Recent studies suggest that folic acid nutritional status may be poor among Canadian Indians, particularly among those living in isolated areas. However the prevalence and causes of folic acid deficiency have not been assessed. The present study was conducted in order to assess the magnitude of the problem among British Columbia Indians and to examine the possible relationship between low dietary intakes of folic acid and the occurrence of low blood folate values. Using a 24-hour diet recall, dietary folate intakes were estimated at four relatively isolated Indian reserves (106 subjects) and at three reserves adjacent to urban centres (144 subjects). A more detailed study, involving estimation of dietary folate intake, measurement of serum and red blood cell folate, and examination of related hematological parameters was undertaken at one isolated reserve (Fort Ware, 28 subjects) and two non-isolated reserves (Necoslie and Sechelt, 63 subjects) as well as at a school residence (70 children, age 6 to 16 years). Meal samples were collected and assayed for folic acid, in order to verify the recall calculations. Results indicate that calculated and assayed folate values are similar and are significantly correlated (r=.9694). Total folate consumption is significantly higher at non-isolated reserves than at isolated reserves, and males consume significantly more folic acid than do females. Dietary folic acid intake is higher at the residence than at the reserves. Serum folate values are significantly correlated with dietary folate intake. Serum values are lower at Fort Ware than at Necoslie and Sechelt. Children living on reserves have lower serum folate values than do children living in residence, and have a larger proportion of children classified as "at risk". On the basis of red cell folate values, 16 to 45% of the subjects at the three reserves are classified as "at risk", however, no evidence of megaloblastic anemia is indicated from the hematological examinations. It is concluded that many individuals are either bordering on or are deficient with respect to folic acid. This appears to be a more serious problem at isolated reserves than at those adjacent to urban centres and it is suggested that this is a consequence of the availability, variety and selection of foods. / Land and Food Systems, Faculty of / Graduate

Dementia is prevalent among elderly people. As the world population ages, it is projected that the number of people affected by dementia may triple in the next 50 years. Over the last two decades, research has focused on identifying potentially modifiable risk factors in development and progression of dementia, such as vitamin B12 and folate. Results concerning the effects of low folate and vitamin B12 on cognitive performance are mixed. The main objective of the present study was to investigate the effects of vitamin deficiency on cognitive functioning in a clinical sample of elderly individuals with cognitive problems using a comprehensive neuropsychological assessment. A retrospective chart-review was performed on the 102 records of patients from the Geriatrics Clinic at the University of North Texas Health Science Center who presented with cognitive deficits. Charts were reviewed to obtain data on vitamin supplementation, vitamin status, history of chronic conditions and other biochemical data. The available database was used to obtain data on neuropsychological assessment. The study demonstrated mild association between vitamin B12 and folate status and cognitive deficits. There appeared to be a higher cut-off level that is above the traditionally used levels for vitamin B12 and folate deficiency concentrations at which cognitive deficits became more pronounced. Clinical applications, limitations and suggestions for future research were discussed.

