nmol/L) and residents in autumn (35.2 nmol/L, p=0.81). Notably, few newcomers (13%) and residents (7%) had 25OHD concentrations >50 nmol/L. There was a small seasonal variation in 25(OH)D concentration with the difference between zenith (summer/autumn) and nadir (winter/spring) was 5 nmol/L, 6 nmol/L, and 12 nmol/L among the newcomers arriving in spring, autumn and residents, respectively. There was no seasonal variation in bone turnover markers. There was a positive, albeit small, association between vitamin D and knee extensor isometric torque. Mixed modelling predicted that each 1 nmol/L increase in 25(OH)D would increase peak torque by 1 Nm (p=0.04). If extrapolated to higher 25(OH)D, the change in muscle strength would be clinically meaningful. In the second study, 117 Asians in Kuala Lumpur (3°N) and 110 non-Europeans (78% Asians) in Aberdeen were recruited and monitored for one year [every 3 months for participants in Aberdeen and during Southwest monsoon (SWM; July-Sept) and Northeast monsoon (NEM; Nov-Feb) in Kuala Lumpur]. Personal sunlight exposures were assessed by polysulphone film badges and a web-based questionnaire. Asians living in their usual environment (Kuala Lumpur) had similar sunlight behaviours to Asians living in Aberdeen. Sunlight was the major source of vitamin D in Kuala Lumpur during both seasons (median % cutaneous in SWM = 61%; NEM = 59%), but only during summer in Aberdeen (52%). Dietary intakes provided the most source of vitamin D in Aberdeen during autumn (94%), winter (97%) and spring (56%). This thesis has added evidence to the current limited observations on vitamin D and muscle strength, particularly in the cohort of young adults migrating from low to high latitudes. Intervention studies are yet to be conducted with a speculation that an increase in vitamin D status may show a positive impact on muscle strength. The extent of low sunlight behaviour among healthy adults in Kuala Lumpur is of concern.

Background: African Americans have disproportionately higher burden of prostate cancer compared to European Americans. However, the cause of prostate cancer disparities is still unclear. Several roles have been proposed for calcium and vitamin D in prostate cancer pathogenesis and progression, but epidemiologic studies have been conducted mainly in European descent populations. Here we investigated the association of calcium and vitamin D intake with prostate cancer in multiethnic samples. Methods: A total of 1,657 prostate cancer patients who underwent screening and healthy controls (888 African Americans, 620 European Americans, 111 Hispanic Americans, and 38 others) from Chicago, IL and Washington, D.C. were included in this study. Calcium and vitamin D intake were evaluated using food frequency questionnaire. We performed unconditional logistic regression analyses adjusting for relevant variables. Results: In the pooled data set, high calcium intake was significantly associated with higher odds for aggressive prostate cancer (ORQuartile (1 vs. Quartile) (4) = 1.98, 95% C.I.: 1.01-3.91), while high vitamin D intake was associated with lower odds of aggressive prostate cancer (ORQuartile 1 vs. Quartile (4) = 0.38, 95% C.I.: 0.18-0.79). In African Americans, the association between high calcium intake and aggressive prostate cancer was statistically significant (ORQuartile 1 vs. Quartile 4 = 4.28, 95% C.I.: 1.70-10.80). We also observed a strong inverse association between total vitamin D intake and prostate cancer in African Americans (ORQuartile 1 vs. Quartile 4 = 0.06, 95% C.I.: 0.02-0.54). In European Americas, we did not observe any significant associations between either calcium or vitamin D intake and prostate cancer. In analyses stratifying participants based on Body Mass Index (BMI), we observed a strong positive association between calcium and aggressive prostate cancer and a strong inverse association between vitamin D intake and aggressive prostate cancer among men with low BMI (<27.8 kg/m(2)), but not among men with high BMI (>= 27.8 kg/m(2)). Interactions of race and BMI with vitamin D intake were significant (P-Interaction < 0.05). Conclusion: Calcium intake was positively associated with aggressive prostate cancer, while vitamin D intake exhibited an inverse relationship. However, these associations varied by race/ethnicity and BMI. The findings from this study may help develop better prostate cancer prevention and management strategies.

