Cynara Gomes Barbosa

Deficiência de magnésio e resistência à insulina em pacientes com diabetes mellitus tipo 2

Magnesium is a predominantly intracellular ion, and it is a cofactor in more than 300 enzymatic reactions, like tyrosinokinase activity. Its deficiency may increase insulin resistance, especially in patients with metabolic syndrome or type 2 diabetes. This study evaluated in 27 patients with poorly controlled type 2 diabetes if there was correlation between intracellular magnesium levels, laboratorial indexes of insulin resistance and glycemic control. Decreased serum and intracellular magnesium depletion were found in 75% and 30.8% of patients, respectively. A negative correlation between intracellular magnesium levels (ICMg) and BMI and HbA1 was found. The homeostasis model assessment for insulin resistance (HOMA-IR) was higher than 3.0 in 59.2% of patients and there was a tendency to negative correlation with ICMg levels, although without statistical significance. Despite the small number of patients, this study shows that magnesium deficiency is frequent in patients with diabetes and its correlation with insulin resistance should be more studied.

Risk factors for Toxocara spp. seroprevalence and its association with atopy and asthma phenotypes in school-age children in a small town and semi-rural areas of Northeast Brazil.

Toxocara canis, Toxocara cati, are roundworms that live in the intestines of dogs and cats, respectively, and are predominantly agents of human toxocariasis. Studies have suggested that Toxocara spp. seroprevalence increases levels of total and aeroallergen-specific IgE (sIgE), asthma prevalence and asthma morbidity. Nevertheless, other work reported a negative association between Toxocara spp. seropositivity with skin hypersensititity and a positive association with sIgE. The objective of the present study was to evaluate risk factors for acquiring Toxocara spp. infection and to investigate possible significant association between its seroprevalence with atopy and asthma. Students from elementary schools, residents in a small town and its surroundings of Northeast Brazil, underwent blood sampling to measure levels of anti-Toxocara spp. IgG, peripheral blood eosinophils, and specific IgE to aeroallergens. We used univariable and multivariable logistic regression analyses to assess possible risk factors for Toxocara spp. seropositivity and its association with atopy, wheeze/asthma with asthma phenotypes, in a sample of 791 elementary school children aged 6-13 years. Toxocara spp. seroprevalence reached 63.6%; 49.9% had sIgE; 7.2% and 3.3% had atopic wheeze/asthma and non-atopic wheeze/asthma respectively. Risk factors associated with Toxocara spp. seropositivity were: contact with dogs (adj. OR 2.33; 95% CI=1.70-3.19) and cats (adj. OR 3.09; 95% CI=2.10-4.55), and male sex (adj. OR 2.21; 95% CI=1.62-3.02). The presence of anti-Toxocara IgG was statistically associated with blood eosinophils >4% and >10% (adj. OR 1.84; 95% CI=1.33-2.55 and adj. OR 2.07; 95% CI=1.45-2.97, respectively), and atopy (adj. OR 2.00; 95% CI=1.49-2.68), but it was not associated with wheeze/asthma. Concluding, the results obtained in this study showing the association of Toxocara spp. seroprevalence with sIgE may suggest a possible immunological cross-reactivity between IgE epitopes from Toxocara spp. and aeroallergens.

