Nelson Sass

Cytokine genotyping in preeclampsia.

Problem  Considering that cytokines are involved in preeclampsia (PE) pathogenesis and that cytokine gene polymorphism may affect cytokine production, our purpose was to investigate the association of PE with tumor necrosis factor (TNF)‐α (−308), transforming growth factor‐β1 (+10; 25), interleukin (IL)‐10 (−1082), IL‐6 (−174), and interferon‐γ (+874) polymorphisms.

Obstetric and perinatal effects of active and/or passive smoking during pregnancy

CONTEXT Cigarette smoke, whether inhaled voluntarily or not, causes damage to the mother-infant pair. The antenatal period may present the best opportunity for performing effective anti-smoking campaigns. OBJECTIVE To study the obstetric and perinatal effects of smoking on pregnancy and the infant. TYPE OF STUDY Prospective study, interviewing pregnant women who were randomly selected at the maternity hospital as they were being discharged after giving birth. SETTING Hospital Municipal Vereador José Storópolli, São Paulo, Brazil. METHODS 758 patients were interviewed regarding smoke inhalation before being discharged from the maternity hospital. The groups were formed by 42 active smokers, 272 passive smokers, 108 who inhaled smoke both actively and passively, and 336 non-smokers. The groups were compared regarding age, parity, school education, incidence of spontaneous abortion, rate of caesarian births, average gestational age at birth, rate of low birth weight and adequacy of weight in relation to the gestational age of newborn infants. For all variables we considered p < 0.05 as statistically significant. RESULTS There was a high rate (55.7%) of pregnant smokers, including 5.5% active, 35.9% passive and 14.3% active-passive smokers. Active and active-passive smokers were older and had higher parity. Active smokers had lower education levels and higher rates of previous spontaneous abortion. The weights of newborn babies were lower for smoking mothers. DISCUSSION The study was performed among patients that were mostly of low economic, social and cultural levels, thus possibly explaining the high incidence of smokers. Worse still was that 35.9% of the non-smokers were actually passive smokers. These rates we report were similar to those from the literature. The typical receptiveness of teenage girls to unrestricted advertising in the media contributes towards an early start to acquiring the habit of smoking, including during pregnancy in our country. We emphasize the difficulties in quantifying exposure to cigarettes even among active smokers. CONCLUSIONS Cigarette smoke, whether inhaled voluntarily or not, has an unfavorable effect on the mother-infant pair.

Role of interleukin 8 in uterine natural killer cell regulation of extravillous trophoblast cell invasion.

BACKGROUND Extravillous trophoblast cell (EVT) invasion of maternal tissues is critical for successful pregnancy. Decidual factors, including uterine natural killer (uNK) and T cell derived cytokines play a role in regulating this process. Interleukin (IL) 8 has been implicated as a regulator of EVT invasion. HYPOTHESIS uNK cell stimulation of EVT invasion is associated with IL-8 levels. METHODS CD8+, total decidual and CD56(+) uNK cells (8-10 and 12-14 weeks gestational age) were cultured. IL-8 mRNA and protein levels were determined. IL-8 receptors (IL-8RA and IL-8RB) were localised in first trimester placental bed biopsies. The effect of IL-8 +/- IL-8 neutralising antibodies and CD8+ T cell or uNK cell supernatants +/- IL-8 neutralising antibodies on EVT invasion was assessed. EVT secreted levels of MMP-2, MMP-9, uPA, PAI-1 and PAI-2 were assessed by substrate zymography or Western Blot. RESULTS High levels of IL-8 protein and mRNA were detected in all samples. IL-8RA and IL-8RB were expressed by EVT. Exogenous IL-8 stimulated EVT invasion in a paracrine manner. uNK cell supernatants, but not CD8+ cell supernatants, stimulated EVT invasion. IL-8 neutralising antibody partially abrogated this uNK cell stimulated invasion. IL-8 increased levels of secreted MMP-2, but did not alter any of the other proteases or protease inhibitors tested. CONCLUSION uNK cell stimulation of EVT invasion is partially mediated by IL-8. Unstimulated CD8+ T cells do not alter EVT invasion despite secreting similar levels of IL-8 as uNK cells.

Cytokine gene polymorphisms in preeclampsia and eclampsia

The clinical spectrum of preeclampsia (PE) ranges from mild hypertension to severe vasospasm associated with convulsions and multiple organ damage. The biological factors that determine the progression of PE to eclampsia (E) are unknown. Endothelial cell activation seems related to an impaired maternal immune response. The production of cytokines, IL-10 and TGF-β1, is apparently suppressed, and altered IL-2/IL-10 and TNF-α/IL-10 ratios have been reported in preeclamptic cases. The relationship between PE and cytokine gene polymorphism has been studied, but there are few studies that include eclamptic patients. This study aimed at investigating whether polymorphisms in genes, TNF-α promoter (−308 G>A), IL6 promoter (−174 G>C), IFN-γ intron 1 (+874 A>T), IL10 promoters (−1082 A>G), (−819 C>T) and (−592 C>A) and TGF-β1 codon 10 (+869 T>C) and codon 25 (+915 G>C) are associated with E and/or PE. Genotyping was carried out in 266 Mulatto women from the northeastern region of Brazil who were referred to a single maternity hospital: 92 with PE, 73 with E and 101 normotensive controls. The χ2 or Fishers exact tests were used to compare genotype frequencies. Among the six single-nucleotide polymorphisms (SNPs) studied, we found no difference in genotype frequencies between the groups. There was a higher frequency of IFN-γ (+874 A) in eclamptic patients in comparison with that in controls. (70.3 vs. 57.8%, respectively; P=0.02). There were no other significant differences in allelic frequencies between eclamptic, preeclamptic and control groups We found no independent association between any single SNP and PE or E risk in this population of Mulatto women from the northeastern region of Brazil.

