Elvira Guerra-shinohara - Academia.edu (original) (raw)

Papers by Elvira Guerra-shinohara

Research paper thumbnail of Relationship between total homocysteine and folate levels in mother-baby pairs according to maternal levels of vitamin B12

Revista Brasileira De Ciencias Farmaceuticas, 2000

Research paper thumbnail of Development of the nutritional condition of pregnant women assisted by the basic health network, Santo André, Brazil

Research paper thumbnail of Subject Index Vol. 124, 2010

Acta Haematologica, 2010

Acquired haemophilia 40 Acute myelogenous leukemia 206-myeloid leuk(a)emia 61, 98 Adiponectin 191... more Acquired haemophilia 40 Acute myelogenous leukemia 206-myeloid leuk(a)emia 61, 98 Adiponectin 191 Adult T-cell leukemia/lymphoma 171 Adverse effects 125 Aetiology, haemophilia 40 Allogeneic hematopoietic stem cell transplantation 171-cells 134 AMD3100 235 Amphotericin B lipid formulation 98 Anemia 86 Annexin V 79 Anti-CD14 141 Anti-CD19 141 Anti-CD3 141 Anti-CD34 141 Anti-CD4 141 Anti-CD8 141 Antifungal prophylaxis 206 Anti-Helicobacter pylori IgG antibodies 141 Anti-human T lymphocyte porcine immunoglobulin 245 Aplastic anemia 19 Apoptosis 72, 79 Arg304Gln mutation 229 Autoimmune disease 19 Autoimmunity 5 Autologous peripheral blood stem cell transplantation 235-stem cell mobilization 235-transplantation 61 Bisphosphonates 79 Bleeding disorders 40 Bone marrow transplantation 134 Bortezomib 34 Bowen's disease 105-Carrageenan 218 Caspofungin 98 CD34+ cells 235 Cell proliferation 72 Cephalosporin 197 Chronic lymphocytic leukemia 57, 105-myeloid leukemia 105 Circulating endothelial cell 79 Clinical genetics 162 Continuous erythropoietin receptor activator 27 253

Research paper thumbnail of Molecular changes associated with hereditary hemochromatosis

Revista Brasileira de …, 2009

O ferro é um elemento químico indispensável ao seres humanos e praticamente encontrado em todos o... more O ferro é um elemento químico indispensável ao seres humanos e praticamente encontrado em todos os seres vivos. Este íon faz parte de proteínas e enzimas importantes no transporte de oxigênio (hemoglobina e mioglobina), na síntese de DNA (ribonucleotídeo redutase), na produção de energia oxidativa (citocromo, catalase e peroxidase), na respiração mitocondrial (succinato desidrogenase) e na inativação de radicais livres (xantina oxidase). A concentração média de ferro no organismo de um indivíduo adulto é de 4 a 5 g, sendo Alterações moleculares associadas à hemocromatose hereditária Molecular changes associated with hereditary hemochromatosis

Research paper thumbnail of Folato, vitamina B12 e ferritina sérica e defeitos do tubo neural

RBGO, 1998

Instituições onde o trabalho foi desenvolvido: 1 Faculdade de Saúde Pública da USP 2 Instituto Ad... more Instituições onde o trabalho foi desenvolvido: 1 Faculdade de Saúde Pública da USP 2 Instituto Adolfo Lutz 3 Setor de Medicina Fetal da disciplina de Obstetrícia da UNIFESP, Escola Paulista de Medicina Correspondência: Gizele Thame R. Aibi, 146 - ap. 62 Alto da Lapa ...

Research paper thumbnail of Serum folate by two methods in pregnant women carrying fetuses with neural tube defects

Clinical chemistry, 2002

Neural tube defects (NTDs) are the most common severe congenital malformations that occur as a re... more Neural tube defects (NTDs) are the most common severe congenital malformations that occur as a result of failure of neural tube closure at the beginning of pregnancy (24–28 days after conception). Genetic (4)(2)(3), environmental (4), and nutritional factors (5)(6)(7)(8)(9) ...

Research paper thumbnail of Low ratio of S-adenosylmethionine to S-adenosylhomocysteine is associated with vitamin deficiency in Brazilian pregnant women and newborns

American Journal of Clinical Nutrition

Background: Pregnant women with low cobalamin concentrations are unable to provide the necessary ... more Background: Pregnant women with low cobalamin concentrations are unable to provide the necessary amount of cobalamin to their fetuses. The effect of low maternal cobalamin concentrations on transmethylation metabolism in pregnant women and their newborns is unknown. Objective: We investigated the relation between maternal and neonatal cobalamin concentrations and changes in total homocysteine (tHcy), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH). Design: Hematologic data and concentrations of cobalamin, red blood cell folate, serum folate, tHcy, methylmalonic acid, SAM, SAH, and other metabolites were measured in 119 serum specimens from pregnant Brazilian women (gestational age: 37-42 wk) and their newborns' placental veins at the time of delivery. Results: The tHcy concentrations were higher in placental vein serum from newborns whose mothers had low cobalamin. Serum SAH concentrations were elevated and serum SAM and methionine concentrations were decreased in pregnant women with lower cobalamin concentrations. SAM:SAH was significantly decreased in both cobalamin-deficient pregnant women and their newborns. Conclusions: Lower maternal cobalamin concentrations are associated with higher tHcy and lower SAM:SAH in newborns. Because SAM:SAH is closely linked with the activity of numerous enzymatic methylation reactions, these results suggest that methylation could be impaired in cobalamin-deficient pregnant women and their newborns.

