Progesterone modulates TNF receptors expression by Jurkat cells cultured with plasma from pregnant women with preeclampsia.

Pregnant women with preeclampsia (PE) present a shift in the immune response to an inflammatory profile. This deviation could be due to the interaction of tumor necrosis factor (TNF) with TNFR1 and TNFR2 receptors, besides the failure in modulation of inflammation regulatory mechanisms. This study evaluated the effects of progesterone on the expression of TNFR1 and TNFR2 by Jurkat cells after stimulation with plasma from PE and normotensive (NT) pregnant women. Jurkat cells were cultured with or without progesterone in a medium containing 20% (v/v) plasma from PE or NT women. The expression of TNF receptors was evaluated by flow cytometry. The concentration of soluble forms of TNF receptors and cytokines was determined in culture supernatant and plasma by ELISA. The plasma of PE women showed significantly higher concentrations of sTNFR1 and TNF and lower concentrations of sTNFR2 compared to the NT group. TNFR1 receptor expression was increased in Jurkat cells, while TNFR2 was decreased after culture with PE plasma when compared with Jurkat cells cultured with progesterone and plasma from NT women. The concentration of sTNFR1, TNF, and IL-10 in the culture supernatant of Jurkat cells was increased after culture with PE plasma, while the sTNFR2 receptor was decreased when compared to the NT group. Results demonstrate that in preeclamptic women a systemic inflammation occurs with an increase of inflammatory molecules, and progesterone may have a modulating effect on the expression of TNF receptors, shifting Jurkat cells towards an anti-inflammatory profile with greater expression of TNFR2.

Plasma eNOS Concentration in Healthy Pregnancy and in Hypertensive Disorders of Pregnancy: Evidence of Reduced Concentrations in Pre-Eclampsia from Two Independent Studies.

Hypertensive disorders of pregnancy (HDP), comprising gestational hypertension (GH) and pre-eclampsia (PE), are leading causes of maternal and perinatal morbidity and mortality. Both GH and PE are characterized by new-onset hypertension, but PE additionally includes proteinuria and/or end-organ damage. Impaired nitric oxide (NO) bioavailability may lead to endothelial dysfunction in GH and PE, and the primary source of vascular NO is endothelial NO synthase (eNOS). However, no previous study has investigated plasma eNOS concentrations in patients with GH and PE. In this study, we compared plasma eNOS concentrations in healthy pregnancies and HDP in two independent cohorts. The primary study included 417 subjects, with 43 non-pregnant (NP) and 156 healthy pregnant (HP) women and 122 patients with GH and 96 with PE. The replication study included 85 pregnant women (41 healthy and 44 pre-eclamptic). Plasma concentrations of eNOS were measured using a commercial ELISA kit provided by R&D Systems, and plasma nitrite concentrations were assessed using two ozone-based chemiluminescence assays. Correlations between plasma eNOS concentrations and plasma nitrite concentrations, as well as clinical and biochemical parameters, were evaluated by either Spearman's or Pearson's tests. In the primary study, NP women and HDP had significantly lower plasma eNOS concentrations compared to HP; concentrations were even lower in PE compared to GH. Plasma eNOS concentrations were reduced but not significant in early-onset PE, PE with severe features, preterm birth, and intrauterine growth restriction. No correlation was observed between plasma eNOS and nitrite levels. In HDP, there was a significant positive correlation between levels of eNOS and hemoglobin (r = 0.1496, p = 0.0336) as well as newborn weight (r = 0.1487, p = 0.0316). Conversely, a negative correlation between eNOS levels and proteinuria was observed (r = -0.2167, p = 0.0179). The replication study confirmed significantly reduced plasma concentrations of eNOS in PE compared to HP. Our findings provide evidence of reduced plasma eNOS concentrations in HDP; they were particularly lower in PE compared to GH and HP in two independent studies.

Modulatory effect of two regimens of magnesium sulfate on the systemic inflammatory response in pregnant women with imminent eclampsia.

