Association of the clinical profile and overall survival of pediatric patients with acute lymphoblastic leukemia

IntroductionThe clarification of etiopathology, the improvement of chemotherapy regimens and their risk stratifications, and the improvement in treatment support have increased the survival of children and adolescents affected by Acute Lymphoblastic Leukemia (ALL) past few years. This study aimed to estimate overall survival (OS) and event-free survival (EFS) in an onco-hematology treatment center in Brazil, reports the main clinical-laboratory characteristics of patients at diagnosis, verify the frequency of treatment-related adverse effects and the main causes of death.Material and methodsRetrospective analysis involving patients diagnosed with ALL, treated with the protocol of the Brazilian Group for Treatment of Leukemias in Childhood (GBTLI), between 2010 and 2020 was carried out; the outcomes (relapse, deaths, development of new neoplasms) were analyzed SPSS® software was used for the statistical analyses, and the p-value was considered significant when less than 0.05 for all analyses.Results109 patients were included in the study; the median age was 5 years, with a slight predominance of males. Sixty-six patients were classified as high-risk (HR) group and 43 patients were classified as low-risk (LR) group. After 5 years of diagnosis, the OS was 71.5%, and the EFS was 65%. No statistical difference was found between the HR and LR groups for OS and EFS, while leukocyte counts were statistically associated with the outcome of death (p = 0.028). Among the patients, 28 (25.6%) died due to infection accounting 46.4% of death causes. Among the 34 patients with unfavorable outcomes (death and/or relapse), 32 had no research for the minimal residual disease at the end of remission induction, and 25 were not investigated for the presence of chromosomal abnormalities. The most reported complications and treatment-related adverse effects were increased liver transaminases (85.9%), airway infection (79.4%), oral mucositis (67.2%), febrile neutropenia (64.4%), and diarrhea (36.4%).ConclusionsThe rates of OS and EFS obtained in this cohort are similar to those obtained in the few previous similar studies in Brazil and lower than those carried out in developed countries. The unavailability of prognostic tests may have hindered risk stratification and influenced the results obtained

Evaluation of Cardiometabolic Parameters among Obese Women Using Oral Contraceptives

BackgroundCombined 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.MethodsWe 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.ResultsCOC 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).ConclusionObesity 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

Células endoteliais ativadas pelo heme: avaliação de diferentes abordagens terapêuticas