BACKGROUND: Patients suffering from inflammatory bowel disease (IBD) are at increased risk of vitamin D deficiency. Daily or weekly vitamin D supplementation has not proven to be effective in improving vitamin D status, and it is thought that this failure has been primarily due to a lack of compliance. Circulating vitamin D is crucial to bone growth and development in children and adolescents. However, more recent data has demonstrated that vitamin D also plays a significant role in the maintenance and regulation of the immune system. OBJECTIVES: The primary aim of this study is to investigate the safety and efficacy of administering high dose oral vitamin D therapy in pediatric patients with IBD. We chose to study patients receiving Remicade, an immunosuppressive monoclonal antibody therapy administered intravenously, as the need for scheduled hospital-based infusions provides a unique opportunity to ensure compliance in our study population. METHODS: We identified consecutive pediatric patients with IBD with a recent 25-hydroxyvitamin D (25OHD) level < 30ng/mL, maintained on Remicade, and with no history of kidney or liver disease for inclusion in the study from November 2017 and November 2018. Enrolled patients received one-year of open-label therapy. Vitamin D treatment doses were assigned by Remicade interval and patients received either 50,000 international units (IU) (every 4-5 weeks) or 100,000 IU (every 6-8 weeks) vitamin D3 orally at the time of their Remicade infusions. In addition to vitamin D levels, spot urine calcium to creatinine ratios, serum calcium, phosphorus, and blood urea nitrogen (BUN) levels, quality of life metrics, and surveys pertaining to dietary vitamin D intake and ultraviolet B (UVB) radiation exposure were collected throughout the study period. RESULTS: Baseline vitamin D status in enrolled patients did not differ by gender, dosing group, diet, or diagnosis (Crohn disease or ulcerative colitis). Subjects reached steady-state serum 25OHD levels after three doses administered over a span of 4 to 8 months, our data demonstrated an increase in average 25OH vitamin D levels from 21.17 ng/mL to 28.19 ng/mL in the 50,000 IU and 23.00 ng/mL to 33.18 ng/mL in the 100,000 IU dose groups, respectively. The improvement in vitamin D status did not correlate with changes in quality of life or disease activity. The response to vitamin D therapy was independent of diet, sun exposure, race, gender, diagnosis, or season of enrollment. There were no adverse events, including changes in urine calcium to creatinine excretion or serum BUN and creatinine values. Several patients manifest a small decrease in serum phosphorus during the initial phase of the study. However, these changes were transient and no subjects exhibited clinical signs or symptoms of hypophosphatemia. CONCLUSION: High dose, interval vitamin D supplementation achieved steady-state 25OHD levels of 30 ng/mL or greater, with no signs of toxicity in patients enrolled in this pilot study. These data suggest that high-dose interval therapy may be a feasible treatment option that bypasses limitations related to difficulties with patient compliance. Further studies are necessary to determine optimal dosage regimens and to assess endpoints related to immune function and improvements to gastrointestinal health.

A hipovitaminose D hoje é considerada uma pandemia suas causas e consequências tem sido muito estudadas. Quando a população atendida é de pessoas vivendo com HIV/Aids as comorbidades parecem ser abreviadas tanto pela infecção viral como pela introdução da TARV. A Infecção Pelo HIV, apesar da terapia antirretroviral aumentar a expectativa de vida dos portadores do vírus, novos desafios se impõe no manejo clínico dos pacientes, tais como alterações neurológicas, distúrbios metabólicos como dislipidemias, lipodistrofia, resistência à insulina e osteopenia e osteoporose.. O objetivo foi avaliar a eficácia da suplementação de vitamina D em pacientes infectados pelo HIV, a despeito de tudo que é sabido de complicações e comorbidades advindas da infecção e dos efeitos adversos da terapia antirretroviral. Realizou-se um ensaio clínico controlado, randomizado, duplo cego, onde metade da coorte de 36 PVHA foram suplementadas com vitamina D (grupo 1) por 06 meses e 37 PVHA (grupo 2) com placebo. Como resultado verificou-se que a suplementação de colecalciferol (vitamina D3) foi eficaz, 80% dos pacientes tiveram níveis sanguíneos normalizados em seis meses de uso. Importante destacar a significância que houve em relação aos níveis de vitamina D e fumo, além disso o grupo que suplementou com vitamina teve resultado significativo(p<0,001) em relação ao aumento dos linfócitos TCD4. O Efavirenz pode influir de maneira negativa nos níveis de vitamina D e que a suplementação se faz necessária como um provável coadjuvante na melhora do CD4 e a dosagem adequada resulta na eficácia do tratamento. / Hypovitaminosis D today is considered a pandemic its causes and consequences have been much studied. When the population served is people living with HIV / AIDS, the comorbidities seem to be shortened by both viral infection and the introduction of ART. HIV infection, although antiretroviral therapy increases the life expectancy of HIV patients, new challenges are imposed in the clinical management of patients, such as neurological changes, metabolic disorders such as dyslipidemia, lipodystrophy, insulin resistance and osteopenia and osteoporosis. The aim of this study was to evaluate the efficacy of vitamin D supplementation in HIV-infected patients, despite the known complications and comorbidities of the infection and the adverse effects of antiretroviral therapy. A double-blind, randomized, controlled clinical trial was conducted in which half of the cohort of 36 PLHA were supplemented with vitamin D (group 1) for 6 months and 37 PLHA (group 2) with placebo. As a result cholecalciferol (vitamin D3) supplementation was found to be effective, 80% of patients had normalized blood levels at six months of use. It is important to highlight the significance of vitamin D and smoking levels, and the group that supplemented with vitamin had a significant result (p <0.001) in relation to the increase in CD4 T lymphocytes. Efavirenz may have a negative effect on vitamin D levels and that supplementation is necessary as a likely adjunct to CD4 enhancement and adequate dosing results in treatment efficacy.

