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Untersuchungen zur N-terminalen Glykierung und Bildung N-terminaler 2(1H)-Pyrazinonstrukturen in Lebensmitteln und in vivoKunert, Ilka 07 August 2009 (has links) (PDF)
Sowohl bei der Forschung der Maillard-Reaktion in Lebensmitteln als auch im menschlichen Körper lag das Hauptaugenmerk bislang auf der Reaktion der Carbonylfunktion mit den Aminofunktionen der Seitenketten wie Lysin oder Arginin, da sie in vielen Lebensmitteln oder physiologischen Proteinen die größte Quelle an Aminofunktionen darstellen. Dagegen wurde eine vergleichbare Reaktion mit dem N-Terminus von Aminosäuren, Peptiden oder Proteinen weniger beachtet, obgleich in lysinarmen oder peptidhaltigen Lebensmitteln die N-terminalen Aminofunktionen dominieren und die Seitenketten körpereigener Proteine räumlich für einen Angriff der Carbonylfunktion unzugänglich sein können.
Da in den HA-Nahrungen die allergieauslösenden Proteine hydrolytisch gespalten vorliegen, stehen für eine mögliche Amadori-Produktbildung gegenüber den konventionellen Säuglingsnahrungen quantitativ mehr alpha-Aminogruppen als epsilon-Aminogruppen zur Verfügung. Demzufolge sollte für die Beurteilung von HA-Nahrungen eine Methode entwickelt werden, mit deren Hilfe eine Aussage über die Amadori-Produktbildung auch am N-Terminus getroffen werden kann. Aufbauend auf den Ergebnissen der Furoylmethylderivate-Bestimmung (FMAA-Bestimmung) in peptidhaltigen Lebensmitteln, war es ein weiteres Ziel der vorliegenden Dissertation die entwickelte Methode auch auf ihre Anwendbarkeit auf die Beurteilung des Glykierungsstatus des Hämoglobin in vivo zu testen. Nach der N-terminalen Amadori-Produktbildung im Zuge der frühen Phase der Maillard-Reaktion lag im zweiten Teil der Dissertation das Hauptaugenmerk auf die fortgeschrittene Phase der Maillard-Reaktion am N-Terminus von Peptiden oder Proteinen. Der Schwerpunkt lag dabei auf der Bildung von 2-(1H)-Pyrazinonen im komplexen trockenen Lebensmittel und in vivo.
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Infant Anemia and Micronutrient Status : Studies of Early Determinants in Rural BangladeshEneroth, Hanna January 2011 (has links)
Anemia and micronutrient deficiencies in infancy are common in low-income settings. These are partly due to maternal malnutrition and may impair child health and development. We studied the impact of maternal food and micronutrient supplementation, duration of exclusive breastfeeding (EBF), growth and infection on infant anemia and micronutrient status. In the MINIMat trial in Matlab, Bangladesh, pregnant women were randomized to Early or Usual promotion of enrolment in a food supplementation program and to one of three daily micronutrient supplements. Capsules containing 400µg folic acid and (a) 30 mg iron (Fe30Fol), (b) 60 mg iron (Fe60Fol), (c) 30 mg iron and other micronutrients (MMS) were provided from week 14 of gestation. Capsule intake was assessed with the eDEM device recording supplement container openings. Blood samples (n=2377) from women at week 14 and 30 were analyzed for hemoglobin (Hb). Duration of EBF and infant morbidity was based on monthly maternal recalls. Infants were weighed and measured monthly. Blood samples (n=1066) from 6-months-old infants were analyzed for Hb and plasma ferritin, zinc, retinol, vitamin B12 and folate. In women, Hb increase per capsule reached a plateau at 60 Fe60Fol capsules, indicating that nine weeks of daily supplementation produced maximum Hb response. Anemia was common (36%) at capsule intakes >60 indicating other causes of anemia than iron deficiency. In infants, vitamin B12 deficiency prevalence was lower in the MMS (26.1%) than in the Fe30Fol group (36.5%), (p=0.003) and zinc deficiency prevalence was lower in the Usual than in the Early group. There were no other differential effects of food or micronutrient supplementation on infant anemia or micronutrient status. Infants exclusively breast-fed for 4-6 months had a higher mean plasma zinc concentration (9.9±2.3 µmol/L) than infants exclusively breast-fed for <4 months (9.5±2.0 µmol/L), (p< 0.01). No other differences in anemia, iron or zinc status were observed between EBF categories. Infection, low birth weight and iron deficiency were independent risk factors for infant anemia. Regardless of studied interventions, prevalence of anemia (43%), deficiency of zinc (56%), vitamin B12, vitamin A (19%) and iron (22%) in infancy was high and further preventive strategies are needed. / MINIMat
