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Determination of iron-overload in thalassemia by hepatic MRI and ferritin; Determinação da sobrecarga de ferro na talassemia pela IRM hepática e ferritina

ANGULO, Ivan L.; COVAS, Dimas T.; CARNEIRO, Antonio A.; BAFFA, Oswaldo; ELIAS JUNIOR, Jorge; VILELA, Guilherme
Fonte: Associação Brasileira de Hematologia e Hemoterapia e daSociedade Brasileira de Transplante de Medula Óssea Publicador: Associação Brasileira de Hematologia e Hemoterapia e daSociedade Brasileira de Transplante de Medula Óssea
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
66.65%
Accumulation of iron in thalassemia causes organ damage and reduces patient survival due to heart lesions in the second decade of life. Iron deposits are monitored by direct (biopsy) and indirect methods (ferritin) with sequential data being better than isolated measurements. This paper compares two indirect measurements of iron overload; a single hepatic iron concentration (HIC) by magnetic resonance and mean ferritin levels over four years. A retrospective study of 25 patients from the Centro Regional de Hemoterapia in Ribeirão Preto, Brazil was carried out. High HIC (above 7 mg per gram of dry weight) was found in 20 patients and high mean serum ferritin (above 2500 μg/L) in 10 patients. Stratification into three levels (low, moderate and high) of iron overload gave similar results in both tests. Many other factors influence de degree of iron overload in thalassemia. No correlation was found using a non-parametric statistical test between HIC and mean serum ferritin. Both methods provide better planning of chelation therapy.; O acúmulo de ferro na talassemia causa lesões orgânicas e reduz a sobrevida do paciente por lesão cardíaca na segunda década da vida, e tem sido avaliado por medidas diretas (biópsia) e indiretas (ferritina). As medidas isoladas carecem de valor...

HFE gene mutations in patients with primary iron overload: Is there a significant improvement in molecular diagnosis yield with HFE sequencing?

SANTOS, Paulo C. J. L.; PEREIRA, Alexandre C.; CANCADO, Rodolfo D.; SCHETTERT, Isolmar T.; SOBREIRA, Tiago J. P.; OLIVEIRA, Paulo S. L.; HIRATA, Rosario D. C.; HIRATA, Mario H.; FIGUEIREDO, Maria Stella; CHIATTONE, Carlos S.; KRIEGER, Jose E.; GUERRA-SHIN
Fonte: ACADEMIC PRESS INC ELSEVIER SCIENCE Publicador: ACADEMIC PRESS INC ELSEVIER SCIENCE
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
66.6%
Rare HFE variants have been shown to be associated with hereditary hemochromatosis (HH), an iron overload disease. The low frequency of the HFE p.C282Y mutation in HH-affected Brazilian patients may suggest that other HFE-related mutations may also be implicated in the pathogenesis of HH in this population. The main aim was to screen for new HFE mutations in Brazilian individuals with primary iron overload and to investigate their relationship with HH. Fifty Brazilian patients with primary iron overload (transferrin saturation >50% in females and 60% in males) were selected. Subsequent bidirectional sequencing for each HFE exon was performed. The effect of HFE mutations on protein structure were analyzed by molecular dynamics simulation and free binding energy calculations. p.C282Y in homozygosis or in heterozygosis with p.H63D were the most frequent genotypic combinations associated with HH in our sample population (present in 17 individuals, 34%). Thirty-six (72.0%) out of the 50 individuals presented at least one HFE mutation. The most frequent genotype associated with HH was the homozygous p.C282Y mutation (n = 11, 22.0%). One novel mutation (p.V256I) was indentified in heterozygosis with the p.H63D mutation. In silico modeling analysis of protein behavior indicated that the p.V256I mutation does not reduce the binding affinity between HFE and beta 2-microglobulin ((beta 2M) in the same way the p.C282Y mutation does compared with the native HFE protein. In conclusion...

