Dissertations / Theses on the topic 'Vitamin D'

Background Vitamin supplements are commonly used in women of reproductive age. There is a range of vitamin supplements such as iron, folate, vitamin B and vitamin D that are used. Deficiencies in vitamin D can result in adverse health outcomes, such as exacerbation of asthma and fractures. Some studies suggest that vitamin D deficiency may be associated with increases in depressive symptoms and severity. These associations need further exploration to ascertain confirmation, with more vigorous research. Furthermore, there has been limited research on the reasons behind vitamin supplement use in women of reproductive age who originate from culturally and linguistically diverse (CALD) populations. These need further exploration to examine the beliefs, attitudes and practices of women regarding vitamin supplement use. Aims and Objectives Aims: To explore vitamin supplements use in women of reproductive age in terms of their beliefs, attitudes and practices particularly in CALD communities, with a focus on vitamin D and its potential role in depression in women of reproductive age. Objectives: 1) To investigate any association of vitamin D deficiency with depression in women of reproductive age. 2) To examine whether vitamin D supplementation results in a decrease depressive symptoms and severity. 3) To explore the beliefs, attitudes and practices of women of reproductive age, including those from CALD backgrounds, in relation to vitamin supplement use. 4) To explore the beliefs, attitudes and practices of CALD women regarding the Hijab and vitamin D. Content of this thesis This thesis is made up of four chapters. Chapter 1 contains the background. The challenges identified in Chapter 1 led to the exploration of the effect of vitamin D on depression in women of reproductive age via a systematic review in Chapter 2. The qualitative study in Chapter 3 describes the factors behind the beliefs, attitudes and practices of women of reproductive age in terms of vitamin supplement use. Lastly Chapter 4 presents general discussion and conclusions from the work described in this thesis. Methods A systematic review was conducted to investigate the effect of vitamin D on depression in women of reproductive age based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement checklist (Chapter 2). A systematic search strategy was deployed in ten databases including Medline, EMBASE, PsycINFO, CINAHL, AMED, International pharmaceutical abstracts, Maternal and infant care, EBM ALL, Global health, and PubMed to identify primary studies that met eligibility criteria. A qualitative study using semi-structured interviews was undertaken to explore the use of vitamin supplements in women of reproductive age. A semi-structured interview guide was developed and applied to facilitate the interview. Participants were recruited through advertisements in pharmacies, medical centres and community centres as well as via the distribution of flyers across a large university campus in Sydney, through social media, word of mouth and snowball sampling. Interviews were audio-recorded and transcribed. Interviews were conducted until thematic saturation was achieved and data was analysed. NVivo12 Plus Qualitative Data Analysis software (QSR International Pty Ltd. Version 12, 2019) was used to analyse the emerging themes. Initial codes were highlighted and organised into general themes and sub-themes, which were reviewed and refined. Results Chapter 2 Systematic review identified a total of 2377 studies through comprehensive search and search of cited references. After removing duplicates and based on title and abstract screening, 128 studies remained. Full text review yielded 21 observational studies (11 cohort studies and 10 cross-sectional studies) that assessed the association between vitamin D deficiency and depression and two intervention studies (two RCTs) that investigated women of reproductive age of 15-49 years in US, Australia, New Zealand, Asia, Europe, Middle East and South America. Two cohort studies that showed no difference in depression scores in relation to vitamin D, while 9 other cohort studies reported that after measuring participants’ depression scores and vitamin D level over time, lower vitamin D levels were associated with higher depression scores. Similarly, there were two cross sectional studies that did not find an association between vitamin D level and depression scores. However, eight other cross-sectional studies showed that low vitamin D levels were linked with higher depression scores. One RCT did not find any improvement in depression symptoms and severity based on the supplementation of vitamin D used. Another RCT showed a reduction in depression scores compared to controls. Chapter 3 Semi-structured interviews were conducted with 25 women aged 19-49 years old, all from CALD backgrounds. The beliefs, attitudes and practices regarding the use of vitamin supplements of women from CALD backgrounds were explored. Thematic analysis generated four main themes: 1) health literary 2) cultural factors that influence vitamin supplement use 3) life circumstances and 4) women’s perception of health outcomes. Health literacy and information sources were key factors that affected women’s decision-making about taking vitamin supplements; and sources such as Google were heavily relied upon. Moreover, cultural factors greatly influenced women’s initiation of vitamin supplement therapy. There were discrepancies regarding the impact of wearing the Hijab on vitamin D status and more research in this area is needed. Conclusion Prior to this research, there has been limited data on CALD women of reproductive age and their beliefs, attitudes and practices in terms of vitamin supplement usage. This body of research was the first to explore the use of vitamin supplements in women of reproductive age particularly from CALD backgrounds. Furthermore, it was also one of the few studies around the world that examined the effect of vitamin D on depression in women of reproductive age. Findings from this body of work demonstrated the reoccurring themes that shaped women’s beliefs, attitudes and practices towards vitamin supplement use specifically include health literacy, cultural factors, life circumstances and women’s perception of health outcomes. This study also ascertained that CALD women of reproductive age had differing levels of health literacy and use of a range of information sources. This study also highlighted differing views regarding the practice of Hijab and rate of vitamin D supplementation. In addition, this study provides a basis for further studies to explore whether the practice of Hijab affects vitamin D levels, which has consequences for recommendations around vitamin D supplementation in countries where the Hijab is commonly worn. There was an indication of an association between vitamin D deficiency and depression symptoms and severity from this research. However, the exact clinical association in terms of vitamin D being a causal factor in developing depression remains unclear. Supplementation with vitamin D that results in changing status from vitamin D deficient to vitamin D sufficient warrants further investigation, specifically to ascertain whether an optimal level is needed to achieve a reduction in depressive symptoms and severity. Thesis overview This thesis presents an analysis of previous research on the role of vitamin D deficiency in depression in women of reproductive age. It explores the role of supplementation with vitamin D on depression symptoms and severity. It also investigates the beliefs, attitudes and practices of women of reproductive age regarding their vitamin supplements usage. It examines the motivations behind usage in women particularly those from CALD backgrounds. Rationale for this study Vitamin D deficiency is common throughout the world, including Australia which has ample sunlight all year round. Low vitamin D status has been associated with multiple adverse health outcomes, one of which is depression (1). Consensus around the optimal level of vitamin D for women of reproductive age remains to be reached. It is critical to establish if a relationship between vitamin D levels and depression exists and what that relationship is in women of reproductive age. In order to evaluate this association, a systematic review of past studies was undertaken to examine the effect of vitamin D on depression in women of reproductive age. This is further discussed in Chapter 2 of this thesis. Similarly, vitamin supplementation use has grown in the last decade worldwide and in Australia (2). This may be due to increased advertising and availability, cultural influences, affordability and increase in the use of social media platforms. It is important to understand the beliefs, attitudes and cultural practices especially in women of reproductive age, around their use of vitamin supplements. In order to explore this research question, a qualitative study was undertaken to explore the use of vitamin supplements in women of reproductive age from CALD backgrounds. This is further discussed in Chapter 3 of this thesis. Research aim, objectives and research questions The overall aim of this project was to explore the use of vitamin supplements in women of reproductive age, with a focus on CALD communities as well as investigating vitamin D and its possible association with depression in women of reproductive age. The specific objectives of this research were to: • Evaluate the effect of vitamin D status on depression and depressive symptoms. • Explore the use of vitamin supplements in women of reproductive age, particularly in women of CALD backgrounds, with a particular focus on vitamin D • Describe the beliefs, attitudes, and practices of women of reproductive age, particularly women from CALD backgrounds, regarding vitamin supplement use. The research questions were: • Does vitamin D deficiency affect depression and depressive symptoms? • What level of vitamin D is needed to decrease depression severity and symptoms? • What level of vitamin D supplementation is required to increase level of vitamin D in order to decrease depression severity and symptoms? • What factors are involved when women of reproductive age initiate vitamin supplement use? • What are the beliefs, attitudes and practices of women of reproductive age around vitamin supplement use? • What are the beliefs and attitudes and practices of women from CALD backgrounds regarding vitamin supplement use? • What are the beliefs and practices of women from CALD backgrounds regarding the Hijab and its possible connection with vitamin D deficiency? Significance This research will contribute to the expanding body of knowledge related to vitamin D deficiency and depression as well as exploring vitamin supplement use in women of reproductive age particularly those from CALD backgrounds. It is the first study to systematically evaluate the effect of vitamin D on depression in women of reproductive age and explore the use of vitamin supplements in CALD women of reproductive age in Australia. This study complements current understanding of the links between vitamin D and depression as well as the differences in the beliefs, attitudes and practices of women from CALD backgrounds regarding vitamin supplement use. Considering existing evidence, public health interventions to decrease the prevalence of vitamin D deficiency in women of reproductive age in Australia are required, in addition to increasing awareness regarding the optimal vitamin D status in order to decrease the risk of depression and depressive symptoms. The identification of several motivating factors associated with vitamin supplement use in women of reproductive age and in particular those from CALD backgrounds is an important first step in future programs of public health research aimed at identifying and targeting culturally appropriate health related information that aides decision making when it comes to vitamin supplement use. This thesis investigates women’s use of vitamin supplements, vitamin D and its possible association with depression in women of reproductive age. The first chapter provides background information on vitamin supplements, vitamin D, depression and population characteristics. The second chapter examines the effect of vitamin D on depression in women of reproductive age in the form of a systematic review. The third chapter explores the use of vitamin supplements in women of reproductive age and in particular, women from CALD backgrounds through a qualitative study. The fourth chapter discusses the significance of all the findings, future research directions and conclusions.

La vitamine D (D3 ou cholécalciférol du règne animal et D2 ou ergostérol du règne végétal) est une hormone pléiotrope qui possède de nombreux effets biologiques incluant la régulation du métabolisme du calcium et du phosphate. Chez l’Homme, ce composé est synthétisé au niveau cutané sous forme inactive. On décrit ainsi le métabolisme de la vitamine D qui conduit à la production de métabolites actifs (par les vitamine D 25- et 1α-hydroxylases codées par les gènes CYP2R1 et CYP27B1) et à leur dégradation par la vitamine D 24-hydroxylase (gène CYP24A1). L’expression des vitamine 1α- et 24-hydroxylases est finement et inversement régulée afin de maintenir l’homéostasie phosphocalcique, grâce à plusieurs boucles de rétrocontrôle impliquant entre autres la forme 1,25-dihydroxylée de la vitamine D et son récepteur VDR, la calcémie et la parathormone, la phosphatémie et le FGF23. La carence en vitamine D et les défauts de son activation sont associés à un phénotype de rachitisme, tandis que les excès en vitamine D sont associés à un phénotype d’hypercalcémie-hypercalciurie par intoxication (surdosage) ou hypersensibilité à la vitamine D (excès d’activation ou défaut de dégradation).L’objectif de ce travail de thèse est d’identifier des causes génétiques de dérégulation du métabolisme de la vitamine D et de préciser leurs mécanismes physiopathologiques par une description précise du phénotype associé. Pour ce faire, nous avons utilisé de façon conjointe les outils de la génétique (séquençage nouvelle génération et Sanger) et de la biochimie (dosage des métabolites) dans une cohorte de patients recrutés grâce au centre de référence maladies rares du métabolisme du calcium et du phosphate.Ce travail a permis de préciser le rôle de deux gènes dans les maladies liées à la dérégulation métabolisme de la vitamine D, CYP2R1 et CYP24A1, par la mise en évidence de mutations perte de fonction chez des patients avec un phénotype de rachitisme à 25-hydroxyvitamine D basse et d’hypersensibilité à la vitamine D respectivement. Notre étude a permis aussi de préciser le phénotype de ces affections. Dans la cohorte des patients étudiés, l’identification de mutations de gènes impactant le métabolisme du phosphate (SLC34A1 et SLC34A3), souligne l’intérêt de l’étude des facteurs régulateurs des activités vitamine D 1α- et 24-hydroxylases.Aucune variation significative dans les régions promotrices proximales de CYP27B1 et CYP24A1 n’a été identifiée. Le peu de connaissances sur l’ensemble des éléments régulateurs chez l’Homme n’a pas permis d’approfondir notre étude. L’identification et l’étude de ces éléments régulateurs distaux permettra de déterminer leur implication dans les maladies rares du métabolisme de la vitamine D
The vitamin D (D3 or cholecalciferol from animal kingdom and D2 or ergosterol from plan kingdom) is a pleiotropic hormone who has numerous biological effects including the regulation of calcium and phosphate metabolism. In humans, this compound is synthetized in skin in an inactive form. Thus, we call vitamin D metabolism the biological process which leads to the production of active metabolites (by enzymes 25- and 1α-hydroxylases encoded by CYP2R1 and CYP27B1 genes) and its degradation by vitamin D 24-hydroxylase (gene CYP24A1). The expression of 1α- and 24-hydroxylases is tightly and inversely regulated to maintain calcium and phosphate homeostasis, thanks to several feedback loops including 1,25-dihydroxyvitamin D and its receptor VDR, serum calcium and parathormone, serum phosphate and FGF23. Vitamin D deficiency and vitamin D activation deficiency are associated with rickets, while vitamin D excess are associated with hypercalcemia-hypercalciuria due to vitamin D intoxication (overdose) or hypersensitivity to vitamin D (activation excess or degradation deficiency).Our aim is to identify genetic causes of vitamin D metabolism deregulation and to specify pathophysiologic mechanisms describing phenotype. Thus, we jointly used the tools of genetics (next-generation and Sanger sequencing) and biochemistry (vitamin D metabolites assay) in a cohort of human patients ascertained thanks to the national center for rare diseases of calcium and phosphate metabolism.This work allowed us to specify the role of two genes in diseases of vitamin D metabolism, CYP2R1 and CYP24A1, showing loss of function mutations in patients with rickets and low 25-hydroxyvitamin D and hypersensitivity to vitamin D, respectively. Our study brought new phenotypic elements in these affections. In our cohort of patients, the identification of mutations leading to phosphate deregulation (in SLC34A1 and SLC34A3) highlights the putative role of regulators of vitamin D 1α- and 24-hydroxylases activities in pathophysiology.No significant variation have been identified in the proximal promoting regions of CYP27B1 and CYP24A1. We could not go further considering the lack of knowledge in regulating regions and factors in humans. Identifying distal regulators will allow to study their implication in rare diseases of vitamin D metabolism

