Do socioeconomic factors explain why maternal smoking during pregnancy is more frequent in a more developed city of Brazil?

The prevalence of smoking during pregnancy in Ribeirão Preto, a rich Brazilian city, was significantly higher (21.4%) than in São Luís (5.9%), a less developed city. To assess which variables explain the difference in prevalence of smoking during pregnancy, data from two birth cohorts were used, including 2846 puerperae from Ribeirão Preto, in 1994, and 2443 puerperae from São Luís, in 1997/98. In multivariable analysis, risk of maternal smoking during pregnancy was higher in São Luís for mothers living in a household with five or more persons (OR = 1.72, 95%CI = 1.12-2.64), aged 35 years or older (OR = 1.98, 95%CI = 0.99-3.96), who had five or more children (OR = 2.10, 95%CI = 1.16-3.81), and whose companion smoked (OR = 2.20, 95%CI = 1.52-3.18). Age of less than 20 years was a protective factor (OR = 0.55, 95%CI = 0.33-0.92). In Ribeirão Preto there was association with maternal low educational level (OR = 2.18, 95%CI = 1.30-3.65) and with a smoking companion (OR = 3.25, 95%CI = 2.52-4.18). Receiving prenatal care was a protective factor (OR = 0.24, 95%CI = 0.11-0.49). Mothers from Ribeirão Preto who worked outside the home were at a higher risk and those aged 35 years or older or who attended five or more prenatal care visits were at lower risk of smoking during pregnancy as compared to mothers from São Luís. Smoking by the companion reduced the difference between smoking rates in the two cities by 10%. The socioeconomic variables in the model did not explain the higher prevalence of smoking during pregnancy in the more developed city.

Are birth weight and maternal smoking during pregnancy associated with malnutrition and excess weight among school age children?

In the late 1980's child malnutrition was still prevalent in Brazil, and child obesity was beginning to rise in the richest regions of the country. To assess the extent of the nutritional transition during the period and the influence of birth weight and maternal smoking on the nutritional condition of schoolchildren, we estimated the prevalence of excess weight and malnutrition in a cohort of Brazilian schoolchildren from 1987 to 1989. We calculated the body mass index (BMI) of 8- to 10-year-old schoolchildren born in Ribeirão Preto in 1978/79. We considered children with a BMI <5th percentile (P5) to be malnourished, children with P5³BMIpregnancy, marital status, and schooling) and type of school using nominal logistic regression. A total of 2797 schoolchildren were evaluated. There was a significant prevalence of malnutrition (9.5%) and excess weight already tended to increase (15.7%), while 6.4% of the children were obese. Excess weight was more prevalent among children attending private schools (odds ratio, OR = 2.27) and firstborn children (OR = 1.69). Maternal smoking during pregnancy protected against malnutrition (OR = 0.56), while children with lower birth weight were at higher risk for malnutrition (OR = 4.23). We conclude that a nutritional transition was under way while malnutrition was still present, but excess weight and related factors were already emerging.

Prenatal management, pregnancy and pediatric outcomes in fetuses with septated cystic hygroma

It has been reported that, compared with simple increased nuchal translucency, fetal cases with septated cystic hygroma (CH) are more likely to face perinatal handicaps. However, pediatric outcomes and proper prenatal counseling for this anomaly have not yet been truly defined. We performed this study to determine pregnancy and pediatric outcomes of fetuses with septated CH. We searched records for cases with septated CH and collected data for structural abnormalities, karyotype analysis, and pregnancy outcomes. Fetuses born with septated CH were also evaluated for their pediatric outcomes. Sixty-nine fetuses with septated CH were enrolled in the study. Results showed that chromosomal abnormalities were present in 28 fetuses (40.6%), and the most common aneuploidy was Turner syndrome (n=14, 20.3%); 16 (23.2%) of the remaining cases, in which aneuploidy was not found, had coexistent structural malformations; 25 (36.2%) cases had normal karyotype and morphology. The total number of live births and infants with unfavorable neurologic follow-up were 13 (18.8%) and 2 (2.9%), respectively. Septated CH is associated with poor perinatal outcomes; therefore, karyotype analysis and ultrasonographic anomaly screening should be performed as initial steps, and expectant management should be offered to couples with euploid fetuses that have normal morphology.

Follicular helper T cell in immunity and autoimmunity

The traditional concept that effector T helper (Th) responses are mediated by Th1/Th2 cell subtypes has been broadened by the recent demonstration of two new effector T helper cells, the IL-17 producing cells (Th17) and the follicular helper T cells (Tfh). These new subsets have many features in common, such as the ability to produce IL-21 and to express the IL-23 receptor (IL23R), the inducible co-stimulatory molecule ICOS, and the transcription factor c-Maf, all of them essential for expansion and establishment of the final pool of both subsets. Tfh cells differ from Th17 by their ability to home to B cell areas in secondary lymphoid tissue through interactions mediated by the chemokine receptor CXCR5 and its ligand CXCL13. These CXCR5+ CD4+ T cells are considered an effector T cell type specialized in B cell help, with a transcriptional profile distinct from Th1 and Th2 cells. The role of Tfh cells and its primary product, IL-21, on B-cell activation and differentiation is essential for humoral immunity against infectious agents. However, when deregulated, Tfh cells could represent an important mechanism contributing to exacerbated humoral response and autoantibody production in autoimmune diseases. This review highlights the importance of Tfh cells by focusing on their biology and differentiation processes in the context of normal immune response to infectious microorganisms and their role in the pathogenesis of autoimmune diseases.

