Erythrocytic changes in patients with Systemic Lupus Erythematosus

Objetivo: Determinar as alterações eritrocitárias em pacientes com Lupus Eritematoso Sistêmico (LES), atendidos no Hospital Geral Universitário (HGU) Cuiabá/MT. Métodos: Amostras de sangue de 40 pacientes, do sexo feminino foram coletadas e processadas (automação ABX Pentra 80 – citometria de fluxo). As análises estatísticas descritivas foram feitas com auxílio do software estatístico IBM SPSS 2.0. Resultados: Dos 40 pacientes analisados, 42,5% apresentaram anemia. As médias dos valores de hematócrito e dosagem de hemoglobina nos pacientes com anemia foram respectivamente de 29,7% e 9,9 g/dL, ao passo que naqueles nos quais não se observou quadro anêmico a média de hematócrito foi de 41,1% e a de dosagem de hemoglobina 13,7g/dL. A anemia normocítica normocrômica foi a mais encontrada (64,7%) sendo observados, nessa situação, índices hematimétricos (VCM, HCM, CHCM e RDW) dentro dos valores de normalidade. As anemias macrocíticas e microcíticas tiveram a mesma representação percentual (17,6%). Entre as anemias macrocíticas, alterações hematimétricas, tais como, RDW aumentado, policromasia e reticulocitose observadas em alguns pacientes sugerem a possibilidade de processos hemolíticos comumente observados nessa patologia. Conclusão: Evidencia-se a necessidade de avaliar cuidadosa e frequentemente os achados do hemograma, pois é uma ferramenta importante na avaliação do paciente e da eficácia do tratamentoObjective: We assessed the prevalence of erythrocytic changes in patients with SLE, at Cuiabá University General Hospital (UNIC-HGU). Methods: blood samples from 40 female patients were collected and processed (ABX Pentra 80 automation – flow cytometry). Descriptive statistical analyses were performed using IBM SPSS 2.0 statistical software. Results: 42.5% of the 40 patients showed lowered concentrations of hemoglobin. The hematocrit and hemoglobin dosage averages of the anemic patients were respectively of 29.7% and 9.9 gdL, while those without anemia showed 41.1% of hematocrit average and hemoglobin average dosage of 13,7gdL. Normocytic and normochromic anemia was the most prevalent, founded in 64.7% of the anemic patients, with normal hematimetric indices. In cases of macrocytic anemia, hematimetric changes, such as increased RDW, policromasy and reticulocytosis observed in some patients suggest hemolytic processes, commonly observed in these patients. Conclusion: Anemia was found in 42% of the patients and careful observation of the erythrocytic changes is an important tool in the follow up of LES patient

Deletion of 17p13 and LIS1 gene mutation in isolated lissencephaly sequence

Classical lissencephaly is a neuroblast migration disorder that occurs either as isolated lissencephaly sequence or in association with malformation syndromes, such as the Miller-Dieker syndrome. in this work, alterations of the LIS1 gene in patients diagnosed as having isolated lissencephaly sequence were investigated. Ten patients were evaluated for the following aspects: classical cytogenetics by karyotyping using solid staining and G-banding; molecular cytogenetics using fluorescent in situ hybridization with a specific probe for the critical region of isolated lissencephaly sequence; and molecular analysis using deoxyribonucleic acid sequencing. Classical cytogenetic analysis indicated apparently normal karyotypes in all patients, but fluorescent in situ hybridization revealed a 17p13.3 microdeletion in one. in another patient, deoxyribonucleic acid sequencing disclosed a 1 base pair insertion in exon 4 within a sequence of eight consecutive adenine residues (162-163insA), a mutation that predicts a truncated protein. Two different polymorphisms were also detected: a T > C substitution in intron 6 (c.568 + 27bp T > C) and a C > T substitution in the nontranslated region of exon 11 (1250 C > T). These results indicate that cytogenetic analysis and molecular investigation of the LIS1 gene are not always sufficient to determine the disease etiology. These findings are consistent with previous studies and suggest the involvement of other genes in cortical malformation. (c) 2006 by Elsevier Inc. All rights reserved.Universidade Federal de São Paulo, Dept Morfol, Disciplina Genet, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Diagnost Imagen, BR-04023900 São Paulo, BrazilUniv Cuiaba, Fac Med, Disciplina Embriol, Cuiaba, BrazilUniversidade Federal de São Paulo, Dept Morfol, Disciplina Genet, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Diagnost Imagen, BR-04023900 São Paulo, BrazilWeb of Scienc

Association between Genetic Variants in NOS2 and TNF Genes with Congenital Zika Syndrome and Severe Microcephaly

Zika virus (ZIKV) causes Congenital Zika Syndrome (CZS) in individuals exposed prenatally. Here, we investigated polymorphisms in VEGFA, PTGS2, NOS3, TNF, and NOS2 genes as risk factors to CZS. Forty children with CZS and forty-eight children who were in utero exposed to ZIKV infection, but born without congenital anomalies, were evaluated. Children with CZS were predominantly infected by ZIKV in the first trimester (p < 0.001) and had mothers with lower educational level (p < 0.001) and family income (p < 0.001). We found higher risk of CZS due the allele rs2297518[A] of NOS2 (OR = 2.28, CI 95% 1.17–4.50, p = 0.015). T allele and TT/CT genotypes of the TNF rs1799724 and haplotypes associated with higher expression of TNF were more prevalent in children with CZS and severe microcephaly (p = 0.029, p = 0.041 and p = 0.030, respectively). Our findings showed higher risk of CZS due ZIKV infection in the first trimester and suggested that polymorphisms in NOS2 and TNF genes affect the risk of CZS and severe microcephaly

Contribution of miR-124 rs531564 polymorphism to the occurrence of congenital Zika syndrome

Zika virus (ZIKV) cause Congenital Zika Syndrome (CZS) in individuals exposed during pregnancy. Studies have shown that ZIKV infection positively regulates the miR-124 expression in neural cells, which leads to a decrease of TFRC, a gene targeted of this miRNA. Both miR-124 and TFRC exhibit a pivotal role in nervous system development. Therefore, in this study we aimed to investigate whether genetic variants that affect the expression of these genes could act together with ZIKV to increase the risk of individuals developing CZS. TFRC rs406271 and MIR-124-1 rs531564 polymorphisms were genotyped, using TaqMan® Genotyping Assays, in a sample of children who were exposed to ZIKV during pregnancy, of whom 40 were born with CZS and 48 without congenital anomalies. We identified that individuals with CZS presented a higher frequency of CG genotype of rs531564 polymorphism in MIR-124-1 (p=0.048), which is associated with increased expression of miR-124. Since ZIKV also upregulates the expression of this miRNA, the presence of CG genotype in individuals exposed to the virus could lead to a scenario of overexpression of miR-124 in the brain. Since teratogenesis is a multifactorial event, this genetic finding could partly explain why such individuals are more susceptible to CZS, considering both the downregulation of important neurodevelopment genes, as well as deregulation of the neurogenesis process. Thus, we provide preliminary evidence about a possible genetic risk factor to CZS and highlight the importance of analyzing functional polymorphisms related to epigenetic modulators of neurodevelopment genes in the context of ZIKV teratogenesis.</p