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Diabetes is a significant health burden worldwide. The most common types of diabetes, type 1 and type 2 diabetes are typically characterized by complete insulin deficiency and varying degrees of insulin deficiency, respectively. Glycated hemoglobin (HbA1c), formed when hemoglobin and glucose combine through glycation, can be used to monitor treatment in diabetic patients, and thus prevent future complications of the disease. HbA1c can be measured using point-of-care (POC) instruments, providing rapid results and immediate feedback on HbA1c levels. Measurement with POC instruments can reduce the need for additional visits for blood sampling, thereby lowering costs for both patients and healthcare systems. The main purpose of this study was to verify HbA1c on the POC instruments QuikRead Go and DCA Vantage by comparing the results with the reference method Cobas Pro and by comparing capillary and venous blood samples. The study utilized 30 venous patient samples, including 20 samples already analyzed on Cobas Pro and 10 samples collected venously and capillary from volunteer individuals. The coefficient of variation (CV) for QuikRead Go fell within the quality goal, while DCA Vantage exceeded the goal. The results demonstrated good agreement between capillary blood samples analyzed on POC instruments and venous samples analyzed on Cobas Pro. However, a statistically significant difference was found comparing venous samples analyzed on POC instruments and Cobas Pro. The results suggest that capillary sampling should be used for analysis on POC instruments. Certain limitations of the study should be considered when using QuikRead Go and DCA Vantage in practice.

L’étude du cerveau humain est un domaine en plein essor et les techniques non-invasives de l’étudier sont très prometteuses. Afin de l’étudier de manière non-invasive, notre laboratoire utilise principalement l’imagerie par résonance magnétique fonctionnelle (IRMf) et l’imagerie optique diffuse (IOD) continue pour mesurer et localiser l’activité cérébrale induite par une tâche visuelle, cognitive ou motrice. Le signal de ces deux techniques repose, entre autres, sur les concentrations d’hémoglobine cérébrale à cause du couplage qui existe entre l’activité neuronale et le flux sanguin local dans le cerveau. Pour être en mesure de comparer les deux signaux (et éventuellement calibrer le signal d’IRMf par l’IOD), où chaque signal est relatif à son propre niveau de base physiologique inconnu, une nouvelle technique ayant la capacité de mesurer le niveau de base physiologique est nécessaire. Cette nouvelle technique est l’IOD résolue temporellement qui permet d’estimer les concentrations d’hémoglobine cérébrale. Ce nouveau système permet donc de quantifier le niveau de base physiologique en termes de concentrations d’hémoglobine cérébrale absolue. L’objectif général de ma maîtrise était de développer un tel système afin de l’utiliser dans une large étude portant sur la condition cardiovasculaire, le vieillissement, la neuroimagerie ainsi que les performances cognitives. Il a fallu tout d’abord construire le système, le caractériser puis valider les résultats avant de pouvoir l’utiliser sur les sujets de recherche. La validation s’est premièrement réalisée sur des fantômes homogènes ainsi qu’hétérogènes (deux couches) qui ont été développés. La validation des concentrations d’hémoglobine cérébrale a été réalisée via une tâche cognitive et appuyée par les tests sanguins des sujets de recherche. Finalement, on présente les résultats obtenus dans une large étude employant le système d’IOD résolue temporellement en se concentrant sur les différences reliées au vieillissement. / Our understanding of the functional organization of the human brain has been greatly influenced by the development of new medical imaging techniques. Pr. Hoge’s research has focused on the use of functional magnetic resonance imaging (fMRI) and continuous diffuse optical imaging (DOI) for non-invasive localization and quantification of brain activity associated with behavioral stimuli or tasks (e.g. cognitive, motor or visual). The respective signals of both techniques are based on cerebral haemoglobin concentrations because of the coupling that exists between neuronal activity and cerebral blood flow. Relating BOLD fMRI signals with those acquired using DOI has been complicated by the fact that fMRI yields fractional change values, while the majority of DOI methods have provided absolute changes from an unknown baseline. To address this, we adopted a newer technique known as time-resolved DOI, which allows absolute quantification of cerebral haemoglobin concentrations. Time-resolved DOI thus has the capacity to quantify the subject’s resting hemoglobin concentrations in absolute micromolar units. The main objective of my masters’ project was to implement and optimize a time-resolved DOI system for use in a large study exploring the links between cardiovascular fitness, aging, neuroimaging markers, and cognitive performance. In this thesis we describe the fabrication of the system, followed by its characterisation and validation using solid optical phantoms (homogeneous and heterogeneous) developed for this purpose. Haemoglobin concentrations obtained non-invasively with the system are validated against blood draws, while the sensitivity to variations in concentration are assessed during a cognitive task. Finally, we present the results of a large study in which the time-resolved DOI system was used to characterize age-related vascular changes in the brain.

