No contribution of GSTM1 and GSTT1 null genotypes to the risk of neutropenia due to benzene exposure in Southeastern Brazil

Exposure to benzene has been associated with haematological diseases such as neutropenia (NEB) and acute myeloid leukaemia (AML). We tested whether the null genotypes of the GSTM1 and GSTT1 genes, involved in benzene inactivation, altered the risk for NEB in southeastern Brazil. Genomic DNA from 55 NEB patients and 330 controls was analysed by multiplex-polymerase chain reaction. The frequency of the GSTM1, GSTT1 and combined null genotypes was similar in patients and controls (GSTM1, 27.3% vs. 38.8%, p = 0.16; GSTT1, 25.5% vs. 19.7%, p = 0.24; GSTM1/GSTT1, 12.7% vs. 6.7%, p = 0.26; respectively). The distribution of genotype classes in NEB patients was similar to normal controls, suggesting that GSTM1 and GSTT1 null genotypes make no specific contribution to the risk of NEB. As the GSTM1 and GSTT1 null genotypes were previously associated with increased risk for AML in Brazil and elsewhere, we hypothesise that different thresholds of chemical exposure relative to distinct GSTM1 and GSTT1 genotypes may determine whether AML or NEB manifests in benzene exposed individuals from southeastern Brazil. Although indicative, our results still require support by prospective and large scale epidemiological studies, with rigorous assessment of daily chemical exposures and control of the possible contribution of other polymorphic genes involved in benzene metabolism

Comparison of red cell distribution width and a red cell discriminant function incorporating volume dispersion for distinguishing iron deficiency from beta thalassemia trait in patients with microcytosis

The red cell distribution width (RDW), and another red cell discriminant function incorporating RDW (MCV² x RDW/Hgb x 100) were determined in a group of 30 patients with iron deficiency anemia, 30 patients with beta thalassemia trait, and 30 normal subjects. Both RDW and (MCV² x RDW/Hgb x 100) mean values were significantly higher in iron deficiency anemia than in beta thalassemia trait (p<0.001). Taking RDW equal or above 21.0 percent among microcytic anemia patients, we identified correctly 90.0 percent of patients with iron deficiency anemia. The sensitivity and specificity of the test were 90.0 percent (IC 95 percent: 0.75 - 0.96) and 77.0 percent (IC 95 percent: 0.60 - 0.88), respectively. RDW values below 21.0 percent identified correctly 77.0 percent of beta thalassemia trait with a sensitivity and a specificity of 77.0 percent (IC 95 percent: 0.60 - 0.88) and 90.0 percent (IC 95 percent: 0.75 - 0.96), respectively. Taking values of (MCV² x RDW/Hgb x 100) above and below 80.0 percent as indicative of iron deficiency and beta thalassemia trait, respectively, we identified correctly 97.0 percent of those patients in each group. Both sensitivity and specificity were 97.0 percent (IC 95 percent: 0.84 - 0.99). These results indicated that the red cell discriminant function incorporating volume dispersion (MCV² x RDW/Hgb x 100) is a highly sensitive and specific method in the initial screening of patients with microcytic anemia and is better than RDW in differentiating iron deficiency anemia from beta thalassemia trait

Prevalence of homozygosity for the deleted alleles of glutathione S-transferase mu (GSTM1) and theta (GSTT1) among distinct ethnic groups from Brazil: relevance to environmental carcinogenesis?

Marilda de Souza Gonçalves “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”.Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-06-06T18:07:25Z No. of bitstreams: 1 Arruda VR Prevalence of homozygosity.....pdf: 546897 bytes, checksum: 2d475ef7e94a0a8d19354493a1c6c71d (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-06-07T16:07:29Z (GMT) No. of bitstreams: 1 Arruda VR Prevalence of homozygosity.....pdf: 546897 bytes, checksum: 2d475ef7e94a0a8d19354493a1c6c71d (MD5)Made available in DSpace on 2017-06-07T16:07:29Z (GMT). No. of bitstreams: 1 Arruda VR Prevalence of homozygosity.....pdf: 546897 bytes, checksum: 2d475ef7e94a0a8d19354493a1c6c71d (MD5) Previous issue date: 1998State Universtty of Campinas. Hematology-Hernotherapy Center. Campinas, SP, BrasilState Universtty of Campinas. Hematology-Hernotherapy Center. Campinas, SP, BrasilFederal University of Bahia. Saivador, BA, BrasilEvandro Chagas Institute. Belélm, PA, BrasilEvandro Chagas Institute. Belélm, PA, BrasilState Universtty of Campinas. Hematology-Hernotherapy Center. Campinas, SP, BrasilState Universtty of Campinas. Hematology-Hernotherapy Center. Campinas, SP, BrasilEnvironmental related diseases due to occupational carcinogens and toxic substances are a serious problem particularly in developing countries. The glutathione S-transferase system is fundamental for the detoxification of numerous carcinogens and mutagens. The individual inherited susceptibility to chemical carcinogenesis due to glutathione S-transferase mu (GSTMl) and theta (GSTTl) varies significantly among distinct ethnic groups. In this study we determined the prevalence of the null genotype of the GSTMl and GSTTl genes among individuals from three distinct Brazilian racial groups using a multiplex- PCR methodology. The results showed that the highest prevalence of the null genotype for the GSTMl occurred among Caucasians (55%, allele frequency = 0.74), followed by 33% among Brazilian Black subjects (allele frequency = 0.57). and 20% among Amazonian Indians (allele frequency = 0.45). For GSTTl a homogenous distribution of the null genotype was found among Caucasian and African descendants (18.5 and 19% homozygotes, respectively, allele. frequency = 0.43). with a lower prevalence among Amazonian Indians (1 1% of homozygotes, a!lele frequency = 0.34). Whether the deficiency of the GST system contributes to a predisposition to environmental related carcinogenesis in I specific popuiations in Brazil remains to be determined

Arhgap21 prevents abnormal insulin release through actin rearrangement in pancreatic islets from neonatal mice

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOARHGAP21 is a Rho GTPase-activating protein (RhoGAP) that associates with many proteins and modulates several cellular functions, including actin cytoskeleton rearrangement in different tissues. However, it is unknown whether ARHGAP21 is expressed in panc1275358FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2011/12050-7472028/2010-