Orientadores: Nelci Fenalti Höehr, Joyce Maria Annichino-Bizzacchi / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T12:13:12Z (GMT). No. of bitstreams: 1 Barnabe_Aline_D.pdf: 1712567 bytes, checksum: 647e2ea59dbddb21e153a8e6ceae61cc (MD5) Previous issue date: 2014 / Resumo: Folato, vitamina B12 e ferro são nutrientes essenciais, cujas deficiências afetam indivíduos em todas as faixas etárias, sendo consideradas um problema de Saúde Pública no mundo. Níveis reduzidos de folato e vitamina B12 podem estar associados com níveis elevados de homocisteína (Hcy), e que eventualmente resultam em complicações. Entretanto, no Brasil, poucos estudos avaliaram a prevalência dessas deficiências, principalmente de folato e vitamina B12, após a fortificação de farinhas com ácido fólico e ferro. Os objetivos do presente estudo foram: avaliar a prevalência das deficiências de folato, vitamina B12 e ferro em idosos, crianças, gestantes e lactantes após a fortificação de farinhas com ácido fólico e ferro adotado pela ANVISA em 2004; e investigar a contribuição de polimorfismos genéticos sobre os níveis de folato, vitamina B12 e Hcy nestes indivíduos. Os indivíduos foram recrutados em Centros de Saúde da cidade de Campinas entre 2006 a 2007. No total, 719 indivíduos incluindo, 262 idosos, 106 crianças, 291 gestantes e 60 lactantes foram incluídos. As concentrações destes nutrientes foram mensuradas por eletroquimioluminescência; a dosagem de Hcy foi realizada por cromatografia líquida de alta eficiência (CLAE); e os polimorfismos foram investigados por PCR-RFLP. Os resultados mostraram que a prevalência das deficiências de folato, vitamina B12 e ferro no grupo total de indivíduos foram de 0,3%, 5,3% e 12,6%, respectivamente. Praticamente não se observou a deficiência de folato, presente apenas em um idoso e uma gestante, enquanto que a deficiência de vitamina B12 foi prevalente em gestantes (8,9%) e idosos (4,2%). Além disso, a deficiência de ferro e anemia ferropriva foram prevalentes em crianças (9,9% e 4,9%, respectivamente), e gestantes (25,1% e 5,5%, respectivamente). A hiperhomocisteinemia esteve presente principalmente em idosos (34,3%). Com relação aos polimorfismos, apenas as gestantes carreadoras dos alelos CT+TT do polimorfismo no gene MTHFR (C677T) mostraram níveis reduzidos de folato (p=0,030). Através da análise múltipla, observamos que os níveis de Hcy foram determinados principalmente pelo folato (p<0,001), vitamina B12 (p<0,001), gênero (p<0,001) e idade (p<0,001) em idosos; vitamina B12 (p= 0,011) em crianças e folato (p=0,002) em gestantes. Nossos resultados demonstraram que na população avaliada, após 2 anos do início da fortificação de farinhas com ácido fólico e ferro, a deficiência de folato é praticamente inexistente, ao contrário da deficiência de ferro e de vitamina B12. A elevada prevalência da deficiência de vitamina B12 em idosos e gestantes deve ser valorizada na prática, devido ao risco de complicações. O mesmo deve ser observado em relação à deficiência de ferro, prevalente em crianças e gestantes. Portanto, medidas como suplementação e a dosagem desses nutrientes, para grupos populacionais de risco, devem ser implementados em políticas de Saúde Pública. Além disso, a hiperhomocisteinemia observada em idosos pode ser um fator de risco ou um marcador de doença arterial, que é comum nesses indivíduos / Abstract: Folate, vitamin B-12 and iron are essential nutrients, whose deficiencies are considerable public health problems worldwide, affecting all age groups. Low levels of folato and vitamin B12 have been associated with high concentrations of homocysteine (Hcy) and can lead to complications. In Brazil, a few studies evaluated the prevalence of these nutrients, especially, folate and vitamin B12, post acid folic and iron fortification era. The aim of this study was to assess folate, vitamin B12 and iron deficiencies in distinct Brazilian populations including elderly, children, pregnant and lactating women, after the initiation of folic acid and iron fortification by Brazilian authorities. We also investigated the contribution of polymorphisms on folate, vitamin B12 and Hcy levels in these individuals. Folate, vitamin B12 and ferritin levels were measured by chemiluminescence immunoassays, and Hcy levels were determined by high-performance liquid chromatography. Genotype analyses of RFC1 A80G, GCPII C1561T and MTHFR C677T polymorphisms were performed by PCR-RFLP. The individuals were recruited from primary care centers in Campinas ¿ Brazil, between 2006 - 2007. In total 719 individuals, including elderly (262), children (106), pregnant women (291) and lactating women (60) were included. The overall prevalence of low folate, vitamin B-12 and iron status was 0.3%, 5.3% and 12.6%, respectively. Folate deficiency was practically inexistent and was observed only in elderly (n=1) and pregnant women (n=1), whereas vitamin B12 deficiency was frequent in pregnant women (8.9%) and elderly (4.2%). Moreover, iron deficiency and iron deficiency anemia were prevalent in children (9.9% and 4.9%, respectively) and pregnant women (25.1% and 5.5%, respectively). Plasma Hcy concentrations were significantly higher in the elderly (34.3%). Pregnant women carrying the MTHFR 677T allele (CT+TT) showed lower serum folate levels (p=0.030), but none of the polymorphisms investigated in this study affected folate, vitamin B12 and Hcy levels in elderly, children and lactating women. After a multivariate analysis, Hcy levels were predicted by variables such as folate (p<0.001), vitamin B12 (p<0.001), gender (p<0.001) and age (p<0.001) in elderly; vitamin B12 (p= 0.011) in children; and folate (p = 0.002) in pregnant women. Our results demonstrated that folate deficiency is practically inexistent in this population, two years after the initiation of folic acid fortification, in contrast to vitamin B12 and iron deficiency. The high prevalence of vitamin B12 deficiency in elderly and pregnant women is relevant due to health complications. Supplementation and measure of nutrients in some groups of the population should be indicated by Public Health¿s policies. Furthermore, hiperhomocysteinemia in elderly can be a risk factor or a marker of arterial disease, which is common in these individuals / Doutorado / Ciencias Biomedicas / Doutora em Ciências Médicas