Introdução: A anemia e a obesidade infantil representam importantes problemas nutricionais na saúde pública. Estudos realizados na última década evidenciam associação entre anemia, menores níveis de hemoglobina e obesidade, porém são escassos os estudos que avaliam essa associação em crianças, particularmente no Brasil. Objetivos: Avaliar a ocorrência de anemia e sua associação com estado nutricional e outras características infantis, maternas e familiares; investigar associação entre nível de hemoglobina e estado nutricional. Método: Trata-se de subprojeto de uma pesquisa mais ampla, desenvolvida em município de pequeno porte do estado de São Paulo, no período de fevereiro a maio de 2013. Foi realizado em amostra representativa e proporcional de crianças menores de três anos de idade cadastradas nas unidades básicas de saúde do município. A amostra do presente estudo foi constituída por 227 crianças com seis meses ou mais de idade que tinham dosagem do nível de hemoglobina obtida em hemoglobinômetro portátil Agabê®. Para o diagnóstico da anemia, adotou-se a recomendação da OMS (Hb<11g/dL). Verificaram-se peso e estatura; o estado nutricional foi avaliado pelo escore z do IMC/idade e classificado em: magreza; eutrofia; risco de sobrepeso; sobrepeso e obesidade, de acordo com recomendação da OMS. O banco de dados foi construído no software Epi-Info versão 3.5.2, com dupla digitação; as análises foram processadas no Anthro versão 3.2.2 e no software estatístico R. Realizou-se análise univariada com distribuição de crianças anêmicas e não anêmicas e variáveis independentes (infantis, maternas e familiares), utilizando-se teste qui-quadrado. Para investigar associação entre nível de Hb (variável dependente) e variáveis independentes, foram utilizados o teste de correlação de Pearson e a regressão linear múltipla, com inclusão das variáveis com p<0,20. O nível de significância dos testes foi de 5%. O estudo foi aprovado por Comitê de Ética em Pesquisa, autorizado pela Diretoria de Saúde do município e todas as mães assinaram Termo de Consentimento Livre e Esclarecido. Resultados: Anemia afetava 41,8% das crianças, com frequência estatisticamente maior (p<0,05) no segundo semestre de vida (56,3%), entre crianças que não faziam puericultura (60,0%), que se encontravam em aleitamento materno (57,1%), pertencentes a famílias com chefe desempregado (59,3%) e com renda per capita inferior a 0,5 salário mínimo (53,5%). Anemia não se associou com estado nutricional. Os níveis de Hb se associaram (p<0,05) com idade (meses); estado nutricional (escore z de IMC/idade); aleitamento materno na entrevista; fazer puericultura; chefe da família empregado e renda familiar per capita (em salários mínimos). Na análise de regressão linear múltipla, os níveis de hemoglobina se associaram significativamente (p<0,05) apenas com as variáveis fazer puericultura (p<0,003) e estar em aleitamento materno na entrevista (p<0,021): ser acompanhada em consulta de puericultura aumentou os níveis de Hb em 0,96g/dL estar em aleitamento materno no momento da entrevista reduziu os níveis de Hb em 0,50g/dL. Conclusões: Não se constatou associação entre anemia ou menores níveis de Hb e estado nutricional nas crianças menores de três anos de idade, apesar de anemia e excesso de peso constituírem problemas importantes de saúde da criança no município estudado. Os resultados alertam para a necessidade da implementação urgente de intervenções para o controle desses problemas nutricionais na atenção básica. / Introduction: anemia and childhood obesity represent important nutritional problems in public health. Studies carried out in the last decade showed association between anemia, lower levels of hemoglobin and obesity, however there are few studies that evaluate this association in children, particularly in Brazil. Objectives: To evaluate the occurrence of anemia and its association with nutritional status and other characteristics of children, mothers and family members; to investigate the association between hemoglobin level and nutritional status. Method: This is a subproject of a broader research, developed in a small municipality in the state of São Paulo, in the period from February to May of 2013. Was carried out in a representative and proportional sample of children under three years of age enrolled in basic health units in the city. The sample of this study was composed by 227 children with six months or more of age who had dosage of the hemoglobin level obtained in portable hemoglobinometer Agabê®. For the diagnosis of anemia was adopted the WHO recommendation (Hb<11g/dL). Weight and stature were verified; nutritional status was assessed by z score of BMI/age and classified into: thinness; eutrophy, overweight risk; overweight and obesity, in accordance with the WHO recommendation. The database was built in the Epi-Info software version 3.5.2, with double-typing; analyzes were processed in Anthro version 3.2.2 and in the statistical software R. Univariate analysis was performed with distribution of anemic and non-anemic children and independent variables (children, mothers and family), using the chi-square test. To investigate the association between Hb level (dependent variable) and independent variables, were used the Pearson\'s correlation test and multiple linear regression, with inclusion of variables with p<0.20. The significance level was 5%. The study was approved by the Ethics Committee in Research, authorized by the Board of Health of the municipality and all mothers signed the Free and Informed Consent Term. Results: anemia affected 41.8% of the children, with statistically greater frequency (p<0.05) in the second semester of life (56.3%), between children who were not in puericulture (60.0%), who were on exclusive breastfeeding (57.1%), belonging to families with head unemployed (59.3%) and with per capita income of less than 0.5 minimum wage (53.5%). Anemia was not associated with nutritional status. The Hb levels were associated (p<0.05) with age (months); nutritional status (z score of BMI/age); breastfeeding in the interview; do puericulture; head of family employee and per capita family income (in minimum wages). In the multiple linear regression analysis, hemoglobin levels were significantly associated (p<0.05) only with the variables make puericulture (p<0.003) and being in breastfeeding in the interview (p<0.021), be accompanied in puericulture consultation increased levels of Hb in 0.96g/dL and being in breastfeeding at the time of interview reduced the levels of Hb in 0.50g/dL. Conclusions: it was not found association between anemia or lower Hb levels and nutritional status in children below three years of age, although anemia and overweight constitute important problems of child health in the municipality studied. The results alert to the need of urgent implementation of interventions for the control of these nutritional problems in basic care.

