Uma dieta adequada em ferro biodisponível é fundamental para a prevenção da anemia por deficiência de ferro entre mulheres na idade reprodutiva, que são grupo de alto risco para essa morbidade. Dados da Organização Mundial da Saúde indicam que no Brasil, 19% das mulheres não grávidas em idade reprodutiva são anêmicas. Identificar fatores dietéticos associados com o status de ferro pode nortear políticas atuais voltadas à redução da prevalência de anemia, como é a fortificação de farinhas de trigo e milho com ferro. O objetivo deste estudo foi avaliar a associação entre o consumo habitual de alimentos e o status de ferro de mulheres saudáveis na idade reprodutiva. Foram incluídas 127 mulheres entre estudantes de graduação e de pós-graduação de uma Universidade de São Paulo, com idades entre 18 e 45 anos, saudáveis (relato de menstruação regular e ausência de doenças crônicas ou parasitose intestinal) e não expostas a fatores não dietéticos associados com a deficiência de ferro (gravidez, lactação ou doação de sangue recentes). Foram excluídas do estudo as mulheres com alterações hematológicas ou do status inflamatório e aquelas com dados dietéticos inválidos. A partir de três registros alimentares (RA) e de um questionário de frequência alimentar (QFA), estimou-se o consumo habitual de 30 grupos de alimentos, utilizando a estratégia estatística Multiple Source Method (MSM). Os marcadores do status de ferro utilizados foram ferritina sérica, saturação de transferrina e hemoglobina. Associações foram testadas por análise de regressão linear múltipla, controlando-se pelas covariáveis: ingestão energética habitual, índice de massa corporal, uso de anticoncepcionais hormonais, nível de atividade física, cor de pele autodeclarada, tipo da dieta autodeclarada, idade e escore de fluxo menstrual. As análises foram realizadas no programa SPSS versão 21. Do total de 127 mulheres avaliadas, 16 (12,6%) apresentaram deficiência de ferro (ferritina sérica <15 ng/mL), sendo que 4 delas (3,1%) eram anêmicas (Hb<12g/dL). Valores de ferritina foram positivamente associados com o consumo de \"carnes totais e embutidos\" (&#946; = 0,3%; p = 0,032). Por outro lado, o grupo de \"frutas e sucos naturais\" associou-se negativamente com esse biomarcador (&#946; = - 0,1%; p = 0,039). Uma associação direta entre valores de saturação de transferrina e o consumo de \"carnes bovinas\" foi também encontrada (&#946; = 0,078; p = 0,030). Nenhuma estimativa de consumo habitual de alimentos correlacionou-se com as concentrações circulantes de hemoglobina, ainda que uma forte associação negativa entre esse biomarcador e o relato de restrição dietética de carnes tenha sido observada (&#946; = -0,582; p = 0,006). Entre mulheres adultas saudáveis, estimativas de consumo habitual de carnes e frutas podem predizer variações interindividuais nos biomarcadores do status de ferro. Visando a redução do risco para deficiência de ferro, as recomendações de ingestão desses alimentos devem ser contextualizadas num padrão alimentar saudável e variado, com foco especial na adequação do consumo de carnes não processadas, frutas e sucos naturais. / Dietary adequacy in bioavailable iron is essential to prevent iron deficiency anemia among women at childbearing age, population groups at high-risk for this morbidity. Data from the World Health Organization indicate that, in Brazil, 19% of non-pregnant women at childbearing age are anemic. Identifying dietary factors associated with iron status may guide current policies aimed at lowering the prevalence of anemia, such as the fortification of wheat and corn flours with iron. The aim of this study was to evaluate the association of usual food intake with iron status biomarkers among healthy women at childbearing age. We included 127 students of University of São Paulo aged 18 to 45 years, healthy (self-reporting of regular menstruation and lack of a diagnosed chronic diseases or an intestinal parasitosis) and not exposed to non-dietary factors associated with iron deficiency (recent pregnancy, lactation or blood donation). Cases of hematologic or inflammatory status alterations as well as those with invalid dietary data were excluded from the