Pregnancy places great strain upon the body of a woman. Many things contribute to a successful pregnancy, such as healthy eating habits, healthy lifestyle, adequate physical activity, fresh air, good mental health. It is recommended to begin folic acid supplementation even before conception. Folic acid, known as folate, is one of the B vitamins. Pregnancy places greater need for folic acid intake, especially in the early stages, where insufficiency or even deficiency can manifest in a pathological pregnancy, oftentimes fatal. The specific link between the two is not yet very well known. However, several studies have confirmed that there is a positive effect that comes with increased folic acid intake before conception and during the first few weeks of pregnancy, most notably reduced occurrence of neural tube birth defects. General population generally doesn't have adequate intake of folic acid, so there is usually a folic acid deficit before and during pregnancy as well. This can be countered by consuming food high in folate, targeted food enrichment or direct consumption of supplements containing folic acid. The Czech Republic currently doesn't enrich food with folic acid, therefore it is recommended to increase its intake via supplementation. Research investigation through paper questionnaires...

Despite the recent advances in cancer therapy, the successful detections and treatments of cancer still remains a challenge. The existing strategies for early cancer detection are often limited due to their poor sensitivity and specificity. Also, the non-selective action of therapeutic interventions hinders treatment success. Our research was therefore directed towards the engineering of excellent bi-functionalized nanoparticles (NPs) based on carbon dots (CDs) that would improve early cancer detection and overcome the limitations of chemotherapy. With the actively targeting agent, these new NPs are expected to effectively deliver pharmacological agents directly to cancer cells. CDs are carbon-based NPs that are utilized as bioimaging agents and drug delivery systems (DDS) due to their excellent biocompatibility, non-toxicity, unique imaging, and facile surface modification. Using folic acid (FA) as targeting agent, the prepared novel CDs will carry doxorubicin (DOX) covalently and non-covalently to the cancer cells with overexpressed folate receptors. The CDs were first synthesized via the hydrothermal bottom-up approach using citric acid and ethylenediamine as precursors. The prepared CDs were then functionalized by FA via a non-cleavable peptide bond followed by complexation with DOX covalently or non-covalently to obtain the desired FA-CD-DOX NPs. All the NPs and intermediates were characterized using ultraviolet-visible spectroscopy (UV-vis), fluorescence spectroscopy (FL), and Fourier transform infrared spectroscopy (FTIR). Assessment of the drug loading capacity (DLC) and drug loading efficiency (DLE) with UV-vis indicated that the non-covalent NPs have low DLC but high DLE compared to the relatively low DLE and high DLC of covalent NPs. In vitro drug release studies were also carried out in phosphate buffered saline (PBS) systems with various pH. It was found that even though both non-covalent and covalent complexes released more DOX at pH 5.0 than at pH 7.0, the DOX release rate was faster in the non-covalent FA-CD-DOX NPs compared to the covalent FA-CD-DOX. Based on these results, we project increased accumulation of drugs in the more acidic (pH 4.5-5.0) microenvironment of cancer cells compared to that of normal healthy cells under physiological pH (7.4). This new FA-CD-DOX NPs could work as efficient theranostic systems to detect and treat cancer.