Uncoupling and oxidative stress in liver mitochondria isolated from rats with acute iron overload

ANDREU, G. L. Pardo; INADA, N. M.; VERCESI, A. E.; CURTI, C.
Fonte: SPRINGER Publicador: SPRINGER
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
66.67%
One hypothesis for the etiology of cell damage arising from iron overload is that its excess selectively affects mitochondria. Here we tested the effects of acute iron overload on liver mitochondria isolated from rats subjected to a single dose of i.p. 500 mg/kg iron-dextran. The treatment increased the levels of iron in mitochondria (from 21 +/- A 4 to 130 +/- A 7 nmol/mg protein) and caused both lipid peroxidation and glutathione oxidation. The mitochondria of iron-treated rats showed lower respiratory control ratio in association with higher resting respiration. The mitochondrial uncoupling elicited by iron-treatment did not affect the phosphorylation efficiency or the ATP levels, suggesting that uncoupling is a mitochondrial protective mechanism against acute iron overload. Therefore, the reactive oxygen species (ROS)/H(+) leak couple, functioning as a mitochondrial redox homeostatic mechanism could play a protective role in the acutely iron-loaded mitochondria.; FAPESP, Brasil; ""Red de Macrouniversidades de America Latina y el Caribe""

O papel das mutações do gene HFE  e da sobrecarga de ferro na evolução da hepatite crônica pelo VHC; The role of HFE gene mutations and iron overload in the history of chronic hepatitis C

Silva, Ana Lúcia Bernardes da
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 16/09/2009 PT
Relevância na Pesquisa
66.78%
Introdução: A infecção pelo VHC é uma epidemia de proporções globais, que se torna crônica em cerca de 85% dos indivíduos. Sobrecarga de ferro secundária a mutações HFE vem sendo proposta como fator agravante na evolução da hepatite crônica C. Objetivos: Avaliar se sobrecarga de ferro, mutações no gene HFE estão associadas a progressão da fibrose hepática e a carcinoma hepatocelular (CHC) em portadores crônicos VHC. Casuística e Métodos: De um banco de 2300 pacientes matriculados nos Ambulatórios de Hepatologia e de Transplante Hepático do HCFMUSP, selecionaram-se 320 portadores de hepatite crônica C. Os homens (55,6%) apresentaram 50,8 anos de idade em média e as mulheres 54,3. Obtiveram-se dados clínicos e laboratoriais da época da biópsia hepática, admissionais ou com pelo menos um ano de wash-out do tratamento antiviral. Considerou-se sobrecarga bioquímica níveis de ferro, saturação da transferrina e ferritina acima dos valores de referência. Sobrecarga de ferro tecidual foi identificada pela coloração de Perls graus 3-4. As mutações HFE C282Y e H63D foram pesquisadas pela técnica de PCR em tempo real, em DNA extraído de sangue total, após assinatura de TCLE aprovado pelo comitê de ética local. A fibrose hepática foi considerada avançada para graus 3-4 da classificação SBH/SBP e Metavir (n=167...

Hemocromatose hereditária: associação entre as mutações no gene HFE e o estado de ferro em doadores de sangue e pesquisa de mutações nos genes HFE, HJV, HAMP, TFR2 e SLC40A1 em pacientes com sobrecarga de ferro primária; Hereditary hemochromatosis: relationship between HFE gene mutations and iron status in blood donors and HFE, HJV, HAMP, TFR2 and SLC40A1 gene sequencing in primary iron overload patients

Santos, Paulo Caleb Júnior de Lima
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 21/01/2011 PT
Relevância na Pesquisa
66.62%
A hemocromatose hereditária é caracterizada pelo aumento da absorção intestinal de ferro, acarretando progressivo acúmulo no organismo. Os objetivos foram: 1- determinar as frequências das mutações p.C282Y, p.H63D e p.S65C no gene HFE e avaliar os efeitos nas concentrações dos parâmetros do ferro em doadores de sangue; 2- pesquisar mutações nos genes: 2.1- HFE, 2.2- HJV e HAMP, 2.3- TFR2 e SLC40A1, em pacientes portadores de sobrecarga de ferro primária. Participaram 542 doadores de sangue provenientes do Hemocentro da Santa Casa de São Paulo. Foram incluídos 51 pacientes que apresentavam saturação de transferrina ≥ 50% (para mulheres) e ≥ 60% (para homens) e ausência de causas secundárias. Os genótipos para as mutações nos genes HFE foram avaliados pela PCR-RFLP. Foi realizado sequenciamento direto bidirecional para cada éxon dos genes, utilizando o sequenciador Genetic Analizer 3500XL®. Nos doadores de sangue, as frequências dos alelos HFE 282Y, HFE 63D e HFE 65C foram 2,1, 13,6 e 0,6%, respectivamente. Os homens que doaram pela primeira vez, portadores do genótipo HFE 282CY, apresentaram maiores valores de saturação de transferrina; e também os portadores dos genótipos HFE 63DD e 63HD apresentaram maiores concentrações de ferritina sérica...