study. Data from three diet records (DR) and a food frequency questionnaire (FFQ) were used to estimate the usual intake of 30 food groups by employing as the statistical approach the Multiple Source Method (MSM). Biomarkers of iron status were serum ferritin, transferrin saturation index and hemoglobin. Multiple linear regression analysis was used to test associations, with adjustments for the covariates: energy intake, body mass index, hormonal contraceptive use, physical activity level, self-reported skin color, self-reporting of meat dietary restriction, age and a menstrual blood loss score. Analysis were performed in the SPSS program version 21. Among all women, 16 (12.6%) had iron deficiency (serum ferritin < 15 ng/mL), 4 of them (3.1%) were anemic (Hb<12g/dL). In the adjusted models, ferritin values were positively associated with \"total meat and sausages\" intake (&#946; = 0.3%; p = 0.032). On the other hand, \"fruits and natural juices fruits\" intake was negatively associated with this biomarker (&#946; = -0.1%; p = 0.039). A direct association between the transferrin saturation values and \"bovine meat\" intake was also found (&#946; = 0.078; p = 0.030). None of the usual food intake measures was correlated with circulating hemoglobin concentrations, although a strong negative association between this biomarker and self-reporting of meat dietary restriction has been observed (&#946; = - 0.582; p = 0.006). Conclusion: Among adult healthy women, estimates of usual meat and fruit intakes may predict between-person variability of iron status biomarkers. In order to reduce iron deficiency risk, recommendations regarding habitual consumption of these foods must be contextualized in a healthy and varied diet, focusing on the choice of non-processed meats,fruits and natural fruit juice.

In der vorliegenden Arbeit wurde bei Patienten extra- und intrazelluläres Eisen in Knochenmarksbiopsien vor der Transplantation bestimmt und die Ergebnisse mit dem Erfolg der jeweiligen allogenen HSZT verglichen. Das Ziel dieser Untersuchung bestand darin festzustellen, ob es neben dem etablierten Marker Serum-Ferritin (SF) noch andere Marker gibt, welche für den Erfolg der Transplantation bedeutsam sind. Die Erfolgsparameter waren das Überleben, die rückfallfreie Mortalität sowie die akute und die chronische GvHD. Außerdem wurde die Korrelation von Eisenlagern im Knochenmark mit dem Gentyp (HFE-Genotyp) untersucht. Die Transplantation von hämatopoetischen Stammzellen aus dem Knochenmark ist eine anerkannte Behandlung von lebensbedrohlichen hämatologischen Erkrankungen. Dennoch sind bis heute nur eingeschränkt Daten vorhanden, welche die Bedeutung der Eisen- und Ferritinablagerung im Knochenmark des Patienten vor der Transplantation in Verbindung mit dem Erfolg der Knochenmarktransplantation zeigen. Es wurden Knochenmarkbiopsien von 123 Patienten am Institut für Pathologie des Uniklinikums Leipzig histologisch untersucht, die zuvor aus diagnostischen Gründen entnommen wurden. Die Biopsien erfolgten innerhalb der letzten drei Monate vor der Transplantation, bei einem Median von 24 Tagen. In den gewonnen Präparaten wurde die Eisenablagerung mit der Berliner Blau Färbung und einer Makrophagenidentifizierung (CD68+) bestimmt. Dabei wurde ein selber generiertes Grading, in Anlehnung an das Grading von Takkunen, von G0 bis G5 für intrazellulär gespeichertem Eisen und g0 bis g3 für interstitielles Eisen verwendet, um die Eisenablagerung quantitativ per Mikroskop darzustellen. Das relative Verhältnis von eisenbeladenen CD68+/CD68+-Makrophagen und das absolute Verhältnis von CD68+-Makrophagen in Bezug auf alle hämatopoetischen Zellen wurde berechnet. Alle Peripheren Blutentnahmen zur Bestimmung des SF-Werts wurden sieben Tage vor der allogenen HSZT durchgeführt. Das Patientenkollektiv wurde in zwei Gruppen CRP < 5 mg/l und CRP > 5 mg/l eingeteilt, um die bekannten Einschränkungen des SF als Akut-Phase-Protein, zu berücksichtigen. Die Gruppe mit einem CRP-Gehalt < 5 mg/l umfasste so 90 Personen (48 Männer und 42 Frauen, Durchschnittsalter 57 Jahre), der Gruppe > 5 mg/l wurden 33 Patienten (20 männlich und 13 weiblich, Durchschnittsalter 56 Jahre) zugeordnet. Der