OBJECTIVE: This study compared the modulatory effect of two intravenous magnesium sulfate (MgSO4) regimens on the systemic inflammatory response in pregnant women diagnosed with imminent eclampsia. STUDY DESIGN: In a single-blind cross-sectional study, 33 women were allocated according to the Zuspan (n = 16) and Sibai (n = 17) MgSO4 regimens, and treated for 24 h. Blood samples were collected pre-administration of the loading dose, at 24 h of the maintenance dose of MgSO4, and at 48 h, when patients were without treatment. Plasma was used to determine interleukin (IL)-1 beta (IL-1ß), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), heat shock protein (Hsp70), and heme oxygenase-1 (HO-1) by ELISA. RESULTS: The treatment with the Zuspan's regimen didn't change plasma concentrations of TNF-α, IL-10, and Hsp70 in the three-time points studied. However, it decreased IL-1ß at 24 h and 48 h and IL-6 at 48 h, and increased HO-1 concentration at 48 h. On the other hand, compared to the pre-treatment period, Sibai's regimen induced a significant decrease in TNF-α, IL-1ß, IL-6, and Hsp70, while increased HO-1 levels both at 24 h and 48 h and, IL-10 concentration at 48 h. CONCLUSIONS: Sibai's regimen determined an early and efficient immunoregulatory effect on systemic inflammatory response in preeclampsia, suggesting that the maintenance dose of two grams of MgSO4 was better than one gram in the treatment of imminent eclampsia.

Influence of Swimming Program on the Blood Pressure of Pregnant Hypertensive Rats and Their Fetuses.

The hypertension incidence and its complication on pregnant women are growing and can lead to adverse consequences on their fetuses. However, it is known that regular exercise practice can be healthful to hypertensive pregnant women but harmful to fetal growth. So, the objective of this study was to evaluate the effects of exercise beginning before pregnancy or during pregnancy on the maternal blood pressure and reproductive outcome and on the fetal development of spontaneously hypertensive rats (SHR). Pregnant SHR were randomly distributed into three experimental groups: (1) SHR-Control, non-exercised; (2) SHR-Ex0, rats submitted to physical exercise (swimming program) from day zero to 20 of pregnancy; (3) and SHR-ExPr, rats submitted to swimming program before and during pregnancy. At end of pregnancy (day 21), the rats were anesthetized, and reproductive parameters and fetal development were assessed. Blood pressure was reduced at the end of pregnancy in all the groups. Regardless of swimming exposure time, there was reduced maternal weight gain. The exercise decreased fetal weight at term pregnancy, with a higher percentage of small for gestational age (SGA) fetuses and lower number ossification sites, indicating intrauterine growth restriction (IUGR). In conclusion, our findings provide insight to support that swimming exercise in pregnant SHR impairs fetal development, causing IUGR and visceral malformations. Therefore, the indication of physical exercise must be defined very carefully, as it can compromise fetal development.

Downregulation of CD163 in monocytes and its soluble form in the plasma is associated with a pro-inflammatory profile in pregnant women with preeclampsia.

Preeclampsia (PE) is a pregnancy-specific syndrome characterized by a systemic inflammatory response that polarizes peripheral blood monocytes to the M1 phenotype. The classically activated M1 monocytes comprise immune effector cells with an acute inflammatory phenotype. CD163 is a scavenger receptor expressed by monocytes/macrophages that may be shed from their cell membrane after proteolytic cleavage, producing the soluble CD163 molecule (sCD163). This study evaluated CD163 expression by monocytes and sCD163 as well as pro- and anti-inflammatory cytokine concentration in the plasma of pregnant women with PE. Fifty-six women with PE and 28 normotensive pregnant women were included. Plasma levels of sCD163, interleukin-1 beta (IL-1ß), IL-6, IL-10, transforming growth factor beta (TGF-ß1), and tumor necrosis factor-alpha (TNF-α) were determined by ELISA, and CD163 expression by monocytes was assessed by flow cytometry. The expression of CD163 by monocytes was significantly lower in severe and mild PE than in normotensive pregnant. Plasma concentrations of IL-1ß, TGF-ß1, and TNF-α were higher in severe PE than in mild PE and normotensive pregnant women. Both groups of preeclamptic women showed decreased plasma levels of sCD163 and IL-10. Negative correlations between sCD163 and IL-1ß (r = - 0.45; P = 0.014) and between sCD163 and TNF-α concentrations (r = - 0.54; P = 0.001) were observed in the severe PE group. The association between the pro-inflammatory cytokine profile and lower concentrations of sCD163 and IL-10 in plasma from women with severe PE suggests an impairment in the modulation of the systemic inflammatory response in this group of pregnant women with preeclampsia.