Caracterização fenotípica e genotipagem HFE em portadores de doença hepática crônica com sobrecarga de ferro; Phenotypic characteristics and HFE genotyping in patients with liver disease and iron overload

Evangelista, Andréia Silva
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 10/05/2013 PT
Relevância na Pesquisa
66.83%
A doença hepática associada a sobrecarga de ferro pode ocorrer devido a causas genéticas ou secundárias. Esse estudo avaliou pacientes com hepatopatia crônica com sobrecarga de ferro submetidos à pesquisa das mutações HFE no período de 2007-2009 e classificou como portadores de hemocromatose hereditária HFE (HH-HFE) aqueles que apresentavam as mutações C282Y/C282Y ou C282Y/H63D e como sobrecarga de ferro não HFE aqueles que apresentavam outras mutações no gene HFE como C282Y/-, H63D/- e H63D/H63D ou pacientes sem qualquer uma dessas mutações mencionadas. Os objetivos do estudo foram 1) analisar e correlacionar os aspectos fenotípicos e genotípicos de grupo de indivíduos com doença hepática crônica e sobrecarga de ferro; 2) caracterizar o quadro clínico, laboratorial e anatomopatológico, em busca de achados compatíveis com o fenótipo de hemocromatose; 3) Correlacionar o quadro clínico com as mutações no gene HFE. Foram analisados 108 indivíduos portadores de hepatopatia crônica selecionados a partir de saturação de transferrina (ST) > 45% e ferritina sérica > 350 ng/mL. Foram estudados e comparados 16 pacientes no grupo HH-HFE com 92 no grupo sobrecarga de ferro não HFE. Da casuística geral, a idade média ao diagnóstico da doença foi de 46...

Uncoupling and oxidative stress in liver mitochondria isolated from rats with acute iron overload

ANDREU, G. L. Pardo; INADA, N. M.; VERCESI, A. E.; CURTI, C.
Fonte: SPRINGER Publicador: SPRINGER
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
66.67%
One hypothesis for the etiology of cell damage arising from iron overload is that its excess selectively affects mitochondria. Here we tested the effects of acute iron overload on liver mitochondria isolated from rats subjected to a single dose of i.p. 500 mg/kg iron-dextran. The treatment increased the levels of iron in mitochondria (from 21 +/- A 4 to 130 +/- A 7 nmol/mg protein) and caused both lipid peroxidation and glutathione oxidation. The mitochondria of iron-treated rats showed lower respiratory control ratio in association with higher resting respiration. The mitochondrial uncoupling elicited by iron-treatment did not affect the phosphorylation efficiency or the ATP levels, suggesting that uncoupling is a mitochondrial protective mechanism against acute iron overload. Therefore, the reactive oxygen species (ROS)/H(+) leak couple, functioning as a mitochondrial redox homeostatic mechanism could play a protective role in the acutely iron-loaded mitochondria.; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Urinary iron excretion induced by intravenous infusion of deferoxamine in ß-thalassemia homozygous patients