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Marital Status as a Proxy Measure of Social Support and its Influence on Health Status and Depression RatesVogel, Octavia L 04 December 2008 (has links)
Diabetes disproportionately affects minority populations. Social support, and more specifically marriage, has been found to buffer the negative effects of diabetes and depression. Data collected from African Americans with type 2 diabetes in Atlanta and NHANES data were compared to examine whether marriage affects health status and mental health. Approximately, 1742 African Americans aged 18-80 were included in this study. Chi square analysis revealed that married men had lower rates of depression (15.9% vs. 24.7%) compared to unmarried men (p < 0.05), but the same effect was not found in women. The findings show that marriage was not associated with HbA1c, but was associated with rates of depression. The lack of association of HbA1c with marriage may be because marriage may not be the best proxy of social support in the African American community. Future research should focus on alternative forms of social support such as cohabitation, extend family, and friend.
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Développement d’un système de spectroscopie infrarouge résolue temporellement pour la quantification des concentrations d’hémoglobine cérébraleLeclerc, Paul-Olivier 11 1900 (has links)
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.
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Drug use and side effects in the elderly : findings from the Kungsholmen Project /Passare, Galina, January 2005 (has links)
Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 5 uppsatser.
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Fatores associados à prevalência de anemia em crianças menores de cinco anos do estado de Alagoas, Brasil. / Prevalence and risk factors associated with anemia in children of the State of Alagoas, Brazil.Vieira, Regina Coeli da Silva 22 November 2007 (has links)
This work was based on a study of the epidemiological anemia and its importance as a
public health problem in Brazil, particularly in Alagoas and it was inspired and drafted
from the submission of two articles. The first, for review, aimed to systematize the
results of studies published in Brazilian children in the last 10 years in order to provide
estimates of prevalence at the different scenarios where they were made: nursery
schools (ESC), health services (SAU), stocks inequities (INI) and population-based
studies (POP). The results of the 35 selected articles are presented like: prevalence
weighted average (range); ratio of chances, and POPs data as reference (at a confidence
interval of 95%) were ESC: 52.0% (35.0 to 68.8%), 1.21 (1.11 - 1.33), SAU: 64.5%
(55.1 to 89.1%), 2.19 (1.90-2.53), INI: 66.2% (47.5 to 96.4%), 2.03 (1.87-2.21) and
POP: 47.2% (22.2 to 55.6%), P <0.0001 for all comparisons (χ2). Attention was called
to the fact that the prevalence observed among INI was that found at SAU, both
significantly higher than observed in the POP studies, lower medium prevalence, (p
<0.05). The medium prevalence measured in the context of ESC, although small than
the SAU, was significantly above in relation to those verified in the studies of a wider
population (p <0.05), suggesting that the professionals of such areas need to implement
strategies to reduce the problem. From these data, it was concluded that anemia
continues to represent a serious public health problem in this country. The second
article was based on the results of a research conducted in the state of Alagoas, named
Prevalence and factors associated with anemia in children of the state of Alagoas,
Brazil, which was compiled from data obtained in the context of a project entitled
"Diagnosis of the mother and children health in the state of Alagoas." It tried to find out
the prevalence and risk factors relating to anemia in the children of Alagoas. It consisted
of a transversal study with probabilistic sample of children from 6 to 60 months years
old of the state. Through household survey, demographic, socioeconomic,
anthropometric and morbidity information was colleted. The prevalence of anemia was
45.0%. The level of Hb was correlated with age (r = 0.44, P <0.01). The prevalence was
higher in the group of 6 to 12 months (75.2%, OR = 13.9, 95% CI = 6.5-27.9).