Increased expression of NLRP3 inflammasome in placentas from pregnant women with severe preeclampsia.

Preeclampsia is a pregnancy disorder characterized by imbalance between pro- and anti-inflammatory cytokines associated with high plasma levels of uric acid and Interleukin-1 beta (IL-1ß). The inflammasome is a protein complex that mediates innate immune responses via caspase-1 activation promoting secretion of IL-1ß and IL-18 in their active forms, and also release of the high-mobility group box 1 protein (HMGB1). As the placenta seems to play an important role in the pathogenesis of PE, the present study investigated the expression of genes and proteins related to the inflammasome in placentas from pregnant women with severe preeclampsia. Placental tissue was collected from 20 normotensive pregnant women and 20 preeclamptic women, and inflammasome components, NLRP3 (NOD-like receptor family, pyrin domain-containing protein 3), caspase-1, IL-1ß and IL-18, as well as tumor necrosis factor-alpha (TNF-α) and HMGB1 were evaluated by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and also quantified by reverse transcription-qPCR (RT-qPCR). Compared with normotensive pregnant women, placenta from women with PE showed a significant increase in NLRP3, caspase-1, IL-1ß, TNF-α and HMGB1 mRNA. Immunohistochemical staining of NLRP3, caspase-1, IL-1ß and TNF-α in placental villi, as well as the levels of caspase-1, IL-1ß, TNF-α and HMGB1 in placental homogenate were significantly higher in the preeclamptic group than in the normotensive group. However, mRNA expression of IL-18 and its protein concentrations were lower in placentas from preeclamptic women. The results suggest that placentas from pregnant women with preeclampsia show higher expression of NLRP3 inflammasome, which may be involved in the exaggerated inflammatory state in preeclampsia.

Association between cytokine profile and transcription factors produced by T-cell subsets in early- and late-onset pre-eclampsia.

Pre-eclampsia (PE) is an obstetric pathology characterized by abnormal activation of the innate and adaptive immune systems dependent on the imbalance of T helper subsets. The present study aimed to evaluate the gene and protein expression of T helper type 1 (Th1)/Th2/Th17/regulatory T (Treg) cell transcription factors in peripheral blood lymphocytes from pregnant women with PE employing quantitative RT-PCR and flow cytometry techniques, as well as the cytokine profile produced by these CD4+ T-cell subsets in the plasma of pregnant women with PE, classified as early-onset PE (n = 20), late-onset PE (n = 20) and normotensive pregnant women (n = 20). Results showed a higher percentage of CD4+ T cells expressing the RORc transcription factor (Th17) and a lower percentage of cells expressing FoxP3 (Treg) in women with early-onset PE compared with late-onset PE and normotensive groups. A lower gene expression of GATA-3 transcription factor was detected in cells of women with early-onset PE compared with the late-onset PE group. Endogenous plasma levels of interleukin-6 (IL-6), IL-17 and tumour necrosis factor-α were significantly higher in the early-onset PE group than in the late-onset PE and normotensive groups, whereas IL-4 (Th2 profile) and IL-22 (Th17 profile), were not significantly different between the studied groups. The endogenous levels of transforming growth factor-ß and IL-10 were significantly lower in the pre-eclamptic than in the normotensive groups of the same gestational age, with a significant difference between early- and late-onset PE. The results show that in women with PE there is an imbalance between inflammatory and anti-inflammatory profiles in CD4+ T-cell subsets, with polarization to Th17 profiles in the early-onset PE, considered as the severe form of PE.