Introdução - A concentração sérica de vitamina D pode variar em indivíduos de diferentes grupos etários e de diversas regiões geográficas e pode ser influenciada pela exposição solar, estação do ano, bem como pelos valores de IMC e paratormônio (PTH). A classificação utilizada para definir concentração sérica adequada de vitamina D refere valores de 25(OH)D acima de 30 ng/mL. Porém, essa classificação pode estar inapropriada para a população brasileira, devido às particularidades climáticas e alimentares. Objetivo - Verificar as concentrações séricas médias de 25(OH)D e PTH e sua relação com IMC, exposição solar e estação do ano e identificar os valores de corte da 25(OH)D associados à elevação do paratormônio (PTH) em adultos e idosos de amostra representativa da população do município de São Paulo. Métodos - Para esta dissertação foi desenvolvido um artigo original. O artigo original descreve o estudo transversal realizado com indivíduos do estudo ISA-Capital, estudo multicêntrico e de base populacional, onde foram investigados 589 indivíduos, de ambos os sexos, dos grupos etários: 20 a 59 (adultos) e 60 e mais (idosos). Foram coletadas amostras de sangue, para dosagens de 25(OH)D e PTH. Os indivíduos que aceitaram participar da coleta de sangue, também responderam um questionário sobre exposição solar. A análise estatística incluiu a curva ROC, testes t de Student, correlação e ANOVA. Os cálculos foram realizados pelo software SPSS versão 17.0. e p 0,05 foi considerado significante. Resultados - No artigo original observou-se idade média de 54,83 (19,21) anos, sendo 61,3 por cento do sexo feminino e 38,7 por cento do sexo masculino. A concentração sérica média de 25(OH)D foi 50,02 (22,69) ng/mL, já entre os grupos foi de 47,48 (23,03) (adultos) e 52,68 (22,06) ng/mL (idosos) havendo diferença significativa entre eles (p=0,005). Observou-se variação sazonal da concentração sérica de 25(OH)D e correlação positiva entre 25(OH)D e IMC (r = 0,114, p = 0,006). O novo valor de corte 55.8 ng/mL, determinado pela análise da curva ROC, encontrou 67,6 por cento dos indivíduos insuficientes de 25(OH)D e entre os grupos 72,1 por cento (adultos) e 62,8 por cento (idosos). Conclusão - Os resultados demonstram a presença de variação sazonal nas concentrações séricas de 25(OH)D no municipio de São Paulo. O ponto de corte proposto para nossa população indicou elevada prevalência de insuficiência de vitamina D. Portanto, se faz necessário políticas públicas de prevenção de insuficiência de vitamina D visando os efeitos benéficos na saúde e qualidade de vida desta população.
Introduction - The serum concentration of vitamin D may vary in individuals of different age groups and geographic regions and may be influenced by sun exposure, season and by BMI and parathyroid hormone (PTH). The classification widely used as a cut-off for appropriate vitamin D status refers serum 25 (OH) D above 30 ng/mL. However, this classification may be inappropriate for the Brazilian population, due to the particular food and the climate of our population. Objective - To determine the mean serum concentrations of 25(OH)D and PTH and correlate them with BMI, sunlight exposure and season and to identify the cutoff values of 25 (OH) D associated with elevation in PTH. Methods For this dissertation, one original article were developed. Original article describe cross-sectional study performed with subjects from the ISA Capital, multicenter population-based. We investigated 589 individuals were of both sexes, age groups: 20-59 (adults) and 60 (elderly). Blood samples for laboratory measurements of 25(OH)D and PTH were collected. Individuals, who agreed to participate in blood collection, also answered a questionnaire on sunlight exposure. Statistical analysis included ROC curve, Student t test, correlation tests, ANOVA. The calculations were performed by the software SPSS version 17.0. and p 0.05 was considered significant. Results - In the original article, the mean age of participants was 54.83 (19.21) years, 61.3 per cent female and 38.7 per cent were male. The mean serum 25 (OH) D was 50.02 (22.69) ng/mL, between the groups was 47.48 (23.03) (adults) and 52.68 (22.06) ng/ mL (elderly) and significant difference between them (p = 0.005). A seasonal variation in serum 25 (OH) D was observed and positive correlation between 25(OH)D and BMI (r = 0.114, p = 0.006). The new cutoff value 55.8 ng / mL, determined by ROC curve analysis found 67.6 per cent of subjects insufficient 25 (OH) D and between groups 72.1 per cent (adults) and 62.8 per cent (elderly). Conclusion - The results demonstrate the presence of seasonal variation in serum 25 (OH) D in the municipality of Sao Paulo. The cutoff point proposed for our population showed a high prevalence of insufficient vitamin D. Therefore, public policy is needed to prevent vitamin D insufficiency in order to beneficial effects on health and quality of life in this population.

A 700bp portion of the promoter of CYP2D25, the porcine microsomal vitamin D 25-hydroxylase was isolated and sequenced. The computer analysis of the sequence revealed the existence of a putative VDRE at 220 bp upstream of the transcription start site. A CYP2D25 promoter-luciferase reporter plasmid was constructed in order to study the transcriptional regulation of the gene. Treatment with the vitamin D metabolites calcidiol and calcitriol suppressed the promoter, provided that the nuclear receptors VDR and RXR were overexpressed. Phenobarbital was also capable of suppressing the promoter if the nuclear receptors PXR or CAR were overexpressed. The 25-hydroxylases are not expressed solely in liver but in a wide array of other organs as well. It is therefore possible at least in theory to study the vitamin D 25-hydroxylation in human subjects using cells from extrahepatic organs, from which biopsy retrieval is easier than from the liver. Dermal fibroblasts are frequently used to study different pathological conditions in human subjects and they are easy to come by. Dermal fibroblasts were shown to express two vitamin D 25-hydroxylases: CYP27A1 and CYP2R1. The expression pattern of CYP2R1 displayed considerable interindividual variation. The fibroblasts were also capable of measurable vitamin D 25-hydroxylation, which makes dermal fibroblasts a possible tool in studying vitamin D 25-hydroxylation in human subjects. Little is known about the regulation of expression and activity of the human vitamin D 25-hydroxylases. Therefore dermal fibroblasts – expressing CYP2R1 and CYP27A1 – and human prostate cancer LNCaP cells, that express CYP2R1 and CYP2J2, were treated with calcitriol and phenobarbital and efavirenz, two drugs that give rise to vitamin D deficiency. Treatment decreased the mRNA levels of CYP2R1 and CYP2J2 provided that the treated cells also expressed the necessary nuclear receptors. CYP27A1 did not respond to any of the treatments. The treatments also managed to decrease the 25-hydroxylating activity of the cells. The results show that vitamin D 25-hydroxylases can be regulated by both endogenous and xenobiotic compounds.

The aim of this research was to apply analytical epidemiology to examine associations between hypertension and vitamin D status (serum 25-hydroxyvitamin D (25OHD)). The first objective was to appraise and synthesize the research evidence on the relationship between hypertension and 25OHD. The follow-up objective was to complete a sequence of studies exploring the association between hypertension and 25OHD in two populations with high hypertension and vitamin D deficiency rates, Finland and China. The results of the meta-analysis were that higher vitamin D levels were associated with lower hypertension rates. In a prospective study from Finland higher 25OHD levels at baseline were found to associate with less hypertension and a lower pulse rate. On follow-up only low pulse rate remained associated with higher 25OHD. A hypertension prevalence rate of 34% was reported from a cross-sectional survey in Macau 2012. Potentially modifiable predictors of hypertension were found to be smoking, obesity and lack of exercise, sunlight exposure and low intake of fish. Only 45% of this population on whom blood was collected were found to have sufficient vitamin D status (≥50 nmol/L). Young highly educated women were at greatest risk of not being sufficient. Higher sun exposure, fish intake and more physical activity and less sitting were associated with higher 25OHD levels. In the older population (≥55 years) higher 25OHD levels significantly predicted having either lower hypertension or lower pulse rates. The evidence from these series of studies indicates a small consistent association between vitamin D sufficiency and reduction in hypertension risk. These results are consistent with recent meta-analyses of observational studies. The unique finding from this study is that there is an age cohort differential with younger Chinese having lower vitamin D status and in a population with increasing hypertension this fact may have public health consequences in the future.