Boturão-Neto,E.; Marcopito,L.F.; Zago,M.A.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/11/2002 EN
Relevância na Pesquisa
56.73%
The purpose of the present study was to identify noninvasive methods to evaluate the severity of iron overload in transfusion-dependent ß-thalassemia and the efficiency of intensive intravenous therapy as an additional tool for the treatment of iron-overloaded patients. Iron overload was evaluated for 26 ß-thalassemia homozygous patients, and 14 of them were submitted to intensive chelation therapy with high doses of intravenous deferoxamine (DF). Patients were classified into six groups of increasing clinical severity and were divided into compliant and non-compliant patients depending on their adherence to chronic chelation treatment. Several methods were used as indicators of iron overload. Total gain of transfusion iron, plasma ferritin, and urinary iron excretion in response to 20 to 60 mg/day subcutaneous DF for 8 to 12 h daily are useful to identify iron overload; however, urinary iron excretion in response to 9 g intravenous DF over 24 h and the increase of urinary iron excretion induced by high doses of the chelator are more reliable to identify different degrees of iron overload because of their correlation with the clinical grades of secondary hemochromatosis and the significant differences observed between the groups of compliant and non-compliant patients. Finally...

Baroreflex function in conscious rats submitted to iron overload

Cardoso,L.M.; Pedrosa,M.L.; Silva,M.E.; Moraes,M.F.D.; Colombari,E.; Chianca-Jr.,D.A.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/02/2005 EN
Relevância na Pesquisa
66.72%
Our hypothesis is that iron accumulated in tissue, rather than in serum, may compromise cardiovascular control. Male Fischer 344 rats weighing 180 to 220 g were divided into 2 groups. In the serum iron overload group (SIO, N = 12), 20 mg elemental iron was injected ip daily for 7 days. In the tissue iron overload group (TIO, N = 19), a smaller amount of elemental iron was injected (10 mg, daily) for 5 days followed by a resting period of 7 days. Reflex heart rate responses were elicited by iv injections of either phenylephrine (0.5 to 5.0 µg/kg) or sodium nitroprusside (1.0 to 10.0 µg/kg). Baroreflex curves were determined and fitted to sigmoidal equations and the baroreflex gain coefficient was evaluated. To evaluate the role of other than a direct effect of iron on tissue, acute treatment with the iron chelator deferoxamine (20 mg/kg, iv) was performed on the TIO group and the baroreflex was re-evaluated. At the end of the experiments, evaluation of iron levels in serum confirmed a pronounced overload for the SIO group (30-fold), in contrast to the TIO group (2-fold). Tissue levels of iron, however, were higher in the TIO group. The SIO protocol did not produce significant alterations in the baroreflex curve response, while the TIO protocol produced a nearly 2-fold increase in baroreflex gain (-4.34 ± 0.74 and -7.93 ± 1.08 bpm/mmHg...

del 11(q23) as a prognostic factor of iron overload in refractory anemia with ringed sideroblasts

Chauffaille,Maria de Lourdes Lopes Ferrari; Stéfano,José Tadeu; Valério,Rosana Maria; Romeo,Maura; Rodrigues,Maria Madalena; Kerbauy,José
Fonte: Associação Paulista de Medicina - APM Publicador: Associação Paulista de Medicina - APM
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/08/1997 EN
Relevância na Pesquisa
66.42%
We present the case of a patient with MDS RARS subtype with loss of part of the long arm of chromosome 11 del 11(q23). This a cytogenetic abnormality that occurs in 7% to 20% of RARS cases not related to poor prognosis. It seems that this deletion is a marker of iron overload in MDS.

Analysis of HFE gene mutations and HLA-A alleles in Brazilian patients with iron overload