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-04-27T12:44:09Z No. of bitstreams: 1 Caroline Conceição da Guarda Células endoteliais... 2015.pdf: 2457661 bytes, checksum: dcaf9b8c0642cbc1a5e51204f63dc5b0 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-04-27T12:56:41Z (GMT) No. of bitstreams: 1 Caroline Conceição da Guarda Células endoteliais... 2015.pdf: 2457661 bytes, checksum: dcaf9b8c0642cbc1a5e51204f63dc5b0 (MD5)Made available in DSpace on 2017-04-27T12:56:41Z (GMT). No. of bitstreams: 1 Caroline Conceição da Guarda Células endoteliais... 2015.pdf: 2457661 bytes, checksum: dcaf9b8c0642cbc1a5e51204f63dc5b0 (MD5) Previous issue date: 2015Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilA anemia falciforme (AF) é uma doença genética, que possui quadro clínico heterogêneo, caracterizado por crises de dor, priapismo, síndrome torácica aguda, acidente vascular cerebral (AVC) e eventos hemolíticos, dentre outros. A hemólise tem como consequência a liberação de grandes quantidades de hemoglobina e heme livre nos espaços intravasculares, com ativação endotelial. Desta forma, a vasculopatia e a disfunção endotelial são alterações importantes entre os eventos crônicos descritos na AF, que contribuem para a patogênese do AVC, doença renal e hipertensão pulmonar. O heme é uma molécula pró-inflamatória, capaz de ativar diretamente o endotélio vascular, bem como a produção de espécies reativas de oxigênio. Por isso, o objetivo deste estudo foi avaliar a expressão de fator tecidual, óxido nítrico sintase endotelial (eNOS), óxido nítrico (NO) e fator induzível por hipóxia- α (HIF-α) em células HUVEC (Human umbilical vein endothelial cells) ativadas pelo heme, em resposta à ação de drogas que possuem diferentes mecanismos. A produção de fator tecidual, eNOS, e HIF-α pelas células HUVEC foi investigada por ELISA. O óxido nítrico (NO) foi dosado pelo método de Griess, sendo que as células foram estimuladas pelo heme e tratadas ou não com sinvastatina, hidroxiuréia (HU) e ácido ascórbico. A produção de fator tecidual pelas células HUVEC foi influenciada pelo ácido ascórbico e pela HU, e também pela associação entre os dois tratamentos, sugerindo um possível mecanismo de redução das alterações hemostáticas. A produção de nitrito pelas células HUVEC foi aumentada mediante estímulo pelo heme e reduzida quando houve tratamento com HU. Os mecanismos de produção de nitrito, óxido nítrico ou peroxinitrito pelas células quando influenciadas pelas drogas ainda precisam ser mais bem caracterizados. A produção de eNOS quando as células foram estimuladas com heme foi heterogênea, e a interação entre o heme e as drogas na produção da enzima precisa ser melhor caracterizada com o objetivo de compreender os mecanismos de disfunção endotelial. A produção do HIF-α foi aumentada após estímulo das células pelo heme, porém, os tratamentos com sinvastatina e ácido ascórbico ainda precisam ser mais bem compreendidos, uma vez que essas drogas possuem diferentes mecanismos de ação. Desse modo, sugerimos que o microambiente hemolítico vascular da AF requer diferentes abordagens terapêuticas, que devem ser voltadas para os diferentes mecanismos e alvos moleculares descritos na AF, tendo em vista que a inflamação crônica frequente nos pacientes possui diversos efeitos sistêmicos.Sickle cell anemia (SCA) is a genetic disease, which has heterogeneous clinical features, characterized by pain crises, priapism, acute chest syndrome, cerebral vascular accident (CVA) and hemolytic events, among others. Hemolysis causes the release of large amounts of free heme and hemoglobin in intravascular spaces with endothelial activation. Thus, endothelial dysfunction and vascular disease are major chronic events described in SCA, that contribute to the pathogenesis of stroke, renal and pulmonary hypertension. Heme is a pro-inflammatory molecule able to directly activate vascular endothelium, as well as the production of reactive oxygen species. Therefore, the aim of this study was to evaluate the expression of tissue factor, endothelial nitric oxide synthase (eNOS), nitric oxide (NO) and hypoxia inducible factor α (HIF-α) in HUVECs (Human umbilical vein endothelial cells) activated by heme in response to the action of drugs that have different mechanisms. Tissue factor production, eNOS, and HIF-α were investigated in HUVECs and evaluated by ELISA. Nitric oxide (NO) was measured by the Griess technique, and the cells were stimulated by heme and treated or not with simvastatin, hydroxyurea (HU), and ascorbic acid. The tissue factor production by HUVEC cells was influenced by ascorbic acid and the HU and also the association between both treatments, suggesting a possible mechanism for reducing the hemostatic abnormalities. The nitrite production by HUVECs was enhanced by stimulation with heme and was reduced when treatment with HU. The nitrite production mechanisms, nitric oxide or peroxynitrite by cells when affected by drugs should be further characterized. Production of eNOS when cells were stimulated by heme was heterogeneous, and the interaction between the drug, the heme, and the enzyme production needs to be better characterized with the aim of better understand the mechanisms of endothelial dysfunction. The production of HIF-α when the cells were stimulated by heme was increased, but the effects of simvastatin and ascorbic acid still need to be better understood, since these drugs have different mechanisms of action. Thus, we suggest that the hemolytic vascular microenvironment in SCA requires different therapeutic approaches, that need to be directed to the different molecular targets and mechanisms described in the SCA, once the frequent chronic inflammation in these patients has several systemic effects

Heme changes HIF-α, eNOS and nitrite production in HUVECs after simvastatin, HU, and ascorbic acid therapies