Les leishmaniosis són un grup de malalties causades per protozous del gènere Leishmania que es transmeten per vectors. La leishmaniosi visceral (LV) humana pot ser mortal si no es tracta, resultant en 26 000-65 000 morts a l’any. Els cànids són el principal reservori i hostes de Leishmania infantum, l’agent causant de la LV zoonòtica a la conca mediterrània. Es desconeixen els mecanismes que regulen el resultat final de la infecció, però és sabut que el sistema immunitari juga un paper clau en el control de la malaltia. Diversos estudis han demostrat que la vitamina D té un rol important en la resposta immune, activant el sistema immunitari innat i modulant la resposta adaptativa. A més, s’ha descrit la relació entre la deficiència de vitamina D i el risc de patir diverses malalties. L’objectiu de la tesis va ser estudiar si la vitamina D té una contribució rellevant en la leishmaniosi canina (LCan). Per això, es va mesurar la concentració de vitamina D en mostres de sèrum d’una població de gossos sans i malalts residents en zona altament endèmica i se’n va estudiar la relació amb paràmetres parasitològics i immunològics. Els gossos malalts presentaven nivells de vitamina D significativament més baixos que els no infectats i que els infectats asimptomàtics. A més, la deficiència de vitamina D es correlacionava amb paràmetres relacionats amb la progressió de la LCan. També vam investigar si variacions genètiques en el locus del gen del receptor de la vitamina D s’associa amb la progressió de la LCan, però les freqüències al·lèliques dels polimorfismes (SNPs) trobats no van resultar ser estadísticament diferents entre grups. Llavors, vam analitzar la concentració de vitamina D en mostres de sèrum preses en diferents períodes de l’any en una cohort de gossos sans. Els resultats van mostrar que no hi ha variació estacional dels nivells de vitamina D en gossos. També es va analitzar retrospectivament la concentració de vitamina D en gossos amb leishmaniosi clínica i gossos no-infectats a l’inici de l’estudi, quan tots els animals eren negatius a Leishmania, i un any després. Mentre que els gossos sans no van mostrar canvis en els nivells de vitamina D durant l’estudi, els que van desenvolupar leishmaniosi van mostrar una reducció significativa al final de l’estudi. Per tant, la concentració de vitamina D no és un factor de risc per desenvolupar LCan, sinó que disminueix amb el curs de la malaltia. Un model in vitro va demostrar que afegir vitamina D activa (1,25(OH)2D3) comporta una reducció significativa de la càrrega de L. infantum en macròfags canins. Analitzant l’expressió de gens relacionats amb la via de la vitamina D en monòcits canins primaris vam demostrar que l’expressió de la β-defensina CBD103 augmenta significativament amb l’addició de 1,25(OH)2D3. Els resultats van corroborar que la vitamina D juga un paper en el control del paràsit. Per últim, es va estudiar la viabilitat de la vitamina D com a adjuvant per potenciar l’efecte d’una vacuna enfront la leishmaniosi. Es va administrar vitamina D conjuntament amb una vacuna d’ADN encapsulada en liposomes a ratolins BALB/c. Dues setmanes després de la vacunació els animals van ser infectats amb L. infantum. Es va mesurar la càrrega parasitària en òrgans diana i es va avaluar la resposta immune abans de la infecció i sis setmanes després. La vacuna no va reduir significativament la càrrega parasitària, però amb la co-administració de vitamina D es va apreciar una tendència a disminuir-la. L’estudi de la resposta immunològica va suggerir que l’augment de limfòcits T CD4+ i CD8+ podrien haver contribuït en la protecció parcial aconseguida per la vacuna amb la vitamina D com a potenciador.
Las leishmaniosis son un grupo de enfermedades causadas por protozoos del género Leishmania que se transmiten por vectores. La leishmaniosi visceral (LV) humana puede ser mortal si no se trata, resultando en 26 000-65 000 muertes por año. Los cánidos son el principal reservorio y huéspedes de Leishmania infantum, el agente causante de la LV zoonótica en la cuenca mediterránea. Se desconoce el mecanismo que regula el resultado final de la infección, pero se sabe que el sistema inmunitario juega un papel clave en el control de la enfermedad. Varios estudios han demostrado que la vitamina D tiene un rol importante en la respuesta inmune, activando el sistema inmunitario innato y modulando la respuesta adaptativa. Además, se ha descrito la relación entre la deficiencia de vitamina D y el riesgo de sufrir algunas enfermedades. El objetivo de la tesis fue estudiar si la vitamina D tiene una contribución relevante en la leishmaniosis canina (LCan). Para ello se determinó la concentración de vitamina D en muestras de suero de una población de perros sanos y enfermos de leishmaniosis residentes en una zona altamente endémica y se estudió la relación de ésta con parámetros parasitológicos e inmunológicos. Los perros enfermos mostraron niveles de vitamina D significativamente más bajos que los no infectados y que los infectados asintomáticos. Además, la deficiencia de vitamina D se correlacionó con parámetros relacionados con la progresión de la enfermedad. También investigamos si las variaciones genéticas en el locus del gen del receptor de la vitamina D se asocia con la progresión de LCan, pero las frecuencias alélicas de los polimorfismos (SNPs) encontrados no resultaron ser estadísticamente diferentes entre grupos. Posteriormente se analizó la concentración de vitamina D en muestras de suero tomadas en diferentes periodos del año en una cohorte de perros sanos. Los resultados mostraron que no hay una variación estacional de los niveles de vitamina D en perros. También se analizó retrospectivamente la concentración de vitamina D en perros con leishmaniosis clínica y perros no infectados al inicio del estudio, cuando todos los animales eran negativos a Leishmania, y un año después. Mientras que los perros sanos no mostraron cambios en los niveles de vitamina D durante el estudio, los que desarrollaron leishmaniosis mostraron una reducción significativa al final del estudio. Por lo tanto, la concentración de vitamina D no es un factor de riesgo para desarrollar LCan, sino que disminuye con el curso de la enfermedad. Un modelo in vitro demostró que añadir vitamina D activa (1,25(OH)2D3) conlleva una reducción significativa de la carga de L. infantum en macrófagos caninos. Analizando la expresión de genes relacionados con la vía de la vitamina D en monocitos caninos primarios demostramos que la expresión de la β-defensina CBD103 aumenta significativamente con la adición de 1,25(OH)2D3. Los resultados corroboraron que la vitamina D juega un papel en el control del parásito. Por últimos, se estudió la viabilidad de la vitamina D como adyuvante para potenciar el efecto de una vacuna frente la leishmaniosis. Se administró vitamina D junto a una vacuna de ADN encapsulada en liposomas a ratones BALB/c. Dos semanas después de la vacunación los animales se infectaron con L. infantum. Se determinó la carga parasitaria en órganos diana y se evaluó la respuesta inmune antes de la infección y seis semanas después. La vacuna no redujo significativamente la carga parasitaria, pero con la coadministración de vitamina D se apreció una tendencia a reducirla. El estudio de la respuesta inmunológica sugirió que el aumento de linfocitos T CD4+ y CD8+ podrían haber contribuido a la protección parcial conseguida cuando se administró vitamina D como potenciador junto a la vacuna.
Leishmaniasis are a group of neglected vector-borne diseases caused by obligate intracellular protozoan parasites of the genus Leishmania. Human visceral leishmaniasis (VL) can be fatal if left untreated, resulting in 26 000-65 000 deaths per year. Canids are the main reservoir and hosts of L. infantum, the causative agent of zoonotic VL in the Mediterranean Basin. The mechanisms that regulate the outcome of the infection are undisclosed, although it is well known that immune system plays a key role in leishmaniasis disease control. Several studies have shown that vitamin D plays an important immunomodulatory role by activating innate immune system and modulating the adaptive immune response. Furthermore, the relationship between vitamin D deficiency and the risk of suffering from a plethora of health disorders has been described. The aim of the thesis was to study if vitamin D have a relevant contribution in canine leishmaniasis (CanL). Because of that, we measured vitamin D concentration in serum samples from a cohort of healthy and ill dogs from a highly endemic area and we have also studied the relationship of vitamin D concentration with parasitological and immunological parameters. The sick dogs presented significantly lower vitamin D levels than their non-infected and the asymptomatic counterparts. In addition, vitamin D deficiency correlated with several parameters linked to leishmaniasis progression. We also aimed to investigate whether genetic variation within the vitamin D receptor gene locus is associated with the progression of CanL, but the allelic frequencies of the four single nucleotide polymorphisms (SNPs) found were not statistically different between groups. Afterwards, we analysed retrospectively vitamin D concentration in serum samples from a cohort of healthy dogs collected in different periods of the year. The results showed that there is not a seasonal variation of vitamin D concentration in dogs. We also analysed retrospectively vitamin D concentration in serum samples from dogs with clinical leishmaniasis and non-infected healthy dogs, in which we measured vitamin D levels at the beginning of the study, when all dogs were negative for Leishmania, and 1 year later. Whereas non-infected dogs showed no changes in vitamin D levels along the study, those developing clinical leishmaniasis showed a significant vitamin D reduction at the end of the study. Therefore, vitamin D concentration is not a risk factor for developing canine leishmaniasis, but it diminishes with the onset of clinical disease. An in vitro model using a canine macrophage cell line proved that adding active vitamin D (1,25(OH)2D3) leads to a significant reduction in L. infantum load. Analyzing expression of genes related to vitamin D pathway on primary canine monocytes, we showed that defensin CBD103 expression was significantly enhanced after active vitamin D addition. The in vitro results corroborated that vitamin D plays a role in parasitic control. Finally, we studied the suitability of vitamin D as an adjuvant to enhance the effect of a DNA vaccine against VL. BALB/c mice were treated with vitamin D concomitantly with a DNA vaccine encapsulated in liposomes. Two weeks after vaccination, the animals were infected with L. infantum parasites. Parasite load was measured in target tissues and immune response was evaluated before challenge and six weeks post-infection. Our DNA vaccine did not significantly reduce parasite load in liver nor spleen, but vitamin D coadministration showed a tendency to diminish parasite load in target organs. The study of cell response in splenocytes suggested that higher levels of CD4+ and CD8+ T cells may be responsible for the partial protection mediated by the DNA vaccine with vitamin D as enhancer.
Universitat Autònoma de Barcelona. Programa de Doctorat en Farmacologia

Introdução: Uma elevada prevalência de deficiência de vitamina D (DVD) em crianças tem sido observada em todo o mundo, mas poucos são os estudos com relação ao estado nutricional da vitamina D (VD) em lactentes saudáveis. A principal causa da deficiência em crianças saudáveis é o aleitamento materno sem suplementação e a falta ou insuficiência de exposição solar. Objetivos: Determinar as concentrações séricas de VD e verificar sua associação com concentrações de paratormônio (PTH), fosfatase alcalina (FA), cálcio (Ca), fósforo (P) e albumina e uso da suplementação de VD em lactentes saudáveis com idades entre >= 6 e <= 24 meses atendidos em duas Unidades Básicas de Saúde do município de Ribeirão Preto, SP, Brasil. Métodos: Estudo transversal, observacional e analítico em que foram determinadas as concentrações séricas de 25 (OH)D, PTH, FA, Ca, P e albumina de 155 lactentes saudáveis. Informações sobre exposição solar, aspectos sociodemográficos das mães e características clínico-nutricionais dos lactentes foram obtidas por entrevistas com os responsáveis dos lactentes. Concentrações séricas de 25(OH)D maiores que 20ng/ml foram consideradas adequadas, entre 12 a 20ng/ml insuficientes e < 12ng/ml deficientes. Resultados: Dez lactentes (6,5%, Intervalo de Confiança 95% 3,5-11,4) apresentaram insuficiência de VD e nenhum apresentou DVD. Nenhuma alteração nas concentrações séricas de P, Ca e albumina foram detectadas. Apenas um lactente apresentou aumento nas concentrações séricas de PTH e 35,5% dos lactentes apresentaram FA elevada, porém nenhum apresentou DVD ou insuficiência de VD. Não foram encontradas associações entre as concentrações séricas de 25(OH)D e as de FA, Ca e albumina. Houve associação entre concentrações séricas de 25(OH)D e PTH mesmo após ajuste para sexo, idade e Índice de Massa Corporal; também foi observada associação entre concentrações séricas de 25(OH)D e P apenas após o ajuste pelas covariáveis. Não foram verificadas associações entre insuficiência de VD, exposição solar e suplementação de VD. Conclusões: Uma baixa prevalência de concentrações insuficientes de 25(OH)D foi observada. Não foram encontradas associações entre as concentrações séricas de 25(OH)D e PTH, FA, Ca, P e albumina. Da mesma forma, não foram encontradas associações entre de concentrações séricas de 25(OH)D, exposição solar e suplementação de VD.
Introduction: A high prevalence of vitamin D deficiency (VDD) in children has been observed worldwide, but there are few studies on the nutritional status of vitamin D (VD) in healthy infants. The main cause of deficiency in healthy children is breastfeeding without supplementation and lack or insufficiency of sun exposure. Objective: To determine serum concentrations of VD and verify its association with parathyroid hormone (PTH) levels and use of VD supplementation in healthy infants aged >= 6 to <= 24 months attended at two Basic Health Units in Ribeirão Preto city, São Paulo, Brazil. Methods: A cross-sectional, observational and analytical study was performed in which were determined serum concentrations of 25 (OH) D, PTH, alkaline phosphatase (AP), calcium (Ca), phosphorus (P) and albumin of 155 healthy infants. Information of sun exposure, sociodemographic aspects of mothers and clinical and nutritional characteristics of infants were obtained through interviews with responsible for infants. Serum concentrations of 25(OH)D greater than 20ng / ml were considered adequate, between 12 to 20ng / ml insufficient and <12ng/ml, deficient. Results: Ten infants (6.5%, 95% Confidence Interval 3.5-11.4) presented VD insufficiency and none presented DVD. Only one infant had an increase in PTH serum concentrations and 35.5% of infants had high AP but none presented DVD or VD insufficiency. No changes in serum P, Ca and albumin concentrations were detected. No associations were found between serum concentrations of 25 (OH) D and AP, Ca and albumin. There was an association between serum concentrations of 25(OH)D and PTH even after adjusting for sex, age and body mass index; an association between serum concentrations of 25(OH)D and P was observed only after adjustment for covariates. There were no associations between VD insufficiency, sun exposure and VD supplementation. Conclusions: A low prevalence of insufficient concentrations of 25 (OH)D was observed. No associations were found between serum concentrations of 25 (OH)D and PTH, FA, Ca, P and albumin. Likewise, no associations were found between serum concentrations of 25 (OH)D, sun exposure and VD supplementation.

Little is known regarding the vitamin D status of Canadian youth. Our objectives were: (i) to describe the vitamin D status of Québec youth using a representative sample; (ii) examine the relative contributions of diet, physical activity and fat mass to the variance in plasma 25-hydroxyvitamin D{25(OH)D}, the best biomarker of vitamin D status; and (iii) examine the influence of household income and food insecurity on the intakes of dietary vitamin D, calcium and dairy foods.
To describe vitamin D status, we used data from a cross-sectional survey representative of Québec youth aged 9, 13 and 16, the Québec Child and Adolescent Health and Social Survey (QCAHS). For the second objective, 159 youth, aged 8-11 whose parents (at least one) were obese or had the metabolic syndrome were used for cross-sectional analysis in the Québec Adipose and Lifestyle InvesTigation in Youth (QUALITY). Fat mass was measured using Dual X-ray Absorptiometry (DXA) and physical activity was assessed by accelerometer. Finally, we analyzed data from the Canadian Community Health Survey (CCHS), a sample of 8960, 9-18-year-olds representative of Canadian youth for whom a single 24 hour dietary recall, measured height and weight, sociodemographic and information on food insecurity were available.
Greater than 90% of youth had sub-optimal vitamin D levels {plasma 25(OH)D < 75 nmol} at the end of winter and beginning of spring in both the QUALITY and QCAHS study. In the QCAHS study, older youth had a higher prevalence of vitamin D deficiency {25(OH)D < 27.5 nmol} (> 10%) than younger youth and girls from low income households had lower plasma 25(OH)D concentrations. In the QUALITY study, milk consumption and physical activity had modest associations with plasma 25(OH)D corresponding to 2.9 nmol/L and 2.1 nmol/L higher plasma 25(OH)D per standard deviation increase in these exposures, respectively. In the CCHS study, we found evidence that milk intake was being displaced by sweetened beverages amongst low income boys and food insecure girls.
Population wide measures to increase dietary vitamin D intake should be examined in Canadian youth.
Il y a peu de connaisances concernant le statut vitamin D des jeunes Canadiens. Nos objectifs étaient de: (i) décrire le statut vitamin D des jeunes Québécois en utilisant un échantillon représentatif; (ii) examiner la contribution de la diète, l'activité physique et l'adiposité a expliquer la variance du 25-hydroxyvitamin D, {25(OH)D.}, le meilleur biomarqueur du statut vitamine D; et (iii) examiner l'influence du statut socio-économique et l'insécurité alimentaire sur le consommation des produits laitiers, du calcium et de la vitamine D alimentaire.
Pour décrire le statut vitamine D on a utilisé les données transversales d'un échantillon représentatif des jeunes Québecois agés de 9, 13 et 16 ans. Pour le deuxième objectif, 159 jeunes, âgés 8-11 ans avec des parents (au moins un) qui étaient obèses ou avaient le syndrome métabolique etaient utilisés pour une analyse transversale dans l'étude Québec Adipose and Lifestyle InvesTigation in Youth (QUALITY). Le tissu adipeux a été mesuré avec le dual X-ray absorptiometry (DXA) et l'activité physique était mésurer par accéléromètre. Finalement, on a utilisé des données du Canadian Community Health Survey (CCHS), un échantillon de 8960 jeunes, agés de 9-18 ans qui avaient un rappel alimentaire de 24 heures, le poids et la taille mesuré, l'information sociodémograhique et le statut de sécurité alimentaire.
Dans l'étude QUALITY et le QCAHS plus de 90% des jeunes avaient un statut de vitamine D sub-optimal {plasma 25(OH)D < 75 nmol} à la fin de l'hiver et au début du printemps. Dans l'étude QCAHS, les adolescents avaient une prévalence de déficience de vitamine D élevé {25(OH)D < 27.5 nmol} (> 10%) et les filles venant des foyers défavorisés avait des niveaux de vitamine D plus bas. Dans l'étude QUALITY, un augmentation d'un écart-type de la consommation du lait et l'activité physique était associée avec une augmentation du niveau de vitamin D de 2.9 nmol/L and 2.1 nmol/L respectivement. Dans l'étude CCHS nous avons remarqué que les garçons de milieux défavorisés et les filles avec une insécurité alimentaire consommaient moins de lait et le lait étaitremplacé par les breuvages sucrés.
Des mesures pour augmenter la consommation de vitamine D parmi les jeunes Canadiens devraient être examinées.

