Early and late-onset preeclampsia: effects of DDAH2 polymorphisms on ADMA levels and association with DDAH2 haplotypes.

Objective: To examine whether the DDAH2 promoter polymorphisms -1415G/A (rs2272592), -1151A/C (rs805304) and -449G/C (rs805305), and their haplotypes, are associated with PE compared with normotensive pregnant women, and whether they affect ADMA levels in these groups. Methods: A total of 208 pregnant women were included in the study and classified as early-onset (N=57) or late-onset PE (N =49), and as normotensive pregnant women (N = 102). Results: Pregnant with early-onset PE carrying the GC and GG genotypes for the DDAH2 -449G/C polymorphism had increased ADMA levels (P=0.01). No association of DDAH2 polymorphisms with PE in single-locus analysis was found. However, the G-C-G haplotype was associated with the risk for late-onset PE. Conclusion: It is suggested that DDAH2 polymorphisms could affect ADMA levels in PE, and that DDAH2 haplotypes may affect the risk for PE.

Pediatric chronic kidney disease: blood cell count indexes as inflammation markers / Doença renal crônica pediátrica: índices de contagem de células sanguíneas como marcadores de inflamação

Abstract Introduction: Chronic kidney disease (CKD) is defined as a progressive decline of kidney functions. In childhood, the main triggering factors are congenital anomalies of the kidneys and urinary tract (CAKUT) and glomerulopathies. Inflammatory responses present challenges for diagnosis and staging, which justifies studies on biomarkers/indexes. Aim: To define blood cell count indexes and verify their association with pediatric CKD etiology and staging. The included indexes were: Neutrophil-Lymphocyte Ratio (NLR), Derived Neutrophil-Lymphocyte Ratio (dNLR), Lymphocyte-Monocyte Ratio (LMR), Systemic Inflammation Response Index (SIRI), Aggregate Index of Systemic Inflammation (AISI), and Systemic Immune-Inflammation Index (SII). Methods: We determined the indexes in 52 pediatric CKD patients and 33 healthy controls by mathematical calculation. CKD patients were separated in five groups based on the etiology and staging: Group IA: glomerulopathies at stage 1 or 2; IB: glomerulopathies at stage 3 or 4; IIA: CAKUT at stage 1 or 2; IIB: CAKUT at stage 3 or 4; and III: stages 3 or 4 of other etiologies. In addition, we combined all patients with CKD in one group (IV). Group V was a healthy control group. Results: Lower values of LMR were observed for groups IB and IIB compared to group V (p = 0.047, p = 0.031, respectively). Increased values of SIRI were found for group III versus group V (p = 0.030). There was no difference for other indexes when the groups were compared two by two. Conclusion: The LMR and SIRI indexes showed promising results in the evaluation of inflammation, as they correlated with CKD etiologies and specially staging in these patients.

Resumo Introdução: Doença renal crônica (DRC) é definida como um declínio progressivo das funções renais. Na infância, os principais fatores desencadeantes são anomalias congênitas dos rins e trato urinário (CAKUT) e glomerulopatias. Respostas inflamatórias apresentam desafios para diagnóstico e estadiamento, o que justifica estudos sobre biomarcadores/índices. Objetivo: Definir índices de contagem de células sanguíneas e verificar sua associação com etiologia e estadiamento da DRC pediátrica. Os índices incluídos foram: Razão Neutrófilo-Linfócito (NLR), Razão Neutrófilo-Linfócito Derivada (dNLR), Razão Linfócito-Monócito (LMR), Índice de Resposta à Inflamação Sistêmica (SIRI), Índice Agregado de Inflamação Sistêmica (AISI) e Índice de Inflamação Imune Sistêmica (SII). Métodos: Determinamos índices em 52 pacientes pediátricos com DRC e 33 controles saudáveis por cálculo matemático. Pacientes com DRC foram separados em cinco grupos conforme etiologia e estadiamento: Grupo IA: glomerulopatias em estágio 1 ou 2; IB: glomerulopatias em estágio 3 ou 4; IIA: CAKUT em estágio 1 ou 2; IIB: CAKUT em estágio 3 ou 4; e III: estágios 3 ou 4 de outras etiologias. Além disso, combinamos todos os pacientes com DRC em um grupo (IV). Grupo V foi um grupo controle saudável. Resultados: Observamos valores menores de LMR nos grupos IB e IIB comparados ao grupo V (p=0,047; p=0,031, respectivamente). Encontramos valores maiores de SIRI para o grupo III versus grupo V (p=0,030). Não houve diferença para outros índices quando os grupos foram comparados dois a dois. Conclusão: Os índices LMR e SIRI apresentaram resultados promissores na avaliação da inflamação, pois correlacionaram-se com as etiologias da DRC e, principalmente, com o estadiamento desses pacientes.