Association between Placental Lesions, Cytokines and Angiogenic Factors in Pregnant Women with Preeclampsia.

Preeclampsia (PE) is considered the leading cause of maternal and perinatal morbidity and mortality. The placenta seems to play an essential role in this disease, probably due to factors involved in its formation and development. The present study aimed to investigate the association between placental lesions, cytokines and angiogenic factors in pregnant women with preeclampsia (PE). We evaluated 20 normotensive pregnant women, 40 with early-onset PE and 80 with late-onset PE. Placental samples were analyzed for histopathology, immunohistochemistry and determination of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-10 (IL-10), transforming growth factor-beta 1 (TGF-ß1), tumor necrosis factor-alpha (TNF-α), placental growth factor (PlGF), vascular endothelial growth factor (VEGF), fms-like tyrosine-kinase-1 (Flt-1) and endoglin (Eng) levels. Higher percentages of increased syncytial knots and increased perivillous fibrin deposits, and greater levels of TNF-α, TGF-ß1and Flt-1 were detected in placentas from early-onset PE. Levels of IL-10, VEGF and PlGF were decreased in PE versus normotensive placentas. Both the TNF-α/IL-10 and sFlt-1/PlGF ratios were higher in placental homogenate of early-onset PE than late-onset PE and control groups. The more severe lesions and the imbalance between TNF-α/IL-10 and PlGF/sFlt-1 in placentas from early-onset PE allows differentiation of early and late-onset PE and suggests higher placental impairment in early-onset PE.

Applying the maternal near miss approach for the evaluation of quality of obstetric care: a worked example from a Multicenter Surveillance Study.

OBJECTIVE: To assess quality of care of women with severe maternal morbidity and to identify associated factors. METHOD: This is a national multicenter cross-sectional study performing surveillance for severe maternal morbidity, using the World Health Organization criteria. The expected number of maternal deaths was calculated with the maternal severity index (MSI) based on the severity of complication, and the standardized mortality ratio (SMR) for each center was estimated. Analyses on the adequacy of care were performed. RESULTS: 17 hospitals were classified as providing adequate and 10 as nonadequate care. Besides almost twofold increase in maternal mortality ratio, the main factors associated with nonadequate performance were geographic difficulty in accessing health services (P < 0.001), delays related to quality of medical care (P = 0.012), absence of blood derivatives (P = 0.013), difficulties of communication between health services (P = 0.004), and any delay during the whole process (P = 0.039). CONCLUSIONS: This is an example of how evaluation of the performance of health services is possible, using a benchmarking tool specific to Obstetrics. In this study the MSI was a useful tool for identifying differences in maternal mortality ratios and factors associated with nonadequate performance of care.

Monocytes from pregnant women with pre-eclampsia are polarized to a M1 phenotype.

PROBLEM: This study evaluated whether the monocyte inflammatory state in pre-eclampsia (PE) might be associated with polarization to either M1 classically or M2 alternatively activated monocyte subsets. METHOD OF STUDY: Eighty-five women with (PE) and 52 normotensive (NT) pregnant women matched for gestational age were included. Expression of surface receptors characteristic of M1, such as Toll-like receptor (TLR)2, TLR4, and CD64, or M2, such as CD163 and CD206 monocyte subsets were evaluated in peripheral blood monocytes by flow cytometry. Tumour necrosis factor-alpha (TNF-α), interleukin-(IL)-12p40, IL-12p70, and IL-10 were evaluated in the supernatant of monocyte cultures by ELISA. RESULTS: Expression of TLR4 and CD64 by monocytes from pre-eclamptic women was significantly higher, while the expression of CD163 and CD206 expression was significantly lower compared with NT pregnant women. Endogenous production of TNF-α, IL-12p40, and IL-12p70 by monocytes was increased, while synthesis of IL-10 was lower in women with PE than in NT pregnant women. CONCLUSIONS: Monocytes from women with PE are classically activated, producing higher levels of pro-inflammatory cytokines, and express surface receptors characteristic of the M1 subset. These results provide evidence that the systemic inflammatory environment in PE may differentiate and polarize these cells to the M1 phenotype.