Research paper thumbnail of ABCB1 haplotypes are associated with P‑gp activity and affect a major molecular response in chronic myeloid leukemia patients treated with a standard dose of imatinib

Oncology Letters, 2014

Despite the high efficacy of imatinib mesylate (IM) treatment for chronic myeloid leukemia (CML) ... more Despite the high efficacy of imatinib mesylate (IM) treatment for chronic myeloid leukemia (CML) patients, some individuals develop resistance due to impaired bioavailability. It has been previously demonstrated that the haplotypes for ATP-binding cassette subfamily B member 1 (ABCB1)with c.1236C>T, c.3435C>T and c.2677G>T/A polymorphisms markedly affect the secondary structure of ABCB1 mRNA and its activity. These modifications may affect efflux transporter activity and response to treatment with IM. The aim of the present study was to investigate the influence of ABCB1 haplotypes on P-glycoprotein (P-gp) activity, IM plasma levels and IM response. In total, 28 chronic-phase CML patients treated with a standard dose of IM (400 mg/day) were studied. The patients were selected according to the haplotypes of ABCB1, with c.1236C>T, c.3435C>T and c.2677G>T polymorphisms, and were classified into two groups based on the presence of the mutated allele in each genotype for the three ABCB1 polymorphisms. In addition, expression of P-gp and breakpoint cluster region-abelson 1 (BCR-ABL1), ABCB1 and solute carrier family 22 member 1 (SLC22A1) mRNA were evaluated. The P-gp activity in the wild-type group was found to be higher than that in the mutated group (59.1 vs. 38.3%; P= 0.001).

Research paper thumbnail of Concentrations of blood folate in Brazilian studies prior to and after fortification of wheat and cornmeal (maize flour) with folic acid: a review

Revista Brasileira de Hematologia e Hemoterapia, 2014

In July 2004, the Brazilian Ministry of Health through the National Health Surveillance Agency ma... more In July 2004, the Brazilian Ministry of Health through the National Health Surveillance Agency made the fortification of wheat flour and cornmeal (maize flour) with iron and folic acid mandatory, with the intention of reducing the rate of diseases such as neural tube defects. The aim of the study was to investigate the impact of the folic acid fortified wheat flour and cornmeal on serum and red blood cell folate levels and on the reduction of neural tube defects in different Brazilian studies. In order to compare folate concentrations in the Brazilian population prior to and following the implementation of mandatory fortification of wheat and cornmeal, studies that involved blood draws between January 1997 and May 2004 (pre-fortification period), and from June 2004 to the present (post-fortification period) were chosen. The data search included PubMed and Scopus databases as well as the Brazilian Digital Library of Theses and Dissertations. The following keywords were employed for the query: folate, folic acid, fortification, Brazil, healthy population, the elderly, children and pregnant women. A total of 47 Brazilian studies were selected; 26 from the pre-fortification period and 22 after the fortification implementation. The studies were classified according to the cohort investigated (pregnant women, children, adolescents, adults and the elderly). After the implementation of flour fortification with folic acid in Brazil, serum folate concentrations increased in healthy populations (57% in children and adolescents and 174% in adults), and the incidence of neural tube defects dropped. Folic acid fortification of wheat flour and cornmeal increased the blood folate concentrations and reduced the incidence of neural tube defects.

Research paper thumbnail of Reduced ABCG2 and increased SLC22A1 mRNA expression are associated with imatinib response in chronic myeloid leukemia

Medical Oncology, 2014

Imatinib mesylate (IM) has become a standard of care in chronic myeloid leukemia (CML) therapy. S... more Imatinib mesylate (IM) has become a standard of care in chronic myeloid leukemia (CML) therapy. Single nucleotide polymorphisms (SNPs) and altered expression in drug transporter genes may influence IM response. In order to investigate whether mRNA expression and SNPs in drug transporters are associated with IM resistance, we studied 118 chronic-phase CML patients receiving the standard dose of IM (400 mg/day). They were assigned as responders and nonresponders according to European LeukemiaNet criteria (2009). mRNA expression in samples at diagnosis (without IM therapy) and outcomes after IM failure were also evaluated in subgroups of patients. Major molecular response (MMR), complete molecular response and primary and secondary resistance were all assessed. BCR-ABL1, ABCB1, ABCG2, SLC22A1 and SLCO1A2 mRNA expression and SNPs in ABCG2 and SLC22A1 genes were analyzed. ABCG2 mRNA expression in the non-responders was higher before and during IM therapy. Furthermore, ABCG2 was overexpressed in those who did not achieve MMR (P = 0.027). In a subgroup of patients who switched to second-generation tyrosine kinase inhibitors, high mRNA expression of ABCG2 was associated with a risk of 24 times that of not achieving complete cytogenetic response (OR 24.00, 95 % CI 1.74-330.80; P = 0.018). In the responder group, patients who achieved MMR (P = 0.009) presented higher mRNA levels of SLC22A1. The SNPs were not associated with mRNA expression of ABCG2 and SLC22A1. Our data suggest that elevated ABCG2 expression (an efflux transporter) could be associated with IM resistance and could impact on second-generation TKI response, whereas high SLC22A1 expression (an influx transporter) may be associated with a successful IM therapy in CML patients.