Background: Older people presenting with hip fractures requiring surgery have a high prevalence of hypovitaminosis D, which is an important modifiable risk factor for falls and fractures. Inadequate sun exposure is the main reason for vitamin D deficiency in older people. Vitamin D supplements, with or without calcium have been shown to reduce falls and fracture risk in this population. Undertreated pain is a risk factor for delirium and a barrier to rehabilitation interventions following a hip fracture. A small number of randomised controlled trials (RCTs) have shown increased 25-OHD levels with a loading dose of vitamin D may improve falls and fractures. Low vitamin D levels have also been implicated in pain generally, as well as static and dynamic pain responses to mobility. It is not known whether oral vitamin D replenishment using a loading dose is effective, and if it is, what is the interplay this is with patient characteristics, in particular self-reported pain rating levels, lower limb mobility and 25-OHD levels. Aims: The aims of this research were (1) to characterise the predictive factors of 25-OHD levels; (2) to characterise the predictive factors of self-reported pain after hip fracture; (3) to determine the benefit of early loading-dose oral vitamin D replenishment and determine the 25-OHD response; (4) to evaluate safety profile of an initial high-dose (250,000IU) vitamin D followed by daily maintenance for 6 months; (5) to monitor its effects on functional mobility, falls, fractures, grip strength, health related quality of life and mortality. Methods: Participants of the REVITAHIP RCT cohort (mean age of 220 participants was 83.9 (SD 7.2) years and 77.1% were women): Active (111) and Placebo (107) participants were randomised to loading dose (250000IU vitamin D3) vs placebo followed by 6 months maintenance oral therapy (vitamin D3/calcium: 800IU/600mg) daily. Primary outcome measures are 2.4m gait-velocity, with secondary outcome measures of falls, fractures (Week-4), 25-OHD levels, quality-of-life measure (EQ-5D), mortality at weeks-2, 4 and 26 with additional measures of pain (via the numerical rating scale [NRS]) were correlated with patient characteristics in this cohort. Results: Hypovitaminosis D (25-OHD <50nmol/L) was present in 46.8% of participants and 15.4% had 25-OHD levels lower than 30nmol/L. Multivariate regression models demonstrated higher baseline vitamin D levels were significantly associated with higher premorbid Barthel Index scores and lower post-operative NRS pain levels. Further, the mean (SD) NRS pain score was 3.5 (2.3). More than half (61.9%, n=113) had NRS>3 and 18.1% (n=52) had NRS>5. Using the EQ-5D pain sub-score, 78.1% had moderate pain or discomfort and 7.9% had extreme pain or discomfort. Using a multivariate regression model, postoperative NRS was significantly higher in persons with a higher comorbidity count, those previously living independently alone, and surgical fixation with hemiarthroplasty. After loading dosing administration, 25-OHD levels were significantly higher for the Active group when compared to the Placebo group at 2 weeks (73 vs 66 nmol/L; p=.019) and at 4 weeks (83 vs 75nmol/L; p=.030). At week 4, the Active group had a significantly lower percentage of people with suboptimal 25-OHD levels (3.2% vs 15.4%, p=.019). At week 4, participants in the Active group had a gait velocity over 2.4m of 0.42m/s compared with 0.39m/s in the placebo group (p=.490). To week 4, seven (6.3%) participants in the Active group reported 1 or more falls compared to twenty-three (21.1%) in the Placebo group (χ2 = 4.327; p=.024) but there were no differences in fractures (2.7% vs 2.8%, p=.964) or grip strength. The number of deaths was non-significantly lower in the Active group compared with the Placebo group at 4 weeks (1 vs 3, p = .295). There was a trend for Active participants to have a higher total EQ-5D scores at Week 26 (88.1+/-13.2 vs 84.3+/-15.8, F=2.87, p=.092). Active participants were significantly more likely to present with ‘no pain or discomfort’ at Week 26 (96.4% vs 88.8%, p=.037). One case of hypercalcemia at 2 weeks was noted in the Active group which normalised after 4 and 26 weeks. Discussion and Conclusions: This study cohort shared similar demographic characteristics and comorbidities with other cohorts of people with hip fracture. Hypovitaminosis D was not as prevalent as previously documented. Patients taking vitamin D supplements and with higher premorbid Barthel Index, reflecting greater independence and activity, tended to have higher 25-OHD levels at baseline. Further, lower NRS pain ratings following surgery were associated with higher vitamin D levels. Overall, the levels of pain reported by this cohort are acceptable although approximately 10% to 15% had higher than reasonable levels of pain. Despite a higher than expected baseline 25-OHD level and moderate increases in 25-OHD levels, participants in the Active REVITAHIP group resulted in a greater percentage with target 25-OHD levels (>50nmol/L) compared with the placebo group with no significant differences in gait velocity at 4 weeks. Lower numbers of falls and improved pain control were noted in the Active group over the study period. In this cohort, there was a higher than expected baseline 25OH level which could have underestimated the effect of the intervention in a group with lower baseline 25-OHD levels.

Abstract The aim of the present study was to examine associations between serum 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D[(1,25(OH)2D]—the circulating and active forms of vitamin D—and periodontal infection. The data were gathered from a case-control study (63 periodontitis patients and 30 periodontally healthy controls) and an intervention study among individuals with type 1 diabetes mellitus (T1DM, 80 patients at the baseline and 65 after periodontal treatment). The periodontal data and the levels of serum 25(OH)D, 1,25(OH)2D and parathyroid hormone (PTH) were available. A third data set included periodontal data and the serum level of 25(OH)D of 1262 non-smoking and non-diabetic 30–49-year-old individuals (Health 2000 Survey). Serum 25(OH)D analyses were done using enzyme-linked immunoassay and radioimmunoassay, 1,25(O)2D analyses using enzyme-immunoassay after purification of 1,25(OH)2D by immunoextraction and PTH analyses using electrochemiluminescence immunoassay. In the case-control study individuals with a low serum 1,25(O)2D level were more likely to belong to the periodontitis group than to the periodontally healthy group and an inverse association was observed between serum 1,25(OH)2D and severity of periodontitis at the baseline of the intervention study. Serum 1,25(OH)2D increased significantly after periodontal treatment in the T1DM patients; a finding that was considered suggestive of a causal relationship between serum 1,25(OH)2D and periodontal infection. Also, serum PTH increased after periodontal treatment; this increase, which was statistically significant (p = 0.016) in patients with moderate or severe periodontitis, may partly account for the earlier observed post-treatment increase in serum 1,25(OH)2D level. Possible explanations for low serum 1,25(OH)2D in periodontal infection may be increased degradation of 1,25(OH)2D, increased use of 1,25(OH)2D, or decreased hydroxylation of 25(OH)D The association between serum 25(OH)D level and periodontal infection was weak, if existent. An inverse association between serum 25(OH)D and the severity of periodontal infection was observed only in the T1DM patients. Among individuals with low plaque level, those in higher 25(OH)D quintiles tended to have fewer teeth with deepened periodontal pockets than those in lower quintiles; a finding which was interpreted to mean a slight protective role of 25(OH)D against periodontal infection
Tiivistelmä Tutkimuksen tarkoituksena oli selvittää seerumin 25-hydroksivitamiini D:n [25(OH)D, D-vitamiinin varastomuoto] ja 1,25-dihydroksivitamiini D:n [1,25(OH)2D, D-vitamiinin aktiivinen muoto] tasojen yhteyttä parodontiumin alueen infektiosairauksiin. Tulokset perustuvat kolmeen tutkimusasetelmaan: tapaus-verrokki-tutkimus (63 parodontiitti-potilasta, 30 verrokkia), interventio-tutkimus [80 tyypin 1 diabetes mellitus (T1DM) potilasta, joista 65 osallistui seurantaan parodontologisen hoidon jälkeen] ja poikittaistutkimus Terveys 2000 tutkimuksen osa-aineistossa (1262 30-49 vuotiasta tupakoimatonta ei-diabeetikkoa). Tapaus-verrokki- ja interventiotutkimuksissa tutkittiin myös seerumin parathormoonin (PTH) yhteyttä parodontaali-infektioon sekä PTH:n vaikutusta seerumin 1,25(OH)2D tasoon infektion hoidon jälkeen. D-vitamiinin ja PTH:n tasot määritettiin immunologisin menetelmin. Yhteyksiä tutkittiin käyttäen vakioituja monimuuttujamalleja. Tapaus-verrokki-tutkimuksessa yksilöt, joilla seerumin 1,25(OH)2D taso oli alhainen, kuuluivat todennäköisemmin parodontiitti- kuin verrokkiryhmään. Interventiotutkimuksen alkutilanteessa seerumin 1,25(OH)2D:n ja parodontaali-infektion vaikeusasteen välillä vallitsi tilastollisesti merkittävä käänteinen yhteys ja taso nousi merkittävästi infektion hoidon jälkeen. Myös seerumin PTH taso nousi parodontaali-infektion hoidon jälkeen; nousu oli tilastollisesti merkittävä (p = 0.016) pitkälle edennyttä parodontiittia sairastavilla. Interventiotutkimuksen tulokset viittaavat kausaaliseen yhteyteen 1,25(OH)2D:n ja parodontaali-infektion välillä. Alhainen seerumin 1,25(OH)2D pitoisuus infektion vallitessa voi selittyä sen suurella käytöllä immuunipuolustukseen infektion aikana tai lisääntyneellä hajoamisella. Tason nousu hoidon jälkeen tukee edellä mainittua. PTH on 25(OH)D:n hydroksylaation pääsäätelijä ja 1,25(OH)2D:n nousua hoidon jälkeen voi osittain selittää myös seerumin PTH tason kohoaminen. Seerumin 25(OH)D:n ja parodontaali-infektion välillä havaittu yhteys oli heikko, mutta ei täysin sulje pois 25(OH)D:n suojaavaa vaikutusta. Käänteinen yhteys löytyi vain interventiotutkimuksen alkutilanteessa T1DM potilailla. Infektion hoito ei vaikuttanut 25(OH)D tasoon. Terveys 2000 tutkimuksen osa-aineistossa havaittiin hyvän suuhygienian omaavilla jonkin verran alhaisempi määrä syventyneitä ientaskuja ylemmissä kuin alemmissa 25(OH)D kvintiileissä

The accurate assessment of human diabetic somatic polyneuropathy (DSPN) is important to define at risk patients, predict deterioration, and assess the efficacy of pathogenetic treatments. Corneal confocal microscopy (CCM) has been proposed as a surrogate endpoint for DSPN. Approximately 50% of patients with DSPN experience neuropathic pain or symptoms and the underlying reasons are not clearly elucidated. Vitamin D deficiency has been associated with diabetic complications including DSPN and diabetic retinopathy (DR). However there is a paucity of data regarding the interaction of vitamin D status with diabetic complications. This thesis shows that CCM can readily detect small fibre neuropathy prior to large fibre involvement and assess rapidly progressive nerve fibre loss prior to conventional thermal threshold testing. CCM has a superior diagnostic capabilities compared to intra-epidermal nerve fibres and correlates better with nerve conduction studies. Patients with LADA have a greater prevalence of small fibre neuropathy compared to matched patients with type 2 diabetes. Vitamin D deficiency is highly prevalent in patients with diabetes and despite relatively aggressive replacement regimens are inadequate in raising vitamin D levels in a significant proportion of patients. Vitamin D deficiency is not associated with DR but there is a strong association between painful DSPN and vitamin D insufficiency and more so with overt deficiency.