Gene expression and protein localization of TLR-1, -2, -4 and -6 in amniochorion membranes of pregnancies complicated by histologic chorioamnionitis.

OBJECTIVES: To determine whether histologic chorioamnionitis is associated with changes in gene expression of TLR-1, -2, -4 and -6, and to describe the localization of these receptors in fetal membranes. STUDY DESIGN: A total of 135 amniochorion membranes with or without histologic chorioamnionitis from preterm or term deliveries were included. Fragments of membranes were submitted to total RNA extraction. RNA was reverse transcribed and the quantification of TLRs expression measured by real time PCR. RESULTS: All amniochorion membranes expressed TLR-1 and TLR-4, whereas 99.1% of membranes expressed TLR-2 and 77.4% expressed TLR-6. TLR-1 and TLR-2 expressions were significantly higher in membranes with histologic chorioamnionitis as compared to membranes without chorioamnionitis in preterm pregnancies (p=0.003 and p<0.001, respectively). Among the membranes of term pregnancies there were no differences in the expressions of such receptors regardless of inflammatory status. Regarding TLR-4 and TLR-6 expression, there was no difference among membranes with or without histologic chorioamnionitis, regardless gestational age at delivery. TLR-1, TLR-2, TLR-4 and TLR-6 expressions were observed in amniotic epithelial, chorionic and decidual cells. CONCLUSION: Amniochorion membranes express TLR-1, TLR-2, TLR-4 and TLR-6 and increased expression of TLR-1 and TLR-2 is related to the presence of histologic chorioamnionitis in preterm pregnancies. This study provides further evidence that amniochorion membranes act as a mechanical barrier to microorganisms and as components of the innate immune system.

High levels of heat shock protein 70 are associated with pro-inflammatory cytokines and may differentiate early- from late-onset preeclampsia.

Preeclampsia (PE), a specific syndrome of pregnancy, can be classified into early and late onset, depending on whether clinical manifestations occur before or after 34 weeks' gestation. We determined whether plasma concentrations of Hsp60 and Hsp70 were related to circulating cytokine levels, as well as kidney and liver functions, in early- and late-onset PE. Two hundred and thirty-seven preeclamptic women (95 with early- and 142 with late-onset PE) were evaluated. Plasma levels of Hsp60, Hsp70, and their specific antibodies, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1, IL-10, IL-12, and soluble TNF-α-receptor I (sTNFRI) concentrations, were determined by enzyme-linked immunosorbent assay (ELISA). Concentrations of Hsp70, TNF-α, IL-1ß, IL-12, and sTNFRI were significantly elevated in patients with early-onset PE compared with women with late-onset PE; IL-10 levels were significantly lower in the early-onset PE group. Concentrations of urea, uric acid, proteinuria, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and lactate dehydrogenase (LDH) were also significantly higher in early-onset PE. The percentage of infants with intrauterine growth restriction was also significantly higher in women with early-onset PE. There were positive correlations between Hsp70 levels and TNF-α, TNFRI, IL-1ß, IL-12, GOT, GPT, LDH, and uric acid concentrations in early-onset PE group. Thus, early-onset PE was associated with greater maternal and fetal impairment. There are differences in pathophysiology between early- and late-onset PE, highlighting by the difference in Hsp70 levels.

sFlt-1/PlGF ratio as a prognostic marker of adverse outcomes in women with early-onset preeclampsia.