Pediatric chronic kidney disease: blood cell count indexes as inflammation markers.

INTRODUCTION: Chronic kidney disease (CKD) is defined as a progressive decline of kidney functions. In childhood, the main triggering factors are congenital anomalies of the kidneys and urinary tract (CAKUT) and glomerulopathies. Inflammatory responses present challenges for diagnosis and staging, which justifies studies on biomarkers/indexes. AIM: To define blood cell count indexes and verify their association with pediatric CKD etiology and staging. The included indexes were: Neutrophil-Lymphocyte Ratio (NLR), Derived Neutrophil-Lymphocyte Ratio (dNLR), Lymphocyte-Monocyte Ratio (LMR), Systemic Inflammation Response Index (SIRI), Aggregate Index of Systemic Inflammation (AISI), and Systemic Immune-Inflammation Index (SII). METHODS: We determined the indexes in 52 pediatric CKD patients and 33 healthy controls by mathematical calculation. CKD patients were separated in five groups based on the etiology and staging: Group IA: glomerulopathies at stage 1 or 2; IB: glomerulopathies at stage 3 or 4; IIA: CAKUT at stage 1 or 2; IIB: CAKUT at stage 3 or 4; and III: stages 3 or 4 of other etiologies. In addition, we combined all patients with CKD in one group (IV). Group V was a healthy control group. RESULTS: Lower values of LMR were observed for groups IB and IIB compared to group V (p = 0.047, p = 0.031, respectively). Increased values of SIRI were found for group III versus group V (p = 0.030). There was no difference for other indexes when the groups were compared two by two. CONCLUSION: The LMR and SIRI indexes showed promising results in the evaluation of inflammation, as they correlated with CKD etiologies and specially staging in these patients.

Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study.

Introduction: SARS-CoV-2 infection during pregnancy can induce changes in the maternal immune response, with effects on pregnancy outcome and offspring. This is a cross-sectional observational study designed to characterize the immunological status of pregnant women with convalescent COVID-19 at distinct pregnancy trimesters. The study focused on providing a clear snapshot of the interplay among serum soluble mediators. Methods: A sample of 141 pregnant women from all prenatal periods (1st, 2nd and 3rd trimesters) comprised patients with convalescent SARS-CoV-2 infection at 3-20 weeks after symptoms onset (COVID, n=89) and a control group of pre-pandemic non-infected pregnant women (HC, n=52). Chemokine, pro-inflammatory/regulatory cytokine and growth factor levels were quantified by a high-throughput microbeads array. Results: In the HC group, most serum soluble mediators progressively decreased towards the 2nd and 3rd trimesters of pregnancy, while higher chemokine, cytokine and growth factor levels were observed in the COVID patient group. Serum soluble mediator signatures and heatmap analysis pointed out that the major increase observed in the COVID group related to pro-inflammatory cytokines (IL-6, TNF-α, IL-12, IFN-γ and IL-17). A larger set of biomarkers displayed an increased COVID/HC ratio towards the 2nd (3x increase) and the 3rd (3x to 15x increase) trimesters. Integrative network analysis demonstrated that HC pregnancy evolves with decreasing connectivity between pairs of serum soluble mediators towards the 3rd trimester. Although the COVID group exhibited a similar profile, the number of connections was remarkably lower throughout the pregnancy. Meanwhile, IL-1Ra, IL-10 and GM-CSF presented a preserved number of correlations (≥5 strong correlations in HC and COVID), IL-17, FGF-basic and VEGF lost connectivity throughout the pregnancy. IL-6 and CXCL8 were included in a set of acquired attributes, named COVID-selective (≥5 strong correlations in COVID and <5 in HC) observed at the 3rd pregnancy trimester. Discussion and conclusion: From an overall perspective, a pronounced increase in serum levels of soluble mediators with decreased network interplay between them demonstrated an imbalanced immune response in convalescent COVID-19 infection during pregnancy that may contribute to the management of, or indeed recovery from, late complications in the post-symptomatic phase of the SARS-CoV-2 infection in pregnant women.

