Development Of PE Research Articles

1392-P: The Potential Role of Placental α2-Adrenergic Receptors in the High Risk of Preeclampsia in Diabetes

Preeclampsia is a life-threatening complication of pregnancy that occurs four times more frequently in the presence of maternal diabetes. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt1), released from the placenta, plays a crucial role in PE development. Alpha 2-adrenoceptor (A2AR) dysfunction has been reported in diabetes, and is implicated in the development of vascular complications. Furthermore, A2AR agonist antihypertensive agents are frequently used to treat patients with preeclampsia, whether they have a disease-modifying role is unclear. We hypothesized that A2AR dysfunction could underlie up-regulation of placental sFlt1 expression, thus ‘driving’ preeclampsia in diabetes. We treated cultured human trophoblasts (HTR8/SVneo) with a stressor often present in the diabetic vasculature, ‘heavily oxidized, glycated’ low-density lipoproteins (HOG-LDL), vs. native LDL (at 100 µg protein/ml) with or without the A2AR agonist, clonidine, and antagonist, yohimbine (24h; both drugs at 10 μM and 100 μM). We determined α2A-, α2B- and α2C-AR mRNA expression (RT-PCR) and immunostaining; sFlt1 mRNA expression and protein release (ELISA); and cell viability (Cell Counting Kit-8 assay). Experiments were repeated three times independently. We found that all three A2AR subtypes were expressed in human trophoblasts. HOG- vs. N-LDL increased sFlt1 mRNA expression (2.0-fold, p<0.001) and protein release (2.5-fold, p<0.01), but neither clonidine nor yohimbine had any effect at either dose. Neither HOG- nor N-LDL altered A2AR expression or cell viability. Overall, the data confirm that modified lipoproteins may promote PE development in women with diabetes via upregulation and release of sFlt1, but do not provide clear evidence that A2ARs are implicated in this process. Further work will investigate whether A2ARs may be modified by other stressors of diabetes, and whether they may affect non-sFlt1 mechanisms for PE. Disclosure R.P. Chow: None. J. Zhao: None. T. Curtis: None. T. Lyons: None. J. Yu: None.

Downregulation of miR-424 in placenta is associated with severe preeclampsia

Previous studies have suggested that altered miRNA expression in the placenta is associated with preeclampsia. The aim of this study was to investigate the expression of miR-424 in placental samples of severe preeclampsia (sPE) and uncomplicated pregnancy patients. miRNA was isolated from placentas obtained from 30 sPE patients and 30 healthy women. Quantitative real-time polymerase chain reaction was used to analyze the expression of miR-424. The prediction of target genes of miR-424 was performed using miRGen database. The function of these target genes was analyzed further by DAVID and Gorilla software. The expression of miR-424 was significantly lower in patients with sPE than in healthy controls. Changed expression of miR-424 in the case of pregnancy-related hypertensive disorders might affect the Wnt signaling pathway. These factors have a strong correlation with the development of PE. Expression of miR-424 in placenta was lower in patients with sPE, suggesting its role in the pathology of sPE.

Histone deacetylase 6 negatively regulated microRNA-199a-5p induces the occurrence of preeclampsia by targeting VEGFA in vitro

BackgroundPreeclampsia (PE) is a special complication during pregnancy, which can cause severe maternal complications and lead the cause of maternal and perinatal death. So far, the etiology and pathogenesis of the disease is still not very clear. Currently, microRNAs (miRNAs) are reported to be the key regulators in the development of PE. MethodsThe miR-199a-5p expression was detected by qRT-PCR. The expression of vascular endothelial growth factor A (VEGFA), placental growth factor (PLGF) and activating transcription factor 3 (ATF-3) were detected by qRT-PCR and Western blot. Transwell-invasion assay wasused to assess the effects of miR-199a-5p, PLGF and ATF-3 on the invasion of HTR-8/SVneo and TEV-1cell lines. Western blot and qRT-PCR were used to assess the related molecular mechanisms. Dual luciferase reporter assay was used to detect the interaction between miR-199a-5p and VEGFA. ResultsHere, weinitially demonstrated that in PE tissues, miR-199a-5p expression was higher than that in normal tissues, while there was sharp reduction in VEGFA. In placental tissues of PE patients, miR-199a-5p exhibited a negatively correlation with VEGFA. The invasion of HTR-8/SVneo and TEV-1 cells was suppressed by miR-199a-5p through direct inhibition of VEGFA expression. In addition, PE tissues were associated with sharp reduction in the protein levels of PLGF, ATF-3 and histone deacetylase 6 (HDAC6) compared with the normal tissues. We further proved that over-expression of PLGF could also promote HTR-8/SVneo and TEV-1 cells invasion through up-regulating ATF-3 expression and down-regulating DNM3 opposite strand (DNM3os) and miR-199a-5p expression. Lastly, we also found that tubacin suppressed HTR-8/SVneo and TEV-1 cells invasion via regulation of miR-199a-5p and VEGFA expression. ConclusionOur data demonstrated the role of miR-199a-5p in the preeclampsia, and proved that miR-199a-5p could act as a potential therapeutic target for the treatment of PE.