O estudo do processo da peroxidação de lipídios tem aumentado nos últimos anos, principalmente devido à implicação dos hidroperóxidos de lipídios (LOOH) em diversos processos patológicos. A decomposição destes LOOH é capaz de gerar subprodutos capazes de promover danos em biomoléculas, incluindo proteínas e DNA. No presente trabalho, utilizando hidroperóxidos de ácido linoléico isotopicamente marcado com átomo de oxigênio-18 (LA18O18OH), fomos capazes de demonstrar que estas moléculas gerararam oxigênio singlete marcado [18(1O2)] em células em cultura. A detecção de tal espécie foi possível através da utilização de uma nova metodologia utilizando um derivado antracenico. Para este propósito foi utilizado o derivado de antraceno 3,3\'-(9,10-antracenodiil) bisacrilato (DADB), cujo produto especifico da reação com o 1O2 (o endoperóxido do DADB DADBO2) do pode ser facilmente detectado por HPLC-MS/MS. De forma a expandir a compreensão dos efeitos tóxicos desses LOOH, investigamos o efeito destes compostos gerados intracelularmente. Para tal, foi utilizado o Rosa bengala (RB), um fotosensibilizador que tem afinidade por espaços apolares como membranas e lisossomos. A fotosenssibilização deste composto foi capaz de induzir a morte celular, e esta morte estaria relacionada a uma maior formação de 1O2 e a um maior acumulo de peróxidos. Nestes estudos foi possível demonstrar que carotenóides e sistemas antioxidantes dependentes de glutationa foram capazes de proteger contra os efeitos tóxicos da fotosensibilização na presença de RB. Adicionalmente foram avaliados os efeitos da hemoglobina (Hb) e do hidroperóxido do ácido linoléico (LAOOH) em uma série de parâmetros toxicológicos, como citotoxicidade, estado redox, a peroxidação lipídica e dano ao DNA. Nós demonstramos que a pré-incubação das células com Hb e sua posterior exposição à LAOOH (Hb + LAOOH) levou a um aumento na morte celular, a oxidação do DCFH, formação de malonaldeído e fragmentação do DNA e que esses efeitos estavam relacionados com o grupo peróxido e ao heme presentes na Hb. Foi demonstrado que as células incubadas com LAOOH e Hb apresentaram um nível maior das lesões de DNA; 8-oxo-7,8-diidro-2 \'desoxiguanosina e 1,N2-etheno-2\'-desoxiguanosina. Além disso, as incubações com Hb levaram a um aumento nos níveis de ferro intracelular, e este alto nível de ferro correlacionada com a oxidação do DNA, avaliadas através da medida de sitios EndoIII e Fpg sensíveis. Nossos resultados comprovam que os LAOOHs apresentaram efeito citotóxico e genotóxico, mesmo em concentrações muito baixas, podendo contribuir para o desencadeamento de processos patologicos como o câncer e doenças cardiovasculares e neurodegenerativas. / The study of the process of lipid peroxidation has increased in recent years, mainly due to the involvement of lipid hydroperoxide (LOOH) in a series of pathological processes. The decomposition of LOOH is able to generate products that can promote damage to biomolecules, including proteins and DNA. In the present work, using linoleic acid hydroperoxide isotopically labeled with 18O2 (LA18O18OH), we demonstrate that these molecules were able to generate labeled singlet oxygen [18(1O2)] in cultured cells. The detection of such species was possible using a new methodology using an anthracene derivative .For this purpose we used the anthracene derivative of 3,3\'-(9,10-antracendiil) bisacrilate (DADB), whose specific reaction product with 1O2 (DADB endoperoxide DADBO2) can be easily detected by HPLC-MS/MS. In order to expand the understanding of the toxic effects of LOOH, we investigated the effect of these compounds generated intracellularly. For this porpoise, we used Rose Bengal (RB), a photosensitizer that has affinity for apolar spaces such as membranes and lysosomes. The photosensitization of this compound was able to induce cell death, and this death was related to increased formation of 1O2 and a higher accumulation of peroxides. In these studies we have shown that carotenoids and glutathione-dependent antioxidant systems were capable of protecting against the toxic effects of photosensitization in the presence of RB. Additionally, we evaluated the effects of hemoglobin (Hb) and linoleic acid hydroperoxide (LAOOH) in a series of toxicological endpoints such as cytotoxicity, redox status, lipid peroxidation and DNA damage. We demonstrated that preincubation of cells with Hb and its subsequent exposure to LAOOH (Hb + LAOOH) led to an increase in cell death, DCFH oxidation, formation of malonaldehyde and DNA fragmentation, and that these effects were related to the peroxide and the heme group. It was demonstrated that cells incubated with LAOOH and Hb showed a higher level of the DNA lesions, 8-oxo-7,8-dihydro-2\'deoxyguanosine and 1,N2-etheno-2\'-deoxyguanosine. Furthermore, incubations with Hb led to an increase in intracellular iron levels, and this high level of iron correlates with the oxidation of DNA, measured as EndoIII and Fpg-sensitive sites. Our results show that the LOOHs showed cytotoxic and genotoxic, even at very low concentrations and may contribute to the onset of chronic malignancies like cancer, cardiovascular and neurodegenerative diseases.