Neuroserpin: A potential biomarker for early-onset severe preeclampsia.

Preeclampsia is a hypertensive disease of pregnancy associated with intense inflammatory and pro-coagulant responses. Neuroserpin is a serine protease inhibitor that has been involved in neurological and immune processes and has not yet been investigated in preeclampsia. Herein, we evaluated neuroserpin levels in association with other inflammatory mediators (IL-17A, IL-33, and CXCL-16) during severe preeclampsia. The mediators' plasma levels were measured by immunoassays in 24 pregnant women with severe preeclampsia (early preeclampsia: N = 17, late preeclampsia: N = 7), 34 normotensive pregnant women, and 32 non-pregnant women. In general, pregnancy was associated with higher levels of neuroserpin, IL-17A, IL-33, and CXCL-16 than the non-pregnant state. However, this increase was attenuated in pregnancies complicated by severe preeclampsia. Although neuroserpin levels did not differ between normotensive pregnant women and pregnant women with severe preeclampsia, neuroserpin levels tended to be lower in early-onset than in late-onset severe preeclampsia. There were positive correlations between neuroserpin and IL-17A, neuroserpin and CXCL-16, and IL-17A and CXCL-16 levels in women with severe preeclampsia. In addition, although the risk for developing severe preeclampsia was higher in older women in this study, maternal age did not significantly influence the mediators' levels, nor their correlations in the preeclampsia group. In summary, our data suggest that neuroserpin might be a potential biomarker for early-onset severe preeclampsia and, that the imbalance among neuroserpin, IL-17A, IL-33, and CXCL-16 levels may be associated with the pathogenesis of preeclampsia, regardless of the maternal age.

Hemostasis and oxidative stress in chronic kidney disease in children and adolescents.

Chronic kidney disease (CKD) can be defined as the progressive loss of renal function, characterized by a decreased glomerular filtration rate (GFR). The etiology of CKD in childhood is mainly associated with congenital anomalies of the kidneys and urinary tract (CAKUT) and with glomerular diseases. The goal of this study was to investigate the hemostasis and oxidative stress in pediatric CKD of different etiologies. Fifty-four CKD children and adolescents and 52 controls were enrolled in this study. The evaluation of hemostasis was carried out by determination of D-dimer (D-Di) and plasminogen activator inhibitor (PAI-1) plasma levels, while oxidative stress was evaluated by thiobarbituric acid reactive substance (TBARS) levels, protein carbonyl content, plasma antioxidant capacity (MTT), and ascorbate. The D-Di was increased in CAKUT stage 3 or 4 patients compared with those with glomerular disease. PAI-1 was increased in patients with glomerular disease compared with CAKUT. Carbonyl protein content was higher in the control group compared with glomerular disease stage 3 or 4 patients. Our findings showed that the reduction in GFR is associated with a state of hypercoagulability. The analysis of integrated networks showed an expansion of connections among hemostatic and oxidative stress markers in CKD children and adolescents compared with controls.

Endothelial dysfunction biomarkers in sickle cell disease: is there a role for ADMA and PAI-1?

Within the spectrum of sickle cell disease (SCD) are sickle cell anemia (SCA), presence of hemoglobin SS (HbSS), hemoglobin SC disease (HbSC), and sickle cell ß-thalassemia (Sß-thal). Asymmetric dimethylarginine (ADMA) competitively inhibits the binding of arginine to NOS, reducing NO production. In patients with HbSS, increased levels of ADMA have been reported, as well as changes in many hemostatic biomarkers, including the plasminogen activator inhibitor type 1 (PAI-1). We hypothesized that high levels of ADMA and PAI-1 may be associated with more severe SCD. Thus, ADMA and PAI-1 levels were determined in 78 individuals including 38 adult patients with SCD and 40 control subjects. Higher levels of ADMA were shown in HbSS and Sß-thal patients compared to controls. Concerning PAI-1, all patients showed high levels of PAI-1 compared to controls. As a role of NO in the pathogenesis of SCD has already been established, we concluded that high levels of ADMA should compromise, at least in part, NO synthesis, resulting in endothelial dysfunction. Elevated plasma levels of PAI-1 in all patients may indicate not only endothelial dysfunction but also a hypofibrinolytic state favoring thrombotic complications. Finally, high levels of ADMA and PAI-1 may be associated with more severe SCD.