durchschnittliche CRP-Gehalt in dieser Gruppe betrug 18,6 mg/l, bei einer Spanne von 5,7 mg/l - 56,9mg/l. In der Gruppe < 5 mg/l wurde ein veränderter HFE-Genotyp bei 27 Patienten gefunden. Der Median des SF betrug 2009 ng/ml, wobei 25 % der Patienten, einen SF-Gehalt von über 3000 ng/ml hatten. Der Median der vor der Transplantation verabreichten EKs lag bei 26 Konzentraten. In dem Patientenkollektiv CRP < 5mg/l zeigte sich eine starke Signifikanz bei den Korrelationen zwischen den SF-Werten und der verabreichten Anzahl an EKs (r = 0,59; p = 0,001), womit SF als valider Marker, zur Bestimmung des Körpereisens, bestätigt werden konnte. Der von uns generierte Eisenscore zeigte hinsichtlich der intrazellulären Eisenspeicherung ebenfalls eine signifikante Korrelation (r = 0,38; p = 0,005) mit der Anzahl der verabreichten EKs und konnte somit eine exogene Eisenzufuhr, im phagozytierenden System, semiquantitativ gut darstellen. Bezüglich der interstitiellen Eisenablagerung zeigte sich hingegen keine Korrelation (r = 0,19; p = 0,09). Auch die Korrelation von Gesamt-Makrophagengehalt an der Hämatopoesefläche sowie vom Anteil eisenbeladener CD68+-Makrophagen pro CD68+-Makrophagen insgesamt in den Knochenmarkbiopsien, mit der Anzahl der verabreichten EKs, ergab keine signifikante Übereinstimmung. Der fehlende Zusammenhang lässt sich mit der Schlussfolgerung erklären, dass der Makrophagengehalt eine individuelle, anstatt eine adaptative Größe darstellt. Hinsichtlich weiterer Korrelationen zwischen dem Eisengrading mit den SF-Werten ergab sich, dass höhere SF-Werte mit vermehrter intrazellulärer Eisenspeicherung (p = 0,005; r = 0,32), interstitieller Eisenablagerung (p = 0,007; r = 0,31) sowie mit einer höheren Anzahl eisenbeladenen CD68+ pro CD68+-Makrophagen (p = 0,004; r = 0,33) assoziiert waren. Die Anzahl der Gesamtmakrophagen korrelierte, wie schon bei der Korrelation mit der exogenen Eisenzufuhr durch EKs, nicht mit der Höhe der SF-Werte. Zusätzlich zeigte sich die Eisenspeicherung vom HFE-Genotyp nicht beeinflusst. Dies bedeutet, dass eine heterozygote HFE-Mutation des Patienten das Risiko einer toxischen Eisenüberladung im Rahmen des Transplantationsprozesses nicht erhöht. Bezogen auf die homozygoten Mutationen müssen diese Ergebnisse jedoch, aufgrund der geringen Fallzahl, kritisch betrachtet und durch größere Fallzahlen in weiteren Studien bestätigt werden. Nach einem Median von 24 Monaten kamen die akute und chronische GvHD in jeweils 70 % und 53 % bei Patienten vor. Es haben 58% der Patienten überlebt; die rückfallfreie Mortalität betrug 22 %. Intrazellulär gespeichertes Eisen und interstitiell abgelagertes Eisen konnte bei niedrigen Eisengraden (G0 / G1) SF-Werte > 3000 ng/ml, und damit eine toxische Eisenüberladung ausschließen. Allerdings war eine signifikante Aussage in Korrelation mit höheren SF-Werten nicht gegeben, so dass es nicht möglich war, mit dem Eisengrading eine signifikante Aussage über die rückfallfreie Mortalität die Überlebenszeit oder das Auftreten einer GvHD zu treffen. Jedoch zeigten die erhöhten SF-Werte in dem Patientenkollektiv CRP < 5 mg/l eine hohe Aussagekraft bezüglich des Überlebens (p = 0.002) und der rückfallfreien Mortalität (p = 0.007). Bei Patienten mit SF > 3000 ng/ml betrug der Überlebensanteil und die rückfallfreie Mortalität 37 % und 49 % gegenüber 78 % und 9 % bei Patienten mit niedrigem SF (p = 0.001). Zudem korrelierte SF bei einem Niveau > 3000 ng/ml mit der akuten GvHD (p = 0.002). Eine Korrelation mit der mit der chronischen GvHD fand sich nicht. In dem Patientenkollektiv mit einem CRP-Gehalt > 5 mg/l konnte, aufgrund einer Mortalität von 100% und der Heterogenität der Items, keine statistische Aussage über Korrelationen getroffen werden. Demzufolge bleibt SF eine preiswerte und nicht invasive Option um eine Eisenüberladung zu verifizieren und somit den Erfolg einer allogenen HSZT vorauszusagen, wenn die bekannten Einschränkungen berücksichtigt werden. Obwohl somit die histologische Eisenmessung der serologischen Bestimmung des SF-Wertes unterlegen ist, sollte eine sorgfältige Bestimmung des Eisengehalts an den Knochenmarkbiopsien, die im Rahmen der Standarddiagnostik gewonnen wurden, vorgenommen werden. Nur so kann die Wertigkeit der intrazellulären versus der interstitiellen Eisenspeicherung, vor dem Hintergrund des weiteren Verlaufs der Patienten nach Transplantation systematisch weiter untersucht und verbessert werden.