Die Pathogenese der verzögerten ischämischen Defizite (VIND) nach Subarachnoidalblutung wird mit Produkten der Hämolyse in Zusammenhang gebracht. Topische Hirnsuperfusion mit einer artifiziellen cerebrospinalen Flüssigkeit (ACSF), die L-NA, einen NOS-Inhibitor, in Kombination mit einer erhöhten Kaliumkonzentration erhielt, hat bei der Ratte zu Ischämien geführt. Dieses Phänomen wurde als Cortical spreading ischemia (CSI) bezeichnet. Dabei scheint es während der neuronalen Depolarisation zu einer gestörten Kopplung zwischen cerebralem Metabolismus und Blutfluß zu kommen, die zu einer Vasokonstriktion und schließlich zur Ischämie führt. Die vorliegenden Arbeit beschäfftigte sich zum einen mit der Frage, ob Hämoglobin und hoch Kalium (35 mmol/l) auch zu CSIs führt,und ob es in Folge der CSIs zu cerebralen Parenchymschäden kommt. Methode: 24 Tieren wurde eine ACSF in den künstlich geschaffenen Subarachnoidalraum perfundiert. Diese ACSF enthielt eine erhöhte Kaliumkonzentration (K+ ) von 35 mmol/l und 2 mmol/l freies Hämoglobin (Hb). Unter dieser Versuchsanordnung kam es, als Antwort auf die neuronale Depolarisation, zu einem langandauernden massiven Abfall des rCBF in ischämische Bereiche, der sogenannten cortical spreading ischaemia (CSI). Zum Nachweis eines möglichen cerebralen Parenchymschadens durch die CSI wurden die Gehirne von 11 Versuchstieren histologisch untersucht. Von den 11 histologisch sowie immunhistochemisch gefärbten Hirnpräparaten wiesen 9 Hirne eine ausgeprägte cortikale Zellnekrose auf. Bei den Kontrolltieren, denen entweder nur die erhöhte K+ oder Hämoglobin in der ACSF superfundiert wurde, kam es nicht zum Auftreten von CSIs. und Anzeichen von nekrotischem Zelluntergang waren nicht zu sehen. Schlussfolge: Subarachnoidales Hb kombiniert mit hoch K+ fürt zur cortical spreading ischemia und in weiterer Folge zu ausgedehnten corticalen Infarkten. / The pathogenesis of delayed ischemic neurological deficits after subarachnoid hemorrhage has been related to products of hemolysis. Topical brain superfusion of artificial cerebrospinal fluid (ACSF) containing L-NA a NOS-inhibitor and high concentration of K+ has shown to induce ischemia in rats. Superimposed on a slow vasospastic reaction, the ischemic events represent spreading depolarisation of the neuronal-glial network that trigger acute vasoconstriction. The purpose of the present study was to investigate whether such spreading ischemias in the cortex could be caused also by the hemolysis products hemoglobin and K+ and whether such spreading cortical ischemias lead to brain damage. Methods: A cranial window was implanted in 24 rats. Cerebral blood flow (CBF) was measured using laser Doppler flowmetry, and direct current(DC)potentials were recorded. The ACSF was superfused topically over the brain. Rats were assigned to three groups representing ACSF composition. Analysis included classical histochemical and immunhistochemical studies. Superfusion of ACSF containing Hb combined with high concentration of K+ (35 mmol/L) reduced CBF gradually. Spreading ischemia in the cortex appeared when CBF reached 40 to 70% compared to baseline (which was 100%). This cortical spreading ischemia was characterized by sharp negative shift in DC, which preceded a steep CBF decrease that was followed by a slow recovery. In 9 of the surviving animals widespread cortical infarction was observed at the site of the cranial window and neighbouring areas in contrast to the findings in the two control groups. Conclusion: Subarachnoid Hb combined with high K+ causes cortical spreading ischemia and leads to widespread necrosis of the cortex.