Evidence for the association between vitamin D status and cardiovascular disease (CVD) is reviewed. Cross-sectional analysis of data from the CRESSIDA and MARINA trials revealed a strong association between vitamin D status and arterial stiffness. An increase in vitamin D status measured as serum 25-OH-D concentrations after following advice to consume 1-2 portions of oily fish/wk was demonstrated (9.2 nmol/L, 95% CI 4.2, 14.2). The effects of malted milk drinks fortified with vitamin D2 or D3 at 5 and 10 μg/d vs. placebo taken for 4 wk on serum 25-OH-D metabolite concentrations were compared in 8 subjects/group in winter (minimal UVB exposure): mean increments ± SED vs. placebo were 9.4 ± 2.5 and 17.8 ± 2.4 nmol/L in 25-OH-D2 after 5 and 10 μg D2/d and 15.1 ± 4.7 and 22.9 ± 4.6 nmol/L in 25-OH-D3 after 5 and 10 μg D3/d. A total of 41 predominantly normotensive men and post-menopausal women (50-70 y) were randomly allocated to receive 10 μg/d D2 (Rx) or a placebo malted milk drink for 12 wk in winter. The specified primary outcomes of the trial were 24 h ambulatory blood pressure (BP) and flow mediated dilation (FMD) of the brachial artery. The mean increase ± SED in serum 25-OH-D2 on Rx vs. placebo was 22.8 ± 2.0 nmol/L (P < 0.001). The treatment effects (mean changes on Rx vs. placebo with 95% CI) were 0.17% (-1.62, 1.28; P=0.82) for FMD and -4.3 mm Hg (-7.3, -1.2; P=0.007) and -2.8 mm Hg (-5.4, -0.2; P=0.032) for systolic and diastolic BP respectively. This BP lowering effect of vitamin D2 in the winter months and the null finding with regard to FMD need confirmation with a larger sample. A trial of several years duration is required to demonstrate whether the association of PWV with vitamin D status is causal.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Vitamin D is important for bones and for other body functions. Whether insufficient vitamin D causes CVD is unclear. Previous trials of vitamin D were unable to evaluate effects on CVD. This thesis will (i) review the literature on vitamin D and CVD; (ii) evaluate the observational associations between plasma 25(OH)D levels and CVD; and (iii) describe the design and results of the BEST-D trial. (i) Associations between baseline 25(OH)D levels and cause-specific mortality were evaluated in the Whitehall Resurvey of survivors undertaken in 1995, and findings included in a meta-analysis of similar studies. (ii) The BEST-D study was a randomised trial in older healthy volunteers of the effects of two doses of vitamin D3 (4000 IU or 2000 IU daily) compared to placebo, on blood 25(OH)D concentrations and CVD risk factors including blood pressure and arterial stiffness. (i) The Whitehall Resurvey of 5409 men with mean age of 77 years, among whom there were 3215 deaths showed an approximately linear (log-log scale) inverse association of plasma 25(OH)D concentrations and both CVD and non-vascular causes of death between 30 to 90 nmol/L. The meta-analysis confirmed the associations of 25(OH)D with CVD mortality. (ii) The BEST-D trial showed marked increases in 25(OH)D blood concentrations but no effects of taking higher doses of vitamin D3 for 12 months on blood pressure or arterial stiffness, compared to placebo. Plasma 25(OH)D is inversely associated with both CVD and non-vascular mortality. No effects were found after oral intake of vitamin D3 on blood pressure or arterial stiffness after 1 year. Randomised trials using adequate doses of vitamin D3 are needed, to evaluate causal effects of taking vitamin D on CVD outcomes.

Introdução - O receptor de vitamina D (VDR) é expresso em vários tecidos e quando este se encontra na sua forma ativada, modula a expressão de diversos genes. Esses incluem variações dos níveis circulantes de 1,25(OH) 2 D , variações na densidade mineral óssea, secreção e sensibilidade à insulina em resposta à glicose, suscetibilidade à diabetes tipo 1 e 2, obesidade, dislipidemias e hipertensão arterial. Atualmente, evidências têm sugerido o envolvimento da vitamina D com a síndrome metabólica. Objetivo - Investigar a concentração sérica da vitamina D e sua relação com a síndrome metabólica e avaliar a potencial associação entre estes fatores com a presença de polimorfismos no gene do receptor de vitamina D (VDR) em indivíduos adultos. Métodos - Trata-se de um estudo transversal, onde foram avaliados 372 indivíduos adultos. Foram coletadas amostras sanguíneas para dosagens laboratoriais da 25(OH)D 3 , PTH e exames bioquímicos relacionados à SM, além disso foram realizadas avaliações antropométricas (peso, altura, IMC). A síndrome metabólica (SM) foi classificada usando o critério proposto pelo National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). A resistência a insulina foi estimada pelo cálculo de HOMA IR e a função da célula pelo cálculo de HOMA . A 25(OH)D foi dosada por HPLC e a insuficiência foi determinada pelo ponto de corte da curva Roc (52,6nmol/l). Foram avaliados também PTH intacto e cálcio sérico. Os polimorfismos BsmI e FokI foram detectados através da digestão das enzimas de restrições específicas para cada polimorfismo e confirmados através da técnica PCR alelo específico (ASPCR) ou amplificação de mutação refratária (ARMs) nos indivíduos com e sem SM (52 por cento vs. 48 por cento , respectivamente). A análise estatística inclui construção da curva ROC, teste T de Student, testes de correlação, teste de equilíbrio de Hardy-Weinberg, ANOVA, regressão logística binária (Odds Ratio). Estas análises foram conduzidas no software SPSS para Windows, versão 18 e p < 0,05 foi considerado significante. Resultados - A idade média dos participantes foi 51(15) anos, o IMC médio 29(6) kg/m 3 2 e 48 por cento apresentaram SM. Como esperado, os 3 indivíduos com SM apresentaram maiores valores de idade 57(12) anos, IMC 32(6) Kg/m , circunferência de cintura 103(13) cm, pressão sistólica 138(17) mmHg e diastólica 83(10) mmHg, glicemia de jejum 98(12) mg/dl, triglicérides 165(76) mg/dl, índices HOMA-IR 2.2(1.7) e 116(95), e menores valores de colesterol HDL colesterol 41(11) mg/dl. Com relação às concentrações séricas de 25(OH)D propostas pela análise da curva ROC, 43 por cento dos indivíduos com SM e 57 por cento dos indivíduos sem SM apresentam insuficiência desta vitamina. Correlações entre 25(OH)D 3 3 com PTH (r = -0.153; p = 0.005) e com circunferência da cintura (r = -0.106; p = 0.05) foram observada em todos os participantes. Considerando os polimorfismos do gene VDR, nos pacientes com SM, não houve associação entre o polimorfismo BsmI e os componentes da SM, HOMA e IR, 25(OH)D e PTH. No entanto, indivíduos sem SM, mas com homozigose para polimorfismo BsmI (genótipo recessivo bb ), apresentaram concentrações mais baixas de 25(OH)D 3 3 do que aqueles com o genótipo BB normal. Além disso, os indivíduos com SM e heterozigose para o polimorfismo FokI (genótipo Ff) têm maiores concentrações de PTH e HOMA do que aqueles com genótipo normal FF. Nesse mesmo grupo, os indivíduos com o genótipo recessivo ff têm maior resistência à insulina do que aqueles com genótipo Ff. Por outro lado, os pacientes sem SM, mas carregando o genótipo Ff, apresentaram maiores concentrações de triglicerídeos e baixos níveis de HDL do que aqueles com genótipo FF. A presença de um alelo f no genótipo (Ff ou ff) é, aparentemente, o suficiente para aumentar os níveis de triglicérides e resistência à insulina, quando comparados ao genótipo normal FF. Conclusão - Os resultados demonstram que o polimorfismo FokI no gene VDR associa-se a resistência à insulina e maiores concentrações de PTH em pacientes que apresentam SM. Além disso, o polimorfismo BsmI associa-se a menores concentrações de 25(OH)D em indivíduos sem SM. Portanto, esses novos dados indicam que polimorfismos no gene do VDR estão associados a diferentes fenótipos dos componentes da SM
Introduction - The vitamin D receptor (VDR) is expressed in many tissues and when it is in its activated form modulates the expression of several genes. These include changes in circulating levels of 1,25(OH)2D3, variations in bone mineral density, sensitivity and secretion of insulin in response to glucose, susceptibility to type 1 and 2 diabetes mellitus, obesity, dyslipidemia and hypertension. Currently, evidences have suggested the involvement of vitamin D with the metabolic syndrome. Objective - To investigate the serum concentrations of vitamin D and its relationship with metabolic syndrome (MS) and to evaluate the potential association between these factors with the presence of polymorphisms in vitamin D receptor gene in individuals adults. Methods - This is a cross-sectional study, which evaluated 243 adults and elderly. We collected blood samples for measurements of 25(OH)D3, iPTH, biochemical tests related to MS, and anthropometric evaluation (weight, height, BMI) were also assessed. MS was classified using the criteria proposed by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Insulin resistance and cell secretion were estimated by calculating HOMA IR and HOMA , respectively. The 25(OH)D3 was measured by HPLC and insufficiency was determined by the Roc curve cut-off (52.6 nmol/L). Intact PTH and serum calcium were also evaluated. The BsmI and FokI polymorphisms were detected by enzymatic digestion with specific enzymes and confirmed by allele specific PCR (ASPCR) or amplification of refractory mutation (ARM) in individuals with or without MS (52 per cent vs. 48 per cent , respectively). Statistical analyses include construction of Roc curves, Student T test, correlation tests, Hardy-Weinberg test, ANOVA, binary logistic regression (odds ratio), and TwoStep Cluster. These analyses were conducted with SPSS for Windows, version 18 and p < 0.05 was considered significant. Results - The mean age of participants was 51(15) years, mean BMI was 29(6) kg/m2, and 48 per cent of individuals presented MS. As expected, subjects with MS showed higher values of age (57(12) years), BMI was 32(6) kg/m2, waist circumference was 103(13) cm, systolic blood pressure was 138(17) mmHg, diastolic was 83(10) mmHg, fasting glucose was 98(12) mg/dl, triglycerides was 165(76) mg/dl, HOMA-IR was 2.2(1.7), HOMA was 116(95), and lower levels of HDL cholesterol was observed (41 mg/dl(11)). With respect to serum 25(OH)D3 proposed by ROC curve analysis, 43 per cent of individuals with MS and 57 per cent of individuals without MS presented insufficiency of this vitamin. Correlations between 25(OH)D3, iPTH (r = -0,153, p = 0.005), and waist circumference (r = -0,106, p = 0.05) were observed in all participants. Considering the VDR gene polymorphisms, in patients with MetSyn, there is no association among BsmI polymorphism and components of MetSyn, HOMA IR and , 25(OH)D3, and PTH. However, subjects without MetSyn, but with homozygosis for BsmI polymorphism (recessive bb genotype), presented lower levels of 25(OH)D3 than those with normal BB genotype. In addition, individuals with MetSyn and heterozygosis for FokI polymorphism (Ff genotype) have higher concentrations of PTH and HOMA than those with normal FF genotype. In this same group, subjects with the recessive ff genotype have higher insulin resistance than those with Ff genotype. On the other hand, patients without MetSyn, but carrying the Ff genotype, have higher concentration of triglycerides and lower levels of HDL than those with FF genotype. Interestingly, the presence of one allele f in the (Ff or ff) genotype is apparently enough to increase triglycerides levels and insulin resistance, when compared to the normal FF genotype. Conclusion - The results show that FokI polymorphism in the VDR gene is associated to insulin resistance and higher concentrations of PTH in patients with MetSyn. Moreover, BsmI polymorphism is related to a lower concentration of 25(OH)D3 in individuals without MetSyn. Therefore, the results indicated that VDR gene polymorphisms are associated to different phenotypes of MetSyn components

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

Vitamin D is important in maintaining bone health and has recently been proposed to have additional roles in the immune system and brain development. The estimated average requirement (EAR) and recommended dietary allowance (RDA) for vitamin D established by the Institute of Medicine (IOM) in 2011 is 10µg/day and 15µg/day, respectively. When this study was initiated, little information was available on whether vitamin D intakes below the recommendations in young children result in biochemical evidence of vitamin insufficiency or deficiency. Therefore the aims in this thesis were; to estimate vitamin D intakes in children, and the contribution of natural and fortified foods, and supplements; to determine the proportion of children consuming vitamin D below and above the intake recommendations; to use biochemical measures of plasma 25(OH)D to determine the proportion of vitamin D sufficient, insufficient and deficient children; and to estimate the importance of vitamin D intake and season to the children’s plasma 25(OH)D. This was a cross-sectional design with 200 children from Vancouver BC, aged 5.75 years. Vitamin D intakes were estimated using a food frequency questionnaire and 24 hr dietary recalls. Plasma 25 (OH)D was determined by HPLC-tandem mass spectrometry. The median vitamin D intake from foods was below the EAR and RDA. The children obtained 85.9% of their dietary vitamin D from supplements and fortified foods and 14.1% from natural food sources. Total median vitamin D intakes in children given or not given supplements was 13.0 (9.0) µg/day and 4.8 (3.7) µg/day, respectively, P< 0.001. Using the FFQ, 51% and 76% of the children did not meet the EAR and RDA for vitamin D, respectively. However, only 4.7% and 19.0% had a plasma 25 (OH)D below 40 nmol/L or 50 nmol/L, respectively. Unexpectedly, only 12.5% of the children who did not meet the EAR during winter months had a plasma 25 (OH)D below 40 nmol/L. The results in this thesis suggest that children depend on supplements and fortified foods to achieve the current vitamin D intake recommendations. However, despite apparent low vitamin D intakes, few children show biochemical evidence of vitamin D insufficiency, even during winter months.

