451 resultados para Heme.
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Bioinorganic Chemistry and Applications Volume 3 (2005), Issue 1-2, Pages 81-91
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Plasmodium parasites degrade host hemoglobin to obtain free amino acids, essential for protein synthesis. During this event, free toxic heme moieties crystallize spontaneously to produce a non-toxic pigment called hemozoin or ß-hematin. In this context, a group of azole antimycotics, clotrimazole (CTZ), ketoconazole (KTZ) and fluconazole (FCZ), were investigated for their abilities to inhibit ß-hematin synthesis (IßHS) and hemoglobin proteolysis (IHbP) in vitro. The ß-hematin synthesis was recorded by spectrophotometry at 405 nm and the hemoglobin proteolysis was determined by SDS-PAGE 12.5%, followed by densitometric analysis. Compounds were also assayed in vivo in a malaria murine model. CTZ and KTZ exhibited the maximal effects inhibiting both biochemical events, showing inhibition of β-hematin synthesis (IC50 values of 12.4 ± 0.9 µM and 14.4 ± 1.4 µM respectively) and inhibition of hemoglobin proteolysis (80.1 ± 2.0% and 55.3 ± 3.6%, respectively). There is a broad correlation to the in vivo results, especially CTZ, which reduced the parasitemia (%P) of infected-mice at 4th day post-infection significantly compared to non-treated controls (12.4 ± 3.0% compared to 26.6 ± 3.7%, p = 0.014) and prolonged the survival days post-infection. The results indicated that the inhibition of the hemoglobin metabolism by the azole antimycotics could be responsible for their antimalarial effect.
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Dissertation presented to obtain the Ph.D degree in Biology
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Inorganic Chemistry 50(21):10600-7
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J Biol Inorg Chem (2011) 16:1241–1254 DOI 10.1007/s00775-011-0812-9
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Protein Sci. 2009 Mar;18(3):619-28. doi: 10.1002/pro.69.
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J Biol Inorg Chem (2008) 13:1185–1195 DOI 10.1007/s00775-008-0414-3
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J Biol Inorg Chem (2008) 13:1321–1333 DOI 10.1007/s00775-008-0416-1
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Acc. Chem. Res., 2006, 39 (10), pp 788–796 DOI: 10.1021/ar050104k
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J Biol Inorg Chem (2006) 11: 548–558 DOI 10.1007/s00775-006-0104-y
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Biochemistry, 2004, 43 (46), pp 14566–14576 DOI: 10.1021/bi0485833
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Eur. J. Biochem. 270, 3904–3915 (2003) doi:10.1046/j.1432-1033.2003.03772.x
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Dissertação para obtenção do Grau de Doutor em Bioquímica, ramo de Biotecnologia
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Introduction. This study aims to compare the molecular gene expression during ischemia reperfusion injury. Several surgical times were considered: in the beginning of the harvesting (T0), at the end of the cold ischemia period (T1), and after reperfusion (T2) and compared with graft dysfunction after liver transplant (OLT). Methods. We studied 54 patients undergoing OLT. Clinical, laboratory data, and histologic data (Suzuki classification) as well as the Survival Outcomes Following Liver Transplantation (SOFT) score were used and compared with the molecular gene expression of the following genes: Interleukin (IL)-1b, IL-6, tumor necrosis factor-a, perforin, E-selectin (SELE), Fas-ligand, granzyme B, heme oxygenase-1, and nitric oxide synthetase. Results. Fifteen patients presented with graft dysfunction according to SOFT criteria. No relevant data were obtained by comparing the variables graft dysfunction and histologic variables. We observed a statistically significant relation between SELE at T0 (P ¼ .013) and IL-1b at T0 (P ¼ .028) and early graft dysfunction. Conclusions. We conclude that several genetically determined proinflammatory expressions may play a critical role in the development of graft dysfunction after OLT.
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As porfírias são um conjunto de doenças metabólicas raras que resultam, maioritariamente, de um defeito geneticamente programado das enzimas da biossíntese do grupo heme. As manifestações clínicas são muito variáveis, assim como a sua gravidade e prognóstico. A fotossensibilidade é característica das porfírias cutâneas. O diagnóstico diferencial pode ser difícil devido à inespecificidade dos sintomas e à sobreposição dos achados laboratoriais. O tratamento ainda é controverso, embora a evicção da exposição solar seja essencial. Neste artigo pretende-se realizar uma revisão teórica sobre as porfírias com manifestações cutâneas em idade pediátrica, enfatizando o diagnóstico e tratamento de cada subtipo.