Multivariate analysis identified the following variables associated to anemia: children's
age ≤ 36 months (P = 0.012), diarrhoea in the last 15 days (P = 0.011), no
supplementation of retinol (P = 0.027), residences with five or more people (P = 0.032)
and lower maternal height (P = 0.044). The prevalence of anemia showed that its
magnitude characterizes an important public health problem. Not only the poor
socioeconomic conditions explain these results, but also the deficiency in health care,
characteristics that should guide public policies for the prevention and control. / Fundação de Amparo a Pesquisa do Estado de Alagoas / Considerando a importância epidemiológica da anemia como problema de saúde pública
no Brasil e, em especial em Alagoas, elaborou-se a presente Dissertação, na qual o tema
é abordado a partir da apresentação de dois artigos. O primeiro, de revisão, teve por
objetivo sistematizar os resultados de estudos em crianças brasileiras publicados nos
últimos 10 anos, de modo a propiciar estimativas de prevalência conforme os diferentes
cenários onde foram realizados: creches/escolas (ESC), serviços de saúde (SAU),
populações em iniqüidades (INI) e estudos de base populacional (POP). Os resultados
dos 35 artigos selecionados estão assim apresentados: prevalência média ponderada
(amplitude); razão de chances, tendo os dados de POP como referência (intervalo de
confiança a 95%), foram ESC: 52,0% (35,0 a 68,8%); 1,21 (1,11-1,33), SAU: 64,5%
(55,1 a 89,1%); 2,19 (1,90-2,53), INI: 66,2% (47,5 a 96,4%); 2,03 (1,87-2,21) e POP:
47,2% (22,2 a 55,6%) com P < 0,0001 para todas as comparações (χ2). Chamou a
atenção o fato da prevalência observada entre INI ter sido semelhante à encontrada em
SAU, ambas significativamente superiores à observada nos estudos de POP, menor
prevalência média, (p<0,05). A prevalência média aferida no contexto de ESC, embora
inferior a dos SAU, situou-se significativamente acima da verificada nos estudos de
maior abrangência populacional (p<0,05), sugerindo que os profissionais desses espaços
precisam implementar estratégias de atenção ao problema. A partir desses dados,
concluiu-se que a anemia continua a representar um grave problema de saúde pública
neste País. O segundo baseado em resultados de investigação conduzida no estado de
Alagoas, denominado Prevalência e fatores associados à anemia em crianças do estado
de Alagoas, Brasil, foi elaborado a partir de dados obtidos no contexto de um projeto
intitulado Diagnóstico de saúde da população materno-infantil do estado de Alagoas .
Teve por objetivo conhecer a prevalência e os fatores de risco associados à anemia em
crianças do estado de Alagoas. Consistiu em estudo transversal com amostra
probabilística das crianças de 6 a 60 meses do Estado. Por meio de inquérito domiciliar,
coletaram-se informações demográficas, socioeconômicas, antropométricas e de
morbidade. A prevalência de anemia foi de 45,0%. O nível de Hb se correlacionou à
idade (r=0,44; P<0,01). A prevalência máxima ocorreu na faixa etária de 6 a 12 meses
(75,2%; RC=13,9; IC95%=6,5-27,9). A análise multivariada identificou as seguintes
variáveis associadas à anemia: idade da criança ≤ 36 meses (P=0,012), diarréia nos
últimos 15 dias (P=0,011), não suplementação com retinol (P=0,027), domicílio com
cinco ou mais pessoas (P=0,032) e menor estatura materna (P=0,044). A prevalência de
anemia apresentou magnitude que a caracteriza como importante problema de saúde
pública. Não somente as precárias condições socioeconômicas explicam esses
resultados, mas também a deficiência na assistência à saúde, características que devem
nortear as políticas públicas de prevenção e controle.