Research paper thumbnail of Iron deficiency and frequency of HFE C282Y gene mutation in Brazilian blood donors

Transfusion Medicine, 2009

Limited data are available about iron deficiency (ID) in Brazilian blood donors. This study evalu... more Limited data are available about iron deficiency (ID) in Brazilian blood donors. This study evaluated the frequencies of ID and iron-deficiency anaemia (IDA) separately and according to frequency of blood donations. The protective effect of the heterozygous genotype for HFE C282Y mutation against ID and IDA in female blood donors was also determined. Five hundred and eight blood donors were recruited at the Blood Bank of Santa Casa in Sao Paulo, Brazil. Haemoglobin and serum ferritin concentrations were measured. The genotype for HFE C282Y mutation was determined by polymerase chain reaction followed by restriction fragment length polymorphism analysis. The ID was found in 21.1% of the women and 2.6% of the men whereas the IDA was found in 6.8 and 0.3%, respectively. The ID was found in 11.9% of the women in group 1 (first-time blood donors) and the frequency increased to 38.9% in women of the group 3 (blood donors donating once or more times in the last 12 months). No ID was found in men from group 1; however the ID frequency increased to 0.9% in group 2 (who had donated blood before but not in the last 12 months) and 5.0% in group 3. In summary, the heterozygous genotype was not associated with reduction of ID or IDA frequencies in both genders, but in male blood donors it was associated with a trend to elevated ferritin levels (P = 0.060). ID is most frequent in Brazilian women but was also found in men of group 3.

Research paper thumbnail of Polymorphisms in antithrombin and in tissue factor pathway inhibitor genes are associated with recurrent pregnancy loss

Thrombosis and Haemostasis, 2012

Recurrent pregnancy loss (RPL) is a multifactorial condition. The effect of antithrombin (SERPINC... more Recurrent pregnancy loss (RPL) is a multifactorial condition. The effect of antithrombin (SERPINC1), protein C (PROC), thrombomodulin (THBD) and tissue factor pathway inhibitor (TFPI) single nucleotide polymorphisms (SNPs) on the risk of RPL is thus far unknown. Our objective was to determine the association of SNPs in the above mentioned genes with RPL. We included 117 non-pregnant women with three or more consecutive losses prior to 20 weeks of pregnancy without a previous history of carrying a fetus to viability, and 264 healthy fertile non-pregnant women who had at least two term deliveries and no known pregnancy losses. The PROC (rs1799809 and rs1799808), SERPINC1 (rs2227589), THBD (rs1042579) and TFPI (rs10931292, rs8176592 and rs10153820) SNPs were analysed by Real Time PCR. Genotype frequencies for PROC 2418A>G, PROC 2405C>T, THBD 1418C>T, TFPI (T-33C and TFPI C-399T) SNPs were similar in cases and controls. The carriers of SERPINC1 786A allele (GA + AA genotypes) had an increased risk for RPL (odds ratio [OR]: 1.77, 95% confidence interval [CI]: 1.05-3.00, p= 0.034) while women carrying the TFPI -287C allele (TC + CC genotypes) had a protection effect on having RPL (OR: 0.46, 95% CI: 0.26-0.83, p= 0.009). The TCC haplotype for TFPI T-33C/ TFPI T-287C/ TFPI C-399T SNPs was less frequent in cases (5.7%) than in controls (11.6%) (OR: 0.45, 95% CI: 0.23-0.90, p= 0.025). In conclusion, our data indicate that SERPINC1 786G>A variant increases the risk for RPL, while TFPI T-287C variant is protective; however, further studies are required to confirm our findings.

Research paper thumbnail of Evolucion del estado nutricional de embarazadas atendidas en la red basica de salud, Santo Andre, Brasil

Revista Latino-Americana de Enfermagem, 2001

Fujimori E, Cassana LMN, Szarfarc SC, Oliveira IMV, Guerra-Shinohara EM. Evolución del estado nut... more Fujimori E, Cassana LMN, Szarfarc SC, Oliveira IMV, Guerra-Shinohara EM. Evolución del estado nutricional de embarazadas atendidas en la red basica de salud, Santo André, Brasil. Rev Latino-am Enfermagem 2001 maio; 9(3):64-9.

Research paper thumbnail of Homocysteine and lipid profile in children with Juvenile Idiopathic Arthritis

Pediatric Rheumatology, 2007

Background: An increased concentration of plasma homocysteine (Hcy) has toxic effects on vascular... more Background: An increased concentration of plasma homocysteine (Hcy) has toxic effects on vascular endothelium. This seems to be a risk factor of cardiovascular disease, premature stroke and venous thrombosis. The risk is higher in coincidence with other factors like chronic diseases and familiar hypercholesterolemia. The aim of our study was to evaluate plasma Hcy concentration in patients with juvenile idiopathic arthritis (JIA) and its correlation with methotrexate (MTX) therapy, serum folate and B12 vitamin, and hyperlipidemia.

Research paper thumbnail of Elevated serum S-adenosylhomocysteine in cobalamin-deficient megaloblastic anemia

Metabolism, 2007

Impaired methylation due to accumulation of S-adenosylhomocysteine (SAH) may contribute to the pa... more Impaired methylation due to accumulation of S-adenosylhomocysteine (SAH) may contribute to the pathophysiology of cobalamindeficient anemia. We assayed serum S-adenosylmethionine (SAM), SAH, total homocysteine (tHcy), and methylmalonic acid (MMA) in 15 subjects with cobalamin-deficient megaloblastic anemia and compared results with those of 19 subjects with anemia/pancytopenia due to other causes. Cobalamin-deficient subjects had a median hematocrit level of 20% and mean cell volume of 111.7 fL. The median serum cobalamin level was 37 pg/mL, MMA 3030 nmol/L, and tHcy 62.0 lmol/L. SAH was elevated in 13 of 15 subjects (median, 42 nmol/L) and the median SAM value was normal (103 nmol/L), but SAM/SAH ratio was low (2.5). The SAH was higher and SAM/SAH ratio was lower in cobalamin-deficient subjects compared with those with other anemias after excluding 4 patients with renal insufficiency. SAM concentrations were not low in cobalamin deficiency. Cobalamin injections corrected anemia, MMA, tHcy, SAM/SAH ratio, and SAH. Some hematologic variables were inversely correlated with SAH and cobalamin but not tHcy or MMA. In conclusion, serum SAH is elevated in cobalamindeficient subjects with megaloblastic anemia and corrects with parenteral cobalamin therapy. D