Introdução: A anemia e a obesidade infantil representam importantes problemas nutricionais na saúde pública. Estudos realizados na última década evidenciam associação entre anemia, menores níveis de hemoglobina e obesidade, porém são escassos os estudos que avaliam essa associação em crianças, particularmente no Brasil. Objetivos: Avaliar a ocorrência de anemia e sua associação com estado nutricional e outras características infantis, maternas e familiares; investigar associação entre nível de hemoglobina e estado nutricional. Método: Trata-se de subprojeto de uma pesquisa mais ampla, desenvolvida em município de pequeno porte do estado de São Paulo, no período de fevereiro a maio de 2013. Foi realizado em amostra representativa e proporcional de crianças menores de três anos de idade cadastradas nas unidades básicas de saúde do município. A amostra do presente estudo foi constituída por 227 crianças com seis meses ou mais de idade que tinham dosagem do nível de hemoglobina obtida em hemoglobinômetro portátil Agabê®. Para o diagnóstico da anemia, adotou-se a recomendação da OMS (Hb<11g/dL). Verificaram-se peso e estatura; o estado nutricional foi avaliado pelo escore z do IMC/idade e classificado em: magreza; eutrofia; risco de sobrepeso; sobrepeso e obesidade, de acordo com recomendação da OMS. O banco de dados foi construído no software Epi-Info versão 3.5.2, com dupla digitação; as análises foram processadas no Anthro versão 3.2.2 e no software estatístico R. Realizou-se análise univariada com distribuição de crianças anêmicas e não anêmicas e variáveis independentes (infantis, maternas e familiares), utilizando-se teste qui-quadrado. Para investigar associação entre nível de Hb (variável dependente) e variáveis independentes, foram utilizados o teste de correlação de Pearson e a regressão linear múltipla, com inclusão das variáveis com p<0,20. O nível de significância dos testes foi de 5%. O estudo foi aprovado por Comitê de Ética em Pesquisa, autorizado pela Diretoria de Saúde do município e todas as mães assinaram Termo de Consentimento Livre e Esclarecido. Resultados: Anemia afetava 41,8% das crianças, com frequência estatisticamente maior (p<0,05) no segundo semestre de vida (56,3%), entre crianças que não faziam puericultura (60,0%), que se encontravam em aleitamento materno (57,1%), pertencentes a famílias com chefe desempregado (59,3%) e com renda per capita inferior a 0,5 salário mínimo (53,5%). Anemia não se associou com estado nutricional. Os níveis de Hb se associaram (p<0,05) com idade (meses); estado nutricional (escore z de IMC/idade); aleitamento materno na entrevista; fazer puericultura; chefe da família empregado e renda familiar per capita (em salários mínimos). Na análise de regressão linear múltipla, os níveis de hemoglobina se associaram significativamente (p<0,05) apenas com as variáveis fazer puericultura (p<0,003) e estar em aleitamento materno na entrevista (p<0,021): ser acompanhada em consulta de puericultura aumentou os níveis de Hb em 0,96g/dL estar em aleitamento materno no momento da entrevista reduziu os níveis de Hb em 0,50g/dL. Conclusões: Não se constatou associação entre anemia ou menores níveis de Hb e estado nutricional nas crianças menores de três anos de idade, apesar de anemia e excesso de peso constituírem problemas importantes de saúde da criança no município estudado. Os resultados alertam para a necessidade da implementação urgente de intervenções para o controle desses problemas nutricionais na atenção básica. / Introduction: anemia and childhood obesity represent important nutritional problems in public health. Studies carried out in the last decade showed association between anemia, lower levels of hemoglobin and obesity, however there are few studies that evaluate this association in children, particularly in Brazil. Objectives: To evaluate the occurrence of anemia and its association with nutritional status and other characteristics of children, mothers and family members; to investigate the association between hemoglobin level and nutritional status. Method: This is a subproject of a broader research, developed in a small municipality in the state of São Paulo, in the period from February to May of 2013. Was carried out in a representative and proportional sample of children under three years of age enrolled in basic health units in the city. The sample of this study was composed by 227 children with six months or more of age who had dosage of the hemoglobin level obtained in portable hemoglobinometer Agabê®. For the diagnosis of anemia was adopted the WHO recommendation (Hb<11g/dL). Weight and stature were verified; nutritional status was assessed by z score of BMI/age and classified into: thinness; eutrophy, overweight risk; overweight and obesity, in accordance with the WHO recommendation. The database was built in the Epi-Info software version 3.5.2, with double-typing; analyzes were processed in Anthro version 3.2.2 and in the statistical software R. Univariate analysis was performed with distribution of anemic and non-anemic children and independent variables (children, mothers and family), using the chi-square test. To investigate the association between Hb level (dependent variable) and independent variables, were used the Pearson\'s correlation test and multiple linear regression, with inclusion of variables with p<0.20. The significance level was 5%. The study was approved by the Ethics Committee in Research, authorized by the Board of Health of the municipality and all mothers signed the Free and Informed Consent Term. Results: anemia affected 41.8% of the children, with statistically greater frequency (p<0.05) in the second semester of life (56.3%), between children who were not in puericulture (60.0%), who were on exclusive breastfeeding (57.1%), belonging to families with head unemployed (59.3%) and with per capita income of less than 0.5 minimum wage (53.5%). Anemia was not associated with nutritional status. The Hb levels were associated (p<0.05) with age (months); nutritional status (z score of BMI/age); breastfeeding in the interview; do puericulture; head of family employee and per capita family income (in minimum wages). In the multiple linear regression analysis, hemoglobin levels were significantly associated (p<0.05) only with the variables make puericulture (p<0.003) and being in breastfeeding in the interview (p<0.021), be accompanied in puericulture consultation increased levels of Hb in 0.96g/dL and being in breastfeeding at the time of interview reduced the levels of Hb in 0.50g/dL. Conclusions: it was not found association between anemia or lower Hb levels and nutritional status in children below three years of age, although anemia and overweight constitute important problems of child health in the municipality studied. The results alert to the need of urgent implementation of interventions for the control of these nutritional problems in basic care.

