Ana Cristina d'Andretta Tanaka

Rheumatic Heart Disease: Proinflammatory Cytokines Play a Role in the Progression and Maintenance of Valvular Lesions

Heart lesions of rheumatic heart disease (RHD) patients contain T-cell clones that recognize heart proteins and streptococcal M peptides. To functionally characterize heart-infiltrating T lymphocytes, we evaluated their cytokine profile, both directly in situ and in T-cell lines derived from the heart (HIL). Interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, and IL-10 expressions were characterized in 20 heart tissue infiltrates from 14 RHD patients by immunohistochemistry. IFN-gamma-, TNF-alpha-, and IL-10-positive cells were consistently predominant, whereas IL-4 was scarce in the valves. In agreement with these data, the in vitro experiments, in which 13 HILs derived from heart samples of eight patients were stimulated with M5 protein and the immunodominant M5 (81-96) peptide, IL-4 was detected in HIL derived from the atrium (three of six) but not from the valve (zero of seven). IFN-gamma and IL-10 production were detected in culture supernatants in 11 of 13 and 6 of 12 HILs, respectively. The predominant IFN-gamma and TNF-alpha expression in the heart suggests that Th1-type cytokines could mediate RHD. Unlike in reversible myocardium inflammation, the significantly lower IL-4 expression in the valvular tissue (P = 0.02) may contribute to the progression of the RHD leading to permanent valvular damage (relative risk, 4.3; odds ratio, 15.8). The lack of IL-4 in vitro production by valve-derived HIL also emphasizes the more severe tissue destruction in valves observed in RHD.

Mimicry in Recognition of Cardiac Myosin Peptides by Heart-Intralesional T Cell Clones from Rheumatic Heart Disease

Molecular mimicry between Streptococcus pyogenes Ags and human proteins has been considered as a mechanism leading to autoimmune reactions in rheumatic fever and rheumatic heart disease (RHD). Cardiac myosin has been shown as a putative autoantigen recognized by autoantibodies of rheumatic fever patients. We assessed the human heart-intralesional T cell response against human light meromyosin (LMM) and streptococcal M5 peptides and mitral-valve-derived proteins by proliferation assay. Cytokines induced by LMM peptides were also evaluated. The frequency of intralesional T cell clones that recognized LMM peptides was 63.2%. Thirty-four percent of T cell clones presented cross-reactivity with different patterns: 1) myosin and valve-derived proteins; 2) myosin and streptococcal M5 peptides; and 3) myosin, valve-derived proteins and M5 peptides. In addition, several LMM peptides were recognized simultaneously showing a multiple reactivity pattern of heart-infiltrating T cells. Inflammatory cytokines (IFN-γ and TNF-α) were predominantly produced by heart-infiltrating T cells upon stimulation with LMM peptides. The alignment of LMM and streptococcal M5 peptides showed frequent homology among conserved amino acid substitutions. This is the first study showing the cellular response by human heart-infiltrating T cells against cardiac myosin epitopes in RHD patients. The high percentage of reactivity against cardiac myosin strengthens its role as one of the major autoantigens involved in rheumatic heart lesions. T cell reactivity toward myosin epitopes in RHD patients may also trigger the broad recognition of valvular proteins with structural or functional similarities.

PDIA3, HSPA5 and vimentin, proteins identified by 2-DE in the valvular tissue, are the target antigens of peripheral and heart infiltrating T cells from chronic rheumatic heart disease patients.

Rheumatic fever (RF) is a post-infectious autoimmune disease due to sequel of group A streptococcus (GAS) pharyngitis. Rheumatic heart disease (RHD), the major manifestation of RF, is characterized by inflammation of heart valves and myocardium. Molecular mimicry between GAS antigens and host proteins has been shown at B and T cell level. However the identification of the autoantigens recognized by B and T cells within the inflammatory microenvironment of heart tissue in patients with RHD is still incompletely elucidated. In the present study, we used two-dimensional gel electrophoresis (2-DE) and mass spectrometry to identify valvular tissue proteins target of T cells from chronic RHD patients. We could identify three proteins recognized by heart infiltrating and peripheral T cells as protein disulfide isomerase ER-60 precursor (PDIA3), 78kD glucose-regulated protein precursor (HSPA5) and vimentin, with coverage of 45%, 43 and 34%, respectively. These proteins were recognized in a proliferation assay by peripheral and heart infiltrating T cells from RHD patients suggesting that they may be involved in the autoimmune reactions that leads to valve damage. We also observed that several other proteins isolated by 2-DE but not identified by mass spectrometry were also recognized by T cells. The identified cardiac proteins are likely relevant antigens involved in T cell-mediated autoimmune responses in RF/RHD that may contribute to the development of RHD.