Soluble fms-like tyrosine kinase 1 (sFlt-1) is an anti-angiogenic factor released in higher amounts by preeclamptic placentas and it has been implicated in the endothelial dysfunction observed in the disease. In this study we evaluated if circulating sFlt-1/PlGF ratio is useful to predict adverse outcomes in women with early-onset preeclampsia. This is a cohort study of 88 preeclamptic women with singleton pregnancies at ⩽35weeks of gestation. According to definitions used, adverse outcomes occurred in 46.5% (N=43) of the patients. The median sFlt1/PlGF ratio (25th-75th centile) for all patients evaluated was of 42.26 (13.1-226.1). The median sFlt-1/PlGF ratio among women who had any adverse outcome (N=43) versus no adverse outcomes (N=45) was of 227.6 (80.3-346.1) versus 14.4 (3.35-30.0), (P<0.0001). According to our analyses a sFlt-1/PlGF ratio cut-point of ⩾85 gave a sensitivity of 74.0% and specificity of 97.0%. The positive predictive value and the negative predictive value were 96.0% and 80.0%, respectively. The median sFlt-1/PlGF ratio (25th-75th centile) for patients who delivered within <7days was 260.0 (127.7-404.7) as compared to 14.4 (3.35-34.97) for those patients who delivered within two weeks or more (P<0.0001). Our results suggest that sFlt-1/PlGF ratio is a promising marker for adverse outcomes in women with early-onset preeclampsia.

Silibinin modulates the NF-κb pathway and pro-inflammatory cytokine production by mononuclear cells from preeclamptic women.

Preeclampsia (PE) is a complication of human pregnancy associated with an intense inflammatory response involving leukocyte activation, as well as elevated production of pro-inflammatory cytokines. The nuclear transcription factor-kappa B (NF-κB) is present in cells of the immune system and is responsible for transcription of genes coding for pro-inflammatory proteins. Silibinin is the main component of silymarin, a polyphenolic extract obtained from fruits and seeds of Silybum marianum with potent hepatoprotective and anti-inflammatory activities. In this study, we assessed whether silibinin modulated NF-κB activity and the production of pro-inflammatory cytokines by peripheral blood mononuclear cells (PBMCs) from preeclamptic patients. PBMC from women with PE, normotensive (NT) pregnant women, and nonpregnant (NP) women were cultured with or without silibinin (5 µM and 50 µM) and 1 µg/mL lipopolysaccharide (LPS) for 18 h. The supernatants were assayed for tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) by ELISA. Cells were cultured for 30 min to evaluate NF-κB activity. There was increased endogenous activation of NF-κB as well as TNF-α and IL-1ß release by PBMC in the PE group compared with the NT and NP groups. A positive correlation between NF-κB activity and cytokine production was also observed in the PE group. Silibinin was capable of reducing, at least in part, the levels of NF-κB and cytokines TNF-α and IL-1ß in preeclamptic women. We conclude that silibinin exhibits potent anti-inflammatory activity on PBMC from preeclamptic women by downmodulation of NF-κB activation and inflammatory cytokine production.

The safe motherhood referral system to reduce cesarean sections and perinatal mortality - a cross-sectional study [1995-2006].

BACKGROUND: In 2000, the eight Millennium Development Goals (MDGs) set targets for reducing child mortality and improving maternal health by 2015. OBJECTIVE: To evaluate the results of a new education and referral system for antenatal/intrapartum care as a strategy to reduce the rates of Cesarean sections (C-sections) and maternal/perinatal mortality. DESIGN: Cross-sectional study. SETTING: Department of Gynecology and Obstetrics, Botucatu Medical School, Sao Paulo State University/UNESP, Brazil. POPULATION: 27,387 delivering women and 27,827 offspring. DATA COLLECTION: maternal and perinatal data between 1995 and 2006 at the major level III and level II hospitals in Botucatu, Brazil following initiation of a safe motherhood education and referral system. MAIN OUTCOME MEASURES: Yearly rates of C-sections, maternal (/100,000 LB) and perinatal (/1000 births) mortality rates at both hospitals. DATA ANALYSIS: Simple linear regression models were adjusted to estimate the referral system's annual effects on the total number of deliveries, C-section and perinatal mortality ratios in the two hospitals. The linear regression were assessed by residual analysis (Shapiro-Wilk test) and the influence of possible conflicting observations was evaluated by a diagnostic test (Leverage), with p < 0.05. RESULTS: Over the time period evaluated, the overall C-section rate was 37.3%, there were 30 maternal deaths (maternal mortality ratio = 109.5/100,000 LB) and 660 perinatal deaths (perinatal mortality rate = 23.7/1000 births). The C-section rate decreased from 46.5% to 23.4% at the level II hospital while remaining unchanged at the level III hospital. The perinatal mortality rate decreased from 9.71 to 1.66/1000 births and from 60.8 to 39.6/1000 births at the level II and level III hospital, respectively. Maternal mortality ratios were 16.3/100,000 LB and 185.1/100,000 LB at the level II and level III hospitals. There was a shift from direct to indirect causes of maternal mortality. CONCLUSIONS: This safe motherhood referral system was a good strategy in reducing perinatal mortality and direct causes of maternal mortality and decreasing the overall rate of C-sections.