Inaugural address delivered on 2 November 2011
Marietjie Herselman was born in the Langkloof, where she matriculated at the McLachlan High School. She obtained a BSc (Physiology and Dietetics) degree at Stellenbosch University and for the next 18 years worked as a dietitian at Tygerberg Hospital, where she specialised in renal nutrition. She obtained a master’s degree in nutrition in 1985 and in 1991 was appointed as a lecturer in the Department of Human Nutrition, Faculty of Health Sciences, at Stellenbosch University. In the same year she obtained her PhD in nutritional sciences at this university, where she was later promoted to senior lecturer (1995), associate professor (2001) and full professor (2010). From 2008 to 2010 she was appointed first as acting head and later as head of the Division of Human Nutrition. She served on the Professional Board of Dietetics from 1998 to 2003 and also on various sub-committees of the Board. She regularly reviews papers and research applications for scientific councils/associations as well as five national and four international scientific journals. Currently, she serves on the editorial boards of four international scientific journals and in 2008 she was elected as the co-editor (Africa region) of the international journal Nutrition. She successfully delivered 17 master’s students and published 29 scientific papers in national and international journals and three chapters in textbooks. Marietjie also presented papers at 19 international and 37 national conferences. Three international and four national awards were bestowed on her for her research in renal nutrition. She played a leading role in the initiation of the Community Nutrition Security Project (CNSP) in the Breede Valley, as part of Stellenbosch University’s HOPE Project, as well as the NOMA master’s programme in Nutrition, Human Rights and Governance in collaboration with the universities of Oslo and Akershus (Norway) as well as Makerere and Kyambogo (Uganda).

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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
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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

L’obésité s’accompagne d’un état inflammatoire chronique qui joue un rôle délétère.Cet état associé à l’obésité été impliqué dans le développement de complications métaboliques:insulino-résistance et DT2.Chez les obèses,le TA est un site de production de médiateurs pro et/ou anti-inflammatoires, des adipokines.Les modifications et changements de style de vie et les approches thérapeutiques sont privilégiés pour lutter contre l’obésité.Toutefois,les approches préventives ne doivent pas être négligées,des études épidémiologiques ont mises en évidence une corrélation entre obésité et carence en micronutriments.Par ailleurs,il existe une corrélation inverse entre micronutriments lipophiles et caroténoïdes et la prévalence de l’obésité et du DT2.Le but de cette thèse est de comprendre le lien qui existe entre carence en micronutriments,obésité et complications associés.Une étude clinique transversale a été réalisée chez des obèses non diabétiques.Les résultats nous ont permis de montrer qu’il existe une association positive entre b-carotène et sensibilité à l'insuline chez l'obèse,effet pouvant être lié à une modulation de l'expression de certaines adipokines dont l'adiponectine qui est indépendamment associée à la concentration plasmatique en b-carotène.Une étude préclinique a été menée, dont l'objectif évaluer l'impact de la teneur en vitamines alimentaires sur la prise de poids et l'insulino-sensibilité.Des souris ont été soumises à un régime hypovitaminé.A 10 semaines,ce régime favorise la prise de masse grasse,modifie la sensibilité à l'insuline,en agissant au niveau du métabolisme lipidique hépatique,via une diminution des capacités oxydatives
Obesity is associated with chronic inflammatory condition that plays a deleterious role.This inflammatory state associated with obesity was involved in the development of metabolic complications : insulin resistance and T2DM.Obese, AT is a site for the production of pro and/or anti-inflammatory adipokines, and plays a major role in the development of chronic inflammation associated with obesity.Modifications and changes in lifestyle and therapeutic approaches are preferred to deal with obesity. However,preventive approaches should not be ignored,several epidemiological studies have shown a correlation between obesity and micronutrient deficiency.In addition,there is an inverse correlation between lipophilic micronutrients and carotenoids and the prevalence of obesity and T2DM.The purpose of this thesis is to understand the possible link between LM and carotenoids deficiency, obesity and associated physiological disorders.A cross-sectional study was performed in non-diabetic obese patients.The results allowed us to conclude the existence of a favorable effect of b-carotene on insulin sensitivity in obese patients.This effect may be related to modulation of inflammation or the expression of some adipokines(such as adiponectin), either directly or through its pro-vitamin A activity.A preclinical study was performed; the objective is to assess the impact of the vitamins on weight gain and insulin sensitivity.Mice were subjected to a hypovitaminic diet.After 10 weeks of regimen, we observed an increased adiposity and an altered insulin sensibility.This diet probably acts on the hepatic lipid metabolism via a decrease in oxidative capacity

Orientador: Gabriel Hessel
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: As doenças hepáticas crônicas podem induzir à má-absorção de lipídios e vitaminas lipossolúveis e levar ao comprometimento do estado nutricional. O objetivo da pesquisa foi determinar os níveis séricos de vitaminas lipossolúveis (A, D e E) em crianças e adolescentes com atresia biliar (AB) e hepatite auto-imune (HAI) e verificar a relação com o estado nutricional e indicadores laboratoriais e clínicos. O estudo foi transversal e controlado e foram avaliados os pacientes com HAI (n=25) e AB (n=24), e um grupo controle (n=53) pareado por sexo e idade. Os níveis séricos das vitaminas A, D e E foram determinados pela técnica de cromatografia líquida de alta eficiência. Além disso, foi realizada a avaliação antropométrica e a classificação dos pacientes na pontuação de Child-Pugh. Foram empregados os testes de Mann-Whitney, o coeficiente de correlação de Spearman e análise de variância, sendo considerada diferença significativa se p<0,05. Em relação às vitaminas, no grupo controle, constatou-se que os níveis séricos das vitaminas A e E variaram com a idade. Os níveis séricos das vitaminas A, D e E foram maiores no grupo controle em relação aos pacientes com AB e HAI, em conjunto ou separadamente. Em relação ao grupo AB, não foi observado diferença significativa nos níveis séricos das vitaminas A, D e E nos pacientes com ou sem colestase. Os pacientes com AB e HAI, em conjunto, classificados em Child C e Child B apresentaram os menores níveis séricos das vitaminas A e E comparados ao Child A. O déficit nutricional mais grave foi observado nos pacientes com AB com colestase. Verificou-se no grupo AB e HAI em conjunto a correlação do Peso/Idade (P/I), Prega Cutânea Triciptal (PCT), Prega Cutânea Subescapular (PCSE), Circunferência Braquial (CB), Área Adiposa Braquial (AAB) com as vitaminas A e E. Além destes indicadores a vitamina E também se correlacionou com Estatura/Idade (E/I), Índice de Massa Corporal (IMC), Área Muscular Braquial (AMB) e Soma das Pregas Cutâneas (SPG) nos pacientes com HAI e AB, em conjunto. Pode-se concluir que, foi observada deficiência das vitaminas A, D e E nos pacientes com AB e HAI. Quanto maior a gravidade da doença menores foram os níveis séricos das vitaminas A e E, nos pacientes com AB e HAI, em conjunto. Essa mesma relação da gravidade da doença ocorreu para as vitaminas A e D nos pacientes com HAI. Com relação ao estado nutricional, os pacientes com AB, principalmente com colestase, apresentaram maior comprometimento nutricional. Houve correlação diretamente proporcional, principalmente da vitamina E com todas as variáveis antropométricas do grupo de AB e HAI em conjunto
Abstract: The chronic liver diseases can cause malabsorption of lipids and fat-soluble vitamins, leading to a deficient nutritional status. The aim of research was: to evaluate the relation between serum levels of fat-soluble vitamins (A, D and E) on chidren and adolescents with biliary atresia (BA) and auto-immune hepatitis (AIH) with the nutritional status and with laboratorial and clinic indicators. The study was transversal controlled, which were evaluated patients with AIH (n=25) and BA (n=24) and a control group (n=53) lined up by sex and age. The determination of serum levels of vitamins A, D and E was carried out by high performance liquid chromatography. Anthropometrics evaluation and classification of patients on Child-Pugh scale were also used. It was used the Mann-Whitney test, the correlation coefficient of Spearman and variance analysis for data analysis, which was considered significant difference if p< 0.05. Have been evidenced that serum levels of vitamins A and E in healthful group were changed with age. The serum levels of vitamins A, D and E were higher in the healthful group when compared with the patients with BA and AIH together or isolated. No difference in the serum levels of vitamins A, D and E was noted in the BA group with or without cholestasis. The patients with BA and AIH together grouped and classified in Child C and Child B presented the lowest serum levels of vitamins A and E when compared to the patients classified in Child A. The nutritional deficit more intense was observed in the patients with BA and cholestasis. It was verified in the BA and AIH groups together a correlation weight/age (W/A), Triceps Skinfold Thickness (TST), Subscapular Skinfold Thickness (SST), Midarm Circunference (MC) and Midarm Fat Area (MFA), with the vitamins A and E. Besides indicators, the vitamin E was also correlated with Stature/Age (S/A), Body Mass Index (BMI), Midarm Muscle Area (MMA) and SKinfold Sum (SFS) for patients with AIH and BA together. In conclusion, have been observed deficiency of vitamins A, D and E in patients with AB and AIH. For higher serevity of disease, the serum levels of vitamins A e E are lower for patients with AB and AIH together. This same relation occurs for vitamins A and D for patients with AIH. When the nutrition status is evaluated, the patients with AB and cholestasis presented the highest nutritional deficiency. There is a correlation directly proportional, mainly of vitamin E with the anthropometric variables of the AB and AIH groups together
Doutorado
Saude da Criança e do Adolescente
Doutor em Saude da Criança e do Adolescente

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Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Departamento de Ensino. Programa de Pós-Graduação em Saúde da Criança e da Mulher. Rio de Janeiro, RJ, Brasil
Objetivo: avaliar a associação entre os níveis séricos de 25-hidroxivitamina D (25 OHD) e câncer de mama no climatério. Métodos: trata-se de um estudo do tipo casocontrole com mulheres de 45 a 70 anos atendidas nos ambulatórios de mastologia e ginecologia geral do hospital materno-infantil Instituto Fernandes Figueira, localizado no município do Rio de Janeiro. Foram selecionados 39 casos incidentes de câncer de mama e 60 controles. As participantes foram submetidas à entrevista para o preenchimento de um questionário estruturado e em seguida foi realizado a coleta de sangue para a dosagem de 25 OHD. Resultados: foi observada uma prevalência de 80,8% de hipovitaminose D (< 30ng/mL) entre as participantes do estudo. Em relação à estimativa de risco para carcinoma mamário, o grupo com níveis suficientes de 25 OHD não apresentou diferença com significância estatística do grupo com hipovitaminose D. Porém, na análise das estimativas de risco conforme o status menopausal, houve menor chance de exposição e desenvolvimento de câncer de mama nas mulheres pósmenopausadas com níveis suficientes de 25 OHD (OR* 0.53; IC 95%, 0.12-2.41) que as na pré-menopausa com níveis normais de vitamina D (OR* 0.97; IC 95%, 0.13-8.35) quando comparadas ao grupo com hipovitaminose D. Conclusão: Os resultados desse estudo sugerem que a hipovitaminose D entre mulheres pós-menopausadas seja um fator de risco para o câncer de mama durante o climatério. Todavia, ainda são necessários mais estudos que também confirmem essa associação.
Purpose: to evaluate the association between the plasma levels of 25-hydroxyvitamin D and the breast cancer in the climacteric. Methods: it is a kind of case-control study with women between 45 until 70 years old attended in clinics of mastology and ginecology of the maternal-infantile hospital Fernandes Figueira, localized in Rio de Janeiro city. Thirdy-nine incident cases of breast cancer and 60 controls were selected. The participants were submitted to an interview for filling out of a structured questionnaire and forthwith it was made the swab blood for the dosage of 25 OHD. Results: a prevalence of 80,8% of vitamin D deficiency was spotted among the participants of the study. In relation to the estimate of risk for breast cancer, the group with sufficient levels of 25 OHD did not present difference with significance statistic of the group with vitamin D deficiency. Nevertheless, during the analysis of the estimate of risk according to menopausal status, there were less chance of exposition and development of the breast cancer in postmenopaused women with sufficient levels of 25 OHD (OR* 0.53; IC 95%, 0.12-2.41) than the premenopaused women with normal levels of vitamin D (OR* 0.97; IC 95%, 0.13-8.35) when compared to the group with vitamin D deficiency. Conclusion: the results of this study suggests that the vitamin D deficiency among postmenopaused women is a factor of risk for the breast cancer during the climacteric. However, more studies are still necessary to confirm this association.