Risk factors associated with very low birth weight in a low-income population

This study aimed to identify risk factors associated with very low birth weight in a general hospital in Caxias do Sul, Rio Grande do Sul State, Brazil. This was a case-control study of 200 newborns with birth weight from 500 to 1,499 g (cases) and 400 with birth weight from 3,000 to 3,999 g (controls). Infants were from singleton pregnancies, and their mother had received prenatal care at public health services. The dependent variable was birth weight, and independent variables included socioeconomic status, schooling, and gestational and birth status. Univariate and multivariate analyses were performed with a 5% level of significance. Mortality in very low birth weight newborns was 32.5%. The limits of viability were 600 g for birth weight and 26 weeks for gestational age. Variables related to very low birth weight were: maternal age > 35 years (p = 0.01), lack of prenatal care (p < 0.0001), illness during the index pregnancy (p = 0.03), maternal hypertension (p = 0.007), hospitalization during pregnancy (p < 0.0001), and prior history of low birth weight (p < 0.0001). Many premature births were due to avertable factors.

Desistindo da denúncia ao agressor: relato de mulheres vítimas de violência doméstica

The goal of this study is to describe the experience of female victims of domestic violence, who forfeited the lawsuits against their aggressors. The interviews were oriented by the question: What was your experience of forfeiting the denunciation of your aggressor? Three themes emerged from the convergence of the testimonies: time passed from the aggression to the denunciation and then to the forfeiting; the partner, the family, the womens precinct; reflecting about the experience, which described the studied phenomenon. The women expressed ambiguous feelings for their aggressor: affection, anger, humiliation and fear. They recognize that they are dominated and humiliated, but notions of justice and equality between spouses do not appear in the testimonies. Forfeiting can be understood in the context of the reproduction of the traditional family structure, conditioned to economic and social factors. Results highlight implications about the role of the Womens Precinct and the healthcare institutions in the care for women who were victims of domestic violence.The goal of this study is to describe the experience of female victims of domestic violence, who forfeited the lawsuits against their aggressors. The interviews were oriented by the question: What was your experience of forfeiting the denunciation of your aggressor? Three themes emerged from the convergence of the testimonies: time passed from the aggression to the denunciation and then to the forfeiting; the partner, the family, the womens precinct; reflecting about the experience, which described the studied phenomenon. The women expressed ambiguous feelings for their aggressor: affection, anger, humiliation and fear. They recognize that they are dominated and humiliated, but notions of justice and equality between spouses do not appear in the testimonies. Forfeiting can be understood in the context of the reproduction of the traditional family structure, conditioned to economic and social factors. Results highlight implications about the role of the Womens Precinct and the healthcare institutions in the care for women who were victims of domestic violence.

Motivação de gestantes para o aleitamento materno

OBJECTIVE: The present study sought to discover the reasons for expectant mothers to breastfeed. METHODS: This was a qualitative study involving 164 expectant mothers attending prenatal care in two health centers of the city of Sao Paulo. Semi-structured interviews were done to collect data on the reasons to breastfeed. The information was organized in a spreadsheet to search for categories. RESULTS: The main identified categories regarded the childs and womans health and the benefits of breastfeeding and breast milk. The majority of the women (98.8%) regarded breastfeeding favorably. Benefit to the childs health was the reason mentioned most often (73.8%). CONCLUSION: Motivation to breastfeed was based on benefits to the childs health. Breastfeeding is valued regardless of the mothers will.

Situação de saúde materna e perinatal no Estado de São Paulo, Brasil

Pelos dados oficiais disponiveis, para o Estado de Sao Paulo (Brasil) analisou-se a assistencia oferecida na gestacao, no parto e ao recem-nascido e suas relacoes com a mortalidade materna e perinatal. Com referencia ao pre-natal, houve indicios de quantidade de consultas por gestacao, numericamente suficiente, porem de qualidade discutivel. Quanto ao parto observou-se uma alta percentagem de cesarianas (46,2%). A mortalidade materna foi de 4,86 por dez mil n.v., valor este subestimado. A primeira causa de obitos maternos foram as toxemias, seguidas das hemorragias e do aborto, causas estas evitaveis em sua maioria, com uma boa qualidade de assistencia pre-natal e ao parto. Quanto aos obitos do periodo perinatal, o coeficiente foi de 29,2 por mil nascimentos em 1984, valor este tambem elevado. A analise das causas de obitos mostrou que as afeccoes de origem perinatal ocorreram em cerca de 90% dos obitos, tendo como principais causas as hipoxias intra-uterinas, asfixias, sindromes de angustia respiratoria e aspiracao macica. Esses dados revelam a ma qualidade de assistencia recebida por este grupo. Sugere-se que a nova politica de Sistema Unificado e Descentralizado de Saude deveria levar em conta tanto a qualidade de assistencia como a integracao dos servicos para poder-se fazer frente a situacao precaria de saude materna e perinatal do Estado.