Research paper thumbnail of Hemojuvelin and Hepcidin Genes Sequencing in Brazilian Patients with Primary Iron Overload

Genetic Testing and Molecular Biomarkers, 2010

most hereditary hemochromatosis (HH) patients are homozygous for the p.C282Y mutation in the HFE ... more most hereditary hemochromatosis (HH) patients are homozygous for the p.C282Y mutation in the HFE gene. Some studies reported that HH phenotypic expression could be modulated by genetic factors such as HJV and HAMP gene mutations. the aims of this study were to identify HJV and HAMP mutations and to analyze their impact on HH phenotype in non-p.C282Y homozygous individuals. Twenty-four Brazilian patients with primary iron overload and non-p.C282Y homozygous genotype (transferrin saturation >50% in women and >60% in men and absence of secondary causes) were selected. Subsequent bidirectional sequencing of the HJV and HAMP exons was performed. sequencing revealed a substitution in heterozygosis, c.929C > G, which corresponds to p.A310G polymorphism in HJV exon 4 (rs7540883). In the same gene, in another individual, an IVS1-36C > G intronic variant was detected in heterozygosis. In the HAMP gene, an IVS3 + 42G > A intronic variant was identified. There were six (25.0%) patients carrying a heterozygous genotype for the HFE p.C282Y and nine (37.5%) patients carrying a heterozygous genotype for the HFE p.H63D. HJV p.A310G polymorphism and two intronic variants were found, but none of these alterations were associated with digenic inheritance with the HFE gene. Our data indicate that HJV and HAMP functional mutations are not frequent in these patients.

Research paper thumbnail of Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphisms as determinants for elevated total homocysteine concentrations in pregnant women

European Journal of Clinical Nutrition, 2008

To examine the association between methylenetetrahydrofolate reductase (MTHFR) (C677T and A1298C)... more To examine the association between methylenetetrahydrofolate reductase (MTHFR) (C677T and A1298C), methionine synthase (MTR) A2756G and methionine synthase reductase (MTRR) A66G gene polymorphisms and total homocysteine (tHcy), methylmalonic acid (MMA) and S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) levels; and to evaluate the potential interactions with folate or cobalamin (Cbl) status. Two hundred seventy-five healthy women at labor who delivered full-term normal babies. Cbl, folate, tHcy, MMA, SAM and SAH were measured in serum specimens. The genotypes for polymorphisms were determined by PCR-restriction fragment length polymorphism (RFLP). Serum folate, MTHFR 677T allele and MTR 2756AA genotypes were the predictors of tHcy levels in pregnant women. Serum Cbl and creatinine were the predictors of SAM/SAH ratio and MMA levels, respectively. The gene polymorphisms were not determinants for MMA levels and SAM/SAH ratios. Low levels of serum folate were associated with elevated tHcy in pregnant women, independently of the gene polymorphisms. In pregnant women carrying MTHFR 677T allele, or MTHFR 1298AA or MTRR 66AA genotypes, lower Cbl levels were associated with higher levels of tHcy. Lower SAM/SAH ratio was found in MTHFR 677CC or MTRR A2756AA genotypes carriers when Cbl levels were lower than 142 pmol/l. Serum folate and MTHFR C677T and MTR A2576G gene polymorphisms were the determinants for tHcy levels. The interaction between low levels of serum Cbl and MTHFR (C677T or A1298C) or MTRR A66G gene polymorphisms was associated with increased tHcy.

Research paper thumbnail of The influence of iron, vitamin B, and folate levels on soluble transferrin receptor concentration in pregnant women

Clinica Chimica Acta, 2003

Background: Soluble transferrin receptor (sTfR) concentration is high in iron deficiency and in c... more Background: Soluble transferrin receptor (sTfR) concentration is high in iron deficiency and in conditions of increased erythropoiesis. In developing countries like Brazil, pregnant women usually have concurrent iron, vitamin B12, and folate deficiencies. This study investigated the relationship between serum sTfR concentration and iron, vitamin B12, and folate status in pregnant women. Methods: The concentration of the sTfR, hematocrit (Hct),

Research paper thumbnail of Metabolic effects of C677T and A1298C mutations at the MTHFR gene in Brazilian children with neural tube defects

Clinica Chimica Acta, 2002

Methylenetetrahydrofolate reductase (MTHFR) deficiency leads to impairment in folate metabolism a... more Methylenetetrahydrofolate reductase (MTHFR) deficiency leads to impairment in folate metabolism and is implicated as a risk factor for neural tube defects (NTDs). Both C677T and A1298C MTHFR mutations are associated with NTDs, in some populations. The frequencies of the C677T and A1298C MTHFR mutations were determined in 25 children with NTDs, case mothers and 75 healthy individuals from Sao Paulo City. Both C677T and A1298C mutations were analyzed by PCR-FLRP. The effects of MTHFR mutations on folate, vitamin B12 and homocysteine concentrations were also evaluated. C677T and A1298C allele frequencies in NTDs children and mothers were similar to that found in controls. Eleven in 23 NTDs patients and 10 in 21 NTDs mothers had folate or vitamin B12 concentrations in the lower end of the normal range. In NTDs children, C677T MTHFR genotypes did not affect vitamins and homocysteine concentrations, but plasma homocysteine was higher (p=0.028) in patients with 1298AA MTHFR genotype. Moreover, 677CT/1298AA haplotype was associated with lower vitamin B12 concentrations (p<0.05) in NTDs children. MTHFR gene mutations may affect vitamin B12 and homocysteine metabolism in Brazilian children with NTDs.