Copeptin in Preeclampsia Development

Background: Preeclampsia complicates 2-8% of all pregnancies worldwide and is one of the leading causes of maternal and neonatal morbidity and mortality. It occurs after the 20th week of gestation and is characterized by high blood pressure, proteinuria or end-organ disease. The heterogeneous and multi-systemic nature of this disease has led to the elusive pathophysiology which delays timely diagnoses and the clinical treatment of those affected. Objective: Despite the extensive investigations surrounding the inclusion of various potential markers for PE prediction, early diagnosis remains unresolved. Quantification of copeptin, a stable component of the arginine vasopressin (AVP) precursor is shown to be relatively reliable in confirming the circulating levels of AVP. Conclusion: Elevated copeptin levels confirmed in pregnant women have also provided clinical support for its role in PE development. However, its clinical use in predicting disease severity in early-onset pre-eclampsia has been debatable. This review thus recapitulates the current literature surrounding copeptin and its potential as a risk indicator for PE development.</P>

Serum levels of miR-628-3p and miR-628-5p during the early pregnancy are increased in women who subsequently develop preeclampsia.

Preeclampsia pathogenesis involves imbalances of oxidative stress networks including the heat shock protein (HSP) pathway. Micro-RNAs regulate gene networks associated with preeclampsia. Hsp90 and Runx2 are transcriptional targets of miR-628-3p. Considering that potential participation of hsa-miR-628-3p in PE development is still not elucidated, the aim of this study was to evaluate serum microRNA expression of hsa-miR-628-3p and hsa-miR-628-5p and their association with the preeclampsia development. A retrospective nested cohort case-control study was conducted. Serum samples from 16 pregnant women who developed preeclampsia (WWD-PE) during the follow-up period were selected and individually matched to that from 18 women in the cohort who had healthy pregnancies without complications (controls). The levels of hsa-miR-628-3p and hsa-miR-628-5p were measured in serum samples from study groups at 12, 16, and 20 weeks of gestation (WG) using TaqMan probes. Additionally serum levels were measured at the moment of diagnosis, in women with preeclampsia. Serum levels of hsa-miR-628-3p were higher than controls in WWD-PE at 12 WG (RQ = 7.7; P = 0.020), and of hsa-miR-628-5p at 20 WG (RQ = 3.4; P = 0.008). An increase in hsa-miR-628-3p serum levels at 12 WG (RQ = 12.01; P = 0.001) and of hsa-miR-628-5p at 20 WG (RQ = 2.95; P = 0.033) was also observed in women who developed mild preeclampsia, and severe preeclampsia, respectively. Serum hsa-miR-628-3p and hsa-miR-628-5p were differentially expressed between WWD-PE and controls, suggesting a participation of these miRNAs in the development of preeclampsia. Future studies are needed to validate hsa-miR628-3p and -5p as early predictors of preeclampsia.

Investigation of stability of intrauterine aerosol preparation “Yodozol”