A prospective observational study was conducted to investigate the effects of nutrition and related factors on the outcome of pregnancy in nulliparous African American women 16-35 years of age. Blood samples from a subset of these subjects were taken during the first (1st), second (2nd) and third (3rd) trimesters of pregnancy and at delivery. Cord blood samples were also collected at delivery. Levels of selected biochemical variables including serum ferritin, vitamin B12 and folate as well as whole blood folate, and selected hematologic indices were determined and correlated with pregnancy outcome variables. During the second trimester of pregnancy, values for hematocrit and hemoglobin were less than 30% and 11 g/dL, respectively, in 16% and 30% of the participants, respectively. Serum and whole blood (WB) folate increased sequentially during pregnancy. Cord concentrations of serum folate were significantly higher than maternal concentrations at delivery (P<0.05). Serum ferritin declined significantly from 36±5.6 ng/ml in the first trimester to 17±1.5 ng/ml during the 3rd trimester (P<0.05), and returned to the 2nd trimester level (26±2.0 ng/ml) at delivery. Second trimester WB folate was positively related to birth weight (R2=0.21), while gestational age was inversely correlated with 3rd trimester vitamin B12 (R2=0.34). These data suggest that vitamin B12 and folate play an important role in the outcome of pregnancy in this population.

No description available.

Simplex algorithms have been used to optimize for size, number and morphology of lysozyme and apoferritin crystals. This approach requires fewer experiments than the single-factor-at-a-time method or factorial designs and will be useful in conserving materials on the International Space Station. The simplex method has the possible advantage that it conserves on materials by reducing the number of experiments required to optimize a crystallization system. The process is iterative and exploratory and should allow optimum microgravity conditions to be determined which might very well be different from the optimum conditions on Earth. Because the simplex method uses simple mathematical operations to calculate the next set of crystallization conditions it will be easier for crystal growers to implement than factorial designs. Factorial experiments are based on varying all factors simultaneously at a limited number of factor levels. This results in a model that is used to determine the influence of each factor and their interactions. Factorial design experiments are especially useful at the beginning of an experimental study and as a screening tool to investigate a large number of factors. The simplex method is an optimization method which is model-independent and requires no fitting of models to data. Also, when applied to protein crystal growth the simplex method does not rely on an absolute quality score. Instead, with each iteration a comparison is made to the last experiment and the results are assigned as being "better or worse". In this study, commercially obtained apoferritin was purified from 65% monomeric apoferritin to 92% monomeric apoferritin by size exclusion chromatography. Simplex optimization found the best apoferritin crystals were obtained at 15 mg/ml apoferritin, 2.0% CdSO4, 25°C using the hanging drop vapor diffusion method of crystallization and at 24 mg/ml apoferritin, 1.5% CdSO4, 25°C using the containerless crystallization method. For lysozyme, the simplex method found the best crystals at 19 mg/ml lysozyme, 7.0% (w/v) NaCl, pH 4.0, 25°C using the hanging drop vapor diffusion method of crystallization. For both proteins, the optimum conditions were found with less than ten experiments using very little protein. Finally, we report that the factors to be considered in the successful application of this method to crystallization are the number of variables to be studied, the initial conditions, step size and analysis of crystal quality.