Increased reactive oxygen species and tumor necrosis factor-alpha production by monocytes are associated with elevated levels of uric acid in pre-eclamptic women.

PROBLEM: To evaluate associations between hyperuricemia and increases in production of reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-α) in pre-eclamptic pregnancies. METHOD OF STUDY: This study investigated serum uric acid levels, monocyte production of TNF-α, superoxide anion (O(2)(-)) and hydrogen peroxide (H(2)O(2)), as well as superoxide dismutase (SOD) and catalase (CAT) activities in erythrocytes from 30 women with pre-eclampsia (PE) compared with 30 normotensive (NT) pregnant women in the last trimester of pregnancy. RESULTS: Serum uric acid levels (6.1 versus 2.8 mg/dL) as well as endogenous O(2)(-) (2.2 versus 1.6 nm), H(2)O(2) (1.8 versus 1.4 nm) and TNF-α (91.6 versus 40.4 pg/mL) released from monocytes were significantly higher in the pre-eclamptic group than in the NT group (P < 0.05). SOD activity in erythrocytes was also significantly elevated in the PE group (5969.2 versus 4834.7 U/g Hb). No significant difference between groups was observed in relation to CAT activity. CONCLUSIONS: Elevated serum uric acid levels are correlated with higher O(2)(-) and TNF-α production by monocytes in women with PE. This may contribute to the enhanced oxidative and inflammatory state characteristic of this disorder.

Expression of ß defensins 1, 3 and 4 in chorioamniotic membranes of preterm pregnancies complicated by chorioamnionitis.

OBJECTIVE: To quantify the expression of human ß-defensins (HBDs) 1, 3 and 4 in chorioamniotic membranes in pregnancies complicated by prematurity associated with histologic chorioamnionitis. STUDY DESIGN: The study group included 23 fragments of chorioamniotic membranes with histologic chorioamnionitis from women with preterm premature rupture of membranes (PPROM) and preterm labor (PTL) with intact membranes, who had preterm deliveries. As a control group, 30 chorioamniotic membranes without chorioamnionitis at the same gestational age as those in the study group were included. Chorioamniotic membranes were collected for histopathological analyses, and HBD mRNA expression quantification was analyzed by real time PCR. Comparisons were performed using the Mann-Whitney or Kruskal-Wallis tests and all the women were informed and provided written consent. RESULTS: The expression of HBDs mRNA in the fetal membranes was similar in patients without histologic chorioamnionitis (HBD1: 0.7-fold, HBD3: 0.9-fold, HBD4: 0.3-fold) compared to patients with chorioamnionitis (HBD1: 1.1-fold, HBD3: 0.9-fold, HBD4: 0.4-fold; p>0.05). Regarding the gestational complications that resulted in premature delivery, PPROM or PTL, the relative quantification of HBD1, HBD3 and HBD4 showed no statistically significant differences in either the absence or presence of chorioamnionitis. Among patients with histologic chorioamnionitis, patients with PPROM (HBD1: 2.7-fold, HBD3: 0.3-fold, HBD4: 0.7-fold) presented similar mRNA expression to those with PTL (HBD1: 0.7-fold, HBD3: 1.2-fold, HBD4: 0.13-fold; p>0.05). CONCLUSIONS: Chorioamniotic membranes are sources of ß defensins 1, 3 and 4; however, considering the sample size and the methodology applied, mRNA concentrations were not related to the presence of histologic chorioamnionitis.