For standardization, quality control, study of stability and establishment of storage conditions and terms of use, complex preclinical trials of the new development of PE “Biopharm” and the Experimental Station of Epizootology IVM NAAN – aerosol preparation “Yodozol” have been carried out. The methods of evaluation of a medicinal product applied to aerosols are used, which include: determination of changes in appearance, inspection of packaging for leakproofness, measurement of the percentage of contents of the package, the establishment of qualitative and quantitative indicators of active substances, and also the study of microbiological purity of the product. “Yodozol” is a light yellow liquid, 1 ml of which contains 5 mg of iodine and 10 mg of potassium iodide. The drug is used for the prevention and treatment of postnatal intrauterine infections in cows, pigs, sheep and goats (endometritis, pyrometers, cervicitis, vaginitis, delayed digestion caused by microorganisms sensitive to iodine), after obstetrics aid, cesarean section and postpartum sanitation of the uterus. The drug has antimicrobial, anti-inflammatory and analgesic effects, improves the proliferative processes of the genital organs, reduces the time for recovery of animals. The drug is used according to the guidelines, after its production livestock is used without restrictions. The shelf-life, which is the result of the test of the dasg according to the «stability» indicator, has been determined, which was performed under long-term storage in a place protected from light at a temperature range from + 5 ± 2 °С to + 25 ± 2 °С. The studies conducted after 6, 12, 24 and 30 months showed complete compliance of the quality indices with the declared standards when stored for 24 months in the temperature corridor from + 5 °C to + 20 °C. With an increase in storage temperature to + 25 °C or more, a slight quantitative decrease in the concentration of antimicrobial components occurred. In addition, with long-term storage of drugs, release of the contents from the cylinder became uneven and foam acquired a shade less than the saturation rate, increased microbiological contamination. Thus, according to the results of the study, the established shelf life of the preparation is 2 years at the recommended storage temperature from +5 to +20 °С. All studies conducted on the stability of the aerosol intrauterine drug “Yodozol” were included in the registration materials of the medicinal product.

Association Between Gestational Weight Gain and Pregnancy Complications or Adverse Delivery Outcomes in Chinese Han Dichorionic Twin Pregnancies: Validation of the Institute of Medicine (IOM) 2009 Guidelines.

BackgroundExcessive or insufficient gestational weight gain (GWG) is associated with increased risks of pregnancy complications and adverse delivery outcomes in dichorionic twin pregnancies. The provisional Institute of Medicine (IOM) 2009 guidelines suggested the optimal GWG based on limited epidemiological data collected from Western populations. However, such a recommendation has not yet been validated in a Chinese Han population, the world’s largest ethnic group. The objective of this study was to assess the effect of IOM guidelines by determining the neonatal and maternal outcomes associated with gaining weight below, within, and above the IOM provisional guidelines on GWG in Chinese Han twin pregnancies.Material/MethodsA historical cohort study of 350 twin-conceiving Han women in Chongqing Women and Children’s Health Center delivering liveborn twin infants between January 2015 and November 2016 was conducted. The participants were divided into 3 groups according to the 2009 Institute of Medicine recommendations of GWG: a low GWG group, an adequate GWG group, and a high GWG group. The incidence of pregnancy complications and the delivery outcomes were compared between the groups, and the correlation of GWG and pregnancy complications or delivery outcome was investigated by logistic regression analysis.ResultsIn Han Chinese people, the gestational age (GA) at delivery was significantly different among various GWG groups, and low maternal GWG is associated with shorter GA. Although low GWG increased the incidence of VPTD, it did not impact PTD in twin pregnancies. Moreover, GWG was negatively correlated with the incidence of PPROM and was positively correlated with GHP development in twin pregnancies.ConclusionsThe recommendations of the 2009 IOM guidelines about GWG is beneficial in reducing the incidence of VPTD and PPROM in Han Chinese dichorionic twin pregnancies, but failed to eliminate the development of PTD, PROM, GDM, PE, ICP, and SGA.

276. Risk factors for early and late severe preeclampsia

Introduction PE complicates 5–8% of pregnancies and is the leading cause of maternal death-about 60 000 women die from it every year around the world. It should be noted that to date, early (up to 34 weeks) and late (after 34 weeks) PE are seen as two completely separate units, rather than as different clinical forms of the same disease. Objective To study risk factors in women, whose pregnancy was complicated by severe preeclampsia with early and late debut. Methods A retrospective cohort study of 254 histories of pregnant women operated on for severe PE. Results and its discussion The early onset of preeclampsia was in women with multiple pregnancies (4.5%), with genetic thrombophilia (6.4%). Heavy PE with late onset was observed in obese women (23.2%). Primiparity, chronic arterial hypertension, kidney disease are the most common risk factors for severe PE, but do not have significant differences in women with early and late PE. In both early and late PE, the leading position was occupied by chronic arterial hypertension (33%). In contrast to early PE in obese women with late PE, 13.5% occurred. At early PE – disturbances of system of a hemostasis (genetic trombophilia) it is marked in 6,4% of observations. In 24.1% of cases, the somatic history was not burdened. The frequency of occurrence of PE in previous pregnancies did not have significant differences between the groups with early and late PE (11.2% and 12.6%, respectively). In the group of pregnant women due to IVF-the frequency of severe PE was 8.3%. Of these, 6.7% fell to early PE, 1.6% to late PE. In case of multiple pregnancies, the rate of development of severe PE reached 12.2%. Early debut up to 34 weeks is marked in 8,7%, late-3,5%.