Pharmacotherapy used for alcohol and cocaine use disorders in a CAPS-AD of Minas Gerais

Abstract Substance use disorder is one of the major social and public health problems in the world. The present study analyzed the pharmacoepidemiological profile of patients treated at the Psychosocial Treatment Center for Alcohol and Substance Use Disorders (CAPS-AD) for treatment of alcohol use disorders (AUD), cocaine use disorders (CUD) and concomitant alcohol and cocaine use disorders (A-CUD) in the city of Betim-MG. The study used quantitative and descriptive data and was based on the evaluation of medical records of patients attended from January to December 2016. After analyzing 295 medical records, the majority of study participants were male (83.7 %) with an average age of 46.26 for AUD, 28.88 for CUD and 34.29 for A-CUD. The most prescribed drugs for AUD were diazepam (54.1 %), thiamine (37 %), complex B vitamins (29.5 %), and disulfiram (2.7 %); for CUD, diazepam (26.9 %) and haloperidol (23.1 %). It should be noticed that although contraindicated by the guidelines, chlorpromazine (42.3 %, 25.3 %, 20.3 %) was prescribed for CUD, AUD, and A-CUD respectively. Knowing the pharmacoepidemiological profile of CAPS-AD patients is extremely important for making decisions regarding which medicines to make available to the population.

Longitudinal assessment of leukotriene B4, lipoxin A4, and resolvin D1 plasma levels in pregnant women with risk factors for preeclampsia.

OBJECTIVES: We carried out a longitudinal study to compare leukotriene B4 (LTB4), lipoxin A4 (LXA4), and resolvin D1 (RvD1) levels in pregnant women with risk factors for PE - who did (N = 11) or did not develop (N = 17) this clinical condition. DESIGN & METHODS: For both groups, plasma levels of the lipid mediators were measured using immunoassays at 12-19, 20-29, and 30-34 weeks of gestation. RESULTS: LTB4 tended to be upregulated throughout gestation in women who developed PE. Moreover, this increase was significant at 30-34 weeks. Although LXA4 levels also tended to be higher in the PE group, this difference was not significant for the evaluated gestational periods. Pregnant women with PE had lower RvD1 levels and a low RvD1/LTB4 ratio at 30-34 weeks, compared to those in the normotensive pregnant women. Contrarily, RvD1 levels increased at weeks 12-19 in pregnant women who developed PE. Particularly, LXA4 and RvD1 levels were higher at 30-34 weeks than those at 20-29 weeks considering both groups of women. We observed an interaction between the gestational outcome and the gestational period in case of RvD1. CONCLUSIONS: The imbalance among LTB4, LXA4, and RvD1 levels in these preeclamptic women is consistent with the excessive inflammation that underlies the pathogenesis of PE. Although our data highlight the potential for the use of these lipid mediators as clinical markers for PE development, future longitudinal studies must be carried out to confirm these findings.

Clinical Features and Maternal-fetal Results of Pregnant Women in COVID-19 Times.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a disease caused by a newly discovered coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which usually leads to non-specific respiratory symptoms. Although pregnant women are considered at risk for respiratory infections by other viruses, such as SARS and Middle East respiratory syndrome (MERS), little is known about their vulnerability to SARS-CoV-2. Therefore, this study aims to identify and present the main studies on the topic, including the postpartum period. METHODS: In this narrative review, articles were searched in various databases, organizations, and health entities using keywords compatible with medical subject headings (MeSH), such as: COVID-19, pregnancy, vertical transmission, coronavirus 2019, and SARS-CoV-2. RESULTS: The review of the scientific literature on the subject revealed that pregnant women with COVID-19 did not present clinical manifestations significantly different from those of non-pregnant women; however, there are contraindicated therapies. Regarding fetuses, studies were identified that reported that infection by SARS-CoV-2 in pregnant women can cause fetal distress, breathing difficulties and premature birth, but there is no substantial evidence of vertical transmission. CONCLUSION: Due to the lack of adequate information and the limitations of the analyzed studies, it is necessary to provide detailed clinical data on pregnant women infected with SARS-CoV-2 and on the maternal-fetal repercussions caused by this infection. Thus, this review may contribute to expand the knowledge of professionals working in the area as well as to guide more advanced studies on the risk related to pregnant women and their newborns. Meanwhile, monitoring of confirmed or suspected pregnant women with COVID-19 is essential, including in the postpartum period.