Catecol e catecolaminas foram ensaiados sobre as atividades NADPH e NADH oxidásica dos microssomos. Quantidades catalíticas de adrenalina aumentam de duas a três vezes a velocidade de oxidação do NADPH, após um pequeno período de indução. O efeito da adrenalina é suprimido pela superóxido dismutase, se a enzima é adicionada antes de iniciada a reação. O efeito catalítico é atribuído a dois produtos de oxidação da adrenalina pelo íon superóxido; à quinona, produto de oxidação de dois elétrons e ao adrenocromo, produto de oxidação de quatro elétrons. Provavelmente, o adrenocromo reoxida a NADPH citocromo c redutase, e a quinona formada reage com oxigênio, regenerando adrenocromo. A adrenalina não mostrou qualquer efeito sobre a atividade NADH oxidásica, nem sobre a atividade NADPH oxidásica, estimulada por menadiona. Provavelmente, durante estes processos, dois elétrons são transferidos simultaneamente ao oxigênio. Catecol e catecolaminas duplicam a velocidade de oxidação do NADH em presença de quantidades catalíticas de NADH-citocromo b5 redutase e citocromo b5. Este resultado sugere a formação do íon superóxido, durante a autoxidação do citocromo b5. Catecol e p-hidroquinona promovem, cataliticamente, a oxidação da oxihemoglobina e oximioglobina à forma ferri. A velocidade de oxidação da oxihemoglobina mostra dependência de primeira ordem em relação à concentração de hemeproteína e de meia ordem em relação ao difenol ; contudo a altas concentrações dos catalisadores observa-se saturação, com valores de Vmáx similares para ambos os difenóis. É proposto que uma quinona , inicialmente formada, oxida a oxihemeproteína com liberação de oxigênio; por sua vez, a semiquinona oxida uma segunda molécula de oxihemeproteína, sendo que o oxigênio ligado recebe dois elétrons. Exceto para o caso da oximioglobina, que é mais reativa, a forma reduzida do catalisador deve estar presente para se opor ao desaparecimento da semiquinona por dismutação. Desde que se observa a liberação de oxigênio, esperada para a formação de água, o sistema pode ser considerado modelo de oxidase terminal. Infere-se tentativamente, que a oxihemoglobina tem estrutura HbFe2+ ...O2, e que a velocidade da oxidação catalisada é limitada pela velocidade de produção da verdadeira forma reativa, a estrutura ferri-superóxido, HbFe3+...O-2. / Catechol and catecholamines have been assayed upon the microsomal NADPH and NADH oxidase activities. Adrenaline shows a catalytic effect on the NADPH oxidation characterized by a small lag. The two-to three fold increase in rate can be supressed by dismutase if the enzyme is added before superoxide the reaction begins. The catalytic effect is ascribed to two products of adrenaline oxidation by the superoxide ion; to the quinone, the two electron oxidation product, and to the adrenochrome, the four electron oxidation product. Presumably, the adrenochrome reoxidizes the NADPH-cytochrome c reductase, and the formed quinone reacts with oxygen and regenerates the adrenochrome. Adrenaline neither changed, the NADH oxidase activity nor the menadione-stimulated NADPH oxidase activity. Presumably in these processes, two electrons are simultaneously transferred to the oxygen. Catechol and catecholamines doubled the rate of autoxidation of NADH in the presence of catalytic amounts of NADH-cytochrome b5 reductase and cytochrome b5 This result suggests superoxide ion formation in the autoxidation of the cytochrome. Catechol and p-hydroquinone catalytically promote the oxidation of oxyhemoglobin and oxymyoglobin to the ferri-form. Kinetic data for oxyhemoglobin oxidation indicates a first-order dependence upon the hemoprotein concentration and half-order dependence upon diphenol; however at high catalyst concentration, saturation is observed with similar Vmax values for both diphenols despite the difference in reactivity. It is proposed that initially formed quinone oxidizes the hemoprotein with oxygen release; in turn the semiquinone oxidizes a second molecule of hemoprotein and regenerates the quinone, with the bound oxygen acquiring two electrons. Except for the more reactive oxymyoglobin, the reduced form of the catalyst must be present to oppose semiquinone disappearance by dismutation, Since the expected release of 02 for water formation is observed, the system may be considered a model for terminal oxidase. It is tentatively inferred that oxyhemoglobin has the structure HbFe2+...02 and that the rate of the catalyzed oxidation is limited by the rate of generation of the true reacting form, the superoxide ferri structure, HbFe3+...0-2.