Les vitamines D et K sont des micronutriments liposolubles qui participent au bon fonctionnement de l’organisme. Elles jouent des rôles clés dans la prévention de trouble de l'hémostase et de la coagulation, des pathologies osseuses, métaboliques et cardiovasculaires. Cependant, même si ces vitamines sont apportées en quantités suffisantes par notre alimentation, leurs effets bénéfiques sont étroitement conditionnés par leur biodisponibilité. Or, mieux connaitre les mécanismes d’absorption permettrait d’appréhender leur biodisponibilité. Nous avons tout d’abord montré que l’absorption de la vitamine K implique des transporteurs du cholestérol, SR-B1 et CD36. Nous avons également montré que l’entérocyte est non seulement capable d’effluer les vitamines D et K néo-absorbées mais également d’excréter ces vitamines du compartiment sanguin vers la lumière intestinale. Ce phénomène bien connu pour le cholestérol (excrétion transintestinale du cholestérol) implique des transporteurs communs, dont ABCB1 et ABCG5/G8. Dans un second temps, dans le cadre de la relance de la consommation des légumineuses, nous avons mis en évidence que la présence de légumineuses dans un repas limite la biodisponibilité de ces vitamines. En effet, les fibres, phytates, saponines et tanins diminuent leur bioaccessibilité et/ou leur captage. La méthode de cuisson des légumineuses, en affectant leur composition nutritionnelle, peut moduler l’incorporation des vitamines D et K au sein des micelles mixtes et donc affecter leur biodisponibilité. Ces données soulignent ainsi le fait que les légumineuses doivent être cuites de manière appropriée et consommés dans des repas riches en micronutriments
Vitamin D and K are fat-soluble micronutrients that participate to the proper functioning of the organism. They are essential to prevent bleeding, bone, metabolic and cardiovascular disorders. However, even if those vitamins are provided in sufficient quantities in our diet, their health effects are closely linked to their bioavailability. A better knowledge of their absorption mechanisms would help to optimize their bioavailability.Firstly, we showed that vitamin K absorption involves the cholesterol transporters SR-B1 and CD36. We also showed that enterocytes can not only efflux newly absorbed vitamins D and K but also excrete vitamin D and K from the blood compartment to the intestinal lumen. This phenomenon of transintestinal excretioninvolves the cholesterol membrane transporters ABCB1 and ABCG5/G8.Secondly, we showed that the presence of pulses within a meal limits vitamin D and K bioavailability. Indeed, fibers, phytates, saponins and tannins can decrease bioaccessibility and/or uptake of vitamin K. By modulating the nutritional profile of pulses, the cooking method can impact on fat-soluble vitamin transfer to mixed micelles, and in turn affect their bioavailability. These data suggest that pulses must be cooked in an appropriate manner and consumed in micronutrient-rich meals.Keywords: vitamin D, vitamin K, bioaccessibility, intestinal absorption, pulses

Bakgrund: Det kan vara svårt att få i sig tillräcklig mängd D-vitamin för att upprätthålla en normal D-vitamins nivå under vinterhalvåret. Med normal nivå i blodet menas en D-vitaminstatus på omkring 50 nmol/l där risken för benskörhet och dödlighet minskar. Ny forskning talar för att D-vitamin har stor betydelse, inte bara för skelettet, utan också för vårt immunsystem och andra sjukdomar. Syfte: Denna studies syfte var att klargöra några av de hälsoeffekter som D-vitamin har på immunförsvaret. Metod: En litteraturstudie som baserades på tio tidigare utförda studier. Resultat: I resultatet framkom fem områden. Dessa är: Dosering för normala D-vitamin nivåer, D-vitamin effekter på hjärt- och kärlsjukdomar, D-vitamin effekter på cancersjukdomar, D-vitamins effekter på metabolt syndrom och diabetes och D-vitamins effekter på luftvägsinfektioner. Diskussion: Olika studier har forskat på vilka hälsoeffekter D-vitamin har på människans hälsa. Tillskott av D-vitaminhar visat sig ha skyddande effekter och kan även bidra till lägre dödlighet hos utsatta grupper. Effekterna av doseringsregimen för att avgöra vilka nivåer i blod som speglar ett optimalt D-vitaminstatus diskuteras. Konklusion: D-vitaminhar stor betydelse, inte bara för skelettet, utan också för vårt immunsystem. Tillskott av D-vitamin har visat skyddande effekter på ett flertal sjukdomar likt infektioner, typ 2 diabetes, bröstcancer och olika hjärt-kärlsjukdomar.
Background: It may be difficult to get enough D-vitamin to maintain a normal D-vitamin level during the winter months. A normal level in the blood means a D-vitamin status of about 50 nmol/ l, where the risk of osteoporosis and mortality is reduced. New research shows that D-vitamin is of high importance not only for the skeleton, but also for our immune system and other diseases. Purpose: The purpose of this study was to clarify some of the health effects D-vitamin has on the immune system. Method: A literature study based on ten previous studies. Result: There was five areas in the result. These are: Dose for normal D-vitamin levels, D-vitamin effects on cardiovascular disease, D-vitamin effects on cancerous diseases, D-vitamin effects on metabolic syndrome and diabetes and D-vitamin effects on respiratory infections. Discussion: Various studies have researched the health effects D-vitamin has on the human health. Supplements of D-vitamin have been shown to have protective effects and can also contribute to lower mortality in vulnerable groups. The effects of the dosage regimen to determine which levels in blood reflect an optimal D-vitamin status are discussed. Conclusion: D-vitamin is of great importance not only for the skeleton, but also for our immune system. Supplements of D-vitamin have been shown to have protective effects on a variety of diseases like infections, type 2 diabetes, breast cancer and various cardiovascular diseases.

Adipose tissue inflammation is characterised by increased infiltration of macrophages and is associated with a marked increase in the synthesis and release of proinflammatory factors such as TNFα, IL-6 and MCP-1. Studies suggest that these chemokines and cytokines contribute to local tissue inflammation and levels of inflammatory mediators in the systemic circulation. The potential role of the vitamin D receptor in modulating inflammation in obesity has received increasing attention, with evidence suggesting that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has potent immunoregulatory effects. The data presented in this thesis showed adipose tissue expresses the vitamin D receptor, along with vitamin D metabolising enzymes CYP27B1 and CYP24A1. Treatment of adipocytes with 1,25(OH)2D3 reduced the secretion of key cytokines and chemokines involved in the inflammatory response induced by macrophage-secreted factors. MCP-1, IL-6, IL-8 and RANTES production by human adipocytes was significantly downregulated, and western blotting data supports that this was due to the inhibitory effects of 1,25(OH)2D3 on the NF-κB and MAPK signalling pathways. Treatment with 1,25(OH)2D3 also abolished macrophage-induced activation of NFκB, increasing IκBα expression and reducing NFκB p65 phosphorylation. Mitogen-activated protein kinase (MAPK) signalling activated by MC medium was also inhibited by 1,25(OH)2D3 , reducing phosphorylated p38 MAPK and phosphorylated Erk1/2. Investigations into its downstream effects showed 1,25(OH)2D3 decreased macrophage-induced inflammatory cytokine expression, reducing IL-8, MCP-1, RANTES and IL-6. To confirm the involvement of the vitamin D receptor in modulating the inflammatory response in adipocytes, two 1,25(OH)2D3 analogues, ZK159222 and ZK191784, were investigated for its effects on adipocyte-macrophage crosstalk. The anti-inflammatory effects of ZK159222 and ZK191784 are demonstrated for the first time in human adipocytes. ZK159222 treatment increased IκBα in adipocytes stimulated with macrophage-conditioned medium. In contrast, ZK159222 markedly reduced protein expression of phos-NF-κB p65. In studies of MAPK activation, ZK159222 dose-dependently decreased expression of phosphorylated p38 MAPK. ZK191784 treatment was observed to increase IκBα while reduce phosphorylated NF-κB p65 levels compared to vehicle controls. ZK191784 also showed an inhibitory effect on protein expression of phosphorylated p38 MAPK. In addition, both 1,25(OH)2D3 analogues reduced protein secretion of MCP-1 and IL-6 by human adipocytes. Both compounds also significantly reduced IL-8 expression compared to vehicle controls as well as 1,25(OH)2D3 treatment as well as MC-induced RANTES expression. Overall this research demonstrates that vitamin D3 has anti-inflammatory properties in human adipocytes, probably mediated by inhibition of the NFκB and MAPK signalling pathways. Reviewing the current evidence, the data suggests that targeting the vitamin D signalling system in adipose tissue presents a novel approach for modulating adipose tissue function, and in particular, ameliorating inflammation perpetuated by macrophage-adipocyte crosstalk in obesity.

Vitamin D deficiency is a prevalent problem worldwide and data suggest that maternal vitamin D deficiency is associated with adverse maternal and offspring non-skeletal outcomes. We performed a double-blind randomised controlled trial to establish the effect of high-dose (5000 IU) vitamin D supplementation on glucose metabolism measured by the 75g oral glucose tolerance test (OGTT) and insulin resistance on the homeostasis model assessment (HOMA-IR). Additionally, we evaluated the vitamin D status of a multiethnic pregnant population and determined the predictive factors for vitamin D deficiency. Finally, we determined the association between maternal vitamin D status and intrauterine and neonatal growth, and the effects of high-dose vitamin D supplementation on the same parameters. We identified that low maternal vitamin D status at baseline was associated with more adverse glucose tolerance on the OGTT. High-dose vitamin D supplementation improved maternal and infant 25-hydroxyvitamin D (25OHD) but did not improve glucose levels and HOMA-IR. Nearly half of our cohort had 25OHD<50nmol/L. Ethnicity, Δ skin reflectance and vitamin D containing pregnancy multivitamin use predicted baseline vitamin D status. Maternal vitamin D status during pregnancy was not associated with intrauterine growth and high-dose vitamin D supplementation did not affect intrauterine or birth measures.

Inadequate Vitamin D status is observed throughout the world. Endothelial dysfunction is central to the process of cardiovascular disease and Type 2 diabetes, whose global prevalence has significantly increased. In this thesis I have examined the interrelationships of vitamin D status, endothelial dysfunction, systemic inflammation and dyslipidaemia to shed more light on this important area. This has been accomplished through cross sectional clinical trials and a systemic review and meta-analysis of current evidence.

The high prevalence of vitamin D deficiency in Australia is concerning as vitamin D is essential for bone health. This thesis provides the evidence required to explore food-based strategies to improve vitamin D status in the Australian population by: developing Australia’s first comprehensive vitamin D food composition database; generating Australia’s first population representative estimate of usual intakes of vitamin D; and, evaluating the effect of vitamin D food fortification on vitamin D status.