Cançado,Rodolfo Delfini; Guglielmi,Aline Cristiane de Oliveira; Vergueiro,Carmen Silvia Vieitas; Rolim,Ernani Geraldo; Figueiredo,Maria Stella; Chiattone,Carlos Sérgio
Fonte: Associação Paulista de Medicina - APM Publicador: Associação Paulista de Medicina - APM
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2006 EN
Relevância na Pesquisa
66.71%
CONTEXT AND OBJECTIVE: Hemochromatosis is a common inherited disorder of iron metabolism and one of the most important causes of iron overload. The objective was to analyze the presence of C282Y, H63D and S65C mutations in the HFE gene and HLA-A alleles for a group of Brazilian patients with iron overload, and to correlate genotype with clinical and laboratory variables. DESIGN AND SETTING: Prospective study, in Discipline of Hematology and Oncology, Faculdade de Ciências Médicas da Santa Casa de Misericórdia de São Paulo. METHODS: We studied 35 patients with iron overload seen at our outpatient unit between January 2001 and December 2003. Fasting levels of serum iron and ferritin, and total iron-binding capacity, were assayed using standard techniques. Determinations of C282Y, H63D and S65C mutations in the HFE gene and of HLA-A alleles were performed by polymerase chain reaction (PCR). RESULTS: Twenty-six out of 35 patients (74%) presented at least one of the HFE gene mutations analyzed. Among these, five (14%) were C282Y/C282Y, four (11%) C282Y/H63D, one (3%) H63D/H63D, six (17%) C282Y/WT and ten (29%) H63D/WT. No patients had the S65C mutation and nine (25%) did not present any of the three HFE mutations. Four out of five patients with C282Y/C282Y genotype (80%) and three out of four patients with C282Y/H63D genotype (75%) were HLA A*03. CONCLUSION: Analysis of HFE gene mutations constitutes an important procedure in identifying patients with hereditary hemochromatosis...

Determination of iron-overload in thalassemia by hepatic MRI and ferritin

Angulo,Ivan L.; Covas,Dimas T.; Carneiro,Antonio A.; Baffa,Oswaldo; Elias Junior,Jorge; Vilela,Guilherme
Fonte: Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular Publicador: Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2008 EN
Relevância na Pesquisa
66.65%
Accumulation of iron in thalassemia causes organ damage and reduces patient survival due to heart lesions in the second decade of life. Iron deposits are monitored by direct (biopsy) and indirect methods (ferritin) with sequential data being better than isolated measurements. This paper compares two indirect measurements of iron overload; a single hepatic iron concentration (HIC) by magnetic resonance and mean ferritin levels over four years. A retrospective study of 25 patients from the Centro Regional de Hemoterapia in Ribeirão Preto, Brazil was carried out. High HIC (above 7 mg per gram of dry weight) was found in 20 patients and high mean serum ferritin (above 2500 μg/L) in 10 patients. Stratification into three levels (low, moderate and high) of iron overload gave similar results in both tests. Many other factors influence de degree of iron overload in thalassemia. No correlation was found using a non-parametric statistical test between HIC and mean serum ferritin. Both methods provide better planning of chelation therapy.

Impact of iron overload on interleukin-10 levels, biochemical parameters and oxidative stress in patients with sickle cell anemia

Barbosa,Maritza Cavalcante; Santos,Talyta Ellen Jesus dos; Souza,Geane Félix de; Assis,Lívia Coêlho de; Freitas,Max Victor Carioca; Gonçalves,Romélia Pinheiro
Fonte: Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular Publicador: Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2013 EN
Relevância na Pesquisa
66.79%
OBJECTIVE: The aim of this study was to evaluate the impact of iron overload on the profile of interleukin-10 levels, biochemical parameters and oxidative stress in sickle cell anemia patients. METHODS: A cross-sectional study was performed of 30 patients with molecular diagnosis of sickle cell anemia. Patients were stratified into two groups, according to the presence of iron overload: Iron overload (n = 15) and Non-iron overload (n = 15). Biochemical analyses were performed utilizing the Wiener CM 200 automatic analyzer. The interleukin-10 level was measured by capture ELISA using the BD OptEIAT commercial kit. Oxidative stress parameters were determined by spectrophotometry. Statistical analysis was performed using GraphPad Prism software (version 5.0) and statistical significance was established for p-values < 0.05 in all analyses. RESULTS: Biochemical analysis revealed significant elevations in the levels of uric acid, triglycerides, very low-density lipoprotein (VLDL), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), urea and creatinine in the Iron overload Group compared to the Non-iron overload Group and significant decreases in the high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Ferritin levels correlated positively with uric acid concentrations (p-value < 0.05). The Iron overload Group showed lower interleukin-10 levels and catalase activity and higher nitrite and malondialdehyde levels compared with the Non-iron overload Group. CONCLUSION: The results of this study are important to develop further consistent studies that evaluate the effect of iron overload on the inflammatory profile and oxidative stress of patients with sickle cell anemia.