Iron deficiency anemia is the most common nutritional deficiency disease worldwide (Mahan & Escott-Stump, 2004). Iron deficiency anemia is of major concern especially in women of child bearing age and those who follow a vegetarian diet. The objective of this study was to compare the nutrient and hematological values related to iron status in female university students following a vegetarian versus following a nonvegetarian diet. This study took a cross sectional analysis of 39 female students at California Polytechnic State University (Cal Poly State University) in San Luis Obispo, CA. Of the participants 19 were following a vegetarian diet and 20 were following a nonvegetarian diet. To participate, individuals had to be female, current Cal Poly students, and between the ages of 18 and 22 years old. Those taking vitamin or mineral supplements, medications (including oral contraceptives), smokers, and pregnant women were excluded. Characteristic, demographic, and anthropometric data were collected through interview, nutrient intake was accessed by averaging three day food records, and hematological parameters were measured. Statistical analysis used nonparametric techniques including the Mann-Whitney Wilcoxon statistical test for demographics and baseline characteristics, the Spearman Rank Correlation analysis and Fisher’s Exact statistical test for associations between vegetarians and nonvegetarians. Results found no significant difference in iron intake between vegetarians and nonvegetarians, however nonvegetarians had higher mean intakes of iron at 16.82 (SD 6.36) mg/day compared to vegetarians at 14.84 (SD 7.10) mg/day (p=0.482). A similar percentage of vegetarians at 66.7% (n=8) compared to nonvegetarians at 65% (n=13) were under the Recommended Daily Allowance (18 mg per day for females 19 to 30 years of age) for mean iron consumption. There were slightly more nonvegetarians at 10% (n=2) compared to vegetarians at 8.3% (n=1) under the Estimated Average Requirement (8.1 mg/day for females 19 to 30 years of age) for mean iron intake. No significant difference was found for serum iron, serum ferritin, transferrin saturation, and total iron binding capacity between vegetarians and nonvegetarians. Finding revealed serum ferritin, the most common iron status indicator, was lower for vegetarians at 23.16 (SD15.54) ng/mL compared to nonvegetarians at 27.75 (SD 18.01) ng/mL (p=0.47). When looking at the stages of iron balance, there was greater percentage of vegetarians with hematological results (serum iron <40 µg/dL, total iron binging capacity of >410 µg/dL, transferrin saturation <15%, and serum ferritin <10 ng/mL) indicating iron deficiency anemia or stage IV negative iron balance compared to nonvegetarians. There was no significant correlation between iron intake and serum ferritin, however results showed a positive association (r=0.28, p=0.09). In conclusion, vegetarian participants are believed to be at higher risk of developing negative iron balance compared to nonvegetarians due to lower iron consumption and lower serum ferritin concentrations. Female university students following a vegetarian diet should be educated on iron deficiency anemia and prevention of iron depletion.