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Hidroperóxidos de lipídios como fontes de oxigênio molecular singlete (O2 [1Δg]), detecção e danos em biomoléculas / Lipid hidroperoxides as singlet molecular oxygen precursors (O2 [1Δg]), detection and damage to biomoleculesJosé Pedro Friedmann Ângeli 21 July 2011 (has links)
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.
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Avaliação do efeito da intervenção farmacêutica no controle da glicemia de pacientes ambulatoriais portadores do diabetes mellitus tipo 2Mendonça, Juliana Maria Dantas 12 June 2013 (has links)
Diabetes mellitus (DM) is a syndrome of multiple etiologies resulting from lack of insulin and / or the inability of insulin properly exercise its effects. It is considered the world, a public health problem by the position it occupies with high epidemiological incidence and prevalence, besides causing macrovascular and microvascular complications. The DM has two main forms, type 1 (DM1), which appears mostly in childhood or adolescence and type 2 (DM2), the most frequent, accounting for 85% to 90% of cases, usually of insidious onset, especially after 40 years of age, affecting obese individuals in 90% of the time. Cardiovascular diseases (CVD) are responsible for approximately 52% of deaths of patients with DM. The strategy of prevention of these chronic complications essentially depend on the adequate control of blood glucose and other comorbidities, including dyslipidemia and hypertension (SAH). This ivestigação was conducted to evaluate the effect of pharmaceutical intervention on glycemic control in outpatients suffering from DM2.Trata is a longitudinal study with intervention, using 100 subjects during query consecutively diagnosed with DM2 in private clinic endocrinology from May 2011 to February 2012. All patients answered a questionnaire and underwent pharmaceutical intervention, conducted by the researcher. After this intervention, there was a significant reduction of 45% CI 95% in A1C levels. Thus, there was still improvement in outcomes among women (69%) (p = 0.01) and the following parameters: fasting glucose (p = 0.000), frequency of exercise (p = 0.0001), adoption of low-calorie diet (p = 0.0001), adherence to drug therapy (p = 0.024) and BMI (p = 0.012). / O diabetes mellitus (DM) é uma síndrome de etiologia múltipla decorrente da falta de insulina e/ou da incapacidade da insulina exercer adequadamente seus efeitos. É considerado, mundialmente, um problema de saúde pública pela posição epidemiológica que ocupa com altas taxas de incidência e prevalência, além de acarretar complicações macrovasculares e microvasculares. O DM apresenta duas formas principais, o tipo 1 (DM1), que aparece principalmente na infância ou na adolescência e o tipo 2 (DM2), a mais freqüente, responsável por 85% a 90% dos casos, geralmente de instalação insidiosa, principalmente após os 40 anos de idade, acometendo indivíduos obesos em 90% das vezes. As doenças cardiovasculares (DCV) são responsáveis por aproximadamente 52% das mortes dos portadores de DM. A estratégia de prevenção destas complicações crônicas dependem, fundamentalmente, do adequado controle da glicemia e de outras comorbidades, entre elas a dislipidemia e a hipertensão arterial sistêmica (HAS). A presente ivestigação foi conduzida visando avaliar o efeito da intervenção farmacêutica no controle da glicemia de pacientes ambulatoriais portadores de DM2.Trata-se de um estudo longitudinal com intervenção, utilizando-se 100 sujeitos durante consulta, consecutivamente, com diagnóstico de DM2 em ambulatório privado de endocrinologia no período de maio de 2011 a fevereiro de 2012. Todos os voluntários responderam a um questionário e sofreram intervenção farmacêutica, realizada pelo pesquisador. Após esta intervenção, ocorreu uma redução significativa de 45% IC 95% nos níveis de A1C. Diante disso, observou-se ainda melhora nos resultados entre as mulheres (69%) (p=0,01) e nos seguintes parâmetros: glicemia de jejum (p=0,000), frequência de exercícios físicos (p=0,0001), adoção da dieta hipocalórica (p= 0,0001), adesão à terapia medicamentosa (p= 0,024) e IMC (p= 0,012).