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-05-10T15:54:44Z No. of bitstreams: 1 Guarda CC Heme changes....pdf: 517853 bytes, checksum: 521387a5f13e3781b0af22ec40769e20 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-05-10T16:03:23Z (GMT) No. of bitstreams: 1 Guarda CC Heme changes....pdf: 517853 bytes, checksum: 521387a5f13e3781b0af22ec40769e20 (MD5)Made available in DSpace on 2016-05-10T16:03:23Z (GMT). No. of bitstreams: 1 Guarda CC Heme changes....pdf: 517853 bytes, checksum: 521387a5f13e3781b0af22ec40769e20 (MD5) Previous issue date: 2016Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, BrasilThe sickle cell disease (SCD) is a hemolytic genetic anemia characterized by free heme and hemoglobin release into intravascular spaces, with endothelial activation. Heme is a proinflammatory molecule able to directly activate vascular endothelium, thus, endothelial dysfunction and vascular disease are major chronic events described in SCD. The aim of this study was to evaluate the production of endothelial nitric oxide synthase (eNOS), nitrite and hypoxia inducible factor alpha (HIF-α) in HUVECs (human umbilical vein endothelial cells) activated by heme in response to simvastatin, hydroxyurea (HU), and ascorbic acid therapies. eNOS and HIF-α production were evaluated by ELISA and nitrite was measured by the Griess technique. The production of HIF-α increased when the cells were stimulated by heme (p b 0.01), while treatment with HU and simvastatin reduced the production (p b 0.01), and treatment with ascorbic acid increased HIF-1a production by the cells (p b 0.01). Hemeincreased eNOS production, (p b 0.01) but showed a heterogeneous pattern, and the lowest concentrations of all the treatments reduced the enzyme production (p b 0.01). The nitrite production by HUVECs was enhanced by stimulation with heme (p b 0.001) andwas reduced by treatment with HU (p b 0.001), ascorbic acid (p b 0.001) and simvastatin (p b 0.01). In summary, our results suggest that the hemolytic vascular microenvironment in SCD requires different therapeutic approaches to promote clinical improvement, and that a combination of therapies may be a viable strategy for treating patients

Association of homocysteine and inflammatory related molecules in sickle cell anemia

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-05-06T19:17:33Z No. of bitstreams: 1 Vilas-Boas W Association of....pdf: 614959 bytes, checksum: e67cd48c7a295b7265ee44271b784686 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-05-06T19:27:47Z (GMT) No. of bitstreams: 1 Vilas-Boas W Association of....pdf: 614959 bytes, checksum: e67cd48c7a295b7265ee44271b784686 (MD5)Made available in DSpace on 2016-05-06T19:27:47Z (GMT). No. of bitstreams: 1 Vilas-Boas W Association of....pdf: 614959 bytes, checksum: e67cd48c7a295b7265ee44271b784686 (MD5) Previous issue date: 2015Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade do Estado da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação de Hematologia e Hemoterapia da Bahia–Hemoba. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilObjective: Investigate the role of homocysteine (Hcy), Th17-related cytokines, and adhesion molecules in the inflammatory state seen in the sickle cell anemia (SCA). Methods: We studied the Hcy, interleukin (IL)-17, and transforming growth factor β (TGF-β) cytokine levels of 62 SCA patients, as well as the expression levels of inflammatory and endothelial activation markers. Results: We found significant associations between Hcy levels and increased expression of IL-17 and TGF-β among SCA patients, and a positive significant correlation between Hcy and soluble vascular cellular adhesion molecules (sVCAM). SCA individuals had raised IL-17 levels when compared with controls. Discussion: These results suggest a possible role of Hyc in the induction of TGF-β and IL-17. Other authors proposed that Hcy may contribute to the initiation and progression of vascular disease by monocyte activation, resulting in the secretion of cytokines that amplify the inflammatory response. The role of Hcy in cytokine production and oxidative stress in the endothelium may explain the increase of sVCAM expression and, the vascular activation currently described among the SCA individuals with the highest Hcy serum levels. The chronic inflammation was observed in hyperhomocysteinemic mice, with an increased expression of VCAM-1 and plasma levels of tumor necrosis factor-alpha, showing an association of this inflammatory molecule and vascular changes. Conclusion: Our findings suggest that the increased levels of IL-17,Hcy and sVCAM contributes contributes to the vascular inflammation and activation presented by SCA patients, which probably have an important role in vaso-occlusion. On the basis of the presented data, IL-17 and Hcy might be considered as important components in the pathogenesis of SCA

Hydroxyurea in the management of sickle cell disease: pharmacogenomics and enzymatic metabolism