The main objectives of the research presented in this thesis were to understand mechanistic aspects of the photochemistry of ferritin (Ftn) and bioconjugates that consisted of Ftn linked to gold nanoparticles (AuNPs). The photochemistry investigated in this thesis repurposed Ftn from its role in biological systems as an iron-sequestration protein to potential applications in photocatalysis and nanobiomedicine. The first phase of the thesis research developed a mechanistic understanding of the underlying mechanisms involved in the photochemistry of Ftn with relevance to photocatalysis. In particular, research was designed to determine whether the light-induced bandgap excitation of the semiconductor core of horse-spleen ferritin (HSFtn) resulted in electron transfer from the inorganic core to aqueous redox active reactant via electron transport through the 2 nm thick shell of HSFtn. To investigate this mechanistic pathway, 4-5 nm copper (hydr)oxide nanoparticles were mineralized within the internal volume of HSFtn (CuFtn). It was shown that, unlike the native iron oxyhydroxide-bearing (Ferrihydrite; Fh) Ftn, the visible light photoexcitation of the inorganic core of CuFtn (measured optical bandgap to be 3.65 eV) did not exhibit any release of redox-active metal cation from the HSFtn cage into solution. By photoexciting CuFtn in the presence of aqueous chromate (Cr(VI)) it was shown that the Cr(VI) underwent reduction to Cr(III) in solution. The research strategy eliminated the possibility that metal cations escaping from the HSFtn during photoexcitation could be responsible for Cr(VI) reduction. Hence, the research showed for the first time that electrons resulting from a photoexcited metal oxide core of Ftn could transfer through the protein shell to reduce an aqueous redox active reactant. The research also investigated the wavelength-dependent photochemistry of CuFtn to show that bandgap excitation was indeed responsible for the electrons that transfer across the protein shell. In a second project, the research investigated the bioconjugation of anisotropic AuNPs—gold nanorods (AuNRs) and gold nanostars (AuNSs)—to human H-type ferritin (HFtn). After attaching the AuNRs or AuNSs to HFtn, it was shown that the near-infrared (NIR) radiation excitation of the localized surface plasmon resonance (LSPR) of the AuNR or AuNS conjugated to HFtn led to the activation of the Fh core of the protein. This NIR photochemistry (λ = 850 nm light) resulted in the release of Fe(II) from the Ftn and also led to the reduction of Cr(VI) when it was present in the aqueous phase. The novel synthetic protocols to synthesize the bioconjugates focused on attaching the AuNRs and AuNSs to the solvent-exposed cysteines (Cys) on HFtn. The research also developed techniques for the removal of colloidal stabilizing surfactants, such as cetyltrimethyl ammonium bromide (CTAB), and TritonX-100 (TX-100), from anisotropic AuNPs (AuNR/AuNS) before their attachment to HFtn. The removal of the surfactant was not only important for attachment to the HFtn, but it also removed a cytotoxic species so that the bioconjugates could be used in research that had applications to biomedicine. Research also investigated synthetic strategies to form bioconjugates that consisted of spherical gold nanoparticles (AuNSps) attached to HSFtn. In contrast to HFtn, HSFtn contains a few solvent exposed Cys groups. Hence, a challenge that was overcome in this research was to populate the outer surface of HSFtn with thiol groups (-SH) so that AuNSps could be attached. To meet this challenge, the surface primary amine-containing amino acids (Lysine) in HSFtn were modified to active Cys using N-succinimidyl S-acetylthioacetate (SATA). After this chemical modification of HSFtn, it was shown that a relatively high density of AuNSps could be attached to HSFtn. This SATA-modified HSFtn bioconjugate system (AuNSp-HSFtn) exhibited the release of Fe(II) at wavelengths of light where λ > 475 nm. In the absence of AuNSp, HSFtn released Fe(II) during exposure to light at wavelengths of light where λ < 475 nm. The activation of the bandgap at longer wavelengths of light (λ > 475 nm) was due to the excitation of the 532 nm plasmon resonance of AuNSp and the presumed transfer of hot electrons to the inner Fh core of HSFtn. A final project investigated the use of the AuNR-HFtn bioconjugates as a photodynamic strategy