Vitamins play an important role in the nutrition of man and animal. As early as 1897 Eijkman was able to demonstrate the symptoms of thiamine deficiency disease in birds. Since then, vitamins have been reguarded as one of the most essential factors in nutrition. Only small quantities in the diet are necessary, yet lack of any of them will inhibit the growth and produce certain kinds of deficiency diseases.

Indiana University-Purdue University Indianapolis (IUPUI) / Fetal alcohol spectrum disorder (FASD) is a result of prenatal alcohol exposure, producing a wide range of defects including craniofacial, sensory, motor and cognitive deficits. Many ocular abnormalities are frequently associated with FASD including microphthalmia, optic nerve hypoplasia, and cataracts. FASD is highly prevalent in low socioeconomic populations, where it is also accompanied by higher rates of malnutrition and alcoholism. Using zebrafish as a model to study FASD retinal defects has been extremely insightful in understanding the ethanol-induced retinal defects at the cellular level. Zebrafish embryos treated with ethanol from mid-blastula transition through somitogenesis (2-24 hours post fertilization; hpf) showed defects similar to human ocular deficits including microphthalmia, optic nerve hypoplasia, and photoreceptor differentiation defects. Ethanol exposure altered critical transcription factor expression involved in retinal cell differentiation. Retinoic acid (RA) and folic acid (FA) nutrient co-supplementation rescued optic nerve and photoreceptor differentiation defects. Ethanol exposure during retinal morphogenesis stages (16-24 hpf), produced retinal defects like those seen with ethanol exposure between 2-24 hpf. Significantly, during ethanol-sensitive time window (16-24 hpf), RA co-supplementation moderately rescued these defects, whereas, FA cosupplementation showed significant rescue of optic nerve and photoreceptor differentiation. RA, but not FA, supplementation after ethanol exposure could restore ethanol-induced optic nerve and photoreceptor differentiation defects. Ethanol exposure did not affect timing of retinal cell differentiation induction, but later increased retinal cell death and proliferation. Ethanol-treated embryos showed increased retinal proliferation in the outer nuclear layer (ONL), inner nuclear layer (INL), and ciliary marginal zone (CMZ) at 48 hpf and 72 hpf. In order to identify the genesis of ethanol-induced persistent retinal defects, ethanol effects on retinal stem cell populations in the CMZ and the Müller glial cells (MGCs) were examined. Ethanol treated retinas had an expanded CMZ indicated by histology and Alcama, a retinal stem cell marker, immunolabeling, but reduced expression of rx1 and the cell cycle exit marker, cdkn1c. Ethanol treated retinas also showed reduced MGCs. At 72 hpf, ONL of ethanol exposed fish showed fewer photoreceptors expressing terminal differentiation markers. Importantly, these poorly differentiated photoreceptors co-expressed the basic helix-loop-helix (bHLH) proneural differentiation factor, neurod, indicating that ethanol exposure produced immature and undifferentiated photoreceptors. Reduced differentiation along with increased progenitor marker expression and proliferation suggest cell cycle exit failure due to ethanol exposure. These results suggested that ethanol exposure disrupted stem cell differentiation progression. Wnt, Notch and proneural gene expression regulate retinal stem cell proliferation and transition into progenitor cells. Ethanol exposure disrupted Wnt activity in the CMZ as well as Notch activity and neurod gene expression in the retina. RA and FA co-supplementation were able to rescue Wnt activity in the CMZ and rescue downstream Notch activity. To test whether the rescue of these Wnt-active cells could restore the retinal cell differentiation pathways, ethanol treated embryos were treated with Wnt agonist. This treatment could restore Wnt-active cells in the CMZ, Notch-active cells in the retina, proliferation, and photoreceptor terminal differentiation. We conclude that ethanol exposure produced persistent defects in the stem cell Wnt signaling, a critical pathway in retinal cell differentiation. Further analysis of underlying molecular mechanisms will provide insight into the embryonic origins of ethanol-induced retinal defects and potential therapeutic targets to cure this disorder.

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