Nested case-control study reveals increased levels of urinary proteins from human kidney toxicity panels in women predicted to develop preeclampsia.

PURPOSE: The aim of this study was to evaluate the usefulness of urine concentrations of 12 proteins as a risk parameter for developing preeclampsia (PE). METHODS: A nested case-control study was designed to determine protein concentrations in urine from women predicted to develop PE (WPD-PE) and normotensive pregnancies (controls). Protein profiles were determined at 12, 16 and 20 gestational weeks (GW) using the Bio-Plex Pro human kidney toxicity Panel 1 and Panel 2 (Bio-Rad). Receiver operating characteristic (ROC) curve analyses were performed. Correlations between proteins and clinical parameters at the time of PE diagnosis were also assessed. RESULTS: Significant differences were observed in urine cystatin C (Cys C) levels at 16 and 20 GW and clusterin at 20 GW between WPD-PE and controls (P < 0.05). ROC analysis revealed that Cys C at 16 GW had the highest area under the ROC curve (0.758). At 16 GW, patients with urine Cys C levels above 73.7 ng/mL had eightfold increased odds for developing PE (odds ratio 7.92; 95 % CI 1.3-47.5; P = 0.027). A positive correlation was found between urinary Cys C (at 16 and 20 GW) and leukocyte counts, total proteins, aspartate aminotransferase, alanine aminotransferase, bilirubin and lactate dehydrogenase at the time of PE diagnosis (P value < 0.05). CONCLUSIONS: Urinary Cys C and clusterin showed predictive value for PE development in our cohort. Further studies are needed to validate their use as predictive biomarkers for PE and/or their participation in PE pathogenesis.

MYC-induced nuclear antigen (MINA) and preeclampsia.

BACKGROUND: Inadequate trophoblast invasion and the subsequent inflammatory response have been implicated in preeclampsia (PE) pathogenesis. Because MYC-induced nuclear antigen (MINA) gene expression is involved in cell proliferation and differentiation, inflammatory response modulation, and the unpaired regulation of which is associated with human diseases, we sought to investigate the connection between MINA and PE. OBJECTIVE: The aim of this study was to evaluate the possible relationship between the MINA rs4857304 variant and susceptibility to PE development as well as to estimate placental MINA gene expression and its association with PE. METHODS: About 242 pregnant women (126 PE cases and 116 controls) were included. MINA genotyping and gene expression were evaluated by quantitative real-time polymerase chain reaction using TaqMan probes. RESULTS: The G/G genotype of the MINA rs4857304 variant was associated with severe PE (p = 0.027, OR = 1.8, 95% CI = 1.8-3.2). Carriers of one G allele of the MINA rs4857304 variant exhibited a 1.7-fold increased risk of severe PE (p = 0.029, 95% CI = 1.1-3.0). MINA was underexpressed in preeclamptic placentas and MINA expression differed between the mild and severe PE groups. Differences in the expression levels of MINA were found among women with the T/T genotype of the rs4857304 polymorphism and carriers of at least one G allele (p = 0.024). CONCLUSION: PE and its severity are associated with the underexpression of placental MINA, and the G/G genotype of the MINA rs4857304 variant may modify the risk of severe PE among the PE cases evaluated.

HPLC method for quantification of oxidative stress by salicilate hydroxylation in human plasma.

The aim of the present study was to modify and validate a high-performance liquid chromatographic (HPLC) method for determining 2,3 and 2,5 dihydroxybenzoic acid (2,3-DHBA and 2,5-DHBA) from salicylic acid in human plasma. The mobile phase was a mixture of sodium acetate/citrate (pH 2.5) 30 mM-methanol (93:7, v/v). The injection volume was 10 muL. Retention time for 2,5-DHBA, and 2,3-DHBA was 4.5 +/- 0.10 and 5.8 +/- 0.15 min, respectively. The detection and quantification limits were 10 and 40 nM for 2,3-DHBA and 8 and 20 nM for 2,5-DHBA. Linearity was evaluated in the range of 40-1600 nM for both metabolites. Inter- and intra-analysis variation coefficient was below 10%. Good recoveries of more than 99% were obtained for both metabolites using this method.

[Oxidative stress level and placental histological changes during preeclampsia]. / Grado de estrés oxidativo y cambios histológicos placentarios durante la preeclampsia.

BACKGROUND: Oxidative stress has been related to several conditions during pregnancy (preeclampsia, abortions and premature rupture of membranes); it causes higher sensitivity of the endothelial blood vessel constriction and aggravates the endothelium dependent vasodilatación. OBJECTIVE: To determine the oxidative stress level and histological changes in preeclamptic women's placenta. PATIENTS AND METHOD: Longitudinal and comparative study. There were included 25 patients referred from second level health units (IMSS, ISSSTE and Hospital General de Zacatecas). To evaluate oxidative stress level, a sample of blood and placenta were obtained during delivery and a second sample was taken during mediate puerperium (10 days). RESULTS: In control group, total lipidic peroxide levels in serum were 135.6 +/- 7.3 nmol of MDA/mL of serum, compared with the group of moderate hypertension, which registered 222.0 +/- 35.15 nmol MDA/mL. Total lipidic peroxides in serum during puerperium for control group were 150.4 +/- 30.8 and 183.3 +/- 18.51 nmol MDA/mL for the group of moderate hypertension. Placental lipoperoxidation for control group was 0.40 +/- 0.03 microg MDNg, and of 0.32 +/- 0.03 microg MDN/g for the group of mild hypertension. Patients of moderate hypertension group showed an increase at 34% on placental lipoperoxidation over control group. Placental histological alterations where characterized by vascular remodeling loss, deposits of proteinaceous material and macrophagic process. CONCLUSION: Total lipidic peroxide levels in serum increases during preeclampsia. Histological changes refer uterus-placental ischemia that, probably, induces the oxidative stress.