OBJETIVO: A Coronavirus disease 2019 (COVID-19) é uma doença causada por um coronavírus recém descoberto, o severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), que geralmente leva a sintomas respiratórios não específicos. Embora mulheres grávidas sejam consideradas em risco de infecções respiratórias por outros vírus, como SARS e Middle East respiratory syndrome (MERS), pouco se sabe sobre sua vulnerabilidade ao SARS-CoV-2. Portanto, este estudo tem como objetivo identificar e apresentar os principais estudos sobre o tema incluindo o período pós-parto. MéTODOS: Nesta revisão narrativa, foram pesquisados artigos em diversas bases de dados, organizações e entidades de saúde, utilizando palavras-chave compatíveis com o MeSH, tais como: COVID-19, gravidez, transmissão vertical, coronavírus 2019, e SARS-CoV-2. RESULTADOS: A revisão da literatura científica sobre o assunto revelou que as gestantes com COVID-19 não apresentaram manifestações clínicas significativamente diferentes das não gestantes, porém existem terapias contraindicadas. Em relação aos fetos, foram identificados estudos que relataram que a infecção por SARS-CoV-2 em mulheres grávidas pode causar sofrimento fetal, dificuldades respiratórias e parto prematuro, mas não há evidências substanciais de transmissão vertical. CONCLUSãO: Devido à falta de informações adequadas e às limitações dos estudos analisados, é necessário fornecer dados clínicos detalhados sobre as gestantes infectadas pelo SARS-CoV-2 e sobre as repercussões materno-fetais causadas por esta infecção. Assim, esta revisão pode contribuir para ampliar o conhecimento dos profissionais que atuam na área, bem como para orientar estudos mais avançados sobre o risco relacionado à gestante e seu recém-nascido. Enquanto isso, o monitoramento de gestantes confirmadas ou suspeitas com COVID-19 é essencial, incluindo o pós-parto.

Clinical Features and Maternal-fetal Results of Pregnant Women in COVID-19 Times / Características clínicas e resultados materno-fetais de mulheres grávidas com COVID-19

Abstract Objective Coronavirus disease 2019 (COVID-19) is a disease caused by a newly discovered coronavirus, severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), which usually leads to non-specific respiratory symptoms. Although pregnant women are considered at risk for respiratory infections by other viruses, such as SARS and Middle East respiratory syndrome (MERS), little is known about their vulnerability to SARS-CoV-2. Therefore, this study aims to identify and present the main studies on the topic, including the postpartum period. Methods In this narrative review, articles were searched in various databases, organizations, and health entities using keywords compatible with medical subject headings (MeSH), such as: COVID-19, pregnancy, vertical transmission, coronavirus 2019, and SARS-CoV-2. Results The review of the scientific literature on the subject revealed that pregnant women with COVID-19 did not present clinical manifestations significantly different from those of non-pregnant women; however, there are contraindicated therapies. Regarding fetuses, studies were identified that reported that infection by SARS-CoV-2 in pregnant women can cause fetal distress, breathing difficulties and premature birth, but there is no substantial evidence of vertical transmission. Conclusion Due to the lack of adequate information and the limitations of the analyzed studies, it is necessary to provide detailed clinical data on pregnant women infected with SARS-CoV-2 and on the maternal-fetal repercussions caused by this infection. Thus, this review may contribute to expand the knowledge of professionals working in the area as well as to guide more advanced studies on the risk related to pregnant women and their newborns. Meanwhile, monitoring of confirmed or suspected pregnant women with COVID-19 is essential, including in the postpartum period.