utilizing NIR to suppress the growth of cancer cells with the expectation that this process will occur through the mechanism of ferroptosis. We carried out experiments that exposed prostate cancer cells (PC3) to AuNR-HFtn, and during NIR irradiation, they showed the ability to limit the growth of the cells compared to experiments where the cells were exposed to just HFtn or AuNRs. The results suggested that Fe(II) released from the HFtn led to cancer cell death through a process that might be ferroptosis. Future studies will need to investigate this possibility and whether the bioconjugates developed in this thesis will offer a novel therapeutic strategy for cancer/tumor suppression. / Chemistry

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24134号 / 医博第4874号 / 新制||医||1060(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 竹内 理, 教授 中川 一路, 教授 髙折 晃史 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Lactating women have an increased requirement for folate which contributes to their risk for suboptimal folate status. Although milk folate secretion appears to be maintained independent of folate intake and maternal folate status, studies with animal species have demonstrated a relationship between iron deficiency and impaired milk folate secretion. Objectives of this study were to monitor the folate status of lactating women and to examine the relationship among folate intake, dietary iron, folate status, iron status and milk folate. Seven-day dietary records, milk samples, and blood samples were collected monthly for four months from five lactating women. Dietary iron and folate was analyzed. Milk folate, serum ferritin, serum folate, and red blood cell (rbc) folate concentrations were measured. Mean folate and iron intakes were 495 ± l05μg/d and 24 ± 4 mg/d, respectively. All women had normal rbc folate and serum ferritin values during the study. Milk folate increased (p=.06) from 35± 10 μg/L in month one to 69 ± 30 μg/L in month three. Dietary and rbc folate were not significantly correlated with milk folate. There was a significant positive correlation between milk folate and serum folate (r = .48, p= .04) and between milk folate and iron intake (r=.63, p=.003). Results indicate that the folate intake in this population of lactating women was sufficient to maintain adequate folate stores. Results also suggest a relationship between iron intake and milk folate. Research is needed to determine dietary requirements during lactation and to investigate the relationship between dietary iron and milk folate. / Master of Science

Made available in DSpace on 2014-12-17T14:16:23Z (GMT). No. of bitstreams: 1 ValdjaneS.pdf: 2387721 bytes, checksum: d21580a2388ac377d21ffb9abbbd4392 (MD5) Previous issue date: 2009-03-27 / Ferritin is a protein composed of heavy and light chains, non-covalently linked and which accommodates, in its core, thousands of atoms of iron. Furthermore, this protein represents the stock of iron in the body and it is characterized as an acute marker and predictor of diseases, such as iron deficiency anemia, hereditary hemochromatosis and others. Considering the variability of reference values and the analytical methods currently available, the aim of this work was to propose 95% confidence intervals for adults in the State of Rio Grande do Norte, Brazil, after determining the average concentration of serum ferritin for both sexes, beyond its correlation with the age. We analyzed 385 blood samples, collected by venipuncture from individuals residing in the State, after 12-14 hours of fast. The populational sample had 169 men and 216 women between 18-59 years old, which filled a questionnaire on socioeconomic, food habits and accounts about previous and current diseases. The sample collections were itinerant and the results of erythrogram, fasting glucose, alanine aminotransferase, aspartate aminotransferase, &#947;-glutamyl transferase, urea, creatinine, leukocyte count and platelets, beyond C-reactive protein, were issued to each participant, so that, after selection of the apparently healthy individuals, the dosage of serum ferritin was carried out. Statistical analysis was performed using the softwares SPSS 11.0 Windows version, Epi Info 3.3.2 and Graf instant pad (version 3.02), and the random population sample was single (finite population), for which the test of linear correlation and diagram of dispersion were also