Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-07-12T20:15:55Z No. of bitstreams: 1 eduardomachadovilela.pdf: 1157415 bytes, checksum: b9b18ff494ea641d0302b3253fc2dc7f (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-07-13T16:54:31Z (GMT) No. of bitstreams: 1 eduardomachadovilela.pdf: 1157415 bytes, checksum: b9b18ff494ea641d0302b3253fc2dc7f (MD5) / Made available in DSpace on 2016-07-13T16:54:31Z (GMT). No. of bitstreams: 1 eduardomachadovilela.pdf: 1157415 bytes, checksum: b9b18ff494ea641d0302b3253fc2dc7f (MD5) Previous issue date: 2011-05-12 / Este é um estudo de intervenção clínica controlado. O propósito do presente estudo foi avaliar o impacto do tratamento periodontal (TP) sobre marcadores sistêmicos da inflamação e determinar uma associação entre pró-hepcidina (pró-hormônio da hepcidina) e periodontite crônica (PC) em pacientes com doença renal crônica (DRC) que ainda não foram submetidos à diálise. Nesse estudo foram incluídos 56 pacientes com PC moderada a severa, sendo 36 com DRC (grupo DRC) e 20 sem doença sistêmica e com função renal normal (grupo controle). A DRC foi definida de acordo com K/DOQI da National Kidney Foundation. A PC foi definida segundo a Associação Americana de Periodontia (AAP) pelo nível de inserção clínica (NIC) e profundidade de sondagem (PS). Os participantes receberam tratamento periodontal não cirúrgico e os marcadores inflamatórios, proteína C-reativa ultrassensível (PCRus), interleucina-6 (IL-6) e pró-hepcidina foram avaliados antes do TP e três meses após. Os resultados obtidos comprovaram a eficácia do TP com a redução significativa dos valores de NIC e PS no grupo controle (2,37±0,40 vs. 2,02± 0,43, p <0,05 e 2,52±0,41 vs. 1,98± 0,40, p <0,05) e no grupo DRC (2,92±0,92 vs. 2,20± 0,65, p <0,05 e 2,90±1,13 vs. 1,99± 0,82, p <0,05). O TP resultou em uma diminuição estatisticamente significativa nos níveis de PCR-us e IL-6 em ambos os grupos. Adicionalmente, houve uma queda significativa na dosagem sérica de próhepcidina (ng/mL) após o TP tanto no grupo controle (147,39±51,50 vs. 131,72±47,10, p <0,05) quanto no grupo com DRC (166,24±55,70 vs. 153,29±56,90, p <0,05). Além disso, no modelo de regressão linear multivariada, a redução dos níveis de pró-hepcidina após TP foi significativamente e independentemente associada com níveis de IL-6 (p=0,02) no grupo controle. Portanto, concluiu-se que a PC moderada a severa em pacientes com DRC, pode determinar aumento da resposta inflamatória sistêmica. O TP eficaz pode induzir um declínio dessa carga inflamatória sistêmica e uma diminuição na pró-hepcidina sérica. Esta terapia pode constituir uma importante intervenção na melhoria da inflamação observada em pacientes com DRC. / This is an interventional controlled clinical assay. The aim of this study was to determine the impact of periodontal treatment (PT) on the systemic markers of inflammation and to determine a correlation betwen serum level of prohepcidin (prohormone of hepcidin) and chronic periodontitis (CP) in patients with chronic kidney disease (CKD) who were not yet under dialysis. This study included 56 patients with CP moderate to severe, 36 with CKD (CKD group) and 20 without systemic diseases and with normal renal function (control group). CKD was defined as suggested by the K/DOQI of National Kidney Foundation. CP was defined by the clinical attachment level (CAL) and the probing pocket depth (PPD), according to the American Association of Periodontology (AAP). The participants received no surgical periodontal treatment and inflammatory markers ultrasensitive C-reactive protein (us- PCR), interleukin-6 (IL-6), and prohepcidin were evaluated before and 3 months after PT. The results proven effective PT was by measuring decreases in CAL and PPD following PT in the control (2,37±0,40 vs. 2,02± 0,43, p <0,05 and 2,52±0,41 vs. 1,98± 0,40, p <0,05), and CKD groups (2,92±0,92 vs. 2,20± 0,65, p <0,05 and 2,90±1,13 vs. 1,99± 0,82, p <0,05). PT resulted in a statistically significant reduction in us-PCR and IL-6 levels in both groups. Additionally, there was a significant fall in serum prohepcidin (ng/mL) after PT in the control group (147.39±5150 vs. 131.72±47.10, p<0.01) and CKD group (166.24±55.70 vs. 153.29±56.90, p<0.05). Moreover, in multivariated linear regression, the reduction of prohepcidin levels after PT was significantly and independently associated with IL-6 levels (p=0.02) in the control group. However, in conclusion CP moderate to severe in patients with CKD, can determine increase in the systemic inflammatory response. Successful PT, by inducing a decline in the systemic inflammatory burden and a decrease in serum prohepcidin. This terapy might constitute an important intervention in ameliorating of the inflammation seen in patients with CKD.