BACKGROUND: During the mid to late 20th century, parts of Europe and North America began experiencing increasing incidence of inflammatory bowel disease for unknown reasons. Epidemiological studies carried out at the time determined that incidence rates and disease severity were higher in the northern latitudes than in the southern latitudes. LITERATURE REVIEW: In the ensuing years, an inverse association was established between ultraviolet radiation and incidence of Crohn’s disease, a finding that has not proven to be as robust for ulcerative colitis. This association was explored further and vitamin D was implicated to be the factor of ultraviolet radiation which was associated with increased incidence. Currently, all evidence implicating vitamin D in the pathogenesis of Crohn’s disease comes from epidemiological, animal, and in vitro studies, providing strong evidence for an association, but none of which can prove causality. Causality must be proven in prospective clinical trials, which, at present, have come up short in providing statistically significant findings. METHODS: The proposed trial outlined below provides a method of studying the question at hand in a way that has not been previously studied. This is a randomized, double blind, controlled trial which assesses the effect of supplementation of vitamin D in patients with active Crohn’s disease. DISCUSSION: Acceptance of the alternative hypothesis would be a big step forward in the management of Crohn’s disease. It would have wide-ranging implications, resulting in decreased healthcare costs, decreased use of toxic medications, and increased quality of life.

We aimed to elucidate the role of vitamin D supplementation on adipokines through a systematic review and a meta-analysis of randomized placebo-controlled trials (RCTs). The search included PUBMED, Scopus, Web of Science and Google Scholar through July 1st, 2015. Finally we identified 9 RCTs and 484 participants. Meta-analysis of data from 7 studies did not find a significant change in plasma adiponectin concentrations following vitamin D supplementation (mean difference [MD]: 4.45%, 95%CI: -3.04, 11.93, p=0.244; Q=2.18, I(2)=0%). In meta-regression, changes in plasma adiponectin concentrations following vitamin D supplementation were found to be independent of treatment duration (slope: 0.25; 95%CI: -0.69, 1.19; p=0.603) and changes in serum 25-hydroxy vitamin D [25(OH)D] levels (slope: -0.02; 95%CI: -0.15, 0.12; p=0.780). Meta-analysis of data from 6 studies did not find a significant change in plasma leptin concentrations following vitamin D supplementation (MD: -4.51%, 95%CI: -25.13, 16.11, p=0.668; Q=6.41, I(2)=21.97%). Sensitivity analysis showed that this effect size is sensitive to one of the studies; removing it resulted in a significant reduction in plasma leptin levels (MD: -12.81%, 95%CI: -24.33, -1.30, p=0.029). In meta-regression, changes in plasma leptin concentrations following vitamin D supplementation were found to be independent of treatment duration (slope: -1.93; 95%CI: -4.08, 0.23; p=0.080). However, changes in serum 25(OH)D were found to be significantly associated with changes in plasma leptin levels following vitamin D supplementation (slope: 1.05; 95%CI: 0.08, 2.02; p=0.033). In conclusion, current data did not indicate a significant effect of vitamin D supplementation on adiponectin and leptin levels. / Revisión por pares