Resumo Objetivo A Coronavirus disease 2019 (COVID-19) é uma doença causada por um coronavírus recém descoberto, o severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), que geralmente leva a sintomas respiratórios não específicos. Embora mulheres grávidas sejam consideradas em risco de infecções respiratórias por outros vírus, como SARS e Middle East respiratory syndrome (MERS), pouco se sabe sobre sua vulnerabilidade ao SARS-CoV-2. Portanto, este estudo tem como objetivo identificar e apresentar os principais estudos sobre o tema incluindo o período pós-parto. Métodos Nesta revisão narrativa, foram pesquisados artigos em diversas bases de dados, organizações e entidades de saúde, utilizando palavras-chave compatíveis com o MeSH, tais como: COVID-19, gravidez, transmissão vertical, coronavírus 2019, e SARSCoV-2. Resultados A revisão da literatura científica sobre o assunto revelou que as gestantes com COVID-19 não apresentaram manifestações clínicas significativamente diferentes das não gestantes, porém existem terapias contraindicadas. Em relação aos fetos, foramidentificados estudos que relataram que a infecção por SARS-CoV-2 em mulheres grávidas pode causar sofrimento fetal, dificuldades respiratórias e parto prematuro, mas não há evidências substanciais de transmissão vertical. Conclusão Devido à falta de informações adequadas e às limitações dos estudos analisados, é necessário fornecer dados clínicos detalhados sobre as gestantes infectadas pelo SARS-CoV-2 e sobre as repercussões materno-fetais causadas por esta infecção. Assim, esta revisão pode contribuir para ampliar o conhecimento dos profissionais que atuam na área, bem como para orientar estudos mais avançados sobre o risco relacionado à gestante e seu recém-nascido. Enquanto isso, o monitoramento de gestantes confirmadas ou suspeitas com COVID-19 é essencial, incluindo o pós-parto.

Avaliação da qualidade de vida de pacientes com Doença Falciforme / Evaluation of the quality of life of patients with Sickle Cell Disease

INTRODUÇÃO: A doença falciforme (DF) compreende um grupo de anemias hemolíticas hereditárias cuja principal característica é a presença do gene da hemoglobina S (Hb S) que pode combinar-se com outras anormalidades sanguíneas hereditárias. O quadro clínico varia desde quase assintomático até formas graves. A Hidroxiuréia (HU) é a terapia de maior sucesso. É uma doença crônica, cuja prevalência e morbidade são altas no Brasil, dessa forma a qualidade de vida (QV) surge como um importante desafio para os pacientes, familiares e profissionais de saúde. OBJETIVOS: Avaliar a QV de pacientes portadores de DF, suas características sociodemográficas e clínicas. MÉTODOS: Os dados foram coletados através do questionário de QV abreviado (WHOQOL-Bref), questionário sociodemográfico e prontuário clínico. RESULTADOS: foram entrevistados 39 pacientes, entre 18 e 54 anos, tratados na Fundação Hemominas em Divinópolis - MG. A maioria dos pacientes eram homens (56%), homozigotos para a Hb S (80%), solteiros (67%), segundo grau completo (31%) e não usuários de HU (61%). Dentre os pacientes avaliados 53,8% considerou ter boa QV (escore médio 74,2 ±20,3). O escore relacionado à QV geral foi de 71,5. Os domínios físico e meio ambiente obtiveram os menores escores médio (61,5 e 59,0, respectivamente). Não foram encontradas diferenças significativas entre os que utilizavam ou não HU. CONCLUSÕES: Os pacientes com DF apresentaram boa QV, sendo mais comprometida pelos aspectos relacionados ao domínio meio ambiente, (como recursos financeiros) e físico (como dor e desconforto) que se correlacionam com as características clínicas e sociais relacionadas a DF.

Introduction: sickle cell disease (SCD) comprises a group of hereditary hemolytic anemias whose main characteristic is the presence of the hemoglobin S (Hb S) gene that can be combined with other hereditary blood abnormalities. The clinical picture ranges from almost asymptomatic to severe forms. Hydroxyurea (HU) is the most successful therapy. It is a chronic disease whose prevalence and morbidity are high in Brazil, thus quality of life (QoL) emerges as an important challenge for patients, family members and health professionals. Objectives: This study aimed to evaluate the QoL of patients with SCD, their sociodemographic and clinical characteristics. Methods: Data were collected through the abbreviated QoL questionnaire (WHOQOL-Bref), sociodemographic questionnaire and clinical chart. Results: It has interviewed at the Hemominas Foundation in Divinópolis - MG, 39 patients aged 18-54. Most of the patients were male (56%), homozygous for Hb S (80%), unmarried (67%), completed high school (31%) and non HU users (61%). Among the patients evaluated, 53.8% considered having a good QoL (mean score 74.2 ± 20.3). The overall QoL score was 71.5. The physical and environmental domains had the lowest mean scores (61.5 and 59.0, respectively). No significant differences were found among those using or not using HU. Conclusions: Patients with SCD presented good QoL, being more affected by aspects related to the environmental domain (such as financial resources) and physical (such as pain and discomfort) those correlate with clinical and social characteristics related to SCD.

Association among ACE, ESR1 polymorphisms and preeclampsia in Brazilian pregnant women.

