Levels of high-density lipoprotein cholesterol (HDL-C) among children with steady-state sickle cell disease

<p>Abstract</p> <p>Background</p> <p>The search for sickle cell disease (SCD) prognosis biomarkers is a challenge. These markers identification can help to establish further therapy, later severe clinical complications and with patients follow-up. We attempted to study a possible involvement of levels of high-density lipoprotein cholesterol (HDL-C) in steady-state children with SCD, once that this lipid marker has been correlated with anti-inflammatory, anti-oxidative, anti-aggregation, anti-coagulant and pro-fibrinolytic activities, important aspects to be considered in sickle cell disease pathogenesis.</p> <p>Methods</p> <p>We prospectively analyzed biochemical, inflammatory and hematological biomarkers of 152 steady-state infants with SCD and 132 healthy subjects using immunochemistry, immunoassay and electronic cell counter respectively. Clinical data were collected from patient medical records.</p> <p>Results</p> <p>Of the 152 infants investigated had a significant positive association of high-density lipoprotein cholesterol with hemoglobin (P < 0.001), hematocrit (P < 0.001) and total cholesterol (P < 0.001) and a negative significant association with reticulocytes (P = 0.046), leukocytes (P = 0.015), monocytes (P = 0.004) and platelets (P = 0.005), bilirubins [total bilirubin (P < 0.001), direct bilirubin (P < 0.001) and indirect bilirubin (P < 0.001], iron (P < 0.001), aminotransferases [aspartate aminotransferase (P = 0.004), alanine aminotransferase (P = 0.035)], lactate dehydrogenase (P < 0.001), urea (P = 0.030), alpha 1-antitrypsin (P < 0.001), very low-density lipoprotein cholesterol (P = 0.003), triglycerides (P = 0.005) and hemoglobin S (P = 0.002). Low high-density lipoprotein cholesterol concentration was associated with the history of cardiac abnormalities (P = 0.025), pneumonia (P = 0.033) and blood transfusion use (P = 0.025). Lipids and inflammatory markers were associated with the presence of cholelithiasis.</p> <p>Conclusions</p> <p>We hypothesize that some SCD patients can have a specific dyslipidemic subphenotype characterized by low HDL-C with hypertriglyceridemia and high VLDL-C in association with other biomarkers, including those related to inflammation. This represents an important step toward a more reliable clinical prognosis. Additional studies are warranted to test this hypothesis and the probably mechanisms involved in this complex network of markers and their role in SCD pathogenesis.</p

Distúrbios da hemostasia em crianças portadoras de cardiopatias congênitas Hemostatic defects in children with congenital heart disease

As cardiopatias congênitas apresentam elevada prevalência no Brasil, sendo responsáveis por morbi-mortalidade importante, principalmente em menores de 5 anos de idade. Relacionam-se a um perfil complexo de alterações hemostáticas, predispondo tanto a eventos trombóticos como hemorrágicos, e cujo conhecimento é fundamental para o manejo adequado de cada paciente. O presente artigo objetiva descrever as alterações da coagulação relacionadas às cardiopatias congênitas, cianogênicas ou não, em menores de 18 anos de idade, submetidos ou não a procedimentos cirúrgicos.There is a high prevalence of congenital heart diseases in Brazil, which are responsible for high morbidity and mortality, mainly in under 5-year-old children. They are related to a complex profile of hemostatic disorders that lead to thrombotic and hemorrhagic events. Thus knowledge of the diseases is imperative for the adequate management of each patient. The objective of this article is to describe coagulation abnormalities related to congenital cyanotic and non-cyanotic heart diseases, in children, undergoing surgical procedures or not

TNF-alpha and IL-8: serum levels and gene polymorphisms (-308G>A and -251A>T) are associated with classical biomarkers and medical history in children with sickle cell anemia