Research paper thumbnail of Methylenetetrahydrofolate reductase (MTHFR) c677t gene variant modulates the homocysteine folate correlation in a mild folate-deficient population

Clinica Chimica Acta, 2004

Research paper thumbnail of Relationship between total homocysteine and folate levels in mother-baby pairs according to maternal levels of vitamin B12

Revista Brasileira De Ciencias Farmaceuticas, 2000

Research paper thumbnail of Development of the nutritional condition of pregnant women assisted by the basic health network, Santo André, Brazil

Research paper thumbnail of Subject Index Vol. 124, 2010

Acta Haematologica, 2010

Acquired haemophilia 40 Acute myelogenous leukemia 206-myeloid leuk(a)emia 61, 98 Adiponectin 191... more Acquired haemophilia 40 Acute myelogenous leukemia 206-myeloid leuk(a)emia 61, 98 Adiponectin 191 Adult T-cell leukemia/lymphoma 171 Adverse effects 125 Aetiology, haemophilia 40 Allogeneic hematopoietic stem cell transplantation 171-cells 134 AMD3100 235 Amphotericin B lipid formulation 98 Anemia 86 Annexin V 79 Anti-CD14 141 Anti-CD19 141 Anti-CD3 141 Anti-CD34 141 Anti-CD4 141 Anti-CD8 141 Antifungal prophylaxis 206 Anti-Helicobacter pylori IgG antibodies 141 Anti-human T lymphocyte porcine immunoglobulin 245 Aplastic anemia 19 Apoptosis 72, 79 Arg304Gln mutation 229 Autoimmune disease 19 Autoimmunity 5 Autologous peripheral blood stem cell transplantation 235-stem cell mobilization 235-transplantation 61 Bisphosphonates 79 Bleeding disorders 40 Bone marrow transplantation 134 Bortezomib 34 Bowen's disease 105-Carrageenan 218 Caspofungin 98 CD34+ cells 235 Cell proliferation 72 Cephalosporin 197 Chronic lymphocytic leukemia 57, 105-myeloid leukemia 105 Circulating endothelial cell 79 Clinical genetics 162 Continuous erythropoietin receptor activator 27 253

Research paper thumbnail of Molecular changes associated with hereditary hemochromatosis

Revista Brasileira de …, 2009

O ferro é um elemento químico indispensável ao seres humanos e praticamente encontrado em todos o... more O ferro é um elemento químico indispensável ao seres humanos e praticamente encontrado em todos os seres vivos. Este íon faz parte de proteínas e enzimas importantes no transporte de oxigênio (hemoglobina e mioglobina), na síntese de DNA (ribonucleotídeo redutase), na produção de energia oxidativa (citocromo, catalase e peroxidase), na respiração mitocondrial (succinato desidrogenase) e na inativação de radicais livres (xantina oxidase). A concentração média de ferro no organismo de um indivíduo adulto é de 4 a 5 g, sendo Alterações moleculares associadas à hemocromatose hereditária Molecular changes associated with hereditary hemochromatosis

Research paper thumbnail of Folato, vitamina B12 e ferritina sérica e defeitos do tubo neural

RBGO, 1998

Instituições onde o trabalho foi desenvolvido: 1 Faculdade de Saúde Pública da USP 2 Instituto Ad... more Instituições onde o trabalho foi desenvolvido: 1 Faculdade de Saúde Pública da USP 2 Instituto Adolfo Lutz 3 Setor de Medicina Fetal da disciplina de Obstetrícia da UNIFESP, Escola Paulista de Medicina Correspondência: Gizele Thame R. Aibi, 146 - ap. 62 Alto da Lapa ...

Research paper thumbnail of Serum folate by two methods in pregnant women carrying fetuses with neural tube defects

Clinical chemistry, 2002

Neural tube defects (NTDs) are the most common severe congenital malformations that occur as a re... more Neural tube defects (NTDs) are the most common severe congenital malformations that occur as a result of failure of neural tube closure at the beginning of pregnancy (24–28 days after conception). Genetic (4)(2)(3), environmental (4), and nutritional factors (5)(6)(7)(8)(9) ...

Research paper thumbnail of Low ratio of S-adenosylmethionine to S-adenosylhomocysteine is associated with vitamin deficiency in Brazilian pregnant women and newborns

American Journal of Clinical Nutrition

Background: Pregnant women with low cobalamin concentrations are unable to provide the necessary ... more Background: Pregnant women with low cobalamin concentrations are unable to provide the necessary amount of cobalamin to their fetuses. The effect of low maternal cobalamin concentrations on transmethylation metabolism in pregnant women and their newborns is unknown. Objective: We investigated the relation between maternal and neonatal cobalamin concentrations and changes in total homocysteine (tHcy), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH). Design: Hematologic data and concentrations of cobalamin, red blood cell folate, serum folate, tHcy, methylmalonic acid, SAM, SAH, and other metabolites were measured in 119 serum specimens from pregnant Brazilian women (gestational age: 37-42 wk) and their newborns' placental veins at the time of delivery. Results: The tHcy concentrations were higher in placental vein serum from newborns whose mothers had low cobalamin. Serum SAH concentrations were elevated and serum SAM and methionine concentrations were decreased in pregnant women with lower cobalamin concentrations. SAM:SAH was significantly decreased in both cobalamin-deficient pregnant women and their newborns. Conclusions: Lower maternal cobalamin concentrations are associated with higher tHcy and lower SAM:SAH in newborns. Because SAM:SAH is closely linked with the activity of numerous enzymatic methylation reactions, these results suggest that methylation could be impaired in cobalamin-deficient pregnant women and their newborns.