Anemia in Leptospira interrogans infected individuals is one of the most common complications found in the severe form of the disease. Iron plays an important role in the hematopoietic processes; however, its precise metabolism on individuals with leptospirosis is still unknown. Therefore, the aim of this study was to analyze the classic iron markers associated to the storage process in hamsters experimentally infected by L. interrogans serovar Pomona (virulent strain LPF). Four groups with six hamsters each were used; two groups were controls (C7 and C14) and two were experimental groups with infected animals (T7 and T14). Blood samples were collected on the seventh (C7 and T7) and fourteenth days (C14 and T14) post-inoculation (PI). Iron availability was determined in sera samples by the assessment of iron, ferritin, transferrin, and iron binding capacity, whereas the bone marrow was also evaluated for the deposition of this metal by Pearl s reaction. Additionally, the total antioxidant capacity (TAC) and total oxidant status (TOS) were assessed, along with hepcidin and IL-6 levels to be involved in iron metabolism. Based on the results, it was possible to observe the onset of an acute condition with crisis hemolytic and regenerative response. The other parameters showed an increase in seric iron, ferritin, as well as a positive Pearl s reaction in animals from the groups T7 and T14 compared with the control groups. Transferrin levels decreased in animals from the group T14 with saturation index, but without statistical difference among all tested groups. TAC was increased in both periods, while TOS was increased only on day 14 PI. Hepcidin and IL-6 were statistically increased on days 7 and 14 PI. Therefore, it was observed that the serum profile from infected animals showed a strong hemolytic pattern, with some demonstration of ferric tissue sequestration. The results show that iron metabolism is activated in hamsters infected by L. interrogans sorovar Pomona, and therefore has participation in the pathogenesis of the disease. / A ocorrência de anemia em indivíduos infectados por Leptospira interrogans é uma das complicações decorrentes à doença em sua forma mais severa. O ferro tem um papel importante nos processos hematopoiéticos, no entanto, o seu metabolismo preciso em indivíduos com leptospirose ainda é desconhecido. Portanto, o objetivo deste trabalho foi analisar os marcadores clássicos relativos à reserva de ferro no organismo de hamsters experimentalmente infectados com L. interrogans sorovar Pomona, estirpe virulenta LPF. Para isto, foram utilizados 24 hamsters machos, distribuídos em quatro grupos, sendo dois grupos Controles (C7 e C14) e dois Testes (T7 e T14), com 6 animais em cada grupo. Amostras de sangue foram coletadas no sétimo (Grupos C7 e T7) e no décimo quarto dias pós-inoculação (Grupos C14 e T14). A disponibilidade de ferro foi determinada no soro, pela dosagem de ferro sérico, ferritina, transferrina e capacidade de ligação do ferro, ao passo que a medula óssea também foi quantificada quanto à deposição de ferro, através da reação de Pearls. Além disso, a capacidade antioxidante total (CAT) e status total de oxidantes (TOS) foram avaliados, em conjunto com hepcidina e os níveis de IL-6, por serem variáveis envolvidas no metabolismo do ferro. Com os resultados, foi possível observar a instalação de um quadro agudo com crise hemolítico-regenerativa. Nos demais parâmetros, encontrou-se uma elevação do ferro sérico, ferritina, e da positividade na Reação de Pearls, nos dois grupos teste em relação aos controles. A transferrina apresentou uma redução no grupo T14, com índices de saturação, no entanto, sem diferença estatística entre os grupos. Capacidade antioxidante total foi aumentada em ambos os períodos , enquanto TOS foi aumentada apenas no dia 14 PI . Hepcidina e IL-6 foram significativamente elevados nos dias 7 e 14 de PI . Portanto , observou-se que o perfil sérico de animais infectados apresentam um forte padrão hemolítico, com alguma demonstração de sequestro tecidual férrico. Os resultados mostram que o metabolismo do ferro é alterado em hamsters infectados por L. interrogans sorovar Pomona, e que, portanto, tem participação na patogenia da doença.