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Detecção e caracterização molecular de talassemia alfa / Detection and molecular characterization of alpha thalassemiaPENNA, Karlla Greick Batista Dias 27 March 2009 (has links)
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Previous issue date: 2009-03-27 / Alpha thalassemia is a syndrome resulting from disturbances in the synthesis of alpha globin chain that forms the tetramer of the hemoglobin molecule. Alpha thalassemia is classified into four types according to the number of alpha genes affected: silent carrier (-α/αα), alpha thalassemia trait (--/αα or -α/-α) Hemoglobin H disease (-- /-α), and fetalis hydrops (--/--). The decrease in synthesis of alpha globin causes inadequate production of hemoglobin resulting in hypochromic and microcytic anaemia. Also it causes accumulation of beta chains, inside the erythrocytes, resulting in formation of beta chain tetramer of hemoglobin called Hb H. Clinically the individual with thalassemia can be asymptomatic or present
severe anemia. Asymptomatic forms of thalassemia, silent carrier and alpha thalassemia trait, are more difficult to diagnose because of the inclusions bodies of Hb H are not always present. In these situations it is necessary to research
the molecular characterization of the genotype and confirming the presence of alpha thalassemia. This is mainly because the diagnosis by conventional methods, although important, is limited and imprecise. This study evaluated some of the traditional laboratory methods in the detection of alpha thalassemia and associated molecular characterization of the more prevalent deletion forms α3,7 and α4,2. For confirmation and characterization of alpha thalassemia, new oligonucleotides were designed. By conventional PCR technique, using 3.7F/KGB01 primers it was possible to detect the deletion α3,7, differentiating the normal genotype (αα/αα), the heterozygote (-α3,7/αα), and homozygous (-- α3,7/- α3,7). Although it was designed to detect the deletion α3,7, this primers also identified the deletion α4,2 when in homozigose (-α4,2/- α4,2). The primers KGB04/KGB05 detected the deletion α4,2, but without differentiating between the heterozygous and homozygous genotype. The most prevalent deletion founded was the α4,2 (20.0%) which represents 9.2% in the homozygous form (- α4,2/-α4,2). The deletion α3,7 in the heterozygous form was detected in 12.3% of patients. The data demonstrate that the importance of molecular detection for alpha thalassemia is not limited only to the definition of the genotype, but also confirmation of the presence in patients with abnormal erythrogram values, with
regular erythrogram values, with values closed to the boundary values and in neonates. / A talassemia alfa é uma síndrome resultante de distúrbios na síntese da cadeia da globina alfa que formam o tetrâmero da molécula da hemoglobina. A talassemia alfa é classificada em quatro tipos de acordo com o número de genes alfa afetado: portador silencioso (-α/αα); traço alfa talassêmico (--/αα ou -
α/-α); doença de hemoglobina H (--/-α) e hidropsia fetal (--/--). A diminuição na síntese de globina alfa causa a produção inadequada de hemoglobina que resulta em anemia microcítica e hipocrômica. Causa também o acúmulo de cadeias do tipo beta, no interior do eritrócito, pela falta de balanceamento com a síntese da globina alfa afetada. O resultado deste desbalanceamento é a formação de tetrâmeros de cadeias beta denominados Hb H. Clinicamente o indivíduo portador de talassemia alfa pode ser assintomático ou apresentar
anemia severa. As formas assintomáticas da talassemia alfa, o portador silencioso e o traço alfa talassêmico, são mais difíceis de diagnosticar, pois os corpúsculos de Hb H nem sempre estão presentes. Para estas situações faz-se
necessária a investigação molecular visando a caracterização do genótipo e a confirmação da presença da talassemia alfa. Este fato se deve principalmente porque o diagnóstico através de métodos clássicos não moleculares, apesar de
importantes, é limitado e impreciso. O presente trabalho avaliou alguns dos métodos laboratoriais clássicos na detecção de talassemia alfa e associou a caracterização molecular das formas delecionais mais prevalentes α3,7 e α4,2.