Iron overload alters glucose homeostasis, causes liver steatosis, and increases serum triacylglycerols in rats

Silva, Ma?sa; Silva, Marcelo Eust?quio; Paula, Heberth de; Carneiro, Cl?udia Martins; Pedrosa, Maria L?cia
Fonte: Universidade Federal de Ouro Preto Publicador: Universidade Federal de Ouro Preto
Tipo: Artigo publicado em periodico
EN_US
Relevância na Pesquisa
66.56%
The objective of this study was to investigate the effect of iron overload with a hyperlipidemic diet on the histologic feature of hepatic tissue, the lipid and glycemic serum profiles, and the markers of oxidative damage and stress in a rat model. Twenty-four male Fischer rats, purchased from Experimental Nutrition Laboratory, Federal University of Ouro Preto, were assigned to 4 equal groups, 2 were fed a standard cholesterol-free diet (group C or control and CI or control with iron) containing 8.0% soybean oil and 2 were fed a hyperlipidemic diet (group H or hyperlipidemic and HI or hyperlipidemic with iron) containing 1.0% cholesterol and 25.0% soybean oil. A total of 50 mg of iron was administered to rats in groups CI and HI in 5 equal doses (1 every 3 weeks for a 16-week period) by intraperitoneal injections of 0.1 mL of iron dextran solution (100 g Fe2+/L; Sigma, St Louis, Mo). The other rats in groups C and H were treated in a similar manner but with sterile saline (0.1 mL). Irrespective of the diet, iron excess enhanced serum triacylglycerols (P b .05) and reduced serum glucose and glycated hemoglobin levels (P b .05) but did not affect serum cholesterol concentration. Histologic analysis showed steatosis in groups H and to a lesser extent in HI. No significant differences (P N.05) were observed in paraoxonase activities or in serum levels of free or total sulfhydryl radicals...

Hepcidin Gene Promoter c.-1010T and c.-582G Variants are Modulators of Iron Overload Development in Individuals Carrying the H63D Mutation in the HFE Gene

Silva, Bruno; Pita, Lina; Gomes, Susana; Gonçalves, João; Faustino, Paula
Fonte: Instituto Nacional de Saúde Doutor Ricardo Jorge, IP Publicador: Instituto Nacional de Saúde Doutor Ricardo Jorge, IP
Tipo: Conferência ou Objeto de Conferência
Publicado em /11/2011 ENG
Relevância na Pesquisa
66.52%
Mutated HFE gene/protein is usually associated with Hereditary Hemochromatosis (HH). Despite C282Y being the most common HH-associated HFE mutation, others, such as H63D, also have an uncertain role in the pathogenesis of HH. Hepcidin is a crucial regulator of systemic iron homeostasis, controlling both iron absorption by enterocytes and its release by macrophages. Mutations in Hepcidin gene (HAMP) result in the development of a juvenile type of HH. Also, it has been hypothesized that, in certain conditions, some HAMP polymorphisms can modulate iron status. As example, c.-582A>G polymorphism in HAMP promoter can increase serum ferritin levels in beta-thalassemia major patients, but not in normal individuals. HAMP promoter polymorphisms were analysed by DNA sequencing in 266 individuals with ferritin levels higher than 400ng/mL: i) 191 individuals homozygous or heterozygous for the H63D mutation (group 1) and ii) 75 individuals carrying one or more C282Y alleles (HH/CY, HH/YY or HD/CY) (group 2). Also, luminescence assays were performed in Huh-7 cells in order to assess whether the HAMP promoter polymorphisms are changing the hepcidin expression in response to external stimulus. The results revealed that c.-582A>G is in linkage with c.-1010C>T polymorphism. These polymorphisms were found in a significant higher frequency in group 1 (31.2% of allele G and T...