Mid-upper arm circumference in pregnant women and its relation to birth weight

OBJECTIVE In order to determine the relationship between some maternal anthropometric indicators and birth weight, crown-heel length and newborns head circumference, 92 pregnant women were followed through at the prenatal service of hospital in S. Paulo, Brazil. MATERIAL AND METHOD The following variables were established for the mother: weight, height, mid-upper arm circumference, pre-pregnancy weight, gestational weight gain and Quetelets index. For the newborn the following variables were recorded: birth weight, crown-heel length, head circumference and gestational age by Dubowitzs method. RESULTS Significant associations were noted between gestational age and newborn variables. In addition, maternal mid-arm circumference (MUAC) and pre-pregnancy weight were found to be positively correlated to birth weight (r = 0.399; r = 0.378, respectively). The multivariate linear regression shows that gestational age, mothers arm circumference and pre-pregnancy weight continue to be significant predictors of birth weight. On the other hand, only gestational age and mothers age was associated with crown-heel length. Similarly MUAC was significantly associated with crown-heel length (r = 0.306; P = 0.0030). CONCLUSION Maternal mid-upper arm circumference is a potential indicator of maternal nutritional status. It could be used in association with other anthropometric measurements, instead of pre-pregnancy weight, as an alternative indicator to assess women at risk of poor pregnancy outcome.

Saúde e estado nutricional infantil de uma população da região Centro-Oeste do Brasil

OBJECTIVE To evaluate the nutritional status of infants who reside in the city of Campo Grande, State of Mato Grosso do Sul, Brazil. METHODS The method used was that of a cross sectional household study by means of an anthropometric social survey, sampling 652 children from 0 to 59 months of age. RESULTS A low prevalence of nutritional deficit, excepting that of height-for-age, starting in the first year of life, was found. The nutritional status proved to be influenced by the socioeconomic conditions, especially concerning per capita family income. Nearly all children started breast-feeding but were weaned during the first month. Exclusive breast-feeding is of short duration and soon replaced by infant formula. The survey of mother-child assistance demonstrated an excellent coverage of prenatal care, but inadequacy in the follow-up of the childs health at all income levels. CONCLUSIONS The need to carry out changes in the approach to preventive actions and in the monitoring of the nutritional situation of the children, concerning the problems identified in this study in order to allow for the development of differential actions in the nutritional field has been identified.Departamento de Tecnologia de Alimentos e Saude Publica do Centro de Ciencias Biologicas e da Saude da Universidade Federal de Mato Grosso do Sul (UFMS). Campo Grande, MS Brasil (DLBR); Departamento de Nutricao da Faculdade de Saude Publica da Universidade de Sao Paulo (FSP/USP). Sao Paulo, SP Brasil (STP); Departamento de Saude Materno-Infantil da FSP/USP. Sao Paulo, SP Brasil (ACD’AT); Departamento de Computacao e Estatistica do Centro de Ciencias Exatas e Tecnologicas da UFMS (JRZ)OBJETIVO: Avaliar o estado nutricional de criancas residentes em Campo Grande, Mato Grosso do Sul, Brasil. METODOS: Trata-se de um estudo transversal, de base domiciliar, atraves de um inquerito antropometrico-social, com amostra de 652 criancas de 0 a 59 meses de idade. RESULTADOS: Foram encontradas baixas prevalencias de deficts nutricionais, com excecao para deficits de altura/idade, tendo inicio ainda no primeiro ano de vida. O estado nutricional mostrou-se influenciado pelas condicoes socioeconomicas, especialmente a renda per capita familiar. Quase a totalidade das criancas iniciaram a amamentacao, mas o desmame teve inicio ainda no primeiro mes. O aleitamento materno exclusivo e de curta duracao, com oferta precoce de substitutos do leite materno. A analise da assistencia materno-infantil apresentou boa cobertura de pre-natal, mas deficiente no acompanhamento da saude infantil em todas as faixas de renda. CONCLUSOES: Identificou-se a necessidade de realizar alteracoes na abordagem das acoes preventivas de vigilância da situacao nutricional das criancas, para que haja condicoes de desenvolver acoes diferenciadas no campo nutricional.

CXCL9/Mig Mediates T cells Recruitment to Valvular Tissue Lesions of Chronic Rheumatic Heart Disease Patients

Rheumatic fever (RF) is an autoimmune disease triggered by Streptococcus pyogenes infection frequently observed in infants from developing countries. Rheumatic heart disease (RHD), the major sequel of RF, leads to chronic inflammation of the myocardium and valvular tissue. T cells are the main population infiltrating cardiac lesions; however, the chemokines that orchestrate their recruitment are not clearly defined. Here, we investigated the expression of chemokines and chemokine receptors in cardiac tissue biopsies obtained from chronic RHD patients. Our results showed that CCL3/MIP1α gene expression was upregulated in myocardium while CCL1/I-309 and CXCL9/Mig were highly expressed in valvular tissue. Auto-reactive T cells that infiltrate valvular lesions presented a memory phenotype (CD4+CD45RO+) and migrate mainly toward CXCL9/Mig gradient. Collectively, our results show that a diverse milieu of chemokines is expressed in myocardium and valvular tissue lesions and emphasize the role of CXCL9/Mig in mediating T cell recruitment to the site of inflammation in the heart.