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-12-17T17:30:33Z No. of bitstreams: 1 Yahouedehou SCMA Hydroxyurea in the....pdf: 590783 bytes, checksum: bbd5c090cc7d875c0687cd3b8a0c0e4c (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-12-17T17:49:24Z (GMT) No. of bitstreams: 1 Yahouedehou SCMA Hydroxyurea in the....pdf: 590783 bytes, checksum: bbd5c090cc7d875c0687cd3b8a0c0e4c (MD5)Made available in DSpace on 2018-12-17T17:49:24Z (GMT). No. of bitstreams: 1 Yahouedehou SCMA Hydroxyurea in the....pdf: 590783 bytes, checksum: bbd5c090cc7d875c0687cd3b8a0c0e4c (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas. Salvador, BA, Brasil.Universidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas. Salvador, BA, Brasil.Hydroxyurea (HU) was approved to be used in the treatment of sickle cell disease (SCD) because of its anti-sickling potential. However, there is variability in HU response among SCD patients and this can be due to physiological, socioeconomic, environmental, metabolic and/or genetic factors. The present review focuses on the latter two. Three quantitative trait loci, HBG2, BCL11A and HMIP, have been suggested as important markers for HU response. Other genes (ASS1, KLF10, HAO2, MAP3K5, PDE7B, TOX, NOS1, NOS2A, FLT1, ARG1, ARG2, UGT1A1, OR51B5/6, SIN3A, SALL2, SAR1A, UTB, OCTN1, CYP2C9, AQP9, MPO, CYP2E1, and GSTT1) have also been considered. Studies implicate catalase, urease, horseradish peroxidase and enzymes of CYP450 family in HU metabolism. However, little is known about these enzymes. Therefore, further studies are needed to elucidate the metabolic pathway of HU, which will facilitate pharmacogenomic studies and help in identification of candidate genes for predicting HU response

Evaluation of Cardiometabolic Parameters among Obese Women Using Oral Contraceptives

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-10-25T12:05:47Z No. of bitstreams: 1 Ferreira JRD Evaluation....pdf: 475375 bytes, checksum: 8a3eb17fe4acc97f6513e92990e8dd81 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-10-25T12:19:38Z (GMT) No. of bitstreams: 1 Ferreira JRD Evaluation....pdf: 475375 bytes, checksum: 8a3eb17fe4acc97f6513e92990e8dd81 (MD5)Made available in DSpace on 2017-10-25T12:19:38Z (GMT). No. of bitstreams: 1 Ferreira JRD Evaluation....pdf: 475375 bytes, checksum: 8a3eb17fe4acc97f6513e92990e8dd81 (MD5) Previous issue date: 2017“Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ)”Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, BrasilCombined 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

Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters

This study investigated associations between SNPs in genes encoding metabolizing drug enzymes and laboratory parameters in sickle cell anemia patients under hydroxyurea (SCA-HU+). We evaluated hematologic and biochemical parameters by electronic methods and SNPs by PCR-RFLP and multiplex PCR in 35 SCA-HU+ patients and 67 SCA-HU− patients. The HbS, total cholesterol, lactate dehydrogenase, aspartate aminotransferase, total bilirubin and fractions levels, and leukocyte, eosinophil, monocyte, and erythroblast counts were reduced in SCA-HU+ patients (p<0.05). Moreover, they presented higher HbF, C-reactive protein, and ferritin levels and elevated MCH and MCV values (p<0.05). Genotype frequencies of variants GA + AA of MPO −463G>A and c1c2 + c2c2 of CYP2E1 −1293G>C/−1053C>T were higher in SCA-HU+ patients (p<0.05). Independent associations were found between the variant A allele and lower total cholesterol, between c2 allele and low alpha-1 antitrypsin and between the null GSTT1 variant and high indirect and total bilirubin in SCA-HU+ patients. In SCA-HU− patients, independent associations were found between the variant A allele and high uric acid and between c2 allele and high urea. Our results suggest that SNPs MPO −463G>A, CYP2E1 −1293G>C/−1053C>T, and GSTT1 can be associated with alterations in lipid, inflammatory, renal, hemolytic, and hepatic profiles. However, further studies are needed to elucidate these associations

Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-05-15T13:52:03Z No. of bitstreams: 1 Yahouédéhou SC Sickle Cell Anemia Patients....pdf: 1569037 bytes, checksum: 927e424328f30b9d6847ca56d8cc70b6 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-05-15T14:16:24Z (GMT) No. of bitstreams: 1 Yahouédéhou SC Sickle Cell Anemia Patients....pdf: 1569037 bytes, checksum: 927e424328f30b9d6847ca56d8cc70b6 (MD5)Made available in DSpace on 2018-05-15T14:16:24Z (GMT). No. of bitstreams: 1 Yahouédéhou SC Sickle Cell Anemia Patients....pdf: 1569037 bytes, checksum: 927e424328f30b9d6847ca56d8cc70b6 (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas. Salvador, BA, BrasilThis study investigated associations between SNPs in genes encoding metabolizing drug enzymes and laboratory parameters in sickle cell anemia patients under hydroxyurea (SCA-HU+). We evaluated hematologic and biochemical parameters by electronic methods and SNPs by PCR-RFLP and multiplex PCR in 35 SCA-HU+ patients and 67 SCA-HU- patients. The HbS, total cholesterol, lactate dehydrogenase, aspartate aminotransferase, total bilirubin and fractions levels, and leukocyte, eosinophil, monocyte, and erythroblast counts were reduced in SCA-HU+ patients (p A and c1c2 + c2c2 of CYP2E1 -1293G>C/-1053C>T were higher in SCA-HU+ patients (p A, CYP2E1 -1293G>C/-1053C>T, and GSTT1 can be associated with alterations in lipid, inflammatory, renal, hemolytic, and hepatic profiles. However, further studies are needed to elucidate these associations

Comparative study of sickle cell anemia and hemoglobin SC disease: clinical characterization, laboratory biomarkers and genetic profiles

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-10-23T18:13:27Z No. of bitstreams: 1 Aleluia MM Comparative study....pdf: 800893 bytes, checksum: c8b80a42b919e25ef0df820d0d961c28 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-10-23T18:25:49Z (GMT) No. of bitstreams: 1 Aleluia MM Comparative study....pdf: 800893 bytes, checksum: c8b80a42b919e25ef0df820d0d961c28 (MD5)Made available in DSpace on 2017-10-23T18:25:49Z (GMT). No. of bitstreams: 1 Aleluia MM Comparative study....pdf: 800893 bytes, checksum: c8b80a42b919e25ef0df820d0d961c28 (MD5) Previous issue date: 2017Instituto Gonçalo Moniz at the Fundação Oswaldo Cruz (IGM-FIOCRUZ – Bahia - Brazil) (CAAE 08452913.9.0000.0040).Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.Centro de Referência a Doença Falciforme, Itabuna, BA, Brasil / Universidade Estadual de Santa Cruz. Ilhéus, BA, Brasil.Centro de Referência a Doença Falciforme, Itabuna, BA, Brasil / Universidade Estadual de Santa Cruz. Ilhéus, BA, Brasil.Centro de Referência a Doença Falciforme, Itabuna, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.Universidade Federal da Bahia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.Universidade Estadual da Bahia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.In this study, we evaluate the association of different clinical profiles, laboratory and genetic biomarkers in patients with sickle cell anemia (SCA) and hemoglobin SC disease (HbSC) in attempt to characterize the sickle cell disease (SCD) genotypes. Methods: We conducted a cross-sectional study from 2013 to 2014 in 200 SCD individuals (141 with SCA; 59 with HbSC) and analyzed demographic data to characterize the study population. In addition, we determined the association of hematological, biochemical and genetic markers including the βS-globin gene haplotypes and the 3.7 Kb deletion of α-thalassemia (−α3.7Kb-thal), as well as the occurrence of clinical events in both SCD genotypes. Results: Laboratory parameters showed a hemolytic profile associated with endothelial dysfunction in SCA individuals; however, the HbSC genotype was more associated with increased blood viscosity and inflammatory conditions. The BEN haplotype was the most frequently observed and was associated with elevated fetal hemoglobin (HbF) and low S hemoglobin (HbS). The -α3.7Kb-thal prevalence was 0.09 (9%), and it was associated with elevated hemoglobin and hematocrit concentrations. Clinical events were more frequent in SCA patients. Conclusions: Our data emphasize the differences between SCA and HbSC patients based on laboratory parameters and the clinical and genetic profile of both genotypes