Lifetime cost-utility analyses of deferasirox in beta-thalassaemia patients with chronic iron overload: A UK perspective

Karnon, J.; Tolley, K.; Vieira, J.; Chandiwana, D.
Fonte: Adis International Ltd Publicador: Adis International Ltd
Tipo: Artigo de Revista Científica
Publicado em //2012 EN
Relevância na Pesquisa
66.52%
BACKGROUND AND OBJECTIVES: Regular blood transfusions for beta-thalassaemia patients lead to the accumulation of iron deposits in the body. In order to remove such deposits, iron chelation therapy is required. Subcutaneously administered deferoxamine has been the gold standard chelation therapy for over 40 years. Deferasirox is a newer chelation therapy that is taken orally once daily. The objective of this study was to estimate the long-term costs and quality-adjusted life-years (QALYs) associated with deferoxamine and deferasirox in a cohort of transfusion-dependent beta-thalassaemia patients from a UK health service perspective. METHODS: A 50-year annual cycle state transition model comprised three core health states: alive without cardiac complications, alive with cardiac complications, and dead, as well as representing other chronic complications of iron overload: diabetes, hypogonadism, hypoparathyroidism and hypothyroidism. The model was calibrated to identify sets of convergent input parameter values that predicted observed overall survival by mean lifetime compliance with chelation therapy. A pivotal non-inferiority trial informed the main estimates of the effectiveness of deferasirox, which were applied to the calibrated model. Using cost values for the year 2011...

Observational study of iron overload as assessed by Magnetic Resonance Imaging (MRI) in an adult population of transfusion dependent patients with beta thalassaemia: Significant association between low cardiac T2 < 10 ms and the occurrence of cardiac events

Patton, W.; Brown, G.; Leung, M.; Bavishi, K.; Taylor, J.; Lloyd, J.; Lee, S.H.; Tay, L.; Worthley, S.
Fonte: Blackwell Publishing Asia Publicador: Blackwell Publishing Asia
Tipo: Artigo de Revista Científica
Publicado em //2010 EN
Relevância na Pesquisa
66.65%
BACKGROUND: Thalassaemia major patients usually die from cardiac haemosiderosis. Improved strategies are required to modify this risk. AIMS: To assess the significance of cardiac iron overload in patients with beta thalassaemia. METHOD: Observational study of cardiac iron overload as assessed by magnetic resonance imaging (MRI) cardiac T2* relaxometry in 30 adult patients with transfusion-dependent beta thalassaemia. RESULTS: 11/30 patients (37%) had cardiac T2* < 10 ms, 8/30 (27%) in range 10-20 ms and 11/30 (37%) > 20 ms. There was significant inverse correlation between T2* values and values for serum ferritin (SF) and liver iron concentration (LIC) and positive correlation with left ventricular ejection fraction (LVEF). Median LVEF values were 49% in patients with T2* < 10 ms and 58% in patients with T2* > 10 ms (P = 0.02). Very low T2* values <10 ms were strongly associated with the occurrence of cardiac events (congestive heart failure, arrhythmia, cardiac death): occurring in 5/11 patients with T2* < l0 ms and in 0/19 in patients with T2* > 10 ms (P = 0.003 Fisher's exact test; P = 0.002 log rank Kaplan-Meier time to event analysis). There was no significant association between T2* < 10 ms or cardiac events and traditional measures of iron overload...

Effect of iron overload on the severity of liver histologic alterations and on the response to interferon and ribavirin therapy of patients with hepatitis C infection

Souza,R.M.; Freitas,L.A.R.; Lyra,A.C.; Moraes,C.F.; Braga,E.L.; Lyra,L.G.C.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2006 EN
Relevância na Pesquisa
66.79%
The objective of the present study was to determine the presence of hepatic iron overload in patients with chronic HCV infection and to correlate it with histologic alterations, HCV genotype and response to therapy. Liver tissue samples from 95 patients with chronic hepatitis C were divided into two groups: group I, presence of iron overload in hepatic tissue (Perls' staining) and group II, no iron overload. Hepatic iron overload was detected in 30 (31.6%) of 95 patients. Of the 69 patients tested by genotyping, 49 (71.01%) were genotype 1 and 20 (28.99%) genotype non-1. Iron overload was detected in 14 (28.6%) patients with genotype 1 and in 6 (30%) with genotype non-1 (P = 0.906). There was a significant difference in fibrosis stage between groups (P = 0.005). In group I (N = 30), one patient had stage F0/F1 of fibrosis, while in group II (N = 65), 22 (33.8%) patients had minimal or no fibrosis. Fibrosis stage F2/F3 was observed in 70% of group I patients compared to 46.2% of group II. Eighty-five patients were treated with a combination of interferon and ribavirin; 29 of them (34.1%) had a sustained virologic response and 8 (27.6%) of them had hepatic iron overload. Iron overload was detected in 18 (32.1%) of the 56 non-responders (P = 0.73). Hepatic iron overload was frequent among patients with chronic hepatitis C and was associated with a more severe stage of liver fibrosis. There was no association between iron overload and HCV genotype and response to interferon and ribavirin therapy.