Ophthalmic artery Doppler as a measure of severe pre-eclampsia

To identify differences in orbital flow behavior in mild and severe pre‐eclamptic women compared with healthy pregnant women, demonstrated by ophthalmic artery Doppler indexes.

Pregnancy after renal transplantation – a five-yr single-center experience

Abstract:  Background:  There has been an increase in the number of pregnancies in renal transplant recipients. Our aim was to report our experience with a significant casuistic.

Serum lipid levels in pregnancies complicated by preeclampsia

CONTEXT AND OBJECTIVE Pre-eclampsia is a disorder that occurs only during pregnancy. Postpartum changes relating to lipid metabolism may contribute towards the endothelial lesions observed in preeclampsia. Thus, the aim of the present study was to evaluate the lipid profile among patients who present preeclampsia and correlate these parameters with 24-hour proteinuria. DESIGN AND SETTING Cross-sectional analytical study including 77 pregnant patients seen at Hospital Dório Silva. METHODS This study involved 42 women with preeclampsia and 35 healthy pregnant women in the third trimester of pregnancy as controls. Blood samples were obtained from all the patients, and the serum levels of triglycerides, total cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL) and very low density lipoproteins (VLDL) were determined. Cases and controls were matched for maternal age, gestational week and body mass index. RESULTS The VLDL and triglyceride values from the women with preeclampsia were significantly higher than those of the healthy women. There was a positive correlation between increased proteinuria and higher VLDL and triglyceride levels in patients with preeclampsia. CONCLUSION Among the patients with preeclampsia, higher VLDL and triglyceride levels were positively correlated with proteinuria. These observations indicate that the pregnant women who presented elevated lipid levels were more susceptible to cardiovascular disorders and, consequently, pre-eclampsia.

Ophthalmic artery Doppler velocimetry in healthy pregnancy

To establish normative data for ophthalmic artery Doppler parameters throughout a healthy pregnancy, to investigate the possible correlation between these Doppler measurements and gestational age, and to test intraobserver variability.

Pré-eclâmpsia: estresse oxidativo, inflamação e disfunção endotelial

Preeclampsia is a systemic syndrome characterized by inflammatory and antiangiogenic states. The pathogenesis of preeclampsia involves deficient trophoblast invasion that is responsible for altered uterine blood flow and placental oxidative stress. The damaged placenta produces higher concentrations of sFlt-1, a soluble receptor for VEGF and PlGF that is released in the maternal circulation and is involved in endothelial dysfunction. Actually, all processes involved in inflammation, endothelial dysfunction and oxidative stress are strongly correlated and act in a synergistic way. Recent data have shown that an increase in serum concentrations of sFlt-1 initiates 5 to 6 weeks before the clinical manifestations of preeclampsia and these alterations correlate with a decrease in serum concentrations of PlGF. Therefore, both sFlt-1 and PlGF have been suggested to be useful for an early-diagnosis of preeclampsia. The knowledge about the role of antiangiogenic factors in the pathogenesis of preeclampsia has raised the possibility of a therapy involving these factors.In this article we revisited the pathogenesis of preeclampsia addressing its antiangiogenic and inflammatory states.In conclusion, we correlated these alterations with the higher risk for cardiovascular diseases presented by these women in future life.

Renal Evaluation in Women with Preeclampsia

Background/Aims: Preeclampsia (PE) is a cause of glomerulopathy worldwide. Urinary retinol-binding protein (RBP) is a marker of proximal tubular dysfunction, albuminuria is an endothelial injury marker, urine protein:creatinine ratio (PCR) may have a predictive value for renal disease later in life, and, recently, podocyturia has been proposed as a sensitive tool in pregnancy, but it needs to be tested. The aim of this study was to evaluate renal involvement in PE and healthy pregnancy. Methods: Case-control study with 39 pregnant women assessed after 20 weeks of gestation (25 in the control group, CG, and 14 in the PE group) by performing urinary tests. Results: Mean (±SD) age and gestational age of the CG were 26.9 ± 6.4 years and 37.1 ± 5.0 weeks, and of the PE group 26.4 ± 6.9 years and 30.6 ± 5.6 weeks, respectively (p = 0.001). Mean (±SD) urinary RBP (p = 0.017), albuminuria (p = 0.002), and urinary albumin concentration (UAC) ratio (p = 0.006) of the CG were 0.4 ± 0.7 mg/l, 7.3 ± 6.9 mg/l, and 8.2 ± 6.7 mg/g and of the PE group 2.0 ± 4.4 mg/l, 2,267.4 ± 2,130.8 mg/l (p = 0.002), and 3,778.9 ± 4,296.6 mg/g (p = 0.006), respectively. Mean (±SD) urine PCR in the PE group was 6.7 ± 6.1 g/g (p < 0.001). No statistical differences were found between podocyturia in the CG and PE group (p = 0.258). Conclusions: Urinary RBP, PCR, albuminuria, and UAC ratio were elevated in the PE group in comparison to the CG. Podocyturia did not predict PE.