Geraldo Duarte

Tissue inhibitor of matrix metalloproteinase-1 polymorphism, plasma TIMP-1 levels, and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy

Tissue inhibitor of metalloproteinase (TIMP)-1 is a major endogenous inhibitor of matrix metalloproteinase (MMP)-9, which may affect the responsiveness to therapy in hypertensive disorders of pregnancy. We examined whether TIMP-1 polymorphism (g.–9830T>G, rs2070584) modifies plasma MMP-9 and TIMP-1 levels and the response to antihypertensive therapy in 596 pregnant: 206 patients with preeclampsia (PE), 183 patients with gestational hypertension (GH) and 207 healthy pregnant controls. We also studied the TIMP-3 polymorphism (g.–1296T>C, rs9619311). Plasma MMP-9 and TIMP-1 levels were measured by ELISA. GH patients with the GG genotype for the TIMP-1 polymorphism had lower MMP-9 levels and MMP-9/TIMP-1 ratios than those with the TT genotype. PE patients with the TG genotype had higher TIMP-1 levels. The G allele and the GG genotype were associated with PE and responsiveness to antihypertensive therapy in PE, but not in GH. Our results suggest that the TIMP-1 g.–9830T>G polymorphism not only promotes PE but also decreases the responses to antihypertensive therapy.

Prospective evaluation of renal artery resistance and pulsatility indices in normal pregnant women.

To establish normal values for renal artery resistance index (RI) and pulsatility index (PI) during gestation and, by comparison with non‐pregnant controls, to determine if pregnancy affects these indices.

Evaluation of Long-Term Results of Surgical Correction of Stress Urinary Incontinence

A total of 109 patients submitted to surgery for the correction of urinary stress incontinence (USI) by two different techniques, i.e. anterior colporrhaphy (group I, n = 57) when cystocele grade II/III was present, and Burch procedure (group II, n = 52) when cystocele grade I was present, were reevaluated an average of 5 years after surgery (range: 54-66 months). The curve constructed with the reevaluation data showed a sharp superiority of the Burch technique in terms of correction of USI and associated genital prolapses. There was a progressive recurrence rate that stabilized at 5 years, with values of 78.9% in group I and 40% in group II. Anterior colporrhaphy was ineffective for the correction of any of these parameters in group I. The data clearly show the need to improve the presurgical diagnostic methods for the selection of patients that will benefit from treatment: detailed history of the current disease and auxiliary tests such as Q-tip test, transvaginal ultrasound, and urodynamic study. Other factors were associated with ineffective treatment in both groups, such as hypoestrogenism (20/109), excessive weight gain (19/109) and chronic intestinal constipation and/or coughing present in 36 patients, with recurrence in 28 of them.

Gene–gene interactions in the NAMPT pathway, plasma visfatin/NAMPT levels, and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy

Nicotinamide phosphorybosil transferase (NAMPT) polymorphisms affect visfatin/NAMPT levels and may affect the responsiveness to therapy in hypertensive disorders of pregnancy. We examined whether NAMPT polymorphisms (rs1319501 T>C and rs3801266 A>G), or haplotypes, and gene–gene interactions in the NAMPT pathway affect plasma visfatin/NAMPT levels and the response to antihypertensive therapy in 205 patients with preeclampsia (PE) and 174 patients with gestational hypertension. We also studied 207 healthy pregnant controls. Plasma visfatin/NAMPT levels were measured by ELISA. Non-responsive PE patients with the TC+CC genotypes for the rs1319501 T>C, and with the AG+GG genotypes for the rs3801266 A>G polymorphism had lower and higher visfatin/NAMPT levels, respectively. The ‘C, A’ haplotype was associated with response to antihypertensive therapy, and with lower visfatin/NAMPT levels in PE. Interactions among NAMPT, TIMP-1 and MMP-2 genotypes were associated with PE and with lack of response to antihypertensive therapy in PE. Our results suggest that NAMPT polymorphisms affect plasma visfatin/NAMPT levels in nonresponsive PE patients, and that gene–gene interactions in the NAMPT pathway not only promote PE but also decrease the response to antihypertensive therapy in PE.

Quantitation of immunoglobulin A in the human chorioamniotic membrane.

Thirty‐eight chorioamniotic membranes were obtained from normal patients divided into three groups according to time of rupture. A protein extract was obtained by destruction and differential centrifugation and immunoglobulin A was measured by the method of Mancini. The authors demonstrated that it is possible to quantitate immunoglobulin A. No statistically significant differences were observed between groups.

PP002. Study of polymorphisms of the adiponectin gene in women with gestational hypertension and preeclampsia

INTRODUCTION Adiponectin is involved in energy homeostasis by regulating glucose and lipid metabolism. Additionally, it presents anti-inflammatory and anti-atherosclerotic functions. Polymorphisms in adiponectin gene (ADIPOQ) can modulate the concentrations of adiponectin. The influence of these polymorphisms on the development of gestational hypertension (GH) and preeclampsia (PE) is unknown. OBJECTIVES The aim of this work was to examine the influence of polymorphisms in the gene ADIPOQ on the development of gestational hypertension and preeclampsia. METHODS PATIENTS AND METHODS We studied 401 pregnant women: 161 healthy pregnant (HP), 113 pregnant with gestational hypertension (GH) and 127 pregnant with preeclampsia (PE). Polymorphisms ADIPOQ -11391G>A (rs17300539), -11377C>G (rs266729), 45T>G (rs2241766) and 276G>T (rs1501299) were genotyped by allelic discrimination by PCR in real time. Haplotypes were inferred using the PHASE 2.1 program. RESULTS There were no statistically significant differences in allele and genotype frequencies of the polymorphisms studied. In the analysis of haplotypes, we observed small differences in haplotype frequencies between groups, however, none of these differences was statistically significant (P>0.05). CONCLUSION We found no association between the genotypic and allelic variants of the ADIPOQ gene polymorphisms with the development of gestational hypertension and preeclampsia.