Les leucémies aiguës myéloblastiques (LAM) sont un groupe hétérogène de pathologies malignes représentant environ 70% des leucémies aiguës. Il existe une prolifération, dans le cadre des LAM de cellules immatures appartenant à la lignée myéloïde appelées myéloblastes ou communément blastes. Les traitements actuels reposent essentiellement sur la chimiothérapie antimitotique. L’homéostasie du fer est une cible dans le traitement des LAM en induisant la différentiation des blastes. Le mécanisme implique la modulation des ROS. Leur action est synergique avec celle de la Vitamine D (VD) au travers de l’activation de la voie des MAPK. Cette association a été utilisée chez plusieurs patients avec succès permettant un doublement de leur espérance de vie. Nous avons ensuite montré que l’expression du récepteur expression vitamine D (VD) est altérée dans les états indifférenciés / immatures sous-types de LAM et que la diminution de l'expression du VDR et de ces gènes cibles est corrélée à un mauvais pronostic chez les patients. Le mécanisme moléculaire entraînant le blocage de l'expression VDR implique la méthylation de son promoteur. Les souris invalidées pour le VDR ont une expansion du compartiment des cellules souches hématopoïétiques demeurant à un état quiescent ainsi qu’une diminution des niveaux du stress oxydatif en leur sein. En outre, la transformation maligne des cellules déficientes en VDR a abouti à une différenciation myéloïde limitée, à l'augmentation du nombre de progéniteurs hématopoïétiques précoces et ces cellules présentaient un potentiel d'auto-renouvellement accru et étaient résistantes aux inhibiteurs de la méthyltransférase et à la chimiothérapie. Enfin, l'induction de l'expression du VDR dans les modèles de LAM par un traitement combinant des agents de déméthylation et les agonistes de VDR a permis de diminuer la séminalité, de promouvoir la différenciation cellulaire, de bloquer la croissance tumorale et de restaurer la sensibilité à la chimiothérapie. Par conséquent, nous proposons que le VDR est un gène maître contrôlant la séminalité et la prolifération / différenciation cellulaire des cellules souches hématopoïétiques normales et leucémiques. Ainsi, la combinaison d'agents déméthylants et d’agonistes de VDR pourrait à l’avenir être proposée en thérapeutique pour traiter les LAM. / Acute myeloid leukemia (AML) is a heterogeneous group of malignancies representing approximately 70% of acute leukemias. There is a proliferation of immature cells belonging to the myeloid lineage commonly called myeloblasts or blasts. Current treatments are mainly based on antimitotic chemotherapy. Iron homeostasis is a target for the treatment of AML blasts inducing cell differentiation. The mechanism involves the modulation of ROS. Their action is synergistic with that of Vitamin D (VD) through the activation of MAPK. This association has been used successfully in several patients for a doubling of life expectancy. Then, we show that Vitamin D receptor (VDR) expression was impaired in undifferentiated/immature AML subtypes and that decreased expression of VDR and VDR-targeted genes was correlated with a negative prognosis of patients. Molecular mechanism resulting in the blockade of VDR expression involved VDR promoter methylation. VDR-deficient mice showed an expansion of the hematopoietic stem cell compartment which presented an improved quiescent status and decreased ROS levels that have been shown to be involved in both AML differentiation and stem cells longevity. Moreover, malignant transformation of VDR-deficient cells resulted in limited myeloid differentiation, increased numbers of early hematopoietic progenitors and those cells presented an enhanced self-renewal potential and were resistant to DNA methyltransferase inhibitors and to chemotherapy. Finally, induction of VDR expression in AML models by combined treatment of demethylating agents and VDR agonists decreased stemness, promoted cell differentiation, blocked tumor propagation and restored sensitivity to chemotherapy. Therefore, we propose that VDR is a master gene controlling stemness and proliferation/cell differentiation of normal hematopoietic stem cells and leukemic cells. Thus, combination of demethylation agents and VDR agonists may be used therapeutically to treat AML.