LOW LEVEL OF ANTITHROMBIN III AS A WARNING SIGN FOR DEVELOPING THROMBOTIC COMPLICATIONS IN SURGICAL PATIENTS

Introduction.Pulmonary embolism (PE), being the most severe embolic complication, is characterised by low predictability, high mortality and incapacitation rates as well as a correspondingly high economic cost of therapy and aftercare. In this connection, the main purpose of our work is to find a warning for PE development in non-cardiosurgical patients that have undergone intensive therapy under conditions of general surgical ICU, among the indicators of the haemostasis system.Materials and methods. Based at the anaesthesiology and emergency surgical department № 1 of the Kuvatov Republic Clinical Hospital (Russia), the researchers carried out an analysis of the haemostasis system in 430 patients hospitalised between 2010 and 2014. The functional activity of platelets was studied using a Biola 230LA laser platelet aggregation analyser (Russia). The determination of circulating aggregates was conducted using the Wu — Hoak method. Thromboelastography was carried out using a TEG 5000 Thromboelastograph (USA). A Stago STA Compact automated selective haemostasis analyser (France) was used to register indicators that characterise the state of endothelium, the haemostatic coagulation element and thrombosis and fibrinolysis markers.Results. Univariate analysis demonstrated a connection between nosocomial episodes of thrombosis and the following factors: emergency surgery (OR 9.1, p<0.01), peripheral vessel disease (OR 13.5, p=0.01), collapse development in pre-operation period (OR 30, p<0.01), high content of D-dimers (OR 30, p<0.01) and low content of AT III (OR 13.5, p=0.01). The results of multifactor analysis show that the significant diagnostic criteria are high D-dimer content and low AT III venous blood activity.Conclusion. A determination of high risks will enable the incidence of pulmonary embolism to be to minimised as well as provide a timely assessment of the efficiency of preventive measures carried out.

Uterine artery Doppler: Changing Concepts in Prediction and Prevention of PE and FGR

AbstractOne of the most promising screening tools in detection of PE and FGR is uterine artery Doppler velocimetry. The underlying pathology for the development of PE is thought to be due to defective trophoblastic invasion of uterine spiral arteries. Increased impedance during mid-trimester is known to be associated with a high incidence of adverse pregnancy outcomes. High resistance in uterine arteries can be observed as early in the first trimester in cases with impaired placentation. The predictive efficacy of first trimester UtA Doppler has improved after the development of risk specific algorithm by including maternal characteristics, biophysical and biochemical parameters. With the understanding of late onset FGR and PE, it was realised that first trimester UtA Doppler may not serve as an efficient marker to identify this group which led to the evolution of its assessment in third trimester. The importance of UtA Doppler in third trimester is its ability to differentiate a physiologically small baby from a pathologically small fetus, which is growth restricted. PE and FGR remains an important cause of maternal and fetal mortality and its prediction is a challenging task which needs to be done early in gestation. Low dose aspirin when started before 16 weeks in the truly high risk population has proven to significantly reduce PE and FGR. To initiate aspirin therapy, the development of first trimester risk prediction model remains the key component. This paper is a review of the predictive efficacy of UtA Doppler in detecting uteroplacental insufficiency in each of the three trimesters.