Genetic modulation of HbF in Brazilians with HbSC disease and sickle cell anemia

Sickle cell anemia (homozygosity for HbS) and HbSC disease (compound heterozygosity for HbS and HbC) are the most common genotypes of sickle cell disease (SCD). Fetal hemoglobin (HbF), the major genetic modulator of SCD, interferes with deoxyHbS polymerization [1]. Patients with HbSC disease have about half the number of complications as do HbS homozygotes [1], however, their mean HbF levels were 2.4% compared with about 6% in patients with sickle cell anemia [2]. Single nucleotide polymorphisms (SNPs) in quantitative trait loci cis and trans to the β-globin gene cluster are associated with HbF. We analyzed the association of SNPs in BCL11A, (chromosome 2p), in the HBS1L-MYB intergenic region (HMIP) (chromosome 6q), and in the 5′ olfactory receptor (OR) gene cluster of chromosome 11p with HbF in Brazilian patients with SCD. 622 patients were studied. They were not treated with hydroxyurea and were aged ≥6 years. Hemoglobin was analyzed by HPLC. SNPs rs766432 and rs6732518 in BCL11A; rs35959442 and rs11759553 in HMIP; and rs4910755 and 7483122 located in OR51B5-OR51B6 were genotyped by ABI TaqMan Assays. The βS and βC globin haplotypes were investigated with PCR and restriction fragment length polymorphism techniques. Mean HbF was compared according to genotype using the additive genetic model adjusting for age, gender and HbS homozygotes versus HbSC. A dominant genetic model adjusting for age, gender and SCD genotype was used to test the association SNPs with HbF. We tested to see if there was an association between HbF and SNPs in the OR gene cluster region after adjusting for age, gender, SCD genotype and the HBB gene cluster haplotype (Central African Republic [CAR] or Bantu versus absence of a CAR haplotype). To determine if there was a synergistic effect between the SNPs or if the effect exerted on HbF was independent, we developed multivariable linear regression models adjusting for age, gender and SCD disease status and ran stepwise linear regression analyses where we added the most significant SNPs from BCL11A, HMIP one-at-a-time. Data analysis was performed using R version 2.14.1 and the cubic root transformation of HbF [3]. 392 patients were HbS homozygotes (HbF 7.4±4.4%) and 230 had HbSC disease (HbF 2.5±2.3%). The association between HbF and SNPs in the BCL11A, HMIP and the OR gene cluster for all patients combined and for HbS homozygotes and HbSC patients separately are shown in Table I a-c (on-line supplementary material). In the combined group, there is a statistically significant association between HbF levels and both BCL11A SNPs and with HMIP SNP rs11759553 after adjusting for age, gender and the SCD genotype. As the number of minor alleles increase, so does HbF level; in HbS homozygotes a similar result was found; in HbSC disease both SNPs in BCL11A and HMIP were associated with HbF. The association between HbF levels and SNPs in the OR genes, after adjusting fo r HBB haplotype was not significant (Table II, on-line supplementary material). In a stepwise linear regression analysis adding the SNPs to a multivariable linear regression model as described, after adjusting for age, gender and SCD genotype rs35959442 is still significantly associated with HbF indicating that its effect on HbF is independent of rs766432 (Table III, on-line supplementary material). We dichotomized the patients according to the HBB gene cluster haplotype. Brazilians with SCD have a higher prevalence of the CAR haplotype compared with African Americans. This haplotype is associated with lower levels of HbF than other haplotypes [4][5]. Sickle cell anemia patients were heterozygous or homozygous for the CAR haplotype chromosome or lacked a CAR haplotype chromosome; HbSC disease patients had or did not have a CAR haplotype chromosome. Most patients with a CAR haplotype had the minor allele for rs4910755 and rs7483122, both of which are located in the 5′ OR gene cluster of chromosome 11p and could be in linkage disequilibrium with SNPs characterizing this haplotype. HbSC disease patients usually have low HbF levels. Nevertheless, it is a milder condition than sickle cell anemia even though patients are more susceptible to clinical events related to high bloodviscosity. Although HbF in HbSC disease is lower than in HbS homozygotes, BCL11A and HMIP modulate HbF in both genotypes.

Inflammatory mediators in sickle cell anaemia highlight the difference between steady state and crisis in paediatric patients

Instituto Gonc alo Moniz- Fundacao Oswaldo Cruz (IGM-FIOCRUZ) and the Hospital da Crianc a das Obras Sociais Irma Dulce (HCOSID) approved this study, with protocol number 0016.0.225.000-09.

Hemoglobin Variant Profiles among Brazilian Quilombola Communities

Abstract Brazilian Quilombolas are communities composed of African-derived populations that have their territories guaranteed by the Brazilian Constitution. The present study investigated the hemoglobin (Hb) variants among these population groups. This study was conducted in a total of 2843 individuals of Brazilian Quilombola communities of the Bahia, Pará, and Piauí states. All the participants had their Hb profiles evaluated. The Hb S (HBB: c.20A>T) variant was described in all the studied localities. However, the individuals in Bahia State had the highest frequency of the Hb C (HBB: c.19G>A) variant; individuals from Piauí State had a higher frequency of the Hb D-Punjab (HBB: c.364G>C) variant compared to the other states, and individuals from Pará State only carried the Hb S variant. The present study revealed a specific distribution of Hb variants that could represent different waves of African influence in these Brazilian populations.

Evaluation of Cardiometabolic Parameters among Obese Women Using Oral Contraceptives

Background Combined oral contraceptive (COC) use has been associated with an unfavorable impact on carbohydrate and lipid metabolism in diverse populations of normal weight and obese women. The present study aimed to evaluate the cardiometabolic and inflammatory profiles of women in northeastern Brazil with respect to COC use and obesity. Methods We performed a cross-sectional study to verify cardiovascular parameters, including blood pressure (BP), fasting serum glucose, lipid, and inflammatory profile, in a population of women aged 15–45 years, considering obesity and COC use. Our sample consisted of 591 women, 481 women who were COC users, and 110 age-matched women who were COC non-users, classified as obese and non-obese according to BMI. Results COC use and obesity were associated with increased systolic (p ≤ 0.001) and diastolic BP (p = 0.001), blood glucose (p ≤ 0.001), total cholesterol (p = 0.008), low-density lipoprotein cholesterol (p ≤ 0.001), very low-density lipoprotein cholesterol (p ≤ 0.001), triglycerides (p ≤ 0.001), ferritin (p = 0.006), C-reactive protein (CRP) (p ≤ 0.001), and nitric oxide metabolites (p ≤ 0.001), as well as decreased high-density lipoprotein cholesterol (HDL-c) (p ≤ 0.001) in comparison to controls. CRP and HDL-c levels in obese COC users were determined to be outside reference range values. The odds of having lower levels of HDL-c and elevated CRP increased among obese COC users. COC use was independently associated with low levels of HDL-c, especially second-generation progestins (p < 0.001; OR = 8.976; 95% CI 2.786–28.914). Conclusion Obesity and COC use were associated with alterations in lipid and inflammatory cardiometabolic parameters, particularly increased CRP levels and decreased HDL-c, which are considered markers of cardiovascular disease (CVD) risk. Given the need to prevent unintended pregnancy among obese women, together with weight loss counseling, it is important to evaluate the most effective and safest contraceptive methods to avoid the potential risk of developing CVD.