Background Due to small iron stores and rapid growth during the first months of life, infants with low birth weight (LBW) are at risk of iron deficiency (ID). ID in infancy is associated with irreversible impaired neurodevelopment. Preventive iron supplementation may reduce the risk of ID and benefit neurodevelopment, but there is also a possible risk of adverse effects. More than 50% of all LBW infants are born with marginally LBW (MLBW, 2000-2500g), and it is not known if they benefit from iron supplementation. Methods We randomized 285 healthy, Swedish, MLBW infants to receive 3 different doses of oral iron supplements; 0 (Placebo), 1, and 2 mg/kg/day from six weeks to six months of age. Iron status, during and after the intervention was assessed and so was the prevalence of ID and ID anemia (IDA), growth, morbidity and the interplay with iron and the erythropoetic hormones hepcidin and erythropoietin (EPO). As a proxy for conduction speed in the developing brain, auditory brainstem response (ABR) was analyzed at six months. In a follow up at 3.5 years of age, the children were assessed with a cognitive test (WPPSI-III) and a validated parental checklist of behavioral problems (CBCL), and compared to a matched reference group of 95 children born with normal birth weight. Results At six months of age, the prevalence of ID and IDA was significantly higher in the placebo group compared to the iron supplemented infants. 36% had ID in the placebo group, compared to 8% and 4 % in the 1 and 2mg/kg/day-groups, respectively. The prevalence of IDA was 10%, 3% and 0%, respectively. ABR-latencies did not correlate with the iron intake and was not increased in infants with ID or IDA. ABR wave V latencies were similar in all three groups. Hepcidin correlated to ferritin and increased in supplemented infants while EPO, which was negatively correlated to iron status indicators, decreased. At follow up there were no differences in cognitive scores between the groups but the prevalence of behavioral problems was significantly higher in the placebo group compared to those supplemented and to controls. The relative risk increase of CBCL-scores above a validated cutoff was 4.5 (1.4 – 14.2) in the placebo-group compared to supplemented children. There was no detected difference in growth or morbidity at any age. Conclusion MLBW infants are at risk of ID in infancy and behavioral problems at 3 years of age. Iron supplementation at a dose of 1-2 mg/kg/day from six weeks to six months of age reduces the risks with no adverse effects, suggesting both short and long term benefit. MLBW infants should be included in general iron supplementation programs during their first six months of life.

No description available.

L’infarctus du myocarde (IDM) résulte des complications de l’athérosclérose, dont le développement serait initié par une dysfonction endothéliale, s’accompagnant d’un état de stress oxydant. Le fer interagirait dans cette pathogenèse à différents niveaux et aurait également un rôle majeur dans la survenue de la dysfonction endothéliale. L’hepcidine et l’érythroferrone (découverte auparavant sous le nom de myonectine/CTRP 15), participeraient dans la régulation de certaines étapes du métabolisme du fer. La diméthyl-arginine asymétrique (ADMA), marqueur de dysfonction endothéliale, est associée à la plupart des facteurs de risque cardiovasculaire. Son stéréo-isomère, la diméthyl-arginine symétrique (SDMA), a une élimination exclusivement rénale et est considéré comme un puissant marqueur de fonction rénale.Nous nous sommes proposés d’étudier, chez des patients en phase aiguë d’IDM, la signification des paramètres traditionnels du statut du fer, des protéines impliquées dans la régulation du fer, l’hepcidine et la myonectine, ainsi que des dérivés méthylés de la L-arginine, l’ADMA et la SDMA.Dans notre première étude prospective, nous observons que les valeurs de SDMA, et dans une moindre mesure celles d'ADMA, sont associées à la glycémie d'admission et pourraient donc exercer des actions biologiques indépendantes de la fonction rénale. Notre second travail suggère que les patients présentant de l’insuffisance cardiaque à la phase aiguë de l’IDM sont caractérisés par une anémie et un certain degré de carence en fer. Le dosage des nouveaux biomarqueurs de la régulation du métabolisme du fer, l'hepcidine et la myonectine a montré une tendance à l’augmentation de ces taux sériques chez ces patients en lien avec une augmentation de la CRP. Ainsi nos travaux laissent entrevoir les liens qui uniraient, à la phase aiguë de l’infarctus du myocarde, ces nouveaux biomarqueurs régulateurs du métabolisme du fer aux conséquences fonctionnelles des pathologies cardiovasculaires, notamment en termes d’anémie et d’insuffisance cardiaque. / Myocardial infarction (MI) is mostly caused by complications of atherosclerosis, whose the development would be initiated by a dysfunction of the vascular endothelium, characterized by an inflammatory condition and oxidative stress.In this pathogenesis, iron interacts at different levels and also has a major role in the development of endothelial dysfunction. Hepcidin and erythroferrone (discovered earlier as the myonectin/CTRP 15) participate in a major way in regulating certain stages of iron metabolism.Asymmetric dimethylarginine (ADMA), a marker of endothelial dysfunction is associated with most cardiovascular risk factors. Symmetrical dimethyl-arginine (SDMA), its stereoisomer, has an exclusively renal elimination and is considered as a powerful renal function marker.We aimed to study, in patients with acute MI, the meaning of the "traditional" status iron parameters, two proteins involved in the regulation of iron, hepcidin and myonectin, as well as the two L-arginine derivatives, ADMA and SDMA. In our first prospective study, we observe that, in patients with acute MI, the values of SDMA, and only weakly ADMA, are associated with admission blood glucose, beyond traditional dimethylarginine determinants and may therefore have biological activity beyond renal function.Our second work suggests that patients with heart failure in the acute phase of MI present more frequently anemia and a certain degree of iron deficiency. New iron metabolism regulators biomarkers, hepcidin and myonectin showed a trend toward an increase in the serum levels in these patients characterized by an increase in CRP.Thus, our work suggests the links between these new regulators of iron metabolism in acute MI with functional consequences of cardiovascular diseases, particularly in terms of anemia and heart failure.