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas
Nos últimos anos, o papel fisiológico da vitamina D tem sido amplamente estudado. A sua ação primordial no metabolismo do cálcio é já bem conhecida, sendo esta uma das hormonas responsáveis pela manutenção dos níveis de cálcio sérico, através da promoção da absorção de cálcio e fósforo a partir do intestino e da reabsorção óssea de cálcio. No entanto, o interesse clínico na vitamina D não se restringe apenas ao metabolismo fosfocálcio, mas também se manifesta em várias outras condições médicas (diabetes, doenças cardiovasculares, esclerose múltipla, câncer, distúrbios psiquiátricos, doenças neuro-muscular). De facto, evidências recentes correlacionam níveis insuficientes de vitamina D, com um risco aumentado de desenvolvimento de outras doenças, não relacionadas com a componente óssea. A elevada prevalência de níveis inadequados de vitamina D é hoje em dia encarada como um problema de saúde pública que afeta vários países da Europa e os EUA. Por este motivo, e pelo conhecimento do crescente número de doenças associadas a esta deficiência, a medição exata dos níveis de vitamina D tem assumido elevada relevância na clínica. Desta forma, o número de análises para avaliação da quantidade de vitamina D para fins de diagnóstico aumentou significativamente. A concentração de 25- hidroxivitamina D (25(OH)D) é o parâmetro de rotina, mas a determinação de outros metabolitos, em particular a forma fisiologicamente ativa 1,25 dihidroxivitamina D (1,25(OH)2D) pode ser também de interesse clínico. No entanto, os níveis séricos de 25(OH)D são o melhor indicador do conteúdo corporal de vitamina D, uma vez que reflete a quantidade obtida a partir da ingestão e exposição à luz solar, assim como da conversão de vitamina D a partir de depósitos de gordura no fígado. As últimas orientações da Endocrine Society sugerem o rastreio do défice de vitamina D apenas em indivíduos em risco e não na população em geral. Nestes doentes, recomenda-se a medição da 25(OH)D sérica circulante, por um método analítico fiável. Ao longo dos anos, técnicas de quantificação de 25(OH)D e a 1,25(OH)D têm aumentado e evoluído. Estes métodos são baseados em ensaios de ligação competitiva por meio de imunoensaio e cromatografia líquida associados com espectrometria de massa, no entanto estes têm demonstrado vários desafios analíticos, sendo que as vantagens e desvantagens de cada método mudam constantemente com novos desenvolvimentos tecnológicos. Os imunoensaios continuam a ser o modo predominante de medição para 25(OH)D, embora os problemas com a recuperação equimolar dos metabolitos D2 e D3 permanecem um problema. O défice de vitamina D é definido por um valor de 25(OH)D inferior a 20 ng/mL (50 nmol/L). Em indivíduos em risco recomenda-se a ingestão de vitamina D na dieta, de acordo com a idade e situações especiais (gravidez, amamentação, obesidade e toma concomitante de alguns fármacos). Para o tratamento e prevenção do défice de vitamina D sugere-se a utilização de qualquer das isoformas de vitamina D (o colecalciferol ou vitamina D3 e o ergocalciferol ou vitamina D2, em dose dependente do grupo etário e das necessidades específicas.
In recent years, the physiological role of vitamin D have been widely studied intensively. Its primary action on the calcium metabolism is well known, this being one of hormones responsible for the maintenance of serum levels of calcium, by promoting calcium and phosphorus absorption from the intestine and from bone calcium resorption. However, clinical interest in vitamin D is not restricted to the fosfocalcium metabolism but also is affects several other medical conditions (diabetes, cardiovascular disease, multiple sclerosis, cancer, psychiatric disorders, neuro-muscular disease). In fact, recent evidences correlates insufficient levels of vitamin D with an increased risk of developing other diseases, not related to bone component. The high prevalence of inadequate vitamin D levels is nowadays seen as a public health problem that affects several countries in Europe and the USA. For this reason, and the knowledge of the growing number of diseases associated with this deficiency, the exact measurement of vitamin D levels has assumed great relevance in the clinic practice. Thus, the number of assays to determine circulating vitamin D for diagnostic purposes has increased significantly. Circulating 25 hydroxyvitamin D (25 (OH)D) concentration is routinely used, but measurement of other metabolites, especially the physiologically active 1,25 dihydroxyvitamin D (1,25 (OH)2D), are of clinical value. However, serum levels of 25(OH)D are the best indicator of vitamin D body content, as it reflects the vitamin obtained from dietary intake and exposure to sunlight, as well as the conversion of vitamin D from fatty deposits in liver. The latest Endocrine Society guidelines suggest screening for vitamin D deficiency only in individuals at risk and not in the general population. In these patients, it is recommended the measurement of 25(OH)D circulating in serum, by a reliable analytical method. Over the years, the development of the methods to quantify 25(OH)D and 1,25 (OH)2D have increased and evolved. These method are based in competitive binding assays through to immunoassay and liquid chromatography aligned to mass spectrometry, however these have demonstrated various analytical challenges, the advantages and disadvantages of each method are constantly changing with new technological developments. Immunoassay remains the predominant mode of measurement for 25(OH)D although problems with equimolar recovery of the D2 and D3 metabolites remain an issue. The vitamin D deficiency is defined by a value of 25 (OH) D lower than 20 ng/mL (50 nmol/L). In individuals at risk, the intake of dietary vitamin D according to the age and special medical conditions is recommended (pregnancy, breastfeeding, obesity and concomitant intake of drugs). For treatment and prevention of vitamin D deficiency it is suggested the use of any of the isoforms (cholecalciferol or vitamin D3 and ergocalciferol or vitamin D2) in an age-dependent and individual dose.

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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.

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.

Base teórica A deficiência da Vitamina D é um problema mundial, e têm sido associada com inúmeras doenças. Este hormônio pode ser obtido através da alimentação e através da produção na pele pela exposição à radiação ultravioleta B (R-UVB), sendo que a principal fonte é a exposição aos R-UVB. Objetivo Nossos objetivos foram avaliar a prevalência de deficiência da vitamina D de acordo com a estação do ano e seus fatores associados em adultos jovens e saudáveis, na cidade de Porto Alegre, RS, Brasil. Métodos Policiais militares de Porto Alegre, foram convidados a participar do estudo, amostras de sangue foram coletadas no primeiro dia de cada estação, refletindo desta forma a estação que antecedeu a coleta, para dosagem de 25(OH)D3, e PTH plasmáticos, cálcio total, creatinina e albumina no soro foram determinadas no outono. A UV-R foi mensurada a partir da radiação solar por meio de um radiômetro, calculando-se as doses diárias para eritema (D-Ery) e para resposta fotobiológica para síntese da vitamina D na pele humana (D-VitD). Resultados Nossos resultados mostraram uma variação sazonal de 25(OH)D3 (P = 0.000) nos indivíduos estudados, sendo fortemente influenciada pela média da R-UV nos 30 e 45 dias que antecederam as coletas, demonstrando o importante papel da R-UV na produção da vitamina D. A prevalência de 25(OH)D3 abaixo de 20ng/mL variou com as estações (p=0.000), tendo sido nula ou baixa no final do verão e primavera, no entanto, essa prevalência aumentou no final do outono (22%) e inverno (8.7%). Já 6 a prevalência de 25(OH)D3 < 30ng/mL foi alta em todas as estações do ano: inverno (70%), primavera (68%), verão (44%) e especialmente no outono(88%). O único fator associado de modo independente aos níveis de 25(OH)D3 foi a quantidade de UV-R no período que antecedeu a coleta. Conclusão A prevalência de deficiência de vitamina variou de acordo com a estação, em adultos jovens do sexo masculino, na região sul do Brasil, e o único fator associado de modo independente aos níveis de 25(OH)D3 foi a quantidade de R-UV no período que antecedeu a coleta. Palavras chave: Vitamina D, Deficiência de Vitamina D, Radiação ultravioleta, Radiação ultravioleta B.
Background Vitamin D deficiency is a worldwide problem, and has been associated with various diseases. This steroid can be obtained by food intake or by skin production, when exposed to UVB-R. Objective Our aims were to evaluate the prevalence of vitamin D deficiency according to the season and its associated factors in young adults, in Porto Alegre, RS, Brazil. Methods Young men were invited to participate, blood samples were collected on the first day of each season for 25(OH)D3 measurement, and PTH (parathyroid hormone) in plasma, total calcium, creatinine, and albumin in serum were determined in the autumn. UV-R was measured from solar radiation by means of a radiometer, calculating daily doses for erythema (D-Ery) and for photobiological response to vitamin D synthesis in human skin (D-VitD). Results Our results have shown a seasonal variation of 25(OH) D3(P=0.000) in young and healthy men, living in a semitropical region, who were strongly influenced by the mean UV-R in the 30 and 45 days previous, demonstrating the important role of UVR- induced skin production of vitamin D. The prevalence of 25(OH)D3 below 20ng/mL varied with the seasons (p=0.000), having been nil or low in late summer and spring. However, this prevalence increased in late autumn (22%) and winter (8.7%). The prevalence of 25(OH)D3<30ng/mL was high in all seasons of the year: winter (70%), spring (68%), summer (44%) and especially in autumn (88%). Conclusions 8 The prevalence of vitamin deficiency varied according to the season, in young and healthy male adults, in Southern Brazil, and the only factor independently associated with 25(OH)D3 levels was the amount of UV-R in the period prior to collection.

Coronary heart disease (CHD) is the result of the accumulation of atheromatous plaques within the walls of the arteries that supply the myocardium with oxygen and nutrients. The WHO estimated that in 2002, 12.6% of deaths worldwide were from CHD. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/33551

Orientadores: Denise Engelbrecht Zantut Wittmann, Sarah Monte Alegre
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução: Vitamina D tem sido apontada como importante regulador da resposta imune. Estudos tem demonstrado haver relação entre insuficiência de vitamina D e presença de doenças autoimunes como Tireoidite de Hashimoto (TH). É possível que o processo autoimune na TH seja inibido em diferentes estágios pela vitamina D em sua forma ativa. Nossos objetivos foram estudar a prevalência de insuficiência de vitamina D e a relação de suas concentrações séricas com marcadores de função e autoimunidade tireoideana. Material e Métodos: Amostras de sangue foram coletadas de 54 pacientes com TH e 54 indivíduos saudáveis sem diagnóstico de TH com idade entre 18 e 75 anos. Foram realizadas dosagens séricas de vitamina D (25OHD), TSH, T4 livre, cálcio, fósforo, paratormônio (PTH), anticorpos anti-tireoperoxidase (AcTPO), anti-tireoglobulina (AcTG) e anti-receptor de TSH (TRAb). Volume tireoideano foi estimado por ultrassonografia. Foram coletados dados demográficos, de peso, altura, índice de massa corporal (IMC) e tempo de diagnóstico. Pacientes e indivíduos do grupo de controle foram pareados por idade e sexo. O nível de significância estatística adotado foi 5%. Resultados: Prevalência de insuficiência de vitamina D foi encontrada em 68.5% dos pacientes e em 38.9% dos indivíduos do grupo de controle (p =0,002). Houve uma correlação positiva entre níveis de AcTPO e maior volumetireoideano nos pacientes (r = 0,319; p= 0.019). Não houve correlação entre concentração de vitamina D, TSH, T4livre,TRAb, AcTGe volume tireoideano. Conclusões: Demonstramosmaior prevalência deinsuficiência de vitamina Dem pacientescom tireoidite de Hashimotoem relaçãoa indivíduos de um grupo controlesaudável, não havendo correlaçãocom o estado hormnal tireoideanooumarcadores séricos deautoimunidadeda tireóide.Por sua vez, maior volume da tireóidese associou a maior grau de infiltração inflamatóriaautoimune,refletido pelacorrelaçãocom maiores concentrações AcTPO
Abstract: Introduction: Vitamin D has been pointed out as an important immune response regulator. Studies have shown a relationship between vitamin D insufficiency and the presence of autoimmune diseases such as Hashimoto's Thyroiditis (HT). It's possible that the autoimmune process in HT is inhibited in its different stages by vitamin D on its active form .Our aims were to study the prevalence of vitamin D insufficiency and relationship of the serum concentrations with thyroid function and autoimmunity markers. Material and Methods: Blood samples were collected from 54 patients with HT and 54 healthy individuals without a diagnosis of HT, aged 18 to 75 years. We conducted serum 25OH vitamin D, TSH, free T4, calcium, phosphorus, PTH, TPOAb, TgAb and TRAb. Thyroid volume was estimated by ultrasound. Data on demographic, weight, height, body mass index and time since diagnosis were collected. Patients and control subjects were matched by sexand age. The significance level for statistical analysis was 5%. Results: Prevalence of vitamin D insufficiency was found in 68.5% of patients and in 38.9% of subjects in the control group (p= 0.002). There was a positive correlation between TPOAb and volume in patients (p= 0.019). There was no correlation between vitamin D concentration and thyroid volume, TRAb, TgAb, TSH or free T4. Conclusions: We demonstrated a higher prevalence of vitamin D insufficiency in patients with Hashimoto's thyroiditis compared to individuals of a healthy control group, no correlation with thyroid state hormonal or serum markers of thyroid autoimmunity. In turn, greater thyroid volume was associated with a higher degree of autoimmune inflammatory infiltration, reflected by the correlation with higher concentrations AcTPO
Mestrado
Clinica Medica
Mestra em Ciências

Le cancer de la prostate est la deuxième cause de décès masculins par cancer dans les pays industrialisés. PTEN est le gène suppresseur de tumeur le plus souvent muté ou délété dans les cancers de la prostate. Notre étude montre que la perte de Pten induit la prolifération des PEC menant à la formation de PIN. L’hyperprolifération des PEC engendre une réponse de dommages à l’ADN suivie de l’entrée en sénescence des PEC. Des études épidémiologiques ont montré que de faibles taux de Vitamine D sont associés à des cancers agressifs. Nos résultats montrent que Vdr et le Gemini-72, un analogue hypocalcémique de la Vitamine D, a des activités anti-inflammatoires et anti-prolifératives pendant la formation des PIN. De plus, le Gemini-72 induit l’apoptose des PEC sénescentes, module la réponse immunitaire et ainsi réduit le nombre de PIN de haut grade et la réaction stromale. Ainsi, notre étude démontre l’importance de l’axe Vitamine D/VDR dans la carcinogenèse prostatique
Prostate cancer is the 2nd leading cause of cancer-related deaths in males of western societies. Mutations or deletion of the PTEN locus are common in prostate cancer, and are associated with metastasis and resistance to therapeutic castration. Our results show that Pten-loss induces the proliferation of PEC leading to the formation of PIN. The hyperproliferation of PEC induces DDR followed by senescence entry of PEC. Epidemiological studies highlighted that low Vitamin D levels correlate with aggressive prostate cancer. We show that Vdr and Gemini-72, an hypocalcemic Vitamin D analog, have anti-proliferative and anti-inflammatory activities during PIN formation. Moreover, the Gemini-72 induces apoptosis in senescent cells, modulates the immune response and consequently decreases the number of High Grade PIN and reduces the stromal reaction. Thus, our study demonstrate the major role of Vitamin D signaling in prostate carcinogenesis