Nos últimos vinte anos houve um aumento substancial no número de revisões sistemáticas e ensaios clínicos que avaliaram intervenções farmacêuticas para pacientes com doenças crônicas, em especial o diabetes. No entanto, existem poucos estudos que avaliam criticamente tais publicações, bem como modelos de prática desenvolvidos no contexto do sistema público de saúde brasileiro. O presente trabalho teve como objetivos avaliar revisões sistemáticas e ensaios clínicos controlados randomizados sobre serviços clínicos farmacêuticos para pacientes com diabetes e avaliar o efeito de modelo de colaboração médico- farmacêutico conduzido em ambulatório de cuidado secundário para pacientes com diabetes tipo 2 não controlada. Para tanto, busca abrangente da literatura foi conduzida nas bases de dados PubMed, SCOPUS, LILACS, Scielo e DOAJ por revisões sistemáticas e ensaios clínicos controlados randomizados. As revisões sistemáticas foram avaliadas em relação à qualidade da apresentação textual e metodológica, sendo identificados campos para melhorias futuras. A seguir, foi realizada uma descrição dos componentes-chave das intervenções e fontes de heterogeneidade clínica e metodológica entre os ensaios clínicos controlados randomizados. Ainda, foi conduzido um ensaio clinico controlado randomizado no ambulatório de doenças metabólicas do Hospital Universitário da Universidade de São Paulo, com duração de 12 meses, para 80 pacientes com diabetes tipo 2 não controlada. O grupo intervenção recebeu consultas farmacêuticas face a face, com suporte remoto por telefone. O farmacêutico realizou intervenções sistemáticas objetivando resolver ou prevenir problemas relacionados aos medicamentos. Os desfechos primários incluíram a redução e controle dos níveis de hemoglobina glicada. A busca bibliográfica identificou 101 registros, dos quais sete revisões completaram os critérios de inclusão. Em média, apenas dois terços dos itens sobre qualidade da apresentação textual e metodológica foram cumpridos nas publicações. Os problemas mais frequentes incluíram o não registo de protocolo do estudo, a ausência de lista dos estudos excluídos, e a falta de reconhecimento claro do conflito de interesses. A busca por ensaios clínicos randomizados de intervenções farmacêuticas identificou 2271 registros, sendo incluídos 24 na síntese qualitativa. A maioria dos estudos para pacientes com diabetes tipo 2 foi desenvolvida nos Estados Unidos, em ambulatório, com contato individual face a face. Todos realizaram intervenções educativas e o processo de uso dos medicamentos foi avaliado pela maioria deles. A amostra exibiu risco de viés incerto ou alto na maior parte dos itens avaliados, o que resultou em baixa qualidade metodológica. De um total de 80 pacientes, 73 completaram o ensaio clínico, sendo 36 do grupo intervenção e 37 do controle. Comparado ao cuidado usual, o grupo intervenção apresentou maior redução nos níveis de hemoglobina glicada, bem como aumento na taxa de controle da pressão arterial sistólica, na proporção de pacientes aderentes e na pontuação da adesão. Os resultados desta tese apontam que a qualidade da apresentação textual e a metodológica estavam abaixo do ideal entre as revisões e que melhoria no desenho e na descrição das revisões e dos estudos primários é necessária para garantir resultados mais robustos. Ainda, o modelo de cuidado proposto é viável e mais efetivo que o cuidado usual na redução da hemoglobina glicada em pacientes diabéticos tipo 2. / Over the last twenty years, there was an important increase in the number of systematic reviews and clinical trials about pharmacist interventions in patients with chronic diseases, including diabetes. Nevertheless, few studies exist which assess critically such publications, as well as models of practice developed in the context of the Brazilian Public Health System. The study aimed to assess the systematic reviews and randomized controlled trials on clinical pharmacy services for patients with diabetes and to assess the effect of a pharmacist- physician collaborative care model for patients with poorly controlled type 2 diabetes. For this, comprehensive literature search was performed in databases PubMed, SCOPUS, LILACS, Scielo and DOAJ for systematic reviews and randomized controlled trials. The systematic reviews were assessed for the reporting characteristics and methodological quality, been identified rooms for future improvements. The following, it was performed a description of the key components of pharmacist interventions and of the sources of clinical and methodological heterogeneity between randomized controlled trials. In addition, a 12-month randomized controlled trial of pharmacist-physician collaborative interventions for eighty diabetic patients was conducted at University Hospital of University of São Paulo. The pharmaceutical interviews were conducted face-to-face, with remote support by telephone. Pharmacist performed systematic interventions aiming to solve and prevent drug-related problem in the diabetic patients. The primary outcomes included the reduction and control of the levels of glycosylated hemoglobin. The literature search yielded 101 records, of which 7 reviews for diabetic patients satisfied the inclusion criteria. On average, only two-thirds of reporting and methodological quality items were fulfilled in included reviews. The most frequent problems included the non-registration of study protocol, the absence of a list of excluded studies, and unclear acknowledgment of the conflict of interests. The literature search for randomized clinical trials of pharmacist interventions identified 2271 records, 24 of them were included in the qualitative synthesis. The majority of studies was developed in the United States, in ambulatory, with individual contact face to face. All of them performed educational interventions and the process of use of the medications was assessed in the majority of them. The sample showed risk of bias uncertain or high in the majority of the items assessed, which resulted in low methodological quality. Of a total of 80 patients, 73 completed the clinical trial (37 of control and 36 of intervention). In comparison with the usual care, the intervention group presented higher reduction in the levels of glycosylated hemoglobin, as well as increase in the rate of control of the systolic blood pressure, in the proportion of adherent patients and in the score of the medication adherence. The results of this thesis point out that the report and methodological quality was below the ideal in the reviews and that improvement in the design and in the description of the reviews and of the primary studies is necessary to warrant results that are more robust. Still, the model of care proposed is viable and more effective than the usual care in reducing the levels of glycosylated hemoglobin in patients with diabetes type 2.