Research paper thumbnail of ABCB1 haplotypes are associated with P‑gp activity and affect a major molecular response in chronic myeloid leukemia patients treated with a standard dose of imatinib

Oncology Letters, 2014

Despite the high efficacy of imatinib mesylate (IM) treatment for chronic myeloid leukemia (CML) ... more Despite the high efficacy of imatinib mesylate (IM) treatment for chronic myeloid leukemia (CML) patients, some individuals develop resistance due to impaired bioavailability. It has been previously demonstrated that the haplotypes for ATP-binding cassette subfamily B member 1 (ABCB1)with c.1236C>T, c.3435C>T and c.2677G>T/A polymorphisms markedly affect the secondary structure of ABCB1 mRNA and its activity. These modifications may affect efflux transporter activity and response to treatment with IM. The aim of the present study was to investigate the influence of ABCB1 haplotypes on P-glycoprotein (P-gp) activity, IM plasma levels and IM response. In total, 28 chronic-phase CML patients treated with a standard dose of IM (400 mg/day) were studied. The patients were selected according to the haplotypes of ABCB1, with c.1236C>T, c.3435C>T and c.2677G>T polymorphisms, and were classified into two groups based on the presence of the mutated allele in each genotype for the three ABCB1 polymorphisms. In addition, expression of P-gp and breakpoint cluster region-abelson 1 (BCR-ABL1), ABCB1 and solute carrier family 22 member 1 (SLC22A1) mRNA were evaluated. The P-gp activity in the wild-type group was found to be higher than that in the mutated group (59.1 vs. 38.3%; P= 0.001).

Research paper thumbnail of Concentrations of blood folate in Brazilian studies prior to and after fortification of wheat and cornmeal (maize flour) with folic acid: a review

Revista Brasileira de Hematologia e Hemoterapia, 2014

In July 2004, the Brazilian Ministry of Health through the National Health Surveillance Agency ma... more In July 2004, the Brazilian Ministry of Health through the National Health Surveillance Agency made the fortification of wheat flour and cornmeal (maize flour) with iron and folic acid mandatory, with the intention of reducing the rate of diseases such as neural tube defects. The aim of the study was to investigate the impact of the folic acid fortified wheat flour and cornmeal on serum and red blood cell folate levels and on the reduction of neural tube defects in different Brazilian studies. In order to compare folate concentrations in the Brazilian population prior to and following the implementation of mandatory fortification of wheat and cornmeal, studies that involved blood draws between January 1997 and May 2004 (pre-fortification period), and from June 2004 to the present (post-fortification period) were chosen. The data search included PubMed and Scopus databases as well as the Brazilian Digital Library of Theses and Dissertations. The following keywords were employed for the query: folate, folic acid, fortification, Brazil, healthy population, the elderly, children and pregnant women. A total of 47 Brazilian studies were selected; 26 from the pre-fortification period and 22 after the fortification implementation. The studies were classified according to the cohort investigated (pregnant women, children, adolescents, adults and the elderly). After the implementation of flour fortification with folic acid in Brazil, serum folate concentrations increased in healthy populations (57% in children and adolescents and 174% in adults), and the incidence of neural tube defects dropped. Folic acid fortification of wheat flour and cornmeal increased the blood folate concentrations and reduced the incidence of neural tube defects.

Research paper thumbnail of Reduced ABCG2 and increased SLC22A1 mRNA expression are associated with imatinib response in chronic myeloid leukemia

Medical Oncology, 2014

Imatinib mesylate (IM) has become a standard of care in chronic myeloid leukemia (CML) therapy. S... more Imatinib mesylate (IM) has become a standard of care in chronic myeloid leukemia (CML) therapy. Single nucleotide polymorphisms (SNPs) and altered expression in drug transporter genes may influence IM response. In order to investigate whether mRNA expression and SNPs in drug transporters are associated with IM resistance, we studied 118 chronic-phase CML patients receiving the standard dose of IM (400 mg/day). They were assigned as responders and nonresponders according to European LeukemiaNet criteria (2009). mRNA expression in samples at diagnosis (without IM therapy) and outcomes after IM failure were also evaluated in subgroups of patients. Major molecular response (MMR), complete molecular response and primary and secondary resistance were all assessed. BCR-ABL1, ABCB1, ABCG2, SLC22A1 and SLCO1A2 mRNA expression and SNPs in ABCG2 and SLC22A1 genes were analyzed. ABCG2 mRNA expression in the non-responders was higher before and during IM therapy. Furthermore, ABCG2 was overexpressed in those who did not achieve MMR (P = 0.027). In a subgroup of patients who switched to second-generation tyrosine kinase inhibitors, high mRNA expression of ABCG2 was associated with a risk of 24 times that of not achieving complete cytogenetic response (OR 24.00, 95 % CI 1.74-330.80; P = 0.018). In the responder group, patients who achieved MMR (P = 0.009) presented higher mRNA levels of SLC22A1. The SNPs were not associated with mRNA expression of ABCG2 and SLC22A1. Our data suggest that elevated ABCG2 expression (an efflux transporter) could be associated with IM resistance and could impact on second-generation TKI response, whereas high SLC22A1 expression (an influx transporter) may be associated with a successful IM therapy in CML patients.

Research paper thumbnail of Iron deficiency and frequency of HFE C282Y gene mutation in Brazilian blood donors

Transfusion Medicine, 2009

Limited data are available about iron deficiency (ID) in Brazilian blood donors. This study evalu... more Limited data are available about iron deficiency (ID) in Brazilian blood donors. This study evaluated the frequencies of ID and iron-deficiency anaemia (IDA) separately and according to frequency of blood donations. The protective effect of the heterozygous genotype for HFE C282Y mutation against ID and IDA in female blood donors was also determined. Five hundred and eight blood donors were recruited at the Blood Bank of Santa Casa in Sao Paulo, Brazil. Haemoglobin and serum ferritin concentrations were measured. The genotype for HFE C282Y mutation was determined by polymerase chain reaction followed by restriction fragment length polymorphism analysis. The ID was found in 21.1% of the women and 2.6% of the men whereas the IDA was found in 6.8 and 0.3%, respectively. The ID was found in 11.9% of the women in group 1 (first-time blood donors) and the frequency increased to 38.9% in women of the group 3 (blood donors donating once or more times in the last 12 months). No ID was found in men from group 1; however the ID frequency increased to 0.9% in group 2 (who had donated blood before but not in the last 12 months) and 5.0% in group 3. In summary, the heterozygous genotype was not associated with reduction of ID or IDA frequencies in both genders, but in male blood donors it was associated with a trend to elevated ferritin levels (P = 0.060). ID is most frequent in Brazilian women but was also found in men of group 3.