The association of the placental Hypoxia-inducible factor1-α polymorphisms and HIF1-α mRNA expression with preeclampsia

IntroductionEvidence has confirmed that placental/fetal hypoxia plays a key role in both endothelial cell dysfunction and PE pathogenesis. The aim of the present study was to investigate whether maternal/placental hypoxia-inducible factor1-α (HIF1-α) C1772T (rs11549465) and/or G1790A (rs11549467) polymorphisms and HIF1-α mRNA expression are associated with PE development. MethodsThe blood samples of 203 PE and 202 control women and the placenta of 86 PE and 84 control women were collected after delivery. The HIF1-α polymorphisms were genotyped using PCR- RFLP method. The mRNA expression levels were measured by Quantitative Real -Time PCR. ResultsThe present study found no association between maternal HIF1-α rs11549465 and rs11549467 and placental rs11549467 polymorphisms and PE. However, the placental rs11549465 polymorphism was associated with PE in the dominant model. The CT/GG combined genotypes and TG haplotype of placental rs11549465 and rs11549467 polymorphisms were associated with higher risk of PE. The HIF1-α mRNA expression was 3-fold higher in the PE women. The rs11549465 TT genotype was associated with higher HIF1-α mRNA expression in PE women and in total population and rs11549467 GA genotype was associated with higher mRNA expression in total population. The relative mRNA expression of HIF1-α gene was higher in presence of CC/GA, TT/GG and TT/GA combined genotypes. ConclusionThis study found an association between placental but not maternal HIF1-α rs11549465 polymorphism and PE in the dominant model. The HIF1-α mRNA expression was higher in the placenta of PE women and was associated with rs11549465 and rs11549467 polymorphisms.

Oxidative stress markers and thrombomodulin plasma levels in women with early and late severe preeclampsia

BackgroundPreeclampsia (PE) is a pregnancy disease associated with oxidative stress and endothelial dysfunction. It can be classified according to the severity and onset-time of clinical symptoms (early PE:<34 weeks, late PE:≥34 weeks). MethodsWe evaluated markers of oxidative stress (thiobarbituric acid reactive substances-TBARs and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)-MTT) and endothelial lesion (thrombomodulin-TM) in early (N = 24) and late severe PE(N = 22) and normotensive pregnant women(N = 26). ResultsMTT levels were higher in early sPE than in normotensive pregnancy (P = 0.03). No difference was found comparing late sPE versus normotensive pregnancy, and early sPE versus late sPE. TM levels were higher in early sPE comparing to late sPE women (P = 0.05), but no difference was found between early or late sPE versus normotensive groups. TBARs levels did not differ significantly among the three groups. These data suggest that endothelial lesion and the antioxidant status are more pronounced in early sPE. Moreover, lipid peroxidation might be an early event in PE, stimulating a compensatory antioxidant defense later in pregnancy. ConclusionsLongitudinal studies involving pregnant women with risk factors for PE development and including other methods for oxidative stress and endothelial lesion determination should be conducted in order to better evaluate the role of these processes in PE pathogenesis.

RENAL INJURY IN PREECLAMPSIA: THE VIEW OF NEPHROLOGIST (LITERATURE REVIEW)

The growing interest of nephrologists in the problem of kidney injury in preeclampsia is due to its high prevalence (2–14% of all pregnancies) and unpredictable outcome. The pathogenesis of kidney injury in PE is poorly known, however, the role of imbalance of pro- and anti-angiogenic factors – VEGF and sFlt-1 – has been established as one of the most important pathogenetic mechanisms underlying the development of PE. The article presents modern data on the pathogenesis and renal manifestations of PE at different times of its development in comparison with markers of placental angiogenesis. The role of the imbalance of the sFlt-1 / VEGF system in the formation of proteinuria, arterial hypertension and renal dysfunction in PE is discussed, as well as the role of “early” PE as a risk factor for the development of chronic kidney disease.

The clinical course of symptomatic deep vein thrombosis after 3 months of anticoagulant therapy using fondaparinux/edoxaban or fondaparinux/vitamin K antagonist.

BackgroundFor the management of venous thromboembolism (VTE), providing anticoagulant therapy within the therapeutic range has been a major challenge, as conventional therapy with unfractionated heparin (UFH) and vitamin K antagonist (VKA) requires frequent laboratory monitoring and dose adjustment. Recently, fondaparinux and edoxaban are being used as beneficial alternatives to UFH and VKA.MethodsWe evaluated the clinical course of symptomatic deep vein thrombosis (DVT) in patients who received the 3-month anticoagulation therapy with fondaparinux/edoxaban (Group A; n=40) in comparison with the findings from our previous experience of patients who received the fondaparinux/VKA combination (Group B; n=33).ResultsIn both Groups A and B, serum D-dimer was significantly improved after treatment (p<0.001). The thrombus volume assessed by quantitative ultrasound thrombosis (QUT) score was significantly reduced in both groups (p<0.001). There was no difference in the proportion of patients who were normalized (ie, disappearance of DVT) between the groups, although Group A had significantly more patients who were normalized or improved (ie, disappearance and reduction of DVT) (p<0.001). No bleeding event was observed in either group. However, in one patient in Group B, worsening of DVT and development of symptomatic PE were observed.ConclusionFondaparinux/edoxaban therapy is as effective as fondaparinux/VKA. This treatment has the possible advantage in thrombus regression. This would be a beneficial therapeutic option for both patients and physicians.