Genetic modulation of fetal hemoglobin in hydroxyurea-treated sickle cell anemia

viruses, Hydroxyurea, and bone marrow stress due to chronic anemia. Interestingly, patients with sickle cell disease share these risk factors and have been also noted to exhibit an increased risk of malignancies, mostly of the hematologic type. Aside from blood donor screening to decrease the risk of transmission of viruses such as HTLV-1, CMV, and Hepatitis C, optimization of iron chelation practices, and leukoreduction of the transfused blood, there are currently no specific recommendations as far as risk factor modification is concerned. There are no screening guidelines for hematologic malignancies in patients with thalassemia. While the association between thalassemia and hematologic malignancies remains in its early stages, it will be important to continue to explore the field and conduct more large scale studies with long-term follow-up. It is also paramount to remain very attentive to new signs and symptoms patients with thalassemia exhibit that may indicate a hematologic malignancy, with the understanding that some of these findings may overlap with those of thalassemia, such as worsening anemia, fatigue, and splenomegaly.

Genetic Polymorphisms Associated with Environmental Exposure to Polycyclic Derivatives in African Children

Background The nonracial leukopenia may be a result of exposure to polycyclic derivatives (benzene-toluene-xylene (BTX)) and may arise from a possible change in the bone marrow microenvironment. The present study sought to evaluate the association of genetic polymorphisms in xenobiotic-metabolizing enzymes with hematological and biochemical profiles. Methods We evaluated 89 African descendant children, exposed indirectly to benzene derivatives. Laboratory parameters were investigated by automated methods and genetic polymorphisms by PCR-RFLP and PCR multiplex. Results Children with leukopenia had significantly decreased white blood cells (WBCs) and platelet counts, which is not consistent with benign leukopenia. In the same group, we have found that carriers of the CYP2E1 variant allele had decreased WBC and lymphocytes. Those with NQO1 variant allele had decreased WBC, neutrophil, eosinophil, monocyte, and lymphocyte counts. Carriers of the MPO variant allele had decreased WBC, neutrophil, eosinophil, basophil, monocyte, lymphocyte, and platelet counts and an elevated free iron level. Children with GSTT and GSTM null exhibited decreased WBC, neutrophil, basophil, and lymphocyte counts. Our multivariate analysis model reveals that females were independently associated with leukopenia. Conclusion Our results suggest that the polymorphisms investigated were associated with hematological changes in the studied population. These alterations could be heightened by exposure to benzene derivatives.

Data on prevalence and risk factors associated with Toxocara spp infection, atopy and asthma development in Northeast Brazilian school children

In the present article, we provide shortly, data on risk factors for acquiring Toxocara spp. infection and investigate possible associations between this infection with atopy and asthma in school children of a small town and its semi-rural areas of Northeast Brazil. The data set are composed by demographic, social and home environment variables. The detection of anti-Toxocara spp. IgG and specific IgE to aeroallergens was determined by ELISA and ImmunocAP/Phadiatrope systems, respectively. The data presented in this article are related to the article entitled “Risk factors for Toxocara spp. seroprevalence and its association with atopy and asthma phenotypes in school-age children in a small town and semi-rural areas of Northeast Brazil” (M.B. Silva, A.L. Amor, L.N. Santos, A.A. Galvão, A.V. Oviedo Vera, E.S. Silva et al., 2016) [1].

Outcome of B-Cell Acute Lymphoblastic Leukemia in Brazilian Children: Immunophenotypical, Hematological, and Clinical Evaluation

The aim of this study is to investigate the clinical, hematological, and immunophenotypic characteristics of Brazilian children with B-cell acute lymphoblastic leukemia (B-ALL) to identify prognostic biomarkers of the disease. Thirty-three children newly diagnosed with B-ALL were followed between March 2004 and December 2009. Information about the demographic profile, diagnosis, immunophenotype, clinical manifestations, and disease outcome were gathered from the patients’ medical records. Of the 33 patients with B-ALL, 18 were male and 15 female. Eighteen patients were classified as high risk; 13 as low risk, and 2 as true low risk. The frequencies of cluster of differentiation (CD)10, CD19, and CD20 antigens were 69.7%, 81.8%, and 18.2%, respectively. Six patients (18.2%) had aberrant expression of myeloid antigens. At diagnosis, patients immunopositive for CD20 had elevated white blood cell counts (P=0.018) and lower platelet counts (P=0.017). The 6-year overall survival was 67.5%±3.47%. Our results demonstrate the distinct immunophenotypic and prognostic characteristics of patients with B-ALL, which can be related to the Brazilian racial admixture. Consequently, these results will most likely aid in the selection of additional prognostic markers and their use in monitoring the clinical manifestations and treatment response among B-ALL patients.