Oxidative stress levels are correlated with P15 and P16 gene promoter methylation in myelodysplastic syndrome patients.

Oxidative stress and abnormal DNA methylation have been implicated in some types of cancer, namely in myelodysplastic syndromes (MDS). Since both mechanisms are observed in MDS patients, we analyzed the correlation of intracellular levels of peroxides, superoxide anion, and glutathione (GSH), as well as ratios of peroxides/GSH and superoxide/GSH, with the methylation status of P15 and P16 gene promoters in bone marrow leukocytes from MDS patients. Compared to controls, these patients had lower GSH content, higher peroxide levels, peroxides/GSH and superoxide/GSH ratios, as well as higher methylation frequency of P15 and P16 gene promoters. Moreover, patients with methylated P15 gene had higher oxidative stress levels than patients without methylation (peroxides: 460 ± 42 MIF vs 229 ± 25 MIF, p = 0.001; superoxide: 383 ± 48 MIF vs 243 ± 17 MIF, p = 0.022; peroxides/GSH: 2.50 ± 0.08 vs 1.04 ± 0.34, p < 0.001; superoxide/GSH: 1.76 ± 0.21 vs 1.31 ± 0.10, p = 0.007). Patients with methylated P16 and at least one methylated gene had higher peroxide levels as well as peroxides/GSH ratio than patients without methylation. Interestingly, oxidative stress levels allow the discrimination of patients without methylation from ones with methylated P15, methylated P16, or at least one methylated (P15 or P16) promoter. Taken together, these findings support the hypothesis that oxidative stress is correlated with P15 and P16 hypermethylation.

[Serum Erythropoietin as Prognostic Marker in Myelodysplastic Syndromes]. / Eritropoietina Sérica como Marcador Prognóstico em Síndrome Mielodisplásica.

INTRODUCTION: This myelodysplastic syndromes are a heterogeneous entity characterized by dysplasia, hypercellular bone marrow, cytopenias and risk of transformation to acute leukaemia. Prognostic factors, such as bone marrow fibrosis, lactate dehydrogenase and 2-microglobulin elevation have been described, but treatment is mainly based in the International Prognostic Scoring System. MATERIAL AND METHODS: Our aim was to analyze serum's erythropoietin at diagnosis in de novo myelodysplastic syndromes patients, through its impact in overall survival and possible implementation as prognostic marker. Clinical and laboratorial data from 102 patients with de novo myelodysplastic syndromes diagnosed between October/2009 and March/2014 were collected. Survival analysis was performed according to serum erythropoietin level stratification, using Kaplan-Meier methodology. RESULTS: Our 102 patients had a median age of 74 years, with a male:female ratio of 0.8. Mean erythropoietin was significantly lower in refractory cytopenia with unilineage dysplasia patients in contrast with the higher values observed in 5q- syndrome (p < 0.05). Eleven patients progressed to acute leukaemia; these have higher mean erythropoietin values (p < 0.05). In addition, elevated serum erythropoietin was associated with lower survival rates (p = 0.0336). Predictive value of serum erythropoietin was maintained after Cox regression adjustment. In multivariate analysis, serum erythropoietin is an independent survival predictor (p < 0.001). DISCUSSION: Serum erythropoietin is a predictive factor for response to therapy with subcutaneous erythropoietin, and patients with myelodysplastic syndromes with higher values of erythropoietin have poorer response to administration of erythropoietin even at higher doses. Our sample shows that serum erythropoietin also has prognostic value, and in all myelodysplastic syndromes subtypes. Moreover, alone or in combination with other factors or prognostic indices, erythropoietin may enhance the prognostic indices such as the International Prognostic Scoring System, since high levels are associated with progression to acute leukemia and hence lower survival. CONCLUSION: This study suggests that increased erythropoietin levels at diagnosis can by itself be a poor prognosis factor inmyelodysplastic syndromes patients, with higher values in patients with progression to acute leukaemia and decreased overall survival.