BACKGROUND: Genetic, immune and environmental factors are involved in preeclampsia (PE) etiopathogenesis. Considering that hypertension and poor placental perfusion are important features in PE, polymorphisms in the angiotensin-converting enzyme (ACE) and estrogen nuclear receptor 1 (ESR1) genes could be involved in the predisposition and/or development of the disease. The aim of this study was to evaluate if polymorphisms in ACE and ESR1 genes were associated with PE occurrence. MATERIAL AND METHODS: This case-control study included 209 Brazilian pregnant women (107 with severe PE and 102 normotensive controls). The polymorphisms were investigated by polymerase chain reaction (PCR) followed by polyacrylamide gel electrophoresis. RESULTS: No significant difference between PE versus normotensive pregnant women, as well as early versus late PE, was observed when compared the allelic and genotypic frequencies of insertion/deletion polymorphism in intron 16 of the ACE gene and the single nucleotide polymorphisms (SNPs - rs2234693 and rs9340799) of the ESR1 gene. CONCLUSION: This pioneer study involving Brazilian women showed no association among the studied polymorphisms and PE, which suggests that ins/del ACE and SNPs ESR1 do not contribute to this disease occurrence in Brazil.

Longitudinal assessment of D-dimer and plasminogen activator inhibitor type-1 plasma levels in pregnant women with risk factors for preeclampsia.

OBJECTIVE: Investigating D-Dimer/D-Di and plasminogen activator inhibitor type-1/PAI-1 levels throughout gestation in women with preeclampsia/PE risk factors. METHODS: D-Di and PAI-1 plasma levels were determined in 28 women at 12-19, 20-29, 30-34 and 35-40 weeks of gestation. RESULTS: D-Di was lower at 12-19 weeks and higher at 30-34 weeks in women who developed PE versus who did not develop it. D-Di increased throughout gestation in both groups, peaking earlier in pregnant women who developed PE versus who did not develop it. PA1-1 increased across gestation, but it didn't differ between groups. CONCLUSION: D-Di was able to discriminate these groups of women at 12-19 and 30-34 weeks of gestation.

Oxidative stress markers and thrombomodulin plasma levels in women with early and late severe preeclampsia.

BACKGROUND: Preeclampsia (PE) is a pregnancy disease associated with oxidative stress and endothelial dysfunction. It can be classified according to the severity and onset-time of clinical symptoms (early PE:<34 weeks, late PE:≥34 weeks). METHODS: We evaluated markers of oxidative stress (thiobarbituric acid reactive substances-TBARs and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)-MTT) and endothelial lesion (thrombomodulin-TM) in early (N = 24) and late severe PE(N = 22) and normotensive pregnant women(N = 26). RESULTS: MTT levels were higher in early sPE than in normotensive pregnancy (P = 0.03). No difference was found comparing late sPE versus normotensive pregnancy, and early sPE versus late sPE. TM levels were higher in early sPE comparing to late sPE women (P = 0.05), but no difference was found between early or late sPE versus normotensive groups. TBARs levels did not differ significantly among the three groups. These data suggest that endothelial lesion and the antioxidant status are more pronounced in early sPE. Moreover, lipid peroxidation might be an early event in PE, stimulating a compensatory antioxidant defense later in pregnancy. CONCLUSIONS: Longitudinal studies involving pregnant women with risk factors for PE development and including other methods for oxidative stress and endothelial lesion determination should be conducted in order to better evaluate the role of these processes in PE pathogenesis.

Estrogen receptor-alpha gene XbaI A > G polymorphism influences short-term cognitive decline in healthy oldest-old individuals.

METHODS: The individuals were categorized in two groups according to the presence or absence of cognitive decline. Cognitive data were related to genetic information. RESULTS: The XbaI -351 AA genotype was more common among cognitive decliners, while -351G allele carriers showed cognitive stability or improvement. CONCLUSION: These results suggest that ESR-1 could be associated with one-year cognitive decline in healthy oldest-old individuals, since the estrogen pathway may be involved with neuroprotection, even in healthy brain aging.