Effect of physiological overload on pregnancy in women with mitral regurgitation.

OBJECTIVES: to evaluate the structural and functional heart abnormalities in women with mitral regurgitation during pregnancy. INTRODUCTION: Women with mitral regurgitation progress well during pregnancy. However, the effects on the heart of the association between pregnancy and mitral regurgitation are not well established. METHODS: This is a case-control, longitudinal prospective study. Echocardiograms were performed in 18 women with mitral regurgitation at the 12th and 36th week of pregnancy and on the 45th day of the puerperium. Twelve age-matched healthy and pregnant women were included as controls and underwent the same evaluation as the study group. RESULTS: Compared with controls, women with mitral regurgitation presented increased left cardiac chambers in all evaluations. Increasing left atrium during pregnancy occurred only in the mitral regurgitation group. At the end of the puerperium, women with mitral regurgitation showed persistent enlargement of the left atrium compared with the beginning of pregnancy (5.0 ± 1.1 cm vs 4.6 ± 0.9 cm; p < 0.05). Reduced left ventricular relative wall thickness (0.13 ± 0.02 vs 0.16 ± 0.02; p < 0.05) and an increased peak of afterload (278 ± 55 g/cm² vs 207 ± 28 g/cm²; p < 0.05) was still observed on the 45th day after delivery in the mitral regurgitation group compared with controls. CONCLUSIONS: Pregnancy causes unfavorable structural alterations in women with mitral regurgitation that are associated with an aggravation of the hemodynamic overload.

sFlt-1 and IP-10 in women with early-onset preeclampsia.

Intense inflammatory response and an anti-angiogenic state have been implicated in the pathogenesis of preeclampsia. Here, we investigated this hypothesis evaluating the serum concentrations of CXCL10/IP-10, sFlt-1, and PlGF in women with early-onset preeclampsia. CXCL10/IP-10 was measured by Cytometric Bead Array. sFlt-1 and PlGF were measured by automated electrochemiluminescence immunoassay. The median serum concentration of CXCL10/IP-10 was 109.5pg/mL in preeclamptic women, as compared with 52.28pg/mL in the controls (P=0.0028). The mean serum level of sFlt-1 was 13,636pg/mL in preeclamptic women, as compared with 2020pg/mL in the controls (P<0.0001). PlGF levels were significantly lower in women with preeclampsia.

Vaginal flora alterations and clinical symptoms in low-risk pregnant women.

BACKGROUND: To evaluate associations between alterations in vaginal flora and clinical symptoms in low-risk pregnant women. METHODS: Vaginal specimens from 245 pregnant women were analyzed by microscopy for vaginal flora. Signs and symptoms of vaginal infection were determined by patient interviews and gynecologic examinations. RESULTS: Abnormal vaginal flora was identified in 45.7% of the subjects. The final clinical diagnoses were bacterial vaginosis (21.6%), vaginal candidosis (10.2%), intermediate vaginal flora (5.2%), aerobic vaginitis (2.9%), mixed flora (2.9%) and other abnormal findings (2.9%). The percentage of women with or without clinical signs or symptoms was not significantly different between these categories. The presence of vaginal odor or vaginal discharge characteristics was not diagnostic of any specific flora alteration; pruritus was highly associated with candidosis (p < 0.0001). Compared to women with normal flora, pruritus was more prevalent in women with candidosis (p < 0.0001), while vaginal odor was associated with bacterial vaginosis (p = 0.0026). CONCLUSION: The prevalence of atypical vaginal flora is common in our low-risk pregnant population and is not always associated with pathology. The occurrence of specific signs or symptoms does not always discriminate between women with different types of atypical vaginal flora or between those with abnormal and normal vaginal flora.