Introdução: A síndrome mielodisplásica é uma doença heterogénea caracterizada por displasia, medula hipercelular, citopenias e risco de evolução para leucemia aguda. Outros factores de prognóstico, nomeadamente, fibrose medular, elevação da enzima desidrogenase do lactato e 2-microglobulina têm sido descritos, contudo, a decisão terapêutica baseia-se no score do International Prognostic Scoring System. Material e Métodos: Este trabalho teve como objectivo analisar a relevãncia da eritropoietina sérica ao diagnóstico, em doentes com síndrome mielodisplásica de novo, avaliando o seu impacto na sobrevivência global e a sua implementação como factor de prognóstico. Recolhemos dados clínicos e laboratoriais de 102 doentes com síndrome mielodisplásica de novo diagnosticada entre outubro/2009 e março/2014. A análise de sobrevivência foi efectuada recorrendo à metodologia de Kaplan-Meier, de acordo com os valores de eritropoietina. Resultados: A amostra, de 102 doentes, apresenta uma mediana de idades de 74 anos e relação masculino/feminino igual a 0,8. Os doentes com o subtipo citopenia refratária com displasia unilinha apresentam, em média, valores de eritropoietina significativamente mais baixos, em oposição aos doentes com o subtipo 5q- que apresentam a média de eritropoietina sérica mais elevada (p < 0,05). Onze doentes evoluíram para leucemia aguda; estes têm, em média, eritropoietina sérica superior (p < 0,05). Adicionalmente, a eritropoietina sérica acima do limite superior da normalidade associa-se a menor sobrevivência (p = 0,0336). Após ajuste do modelo de regressão de Cox, o valor preditivo da eritropoietina para a sobrevivência global manteve-se (p < 0,001). Em análise multivariada, a eritropoietina sérica demonstrou ser um factor de prognóstico independente (p < 0,001). Discussão: A eritropoietina sérica é um factor preditivo de resposta à terapêutica com eritropoietina subcut'nea, sendo que os doentes com síndrome mielodisplásica com valores mais elevados de eritropoietina apresentam uma pior resposta à administração de eritropoietina, mesmo com doses mais elevadas. A nossa amostra demonstra que a eritropoietina sérica apresenta também valor prognóstico, e em todos os subtipos de síndrome mielodisplásica. Além disso, isoladamente ou em associação com outros factores ou índices de prognóstico, poderá melhorar o valor prognóstico de índices como o International Prognostic Scoring System, uma vez que valores elevados de eritropoietina estão associados a progressão para leucemia aguda e, consequentemente, a menor sobrevivência.Conclusão: Os resultados sugerem que o aumento dos níveis séricos de eritropoietina ao diagnóstico pode constituir um factor de mau prognóstico em doentes com síndrome mielodisplásica, associando-se a maior risco de evolução para leucemia aguda e menor sobrevivência global.

Prevalence of immune disturbances and chronic liver disease in family members of patients with primary biliary cirrhosis.

BACKGROUND AND AIMS: Primary biliary cirrhosis (PBC) has been reported in up to 4-6% of first degree relatives of patients with the disease. In addition, immune abnormalities, including hypergammaglobulinemia, autoantibodies and increased frequency of autoimmune disorders, were reported in family members of PBC patients. The aim of the present study was to investigate the prevalence of PBC in relatives of patients with PBC, and to investigate the occurrence of chronic liver disease (CLD) and immune abnormalities in these subjects. METHODS: One-hundred first degree relatives of 26 patients with PBC were interviewed and submitted to physical examination and determination of liver enzymes, gamma-globulin, bilirubin and auto-antibodies, including antinuclear (ANA), antismooth muscle (SMA), antimitochondrial antibodies (AMA) by indirect immunofluorescence (IIF) and anti-M2 antibody by immunoblotting (IB). RESULTS: Immune disturbances were rarely observed in relatives of PBC patients. Higher gamma-globulin levels, SMA and ANA were detected in four, eight and two family members, respectively. In most subjects, these autoantibodies were either in low titers or associated with concurrent diseases. Only four relatives had extrahepatic autoimmune diseases and another eight exhibited other CLD. Primary biliary cirrhosis was detected in a sister of one patient. Additionally, two other relatives of PBC patients who tested negative for AMA by IIF showed reactivity for anti-M2 by IB. CONCLUSIONS: Immune disturbances, including ANA and SMA, are uncommon in family members of PBC patients. Conversely, anti-M2 antibodies and overt PBC do occur in relatives of PBC patients, even in Brazil where the disease is quite rare.