Para a confirmação e caracterização da talassemia alfa, foram desenhados novos oligonucleotídeos. Através da técnica convencional da PCR, utilizando o par de oligonucleotídeos 3.7F/KGB01 foi possível detectar a deleção α3,7, diferenciando o genótipo normal (αα/αα), do heterozigoto ( α3,7/αα) e do homozigoto ( α3,7/ α3,7). Apesar de ter sido desenhado para detectar a deleção α3,7, este par também permitiu detectar a deleção α4,2 quando em homozigose (
α4,2/ α4,2). Utilizando o par KGB04/KGB05 foi possível detectar a deleção α4,2, porém sem diferenciar entre o genótipo heterozigoto e homozigoto. A deleção mais prevalente encontrada foi a α4,2 (20,0%) sendo que destas podemos afirmar que 9,2% estão na forma homozigótica ( α4,2/ α4,2). A deleção do tipo α3,7 na forma heterozigótica foi detectada em 12,3% dos pacientes. Os dados obtidos revelam que a importância da detecção molecular para talassemia alfa não se restringe apenas na definição do genótipo, mas também na detecção deste tipo de talassemia em pacientes que apresentam: quadros hematológicos
alterados, quadros hematológicos normais, mas com valores próximos aos valores limítrofes e em neonatos.
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The trypanosome lytic factor of human serum, a Trojan horseVanhollebeke, Benoît 01 December 2008 (has links)
The trypanolytic factor of human serum :a trojan horse.<p><p><p>African trypanosomes, the prototype of which is Trypanosoma brucei, are protozoan parasites of huge clinical, veterinary and economical importance. They develop in the body fluids of various mammals (including humans) where they face and manipulate many different aspects of the immune system. The extent of this interplay is pivotal to both host and parasite survival, and depending on parasite virulence and host susceptibility, infection duration ranges from some months to several years. At the end, host survival is invariably compromised.<p><p>Humans and few other primates provide however a striking exception to this fatal outcome. They are indeed fully protected against most trypanosome infections through the presence in their blood of a so-called trypanosome lytic factor (TLF). The TLF is known to circulate mainly in the form of a high density lipoprotein particle characterized by the simultaneous presence of two primate-specific proteins: haptoglobin-related protein (Hpr) and apolipoprotein L-I (apoL-I).<p><p>We have contributed to delineate the respective roles played by Hpr and apoL-I in the lysis process.<p><p>ApoL-I was shown to be the exclusive toxin of the TLF. In its absence humans get fully susceptible to any trypanosome infection. The toxin was shown to kill the parasite after endocytosis through the generation of ionic pores in the lysosomal membrane. Those pores dissipate membrane potential and trigger the influx of chloride ions from the cytoplasm into the lysosomal compartment, leading to an eventually fatal uncontrolled osmotic phenomenon. <p><p>ApoL-I efficient delivery to the parasite relies on Hpr. African trypanosomes indeed fulfil their heme nutritional requirements by receptor-mediated internalization of the complex formed by haptoglobin, an evolutionary conserved acute-phase protein, and hemoglobin, resulting from physiological intravascular hemolysis. This heme uptake by the auxotrophic parasites contributes to both growth rate and resistance against host oxidative burst. In human serum, the trypanosome receptor is unable to discriminate between Hp and the closely related TLF-bound Hpr, explaining TLF efficient endocytosis.<p><p>As such, the TLF acts as a Trojan horse, killing the parasite from inside the cell after having deceived its vigilance through the high similarity between heme-delivering haptoglobin and toxin-associated Hpr. <p> / Doctorat en Sciences / info:eu-repo/semantics/nonPublished
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