Oxidative profiles of LDL and HDL isolated from women with preeclampsia.

BACKGROUND: Oxidative stress causes biochemical changes in lipids and proteins; these changes can induce damage to the vascular endothelium and create maternal complications that are characteristic of preeclampsia. In this study, we evaluated the oxidative profile of lipoproteins isolated from women with preeclampsia. METHODS: Thirty women diagnosed with preeclampsia and thirty women without preeclampsia were included in the study. Lipid-damage biomarkers, including conjugated dienes, lipohydroperoxides and malondialdehyde, were measured. The reduction of nitroblue tetrazolium, the formation of dityrosines, and the carbonylation of proteins were assessed as indicators of protein damage. The protective activity of HDL-c was evaluated by the paraoxonase-I activity present on the HDL-c particles. Serum lipid profiles were also quantified in both groups. Data were analysed using Student's t test and the Pearson correlation coefficient. RESULTS: Our results demonstrated in PE women evident oxidative changes in the lipids and proteins in HDL-c and LDL-c particles and the activity of the antioxidant enzyme PON-I decreased 59.9%. HDL-c exhibited self-defence, as demonstrated by the negative correlation between paraoxonase-I activity and the formation of lipohydroperoxides in HDL-c (r = -0.3755, p < 0.005). CONCLUSIONS: LDL-c and HDL-c isolated from women with preeclampsia show oxidative damage to lipids and proteins. We propose an oxidative profile based on the oxidation levels indicated by each of the markers used. We also found that paraoxonase-I is inactivated in the presence of lipohydroperoxides. Antioxidant support might be helpful to reduce oxidative stress in patients with preeclampsia. Further investigations are necessary to define the association between antioxidant activities and preeclampsia.

In vitro progesterone modulation on bacterial endotoxin-induced production of IL-1ß, TNFα, IL-6, IL-8, IL-10, MIP-1α, and MMP-9 in pre-labor human term placenta.

BACKGROUND: During human pregnancy, infection/inflammation represents an important factor that increases the risk of developing preterm labor. The purpose of this study was to determine if pre-treatment with progesterone has an immunomodulatory effect on human placenta production of endotoxin-induced inflammation and degradation of extracellular matrix markers. METHODS: Placentas were obtained under sterile conditions from pregnancies delivered at term before the onset of labor by cesarean section. Explants from central cotyledons of 10 human placentas were pre-treated with different concentrations of progesterone (0.01, 01, 1.0 µM) and then stimulated with 1000 ng/mL of LPS of Escherichia coli. Cytokines TNFα, IL-1ß, IL-6, IL-8, MIP-1α, IL-10 concentrations in the culture medium were then measured by specific ELISA. Secretion profile of MMP-9 was evaluated by ELISA and zymogram. Statistical differences were determined by one-way ANOVA followed by the appropriate ad hoc test; P < 0.05 was considered statistically significant. RESULTS: In comparison to the explants incubated with vehicle, the LPS treatment led to a significant increase in the level of all cytokines. In comparison to the explants treated only with LPS, pre-treatment with 0.01-1.0 µM progesterone significantly blunted (73, 56, 56, 75, 25, 48 %) the secretion of TNF-α, IL-1ß, IL-6, IL-8, MIP-1α, IL-10, respectively. The MMP-9 induced by LPS treatment was inhibited only with the highest concentration of progesterone. Mifepristone (RU486) blocked the immunosuppressive effect of progesterone. CONCLUSIONS: The present results support the concept that progesterone could be part of the compensatory mechanism that limits the inflammation-induced cytotoxic effects associated with an infection process during gestation.

Evidence of an immunosuppressive effect of progesterone upon in vitro secretion of proinflammatory and prodegradative factors in a model of choriodecidual infection.

OBJECTIVE: To evaluate whether progesterone (P4) is able to modulate the secretion of tumour necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), IL-6, IL-8, IL-10 and matrix metalloproteinase-9 (MMP-9) after choriodecidual stimulation with lipopolysaccharide (LPS). DESIGN: Chorioamnionitis-elicited preterm delivery is associated with an uncontrolled secretion of proinflammatory cytokines that may induce MMPs, which modify the fine immunological and structural equilibrium at the fetal-maternal interface. SETTING: Instituto Nacional de Perinatología 'Isidro Espinosa de los Reyes', Mexico City. SAMPLE: Twelve human fetal membranes at term from healthy patients were placed in a two-chamber culture system. METHODS: Choriodecidual and amniotic regions were preincubated with 1.0, 0.1, or 0.01 µmol/l P4 for 24 hours; after which the choriodecidual region was costimulated with 1000 ng/ml of LPS for 24 hours. MAIN OUTCOME MEASURES: Descriptive statistics were obtained for each variable. Data distribution was tested for normality using Kolmogorov-Smirnoff and Shapiro-Wilk tests. When distribution was normal, Student's t test was used to analyse for differences among groups. Mann-Whitney's U test was used when data were not normally distributed. RESULTS: Pretreatment with 1.0 µmol/l P4 significantly blunted the secretion of TNF-α, IL-1ß, IL-6, IL-8 and IL-10. MMP-9 was inhibited with 0.1 µmol/l P4. Mifepristone (RU486) blocked the immunosuppressive effect of P4, suggesting a P4 effect mediated by its receptor. CONCLUSION: These results offer evidence to support the concept that P4 can protect the fetal-placental unit through a compensatory mechanism that partially limits the secretion of proinflammatory and prodegradative modulators.

[Lactic acidosis in recovered asphyctic newborn infants]. / Acidosis láctica en el recién nacido asfíctico recuperado.

Thirty newborn babies delivered by elective caesarean section were studied. They were randomly placed in two groups. The first group consisted of newborns who scored 3 or less on the Apgar scale at one minute and 8 or more after five minutes. The other group included newborns which scored 8 or higher at one minute and 9 at five minutes. Blood samples were obtained from the umbilical cord which allowed for the measuring of the infants' pH, serum gases and pyruvic lactic acid levels. An increased level lactate was found in asphyctic infants. Five cases presented lactic acidosis which continued to be persistent in four of them an hour after they were born. Although increased levels of lactate were found also in the control group, they never presented lactic acidosis. No correlation was found between the pH and lactate levels nor between lactate and bicarbonate. A clear correlation between lactic acidosis and fetal distress was documented. It was concluded that lactate quantification is a useful indicator of neonatal asphyxia. Lactic acidosis; Apgar scores; asphyxia.