Research paper thumbnail of Polymorphisms in antithrombin and in tissue factor pathway inhibitor genes are associated with recurrent pregnancy loss

Thrombosis and Haemostasis, 2012

Recurrent pregnancy loss (RPL) is a multifactorial condition. The effect of antithrombin (SERPINC... more Recurrent pregnancy loss (RPL) is a multifactorial condition. The effect of antithrombin (SERPINC1), protein C (PROC), thrombomodulin (THBD) and tissue factor pathway inhibitor (TFPI) single nucleotide polymorphisms (SNPs) on the risk of RPL is thus far unknown. Our objective was to determine the association of SNPs in the above mentioned genes with RPL. We included 117 non-pregnant women with three or more consecutive losses prior to 20 weeks of pregnancy without a previous history of carrying a fetus to viability, and 264 healthy fertile non-pregnant women who had at least two term deliveries and no known pregnancy losses. The PROC (rs1799809 and rs1799808), SERPINC1 (rs2227589), THBD (rs1042579) and TFPI (rs10931292, rs8176592 and rs10153820) SNPs were analysed by Real Time PCR. Genotype frequencies for PROC 2418A>G, PROC 2405C>T, THBD 1418C>T, TFPI (T-33C and TFPI C-399T) SNPs were similar in cases and controls. The carriers of SERPINC1 786A allele (GA + AA genotypes) had an increased risk for RPL (odds ratio [OR]: 1.77, 95% confidence interval [CI]: 1.05-3.00, p= 0.034) while women carrying the TFPI -287C allele (TC + CC genotypes) had a protection effect on having RPL (OR: 0.46, 95% CI: 0.26-0.83, p= 0.009). The TCC haplotype for TFPI T-33C/ TFPI T-287C/ TFPI C-399T SNPs was less frequent in cases (5.7%) than in controls (11.6%) (OR: 0.45, 95% CI: 0.23-0.90, p= 0.025). In conclusion, our data indicate that SERPINC1 786G>A variant increases the risk for RPL, while TFPI T-287C variant is protective; however, further studies are required to confirm our findings.

Research paper thumbnail of Evolucion del estado nutricional de embarazadas atendidas en la red basica de salud, Santo Andre, Brasil

Revista Latino-Americana de Enfermagem, 2001

Fujimori E, Cassana LMN, Szarfarc SC, Oliveira IMV, Guerra-Shinohara EM. Evolución del estado nut... more Fujimori E, Cassana LMN, Szarfarc SC, Oliveira IMV, Guerra-Shinohara EM. Evolución del estado nutricional de embarazadas atendidas en la red basica de salud, Santo André, Brasil. Rev Latino-am Enfermagem 2001 maio; 9(3):64-9.

Research paper thumbnail of Homocysteine and lipid profile in children with Juvenile Idiopathic Arthritis

Pediatric Rheumatology, 2007

Background: An increased concentration of plasma homocysteine (Hcy) has toxic effects on vascular... more Background: An increased concentration of plasma homocysteine (Hcy) has toxic effects on vascular endothelium. This seems to be a risk factor of cardiovascular disease, premature stroke and venous thrombosis. The risk is higher in coincidence with other factors like chronic diseases and familiar hypercholesterolemia. The aim of our study was to evaluate plasma Hcy concentration in patients with juvenile idiopathic arthritis (JIA) and its correlation with methotrexate (MTX) therapy, serum folate and B12 vitamin, and hyperlipidemia.

Research paper thumbnail of Elevated serum S-adenosylhomocysteine in cobalamin-deficient megaloblastic anemia

Metabolism, 2007

Impaired methylation due to accumulation of S-adenosylhomocysteine (SAH) may contribute to the pa... more Impaired methylation due to accumulation of S-adenosylhomocysteine (SAH) may contribute to the pathophysiology of cobalamindeficient anemia. We assayed serum S-adenosylmethionine (SAM), SAH, total homocysteine (tHcy), and methylmalonic acid (MMA) in 15 subjects with cobalamin-deficient megaloblastic anemia and compared results with those of 19 subjects with anemia/pancytopenia due to other causes. Cobalamin-deficient subjects had a median hematocrit level of 20% and mean cell volume of 111.7 fL. The median serum cobalamin level was 37 pg/mL, MMA 3030 nmol/L, and tHcy 62.0 lmol/L. SAH was elevated in 13 of 15 subjects (median, 42 nmol/L) and the median SAM value was normal (103 nmol/L), but SAM/SAH ratio was low (2.5). The SAH was higher and SAM/SAH ratio was lower in cobalamin-deficient subjects compared with those with other anemias after excluding 4 patients with renal insufficiency. SAM concentrations were not low in cobalamin deficiency. Cobalamin injections corrected anemia, MMA, tHcy, SAM/SAH ratio, and SAH. Some hematologic variables were inversely correlated with SAH and cobalamin but not tHcy or MMA. In conclusion, serum SAH is elevated in cobalamindeficient subjects with megaloblastic anemia and corrects with parenteral cobalamin therapy. D