Fetal interlocking: unusual handling of a rare complication

We report a case of fetal interlocking with a resolution not previously reported in the literature consisting of a combination of vaginal delivery and cesarean section, with longitudinal uterine incision.

PP070. Maternal flow-mediated dilation and nitrite concentration during third trimester of pregnancy and postpartum period.

INTRODUCTION The vascular endothelium is thought to be responsible for cardiovascular adaptations in gestation, such as the decrease in peripheral vascular resistance and the decrease in arterial pressure. There is an increase of nitric oxide (NO) serum levels in normal gestation due to an increment in the activity of the enzyme endothelial nitric oxide synthase (eNOS). OBJECTIVES To compare maternal flow-mediated dilation of the brachial artery (FMD) and the nitrite concentration between the third trimester of pregnancy and postpartum period. Additionally we want to evaluate whether FMD correlates with nitrite concentration. METHODS Eligibility criteria were healthy pregnant women with single fetus, gestational age greater than 28 weeks, nonsmokers, and without personal or family history of vascular disease. Each pregnant woman was examined in the third trimester of pregnancy (3(rd)T) and between 8 and 12 weeks postpartum (PP) to evaluate FMD and nitrite concentrations in the whole blood. We excluded women who were not examined in both periods. We compared the values between the two periods using paired t tests. The correlation between FMD and nitrite concentration was examined by Pearson correlation coefficient. Significance level was set at p<0.05. RESULTS 42 pregnant women were invited for the study. 35 healthy women were elected and 7 of them were excluded for not attending the postpartum evaluation. We found a trend of decreased FMD in the PP period (10.39±5.57 % vs. 8.42±4.21 %, p=0.11; 3(rd)T vs. PP respectively). No significant change was observed in the nitrite concentration (257.41±122.95nmol/L vs.237.16±90.01nmol/L, p=0.28). We did not observe significant correlation between FMD and nitrite during 3(rd)T (r=-0.13, p=0.50) or PP (r=0.14, p=0.48). CONCLUSION Although our sample size did not permit sufficient precision, FMD seems to decrease between the third trimester and postpartum period. Nitrite concentration did not change between the third trimester of pregnancy and the postpartum period, and it was not correlated to FMD. Studies evaluating larger samples are necessary to confirm these findings.

PP071. Evaluation of maternal–fetal doppler parameters and of whole blood nitrite throughout gestation

INTRODUCTION The Doppler method is extensively applied today for the evaluation of pregnancies with involvement of the uteroplacental blood flow. Although increased nitric oxide (NO) formation plays an important role in regulation of systemic vascular resistance during pregnancy, growing evidence indicates that reduced NO formation is associated with hypertensive disorders of pregnancy, especially preeclampsia. OBJECTIVES The studies were to assess the maternal and fetal Doppler parameters and to determine the whole blood nitrite levels during pregnancy. METHODS Thirty-three healthy pregnant women were evaluated during the first (11-14 weeks), second (20-24 weeks) and third trimesters (34-36 weeks) of pregnancy. The maternal (uterine arteries) and fetal (cerebral and umbilical arteries) vessels were evaluated by Doppler velocimetry. venous blood was collected(15mL) for the determination of plasma nitrite by chemiluminescence. RESULTS Regarding the Doppler parameters of the uterine arteries the mean pulsatility index was 1.73, 1.06 and 0.73 in the first, second and third trimesters of pregnancy, respectively. Fetal Doppler showed a mean resistance index of 0.82 and 0.81 for the middle cerebral artery, 0.73 and 0.60 for the umbilical artery in the second and third trimesters, respectively. The mean plasma nitrite concentration was 189.10, 178.28 and 199.57 nmol/ml in the first, second and third trimesters of pregnancy, respectively. CONCLUSION The study demonstrated that a fall in flow resistance occurs in the uteroplacental vessels without changes in plasma nitrite concentrations during pregnancy.

PP129. Assessment of oxidative status markers and no bioavailability in hypertensive disorders of pregnancy

INTRODUCTION Evidences point that an imbalance between overproduction of reactive oxygen species (ROS) and the lack of antioxidant mechanisms may contribute to endothelial dysfunction observed in hypertensives disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertensives (GH). OBJECTIVES In the present study, we expanded these previous findings and evaluated systemically the plasma levels of oxidative stress markers (TBARS [2] and carbonyl [3]) and total antioxidant status (FRAP [1] and reduction of MTT (Medina et al., 2007)), as well as assessed the impact these markers on NO status in healthy pregnant, gestational hypertensive and preeclampsia pregnant. METHODS A total of 99 pregnant were enrolled (38 HP, 33 GH and 28 PE. The lipid peroxidation was assessed by (TBARS, [2]). The determination of carbonyl was performed according to the method of [3] and FRAP assay by Benzie and Strain [1]). Nitrite levels were evaluated using chemiluminescence assay. RESULTS We found similar values of TBARS among groups, and reduced carbonyl levels in HDP. Conversely, significant increases in plasma activity of antioxidant status of were observed in these groups (GH and PE) compared to healthy pregnant (using both MTT or FRAP method). CONCLUSION Although antioxidant compensatory mechanism observed in HDP, the levels of nitrite remain reduced in these pregnant compared to healthy pregnant, suggesting that other mechanisms may be involved in the NO bioavailability. This study was funded by the Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG-Brazil), the Conselho Nacional de Desenvolvimento Cientı´fico e Tecnológico (CNPq).