Sphingosine-1-phosphate-evoked invasion of follicular thyroid cancer cells : evidence for the involvement of HIF-Iα, MMP2 and MMP9

Sphingolipids are widely expressed molecules, which traditionally were considered to have majorly structural properties. Nowadays, however, they are implicated in a wide range of different biological processes. The bioactive lipid sphingosine 1-phosphate (S1P) has emerged during the past decade as one of the most studied molecules due to its proliferative and pro-migratory abilities both during normal physiology and in the pathology of a subset of different diseases. Migration and invasion of cancer cells require changes in cell behavior and modulation of the tissue microenvironment. Tumor aggressiveness is markedly enhanced by hypoxia, in which hypoxia inducible transcription factors 1-2α (HIF-1-2α) are activated to promote metabolism, proliferation and migration. Invasion requires degradation of the extracellular matrix (ECM) achieved by several degrading and remodeling enzymes. Matrix metalloproteinases (MMPs) are broadly expressed and well accepted as proteolytic enzymes with essential roles both in normal physiology and in pathology. Previously, S1P was shown to strongly evoke migration of follicular ML-1 thyroid cancer cells. The objective of this study was to further investigate and understand the mechanisms behind this regulation. In the first project it was demonstrated that S1P enhances the expression and activity of HIF-1α. S1P enhanced the expression of HIF-1α by increasing its synthesis and stability. The S1P-increased HIF-1α was mediated via S1P3, Gi/0, PI3K, PKCβI, ERK1/2, mTOR and translation factors p70S6K and eIF4E. Finally, it was shown that HIF-1α mediated S1P-induced migration. The ECM is constituted of a complex and coordinated assembly of many types of proteins. In order to be able to invade, cells need to break down the ECM, therefore several key players in this event were investigated in the second project. S1P increased the secretion and activity of MMP2 and MMP9 via S1P-receptor 1 and 3 and that these MMPs participated in the S1P-facilitated invasion of ML-1 cells. In this interplay, calpains and Rac1 were involved, both of which are crucial players in migration and invasion. The prognosis for some types of thyroid cancer is relatively good. However, there are forms of thyroid cancers, for which there are no treatments or the current available treatments are inefficient. Thus, new medical interventions are urgently needed. In the third project the significance of the S1P-receptor modulating drug FTY720, which is currently used for the treatment of multiple sclerosis (MS), was studied. The effect of FTY720 was tested on several thyroid cancer cell lines, and it inhibited the proliferation and invasion of all cancer cell lines tested. In ML-1 cells, FTY720 attenuated invasion by blocking signaling intermediates important for migration and invasion of the cells. Moreover, FTY720 inhibited the proliferation of ML-1 cells by increasing the expression of p21 and p27, hence, inducing cell arrest in G1 phase of the cell cycle. Thus, it can be suggested that FTY720 could be used in the treatment of thyroid cancer.

Stromal interaction molecule 1 and its role in the regulation, proliferation and protein expression in follicular ML-1 thyroid cancer cells

Calcium (Ca2+) is involved in the regulation of variety of cellular functions including hallmarks of cancer development such as cellular migration and cellular proliferation. Store-operated calcium entry (SOCE) is a central mechanism in cellular calcium signaling and in maintaining the cellular calcium balance. Stromal interaction molecule 1(STIM1) has been identified as an important constituent of SOCE. In this thesis , the STIM1 proteins are studied for their importance in cellular processes and their effects on the expression of S1P1, S1P2, S1P3, VEGFR-2, and TRPC-1 in follicular ML-1 thyroid cancer cells. The results show the importance of STIM1 proteins in SOCE in these cells. The SOCE is significantly reduced in the STIM1 knockdown cells. The results also show the importance of STIM1 proteins in the expression of S1P2 and VEGFR-2 in these cells, as knockdown of STIM1 was shown to upregulate the expression of S1P2 and VEGFR-2. The migration and proliferation is also considerably reduced in the cells in which STIM1 has been knocked down showing the significance of STIM1 in the migration and proliferation in these cells.

Biomarkers, medical treatment and fetal intrapartum surveillance in intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disorder characterized by maternal pruritus and elevated liver enzymes. It usually begins in the third trimester of pregnancy and resolves spontaneously after delivery. ICP is considered benign for the pregnant woman, but it is associated with an increased risk for unexplained term stillbirth and preterm delivery. There are no specific laboratory markers to diagnose ICP. The diagnosis is currently based on the presence of maternal pruritus and elevated values of alanine aminotransaminases (ALT) and serum bile acids (BA). Recently, ursodeoxycholic acid (UDCA) has been used for treatment. Mechanisms leading to intrauterine fetal death (IUFD) may be multifactorial and are unknown at present. For this thesis, 415 pregnant women with ICP were studied. The aim was to evaluate the value of the liver enzyme glutathione S-transferase alpha (GSTA) as a specific marker of ICP and to assess the effect of maternal UDCA therapy on maternal laboratory values and fetal outcome. The specific markers predisposing the fetus to heart arrhythmia were studied by comparing waveform analysis of fetal electrocardiograms (FECG) during labor in pregnancies complicated by ICP with controls. The levels of maternal GSTA were high and the values correlated with the value of ALT in patients with ICP. UDCA therapy reduced the values of the liver enzymes and alleviated maternal pruritus, but it did not influence maternal hormonal values. Although the newborns experienced an uneventful perinatal outcome, severe ICP was still associated with preterm birth and admission to the neonatal intensive care unit (NICU). There were no significant differences in intrapartum FECG findings between fetuses born to ICP women and controls.