Anemi kan uppstå till följd av förlust av erytrocyter eller försämrad produktion av nya erytrocyter. För att upptäcka och följa upp patienter med anemi är det viktigt att korrekt kunna mäta hemoglobinkoncentrationen (Hb) i blodet. En vanlig metod för att mäta Hb-koncentration är fotometri i kombination med en kemisk omvandling. Liksom alla mätningar med ljus är dessa känsliga för turbiditet i provet. Lipemi är en vanlig källa till turbiditet som kan uppstå till exempel som följd av en fettrik måltid, diabetes mellitus, lever- eller njursjukdomar, alkoholism och vissa läkemedel. Olika instrumenttillverkare har olika metoder för att motverka interferensen av lipemi. Sysmex hematologi-instrument XN-10 använder en fettlösande bärarvätska i sin fotometriska kanal (HGB) och HemoCue mäter vid en andra våglängd som ska kompensera för turbiditet. Sysmex XN-10 har också en optisk kanal (HGB-O) som är till för att räkna retikulocyter genom att mäta deras nukleinsyra- samt Hb-innehåll men ger då också ett beräknat värde på Hb-koncentrationen i hela provet. Syftet med denna studie var att jämföra HGB och den HGB-O för bestämning av Hb-koncentrationen i helblod. Båda kanalerna jämfördes även med HemoCue Hb 201+ vid bestämning av Hbkoncentrationen i svårt lipemiska prover. Hb-mätning på plasma från motsvarande prover utfördes också för att undersöka om värdet motsvarade Hb-höjningen i de lipemiska proverna. Prover analyserade med både HGB och HGB-O på Sysmex XN-10 på klinisk kemi vid Skånes universitetssjukhus i Lund under november månad 2018 (n = 392) jämfördes med hjälp av Spearmans rangkorrelationskoefficient. Lipemi simulerades med fettemulsionen Intralipid i totalt 32 prover. Färdiganalyserade patientprover från föregående dag delades i ett lipemiskt prov med Intralipidtillsats och ett nollprov med tillsats av NaCl-lösning i en motsvarande volym. Differenserna mellan de lipemiska- och nollprovernas Hb-värden testades för signifikans med icke-parametrisk Wilcoxons teckenrangtest. Kruskal-Wallis samt Dunns's tester användes för att visa på signifikanta skillnader mellan de tre metoderna. Signifikansnivån sattes vid p &lt; 0,05. Resultaten visade god korrelation mellan HGB - och HGB-O Hb-värden med ett Spearman korrelationsvärde på 0,982.  Jämförelsen av metoderna vid lipemi visade signifikant skillnad mellan nollprov och lipemiskt prov för HGB- (p &lt; 0,001) men inte HGB-O (p = 0,11) på XN-10. HemoCue Hb 201+ visade också signifikant skillnad (p &lt; 0,001) vid lipemi men med lägre median-värde än HGB och mindre spridning än HGB-O. HGB-O:s median-värde tydde på minst lipemipåverkan men spridningen av differenserna var stor. Spridningen av HGB-O resultaten kan bero på hemolys då endast intracellulärt Hb mäts i denna kanal. Resultaten i denna studie tyder på att HemoCue-metoden är den mest pålitliga vid Hb-mätning av lipemiska prover och därmed det lämpligaste komplementet till HGBmetoden / Anemia can arise from either loss of erythrocytes or impaired production of new erythrocytes. In order to discover and evaluate the treatment of anemic patients, correct Hb measurements are important. A common method to measure Hb concentration is photometry in combination with chemical conversion of the Hb. Like all light-dependent methods this suffers from a vulnerability to turbidity that scatters light. Lipemia is a common cause of turbidity caused by e.g. recent intake of high fat foods, diabetes mellitus, liver or kidney disease, alcoholism and some drugs. Manufacturers of Hb analyzers use different methods to counter the influence of interference from lipemia on measurements. Sysmex XN-10 analyzers use a fat dissolving sheath fluid in its photometric channel (HGB) and HemoCue measures absorbance at a second wavelength to compensate for turbidity. Sysmex XN-10 also has an optic channel (HGB-O) for counting reticulocytes by measuring their nucleic acid and Hb content. At the same time this channel measures Hb equivalents of erythrocytes and gives a calculated value of Hb content in the entire sample. The aim of this study was to compare the photometric and the optical channels for measuring Hb concentration in whole blood. Both the Sysmex XN-10 channels were compared with HemoCue Hb 201+ when measuring Hb concentrations in lipemic samples. Plasma Hb concentration was determined for the corresponding samples in order to investigate correlation between elevation in Hb concentration with and without simulated lipemia and in the plasma after centrifugation. Samples analyzed at Skånes University Hospital in Lund during the month of November 2018 (n = 392) using both HGB and HGB-O on XN-10 were compared using Spearman's signed correlations coefficient. Lipemia was simulated by using the fat emulsion Intralipid in a total of 32 samples. Samples collected and analyzed on the previous day was used for the study. Each sample was split into one part with added Intralipid to form a lipemic sample and one part with NaCl-solution of the same volume as Intralipid in the lipemic sample. The differences between lipemic and non lipemic samples was tested for significance by the non-parametric Wilcoxons signed ranks test for each of the methods. Significance between the three methods was tested by using Kruskal-Wallis and Dunn's tests. Level of significance was set to p &lt; 0.05. The results showed good correlation between earlier test run on both HGB and HGB-O with a Spearman correlation score of 0,982.  A significant difference was found between lipemic and non lipemic samples with the photometric method (p &lt; 0,001) but not the optical method (p = 0,11) on XN10. HemoCue Hb 201+ also showed a significant difference (p &lt; 0,001) between lipemic and non lipemic samples but a lower median than HGB and less deviation than HGB-O. The median of HGB-O indicated that it was influenced the least by lipemia of the three methods but had the greatest deviation of the differences. The greater deviation of HGB-O values may have been caused by hemolysis since the method measures intra cellular Hb. HemoCue shows according to this study the slightest deviation of the three methods and a less heightened median value compared to HGB which confirms the methods suitability as complement to HGB when dealing with lipemic samples.