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-02-10T16:48:34Z No. of bitstreams: 1 Cajado, C. et al. TNF-alpha and...Cytokine 2011, v. 56, p. 312.pdf: 350357 bytes, checksum: 2b5756806e3783c08a408d0e9108bcd1 (MD5)Made available in DSpace on 2014-02-10T16:48:34Z (GMT). No. of bitstreams: 1 Cajado, C. et al. TNF-alpha and...Cytokine 2011, v. 56, p. 312.pdf: 350357 bytes, checksum: 2b5756806e3783c08a408d0e9108bcd1 (MD5) Previous issue date: 2011Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação de Hematologia e Hemoterapia do Estado da Bahia. HEMOBA. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, BrasilSickle cell anemia (SCA) is a disorder characterized by a heterogeneous clinical outcome. In the present study, we investigated the associations between Tumor Necrosis Factor-alpha (TNF-alpha) 308G>A and Interleukin 8 (IL-8) 251A>T gene polymorphisms, medical history and classical biomarkers in children with steady-state SCA. In total, 210 SCA patients aged 2–21 years and 200 healthy controls were studied. Gene polymorphisms, betaS-globin haplotypes and a 3.7-kb deletion in alpha2-thalassemia (a2-thal3.7 kb) were investigated by PCR/RFLP analysis, and cytokine levels were determined by ELISA. Splenomegaly (p = .032) was more prevalent among children younger than 5 years of age. The A allele of the TNF-alpha 308G>A gene polymorphism and the presence of a2-thal3.7 kb were associated with an increase risk of splenic sequestration events (p = .001; p = .046), while the T allele of the IL-8 251A>T gene polymorphism was considered to be a protective factor for splenomegaly events (p = .032). Moreover, the A allele of the TNF-alpha 308G>A gene polymorphism was associated with high TNF-alpha levels (p = .021), and the hemoglobin F and hemoglobin S haplotypes were correlated with serum levels of IL-8. The logistic regression analysis showed significant effects of the TNF-alpha and IL-8 gene polymorphisms, betaS-globin gene haplotypes and a2-thal3.7 kb on the occurrence of splenic sequestration events. Our study emphasizes that the identification of new genetic and immunological biomarkers and their associations with classical markers is an important strategy to elucidate the underlying causes of different SCA phenotypes and their effects on patient outcom

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

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-07-14T12:12:51Z No. of bitstreams: 1 Barbosa, Cynara Gomes et al. genetic modulation...pdf: 51042 bytes, checksum: b6f026b344da92d205aebc63d485ac2c (MD5)Made available in DSpace on 2014-07-14T12:12:51Z (GMT). No. of bitstreams: 1 Barbosa, Cynara Gomes et al. genetic modulation...pdf: 51042 bytes, checksum: b6f026b344da92d205aebc63d485ac2c (MD5) Previous issue date: 2013Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil.Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil.Fundação de Hematologia e Hemoterapia da Bahia (HEMOBA). Salvador, BA, Brasil.Fundação de Hematologia e Hemoterapia da Bahia (HEMOBA). Salvador, BA, Brasil.Boston University School of Medicine. Department of Medicine. Boston, Massachusetts, USA.Boston University School of Public Health. Department of Biostatistics. Boston, Massachusetts, USA.Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil

Associations between TGF-β1 Levels and Markers of Hemolysis, Inflammation, and Tissue Remodeling in Pediatric Sickle Cell Patients

Transforming growth factor beta (TGF-β) is a cytokine with important involvement in biological processes related to the pathogenesis of sickle cell disease (SCD), including endothelial and vascular dysfunction, inflammation, and hematopoietic homeostasis. This study is aimed at investigating associations between levels of TGF-β1 and classical laboratory biomarkers and inflammatory mediators, as well as the tissue inhibitor of metalloproteases-1 (TIMP-1) and matrix metalloproteinase-9 (MMP-9), in pediatric patients (n=123) with SCD in steady state: 84 with sickle cell anemia (HbSS) and 39 with hemoglobin SC disease (HbSC). A healthy control (HC) group of 59 individuals was also included. Hematological and biochemical analyses were carried out using electronic methods. TGF-β1, TIMP-1, and MMP-9 plasma quantifications were performed by ELISA. TGF-β1 plasma levels were higher in HbSS individuals than in HbSC and HC. In individuals with HbSS, TGF-β1 levels were positively correlated with red blood cells, hemoglobin, hematocrit, platelets, and TIMP-1. In addition, HbSS individuals with TGF-β1 levels above the median (≥72.29 ng/mL) also presented increased monocyte counts and decreased albumin levels. In patients with HbSC, TGF-β1 levels were positively correlated with leukocytes, eosinophils, lymphocytes, monocytes, and platelets, as well as levels of TIMP-1, VLDL-C, triglycerides, heme, and AST. Additionally, HbSC individuals with TGF-β1 levels above the median (≥47.80 ng/mL) presented increased leukocyte and platelet counts, as well as increased levels of triglycerides, VLDL-C, MMP-9, and TIMP-1, and decreased HDL-C. Our findings suggest that TGF-β1 may play important roles in vascular remodeling, vasculopathy, angiogenesis, and inflammation in pediatric patients with SCD