Costal cartilage changes in children with pectus excavatum and pectus carinatum

To investigate qualitative and quantitative changes of cartilage lacunae and canals in the costal cartilages in children with PE and PC compared to those with normal chests. Costal cartilages were investigated in 10 children with normal chests (a control group), in 12 children with PE, and in 12 children with PC. Tissue fragments were fixed in 10% neutral formalin and embedded in compacted paraffin. Sections were stained with hematoxylin and eosin. Slides were examined by light microscopy. Cartilage lacunae, hyper- and hypolacunar zones, and cartilage canals were morphometrically examined, followed by statistical data analysis. There was a significant decrease in the number of cartilage lacunae and in the frequency of hyperlacunar zones and an increase in that of hypolacunar zones in the PE and PC groups. There were no significant differences in these parameters between the PE and PC groups; however, there was a tendency to the smallest number of cartilage lacunae and canals in the PC group and that to the preponderance of empty lacunae in the PE group. Only the PC group showed also negative correlations between the proportions of empty lacunae and the age of children. The pathogenesis of PE and PC in children is related to the impaired trophism of costal cartilages due to the smaller number of cartilage channels containing vessels and lacunae with chondrocytes. The development of PE and PC is associated with specific costal cartilage morphological changes that suggest that PE and PC are different manifestations of the same disease, namely connective tissue dysplasia.

Determination of Risk Factors for Pre–Eclampsia in aTertiary Hospital of Bangladesh

Background: Pre-eclampsia is an idiopathic disorder of pregnancy characterized by proteinuric hypertention and still one of the important causes of maternal and fetal mortality.The identification of its predisposing factors before and during early stage of pregnancy will help in reducing the mortality.Objective:The objective of the present study is to determine the risk factors for pre-eclampsia among pregnant women in a tertiary level hospital.Methods: This study was conducted in the Department of Obstetrics and Gynaecology of a tertiary care hospital in Chittagong, Bangladesh, from January to June 2015.A total number of 50 pregnant women with pre-eclampsia who admitted in this hospital were selected as study group.This was hospital based descriptive study.Results: Most of the partcipants were within 21-30 years of age group and mean age 24.06 ± 3.71.The factors that were found to be significant predictors of risk for development of PE were primigravida, low socioeconomic condition,family history of PE &amp; hypertension, past history of PE and hypertention, past history of diabetes mellitus was also associated with development of PE.Chatt Maa Shi Hosp Med Coll J; Vol.16 (1); Jan 2017; Page 29-32

Association study of FOXP3 gene and the risk of 0020 pre-eclampsia

ABSTRACTPre-eclampsia (PE) is a multifactorial pregnancy disorder, with serious consequences for both the mother and the fetus. Despite intense studies, the pathophysiology of PE remains enigmatic. Previous studies suggested that Treg dysfunction is involved in the pathogenesis of PE. We hypothesized that functional variants of the FOXP3 gene might be associated with PE via dysregulation of Treg cells. Of the 276 subjects, we genotyped three variants of FOXP3 by PCR-RFLP and Tetra ARMS-PCR methods. The genotypic frequencies of rs2232365 were found to be protective from the development of PE under codominant [odds ratio (OR) 0.49, 95 percent confidence interval (CI) 0.28–0.87, p-value = 0.043], dominant [odds ratio (OR) 0.54, 95 percent confidence interval (CI) 0.32–0.94, p-value = 0.027] and over dominant [odds ratio (OR) 0.57, 95 percent confidence interval (CI) 0.35–0.92, p-value = 0.02] models. Moreover, the rs3761548 conferred a risk of PE in recessive model [odds ratio (OR) 2.05, 95 percent confidence interval (CI) 1.08–3.88, p-value = 0.025]. However, no mutation was detected in FOXP3 exon2 in any of the studied samples. Based on our results, thought that FOXP3 variants may be an important contributor for the progression of PE in Iranian women.