Submitted by Rosivalda Pereira (mrs.pereira@ufma.br) on 2017-12-06T17:06:52Z No. of bitstreams: 1 JacquelineCantanhede.pdf: 6344249 bytes, checksum: c518cd1af256d3ecceca532df03539a7 (MD5) / Made available in DSpace on 2017-12-06T17:06:52Z (GMT). No. of bitstreams: 1 JacquelineCantanhede.pdf: 6344249 bytes, checksum: c518cd1af256d3ecceca532df03539a7 (MD5) Previous issue date: 2017-09-13 / The Prehypertension is characterized with systolic blood pressure levels between 120 - 139 mmHg and diastolic blood pressure 80-89mmHg, considered an intermediate state for the development of arterial hypertension. Detecting risk factors for prehypertension becomes important to prevent thousands of premature deaths. Vitamin D deficiency has been linked to high blood pressure and consequently to cardiovascular diseases that are responsible for high global morbidity and mortality. Thus, the analysis of the relationship between prehypertension and vitamin D is fundamental because it allows preventive intervention and avoids the progression to hypertension, thus reducing morbidity and mortality due to cardiovascular diseases. The present study aims to evaluate the association between serum 25 (OH) D levels and prehypertension. This is a cross-sectional study with a quantitative approach carried out at the Hospital Universitário da Universidade Federal do Maranhão in São Luís, Maranhão, Brazil. The 161 adults with prehypertensive and normotensive conditions participated in this study. Socio-demographic, anthropometric, behavioral and clinical data of the participants of both genders between 30 and 50 years old were used. Statistical analysis was performed using SPSS® software version 23. Data were treated using descriptive procedures. The Kolmogorov-Smirnov test was used to verify the normality of the variables. The results were considered statistically significant if p <0.05. In relation to the cardiometabolic risk factors, there was a statistically significant difference (p <0.05) between the control group and the study in the parameters evaluated (BMI, WC and WHtR). The prehypertensive group had a higher mean. Participants with excess weight have statistically higher odds of presenting prehypertension (OR = 3.62, 95% CI = 1.79-7.31 p <0.001). Regarding the Cardiometabolic Risk Factors stratified by gender, a statistically higher percentile was observed in females. Regarding systolic and diastolic blood pressure and vitamin D, there was a statistically significant difference (p <0.05) in all variables analyzed. For males, there was no statistically significant difference in the vitamin D variable. Mean SBP and DBP, and vitamin D (36.15 ± 12.31), were higher in the study group. Especially women (33.65 ± 10.41). In this study, the association of vitamin D and the presence of prehypertension was not observed. The serum vitamin D level of most participants was considered adequate. The female population had a higher prevalence of increased cardiometabolic levels and a higher prevalence of inadequate levels of vitamin D. There was no correlation between serum vitamin D levels with anthropometric data and blood pressure levels. / Pré - hipertensão é caracterizada com níveis de pressão arterial sistólica entre 120 -139 mmHg e pressão arterial diastólica 80-89mmHg, considerada um estado intermediário para o desenvolvimento da hipertensão arterial, representa grande fator de risco para as doenças cardiovasculares. Detectar fatores de risco para pré-hipertensão torna-se importante para evitar milhares de mortes prematuras. A deficiência de vitamina D têm sido relacionada com pressão arterial elevada e consequentemente com doenças cardiovasculares que são responsáveis por elevada morbimortalidade mundial. Desta forma, a análise da relação entre pré- hipertensão e vitamina D é fundamental, pois, pode permitir a intervenção preventiva e evita a progressão para hipertensão reduzindo assim a morbimortalidade por doenças cardiovasculares. O presente estudo tem por objetivo avaliar a associação entre os níveis séricos de 25 (OH)D e pré-hipertensão. Trata-se de um estudo transversal, realizado no Hospital Universitário da Universidade Federal do Maranhão no município de São Luís/ Maranhão. Participaram deste estudo 161 adultos em condições de pré-hipertensos e normotensos. Foram utilizados dados sóciodemográficos, antropométricos, comportamentais e clínicos dos participantes de ambos os sexos com idades entre 30 a 50 anos. A análise estatística foi realizada através do software SPSS versão 23. Os dados foram tratados por meio de procedimentos descritivos. O teste de Kolmogorov-Smirnov foi utilizado para verificar a normalidade das variáveis. Os resultados foram considerados estatisticamente significativos se p <0,05. Em relação, aos fatores de risco cardiometabólicos houve diferença estatisticamente significativa (p<0,05) entre o grupo controle e estudo nos parâmetros avaliados índice de massa corpórea, circunferência da cintura e relação cintura estatura. O grupo de pré-hipertensos apresentou maior média. Participantes com excesso de peso tem estatisticamente maior chance de apresentar pré - hipertensão (OR= 3,62; IC 95%=1,79-7,31 p<0,001). Em relação aos Fatores de Risco Cardiometabólicos estratificados por sexo. Observou-se um percentual estatisticamente maior no sexo feminino. Em relação, a pressão arterial sistólica e diastólica e vitamina D, houve diferença estatisticamente significativa (p<0,05) em todas as variáveis analisadas. Para sexo masculino não houve diferença estatisticamente significativa na análise da variável Vitamina D. A média PAS e PAD, e da vitamina D (36,15 ±12,31) foi maior no grupo estudo. Em especial as mulheres (33,65±10,41). Neste estudo não foi observado associação da vitamina D e a presença de pré- hipertensão. O nível sérico de vitamina D da maioria dos participantes foi considerado adequado. A população do sexo feminino apresentou maior prevalência dos níveis cardiometabólicos aumentados e maior prevalência dos níveis inadequado de vitamina D. Não houve correlação entre os níveis séricos de vitamina D com os dados antropométricos e níveis pressóricos.

Abstract available in The Journal of Nutrition, Health, and Aging.