Research paper thumbnail of Hemojuvelin and Hepcidin Genes Sequencing in Brazilian Patients with Primary Iron Overload

Genetic Testing and Molecular Biomarkers, 2010

most hereditary hemochromatosis (HH) patients are homozygous for the p.C282Y mutation in the HFE ... more most hereditary hemochromatosis (HH) patients are homozygous for the p.C282Y mutation in the HFE gene. Some studies reported that HH phenotypic expression could be modulated by genetic factors such as HJV and HAMP gene mutations. the aims of this study were to identify HJV and HAMP mutations and to analyze their impact on HH phenotype in non-p.C282Y homozygous individuals. Twenty-four Brazilian patients with primary iron overload and non-p.C282Y homozygous genotype (transferrin saturation >50% in women and >60% in men and absence of secondary causes) were selected. Subsequent bidirectional sequencing of the HJV and HAMP exons was performed. sequencing revealed a substitution in heterozygosis, c.929C > G, which corresponds to p.A310G polymorphism in HJV exon 4 (rs7540883). In the same gene, in another individual, an IVS1-36C > G intronic variant was detected in heterozygosis. In the HAMP gene, an IVS3 + 42G > A intronic variant was identified. There were six (25.0%) patients carrying a heterozygous genotype for the HFE p.C282Y and nine (37.5%) patients carrying a heterozygous genotype for the HFE p.H63D. HJV p.A310G polymorphism and two intronic variants were found, but none of these alterations were associated with digenic inheritance with the HFE gene. Our data indicate that HJV and HAMP functional mutations are not frequent in these patients.

Research paper thumbnail of Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphisms as determinants for elevated total homocysteine concentrations in pregnant women

European Journal of Clinical Nutrition, 2008

To examine the association between methylenetetrahydrofolate reductase (MTHFR) (C677T and A1298C)... more To examine the association between methylenetetrahydrofolate reductase (MTHFR) (C677T and A1298C), methionine synthase (MTR) A2756G and methionine synthase reductase (MTRR) A66G gene polymorphisms and total homocysteine (tHcy), methylmalonic acid (MMA) and S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) levels; and to evaluate the potential interactions with folate or cobalamin (Cbl) status. Two hundred seventy-five healthy women at labor who delivered full-term normal babies. Cbl, folate, tHcy, MMA, SAM and SAH were measured in serum specimens. The genotypes for polymorphisms were determined by PCR-restriction fragment length polymorphism (RFLP). Serum folate, MTHFR 677T allele and MTR 2756AA genotypes were the predictors of tHcy levels in pregnant women. Serum Cbl and creatinine were the predictors of SAM/SAH ratio and MMA levels, respectively. The gene polymorphisms were not determinants for MMA levels and SAM/SAH ratios. Low levels of serum folate were associated with elevated tHcy in pregnant women, independently of the gene polymorphisms. In pregnant women carrying MTHFR 677T allele, or MTHFR 1298AA or MTRR 66AA genotypes, lower Cbl levels were associated with higher levels of tHcy. Lower SAM/SAH ratio was found in MTHFR 677CC or MTRR A2756AA genotypes carriers when Cbl levels were lower than 142 pmol/l. Serum folate and MTHFR C677T and MTR A2576G gene polymorphisms were the determinants for tHcy levels. The interaction between low levels of serum Cbl and MTHFR (C677T or A1298C) or MTRR A66G gene polymorphisms was associated with increased tHcy.

Research paper thumbnail of The influence of iron, vitamin B, and folate levels on soluble transferrin receptor concentration in pregnant women

Clinica Chimica Acta, 2003

Background: Soluble transferrin receptor (sTfR) concentration is high in iron deficiency and in c... more Background: Soluble transferrin receptor (sTfR) concentration is high in iron deficiency and in conditions of increased erythropoiesis. In developing countries like Brazil, pregnant women usually have concurrent iron, vitamin B12, and folate deficiencies. This study investigated the relationship between serum sTfR concentration and iron, vitamin B12, and folate status in pregnant women. Methods: The concentration of the sTfR, hematocrit (Hct),

Research paper thumbnail of Metabolic effects of C677T and A1298C mutations at the MTHFR gene in Brazilian children with neural tube defects

Clinica Chimica Acta, 2002

Methylenetetrahydrofolate reductase (MTHFR) deficiency leads to impairment in folate metabolism a... more Methylenetetrahydrofolate reductase (MTHFR) deficiency leads to impairment in folate metabolism and is implicated as a risk factor for neural tube defects (NTDs). Both C677T and A1298C MTHFR mutations are associated with NTDs, in some populations. The frequencies of the C677T and A1298C MTHFR mutations were determined in 25 children with NTDs, case mothers and 75 healthy individuals from Sao Paulo City. Both C677T and A1298C mutations were analyzed by PCR-FLRP. The effects of MTHFR mutations on folate, vitamin B12 and homocysteine concentrations were also evaluated. C677T and A1298C allele frequencies in NTDs children and mothers were similar to that found in controls. Eleven in 23 NTDs patients and 10 in 21 NTDs mothers had folate or vitamin B12 concentrations in the lower end of the normal range. In NTDs children, C677T MTHFR genotypes did not affect vitamins and homocysteine concentrations, but plasma homocysteine was higher (p=0.028) in patients with 1298AA MTHFR genotype. Moreover, 677CT/1298AA haplotype was associated with lower vitamin B12 concentrations (p<0.05) in NTDs children. MTHFR gene mutations may affect vitamin B12 and homocysteine metabolism in Brazilian children with NTDs.

Research paper thumbnail of Methylenetetrahydrofolate reductase (MTHFR) c677t gene variant modulates the homocysteine folate correlation in a mild folate-deficient population

Clinica Chimica Acta, 2004