Iron Overload in a Murine Model of Hereditary Hemochromatosis Is Associated with Accelerated Progression of Osteoarthritis Under Mechanical Stress

Camacho, A; Simão, M; Ea, H-K; Cohen-Solal, M; Richette, P; Branco, J; Cancela, M L
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
Publicado em 25/09/2015 ENG
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66.67%
OBJECTIVE: Hereditary hemochromatosis (HH) is a disease caused by mutations in the Hfe gene characterised by systemic iron overload and associated with an increased prevalence of osteoarthritis (OA) but the role of iron overload in the development of OA is still undefined. To further understand the molecular mechanisms involved we have used a murine model of HH and studied the progression of experimental OA under mechanical stress. DESIGN: OA was surgically induced in the knee joints of 10-week-old C57BL6 (wild-type) mice and Hfe-KO mice. OA progression was assessed using histology, micro CT, gene expression and immunohistochemistry at 8 weeks after surgery. RESULTS: Hfe-KO mice showed a systemic iron overload and an increased iron accumulation in the knee synovial membrane following surgery. The histological OA score was significantly higher in the Hfe-KO mice at 8 weeks after surgery. Micro CT study of the proximal tibia revealed increased subchondral bone volume and increased trabecular thickness. Gene expression and immunohistochemical analysis showed a significant increase in the expression of matrix metallopeptidase 3 (MMP-3) in the joints of Hfe-KO mice compared with control mice at 8 weeks after surgery. CONCLUSIONS: HH was associated with an accelerated development of OA in mice. Our findings suggest that synovial iron overload has a definite role in the progression of HH-related OA

Iron overload and genotype 3 are associated with liver steatosis in chronic hepatitis C

Fernández Salazar,L. I.; Álvarez Gago,T.; Aller de la Fuente,R.; Orduña Domingo,A.; Arranz Santos,T.; Calle Valverde,F. de la; Olmo Martín,L. del; Luis Román,D. de; González Hernández,J. M.
Fonte: Revista Española de Enfermedades Digestivas Publicador: Revista Española de Enfermedades Digestivas
Tipo: info:eu-repo/semantics/article; journal article; info:eu-repo/semantics/publishedVersion Formato: text/html; application/pdf
Publicado em 01/12/2004 ENG
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66.52%
Objective: to determine epidemiological, biochemical, virological, and histological factors associated with liver steatosis in chronic hepatitis C. Subjects: the medical histories of 53 patients biopsied for chronic hepatitis C diagnosis between June 2000 and December 2002 were retrospectively studied. Epidemiological, biochemical, and virological data were collected. Patients with hepatitis B virus or human immunodeficiency virus coinfection were excluded. Liver biopsy specimens were reviewed and scored by one pathologist. Weight and height were measured at liver biopsy time. The statistic association between qualitative and quantitative variables and the presence of liver steatosis was studied. Results: steatosis was identified in 52% of biopsies. There was no statistic association with age, sex, method of transmission, duration of infection, alcohol consumption, other diseases, body mass index, glucose, triglycerides, cholesterol, AST, ALT, GGT, alkaline phosphatase, bilirubin, or viral load. Liver steatosis was associated with serum iron, transferrin saturation, and ferritin. Genotype 3 was also associated with steatosis. Piecemeal necrosis, hepatocellular injury, Kupffer cell hyperplasia, liver iron, and portal fibrosis were also associated with steatosis. A multivariate analysis showed that genotype 3...