made. After selection of individuals and determination of serum ferritin, the most discrepant outliers were disregarded (N = 358, Men = 154/Women = 207) and the average value determined for the masculine sex individuals was 167,18 ng / dL; for the feminine sex individuals, the average value obtained was 81,55 ng / dL. Moreover, we found that 25% of men had values < 90,30 ng / dL; 50% &#8804; 156,25 ng / dL and 75% &#8804; 229,00 ng / dL. In the group of women, 25% had values < 38,80 ng / dL; 50% &#8804; 65,00 ng / dL and 75% &#8804; 119,00 ng / dL. Through the correlation coefficient (r = 0,23 with p = 0,003), it is possible to suggest the existence of positive linear correlation between age and serum ferritin for men. The correlation coefficient for women (r = 0,16 with p = 0,025) also confirms the existence of positive linear correlation between serum ferritin and age. Considering the analysis carried out and specific methods corroborating with the proposed benchmarks, we concluded that the average value found for men is higher than that found for women. Furthermore, this scenario rises with age for both sexes, and the 95% confidence intervals obtained were 74 ng/dL &#8804; &#956; &#8804; 89 ng/dL and 152ng/dL &#8804; &#956; &#8804;183ng/dL for the feminine and masculine sex individuals respectively / A ferritina ? uma prote?na composta por cadeias leves e pesadas ligadas n?o- covalentemente e que acomoda, em seu n?cleo, milhares de ?tomos de ferro. Al?m disso, esta prote?na representa os estoques de ferro no organismo e caracteriza-se como marcador de fase aguda e preditor de doen?as como anemia por defici?ncia de ferro, hemocromatose heredit?ria, entre outras. Diante da variabilidade de valores de refer?ncia e m?todos anal?ticos dispon?veis atualmente, a presente pesquisa objetivou propor intervalos de refer?ncia com 95% de confian?a para adultos do Estado do Rio Grande do Norte, ap?s determina??o da concentra??o m?dia de ferritina s?rica para ambos os sexos, correlacionando-as tamb?m com a idade. Foram analisadas 385 amostras de sangue, coletadas ap?s 12-14 horas de jejum por venopun??o, de indiv?duos residentes no Estado, sendo 169 homens e 216 mulheres entre 18-59 anos, os quais responderam a um question?rio relacionado a aspectos s?cio-econ?micos, alimentares, hist?rico de doen?as anteriores e queixas atuais. A coleta teve car?ter itinerante, tendo sido emitidos a cada participante os resultados de eritrograma, glicose em jejum, alanina aminotransferase, aspartato aminotransferase, &#947;- glutamil transferase, ureia, creatinina, contagem de leuc?citos e plaquetas, al?m de prote?na C reativa de modo que, ap?s sele??o dos indiv?duos aparentemente saud?veis, foi feita a dosagem de ferritina s?rica. As an?lises estat?sticas foram realizadas utilizando-se os softwares SPSS Windows vers?o 11.0, Epi Info 3.3.2 e Graf pad instant (vers?o 3.02), sendo que a amostra populacional foi aleat?ria simples (popula??o finita) para a qual foi feito o teste de correla??o linear e diagrama de dispers?o. Ap?s a sele??o dos indiv?duos e determina??o da ferritina s?rica, os outliers mais discrepantes foram desconsiderados, obtendo-se um valor m?dio para os indiv?duos do sexo masculino de 167,18 ng/dL e, para os indiv?duos do sexo feminino de 81,55 ng/dL. Analisando os valores obtidos, temos que 25% dos homens apresentaram valores < 90,30 ng/dL; 50% &#8804; 156,25 ng/dL e 75% &#8804; 229,00 ng/dL. No grupo das mulheres, 25% apresentam valores < 38,80 ng/dL; 50% &#8804; 65,00 ng/dL e 75% &#8804;119,00 ng/dL. Por meio do coeficiente de correla??o, r = 0,23, e p = 0,003, ? poss?vel confirmar a exist?ncia de correla??o linear positiva entre idade e ferritina s?rica dos indiv?duos do sexo masculino, assim como o coeficiente de correla??o r = 0,16 e p = 0,025 confirma a exist?ncia de correla??o linear positiva entre a ferritina s?rica e a idade das mulheres. Diante das an?lises realizadas e corroborando com m?todos espec?ficos para proposi??o de valores de refer?ncia, conclu?mos que o valor m?dio encontrado para homens ? superior ao valor m?dio encontrado para mulheres, elevando-se com a idade para os indiv?duos de ambos os sexos. Al?m disso, os intervalos de refer?ncia determinados com 95% de confian?a, foram de 74 ng/dL &#8804; &#956; &#8804; 89 ng/dL e de 152 ng/dL &#8804; &#956; &#8804; 183 ng/dL, para os indiv?duos dos sexos feminino e masculino, respectivamente