Seroprevalence and risk factors associated with Helicobacter pylori infection in blood donors in Salvador, Northeast-Brazil.

Helicobacter pylori plays an important role in the etiology of peptic ulcer disease. Its prevalence appears to be higher in developing countries. We evaluated the seroprevalence of H. pylori and risk factors associated with infection in voluntary blood donors who attended the main blood center of the city of Salvador, Brazil. The subjects responded to an epidemiological questionnaire, with information about sex, age, race, lifestyle, social-economic level indicators, and residence and hygiene conditions. Anti-H. pylori antibody was determined by ELISA (Cobas Core, Roche). Three hundred and seven subjects were included in the study. Anti-H. pylori antibody results were indeterminate in 33 individuals (10.8%), who were excluded from analysis. Among the remaining 274 subjects, 187 (68.2%) were anti-H. pylori positive. Based on multivariate logistic regression analysis three variables were found to be significantly associated with a higher prevalence of H. pylori infection: absence of plumbing in the residence during childhood, a history of rainwater invading the dwelling during childhood, and low ingestion of milk.

Seroprevalence and risk factors associated with Helicobacter pylori infection in blood donors in Salvador, Northeast-Brazil

Helicobacter pylori plays an important role in the etiology of peptic ulcer disease. Its prevalence appears to be higher in developing countries. We evaluated the seroprevalence of H. pylori and risk factors associated with infection in voluntary blood donors who attended the main blood center of the city of Salvador, Brazil. The subjects responded to an epidemiological questionnaire, with information about sex, age, race, lifestyle, social-economic level indicators, and residence and hygiene conditions. Anti-H. pylori antibody was determined by ELISA (Cobas Core, Roche). Three hundred and seven subjects were included in the study. Anti-H. pylori antibody results were indeterminate in 33 individuals (10.8 percent), who were excluded from analysis. Among the remaining 274 subjects, 187 (68.2 percent) were anti-H. pylori positive. Based on multivariate logistic regression analysis three variables were found to be significantly associated with a higher prevalence of H. pylori infection: absence of plumbing in the residence during childhood, a history of rainwater invading the dwelling during childhood, and low ingestion of milk.

Tratamento endoscópico da estenose péptica piloroduodenal com baläo dilatador / Endoscopic treatment of peptic pyloric duodenal stenosis by dilator balloon

Foram tratados oito pacientes com estenose péptica pilórica e do bulbo duodenal com baläo dilatador sob visäo endoscópica. A úlcera estenosante do bulbo duodenal apresentava-se em atividade em três casos e cicatizada em dois. A úlcera pilórica em um paciente apresentava-se em fase ativa e em dois, cicatrizada. O baläo dilatador foi posicionado na regiäo da estenose com auxílio de fio-guia em dois pacientes; e nos demais, esse posicionamento foi realizado sem fio-guia e sob visäo endoscópica. A dilataçäo foi hidrostática com injeçäo de água no baläo de 15mm de diâmetro em cinco pacientes e pneumática em três, com baläo de 20mm de diâmetro. Näo houve complicaçöes com o procedimento. Seis (75 por cento) pacientes apresentavam-se assintomáticos, sem recidiva de estenose ou da úlcera e com ganho de peso no período de seguimento de três a 34 meses. O método é seguro e eficaz no tratamento das úlcers pépticas estenosantes do piloro e do bulbo duodenal. Com o advento de medicamentos antiulcerosos potentes e a erradicaçäo do Helicobacter pylori, o tratamento dilatador poderá ser importante alternativa à cirurgia