Association of gene polymorphisms of four components of renin-angiotensin-aldosterone system and preeclampsia in South African black women

ObjectiveTo investigate the association of the gene polymorphisms of: angiotensinogen (AGT), renin (REN), angiotensin II receptor 1 (AT1R) and angiotensin II receptor 2 (AT2R), in the pathogenesis of PE in South African Black women. Methodology (Study design)603 pregnant women; 246 normotensive and 357 with PE (early-onset=187, late-onset=170), were recruited. Each study group was subdivided into HIV infected and uninfected groups. The distribution and frequencies of gene polymorphisms of AGT (M235T), REN (C-5312T), AT1R (A1166C) and AT2R (C3123A) were determined in purified DNA by Real Time Polymerase Chain Reaction. ResultsThe distribution of T allele and TT genotype of AGT in PE were significantly higher than the normotensive group (95% vs 91%, OR 1.9, 95%CI 1.2–3.1, p=0.0051; 90% vs 83%, OR 1.84, 95%CI 1.11-3.05, p=0.01) respectively. The distributions of genotypes of REN, AT1R and AT2R were similar in PE and normotensive groups. ConclusionThe T allele of AGT may play a role in the pathogenesis of PE. The genotypes of REN, AT1R and AT2R were not associated with the development of PE.

Matrix metalloproteinase multiplex screening identifies increased MMP-2 urine concentrations in women predicted to develop preeclampsia

Background: Preeclampsia, a pregnancy disorder characterized by hypertension and proteinuria, represents the leading cause of fetal and maternal morbidity and mortality in developing countries. The identification of novel and accurate biomarkers that are predictive of preeclampsia is necessary to improve the prognosis of patients with preeclampsia.Objective: The objective of this study is to evaluate the usefulness of nine urinary metalloproteinases to predict the risk of preeclampsia development.Methods: MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12 and MMP-13 were analyzed in urine (early-pregnancy) from 17 women predicted to develop preeclampsia and 48 controls using the Bio-Plex Pro-Human MMP panel (Bio-Rad, Hercules, CA).Results: Urinary MMP-2 showed differences between groups which allowed us to calculate an increased risk for PE development of up to 20 times among the study population.Conclusion: Increased urinary concentration of MMP-2 at 12 and 16 weeks of gestation predicted an increased risk of developing preeclampsia in the study population.

The complex evaluation of lipid metabolism and blood coagulation system indicators for prediction and early diagnosis of the preeclampsia

Aim. To study informative and prognostic significance of lipid metabolism markers and coagulation system condition for PE early diagnostics in pregnant women during the second gestational trimester with risk evaluation of cardiovascular and metabolic pathologies in the given women category.Materials and methods. The analysis of blood serum samples in 267 pregnant women in II gestational trimester was carried out. The total cholesterol was determined by colorimetric method, enzymatic with CHOD/PAP, TG – by enzymatic colorimetric method, HDL – by homogeneous method, LDL – by direct method. VLDL concentration was calculated according to Fridvald's formula: VLDL = TG/2.2. AF was calculated according to the formula: AF = (TC-HDL-c)/HDL-c. Pregnant women in II and III gestational trimesters also were examined concerning the general assessment of coagulation system condition – the concentration in blood plasma of D-dimer, soluble fibrin (SFMC), fibrinogen, FIPF, protein C activity, AT III, blood plasma clotting time was determined by PT test.Results. Of the 267 pregnant women, in 43 (16.1 %) of them, which formed the main group for research, the development of PE was found. Those pregnant women, who had PE clinical picture of the different severity levels, from the second trimester had significantly elevated TG, VLDL, AF levels, and low level of HDL in blood serum with high concentration of D-dimer (from 80 to 713 ng/ml), as well as protein C low activity in 17.6 % of pregnant women. In the third trimester pregnant women, having PE, fibrinogen content was significantly higher (4.4±1.02); the accumulation of a significant amount of SF, accompanied by FIPF presence in 40 % of pregnant women, was found in 50 % of pregnant women; a significant reducing (˂70 %) of the protein C activity was found in 48 % of patients.Conclusion. Both significant increasing of the soluble fibrin in blood plasma, and reducing of the protein C activity below 70 % are thrombosis prognostic indexes. The control of lipid metabolism and coagulation system indexes is necessary during all stages of pregnancy for estimation of PE risk and cardiovascular,cerebral vascular and metabolic complications prevention