Estrogen receptor-alpha gene XbaI A > G polymorphism influences short-term cognitive decline in healthy oldest-old individuals / Polimorfismo XbaI A > G no gene do receptor do estrogênio-alfa influencia o declínio cognitivo em curto prazo em idosos muito idosos saudáveis

ABSTRACT This prospective study aimed to evaluate the influence of the -351A/G XbaI polymorphism in the estrogen receptor-alpha (ESR-1) gene on global cognitive scores of a community sample of healthy oldest-old individuals within one year of follow up. Methods The individuals were categorized in two groups according to the presence or absence of cognitive decline. Cognitive data were related to genetic information. Results The XbaI -351 AA genotype was more common among cognitive decliners, while -351G allele carriers showed cognitive stability or improvement. Conclusion These results suggest that ESR-1 could be associated with one-year cognitive decline in healthy oldest-old individuals, since the estrogen pathway may be involved with neuroprotection, even in healthy brain aging.

RESUMO Neste estudo prospectivo foi avaliada a influência do polimorfismo -351A/G XbaI do gene do receptor de estrogênio alfa (ESR-1) sobre o desempenho cognitivo global em idosos muito idosos (≥ 75 anos) saudáveis durante um ano. Métodos Os indivíduos foram divididos em dois grupos de acordo com a presença ou ausência de declínio cognitivo. Dados cognitivos foram relacionados à informação genética. Resultados O genótipo XbaI -351 AA foi mais comum entre indivíduos que apresentaram declínio cognitivo, enquanto carreadores do alelo -351G demonstraram estabilidade ou melhora cognitiva. Conclusão Estes resultados sugerem que ESR-1 poderia estar associado ao declínio cognitivo em curto prazo em idosos saudáveis, possivelmente por meio de propriedades neuroprotetoras do estrogênio, mesmo em cérebros idosos saudáveis.

The unexpected beneficial role of smoking in preeclampsia.

We have recently investigated the association between the risk of developing PE and clinical, hemostatic, inflammatory and genetic parameters of 108 severe preeclamptic women. A multivariate logistic regression analysis was performed to assess what variables are independent risk factors for PE. Univariate analysis was performed including the variables in age, smoking condition, multiple pregnancy, blood group, phenotypes and alleles of IL-4, IL-5, IL-10, IL-6, IL-8, IL-12, IL-1ß, IFN-γ, TNF-α, and the plasma levels of FVII, FVIIa, FVIIa-AT, FVIII, FVW, ADAMTS13, D-Di, PAI-1, ADMA. Those variables whose P<0.20 (smoking, multiple pregnancy, blood group, phenotype IL-6, IFN-γ allele, IL-10 allele and FVII) were selected to the multivariate logistic regression. In the final model, only FVII, IFN-γ allele and smoking were independently associated to severe PE (P<0.0001, P<0.0001 and P=0.008, respectively). Increased FVII plasma levels and IFN-γ "T" allele were associated to an increased probability of developing PE (OR 1.001, 95% CI [1.001-1.002], and OR 4.81 95% CI [2.42-9.60], respectively). On the other hand, smoker status was associated with a 4.72 decreased chance of PE occurrence (OR 4.72, 95% CI [1.51-14.75]). In this article we also reviewed the studies that investigate the risk of PE in pregnant women who smoked, as well as the effect of tobacco extract in cells or animal models. The hypotheses proposed to explain the biological mechanism by which smoking during pregnancy reduces the risk of PE was also discussed.

Revisiting HELLP syndrome.

HELLP syndrome was first described in 1982 by Weinstein et al. and the term HELLP refers to an acronym used to describe the clinical condition that leads to hemolysis, elevated liver enzymes and low platelets. The syndrome frequency varies from 0.5 to 0.9% pregnancies and manifests preferentially between the 27th and 37th week of gestation. Approximately 30% of cases occur after delivery. Although the etiopathogenesis of this syndrome remains unclear, histopathologic findings in the liver include intravascular fibrin deposits that presumably may lead to hepatic sinusoidal obstruction, intrahepatic vascular congestion, and increased intrahepatic pressure with ensuing hepatic necrosis, intraparenchymal and subcapsular hemorrhage, and eventually capsular rupture. Typical clinical symptoms of HELLP syndrome are pain in the right upper quadrant abdomen or epigastric pain, nausea and vomiting. However, this syndrome can present nonspecific symptoms and the diagnosis may be difficult to be established. Laboratory tests and imaging exams are essential for differential diagnosis with other clinical conditions. Treatment of HELLP syndrome with corticosteroids, targeting both lung maturation of the fetus is still an uncertain clinical value. In conclusion, three decades after the tireless efforts of Dr. Weinstein to characterize HELLP syndrome, it remains a challenge to the scientific community and several questions need to be answered for the benefit of pregnant women.