Репозиторий Университета

© 2019 Elsevier Ltd Normal pregnancy is associated with an increasing state of activation of the haemostatic system. This activation state is excessive in women with placenta-mediated pregnancy complications (PMPCs), including preeclampsia (PE). Platelet activation plays a crucial pathophysiological role in PE. The very early activation of coagulation in the intervillous space is mandatory for placental growth and morphogenesis but its excesses and/or inadequate control may participate to the emergence of the trophoblastic phenotype of PE. Extracellular vesicles, of endothelial but also of trophoblastic origin, can favour key cellular reactions of preeclampsia, acting as proactive cofactors. The understanding of this intricate relationship between haemostasis activation and PMPCs may provide interesting keys for new pathophysiological therapeutic developments.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. We analyzed diurnal hemodynamic parameters (HR, systolic BP, and diastolic BP) recorded from two groups of edematous and preeclamptic pregnant women. The unidirectional character of changes in the control over the functional state of cardiovascular system was revealed except for the indices, which mark a pathological process: elevated diurnal BP in preeclampsia and diminished percentage of oscillation power in edematous patients. Uniformity of the regulatory changes in patients with and without arterial hypertension can be viewed as manifestation of allostasis developed by the cardiovascular system during pregnancy. In preeclampsia, the greater allostatic load was reflected by the changes in diurnal, daytime, and nighttime BP and in the circadian index calculated for HR, systolic BP, and diastolic BP. In edematous patients, elevation of allostatic load was indicated by the percentage of ultradian rhythms.

© 2017 Taylor  &  Francis. In this study, we tested a hypothesis that a short-term estradiol therapy may reduce blood pressure in preeclampsia by modulating plasma oxidative stress. The intramuscular injections of 10 mg 17-beta-estradiol were prescribed to preeclamptic pregnant women during the 3-day therapy before a labor induction. The analyses of mean arterial pressure (MAP), serum estradiol concentrations, plasma superoxide anion (O2.), hydrogen peroxide (H2O2), nitrites (NO2−), and peroxynitrite (ONOO−) were conducted before and during the therapy. We found that the plasma concentrations of oxidative stress markers, such as O2– and H2O2, are higher in preeclampsia and positively correlated with the MAP value. Moreover, it was shown that the plasma concentration of NO2– as an indicator of NO levels is higher in preeclampsia. A short-term intramuscular application of estradiol decreases the MAP value and the plasma concentration of O.–, H2O2, NO2−, and ONOO– in preeclampsia. A positive correlation between the decrease of MAP values and the decrease of plasma concentrations of O2–, H2O2, and ONOO– was found in preeclampsia during a short-term estradiol therapy. We conclude that the short-term estradiol therapy decreases the MAP value in preeclampsia by modulating the plasma oxidative stress. We speculate that the estradiol metabolism in preeclampsia is an important mechanism that contributes to vascular dysfunction.

© 2018 Informa UK Limited, trading as Taylor  &  Francis Group Objective: The aim of this case series is to raise awareness of obstetric-related atypical haemolytic uraemic syndrome (aHUS) amongst obstetricians and gynaecologists. Study design: Data from 20 consecutive patients, aged 19–38, with obstetric-aHUS manifestation during or immediately after pregnancy are reported. Patients were diagnosed and treatment was initiated between 2012 and 2016. Results: Presentation of aHUS was mainly preceded by preeclampsia and/or haemolysis, elevated liver enzymes and low platelet count syndrome, other obstetric complications, or by diarrhoea. Thrombotic microangiopathy (TMA) was evident in all patients with signs of microangiopathic haemolysis (sharp decline in haemoglobin; mean 67 g/L), elevated lactate dehydrogenase (LDH; mean 2953.1 U/L), schistocytosis, thrombocytopenia (mean platelet count 52.5 × 109/µL), and acute kidney injury (AKI) (hypercreatininaemia, mean 456.4 µmol/L; oliguria or anuria). The majority of patients (80%) initially presented with arterial hypertension. Diagnosis of obstetric-aHUS was complicated, as multiple organs were affected. Time taken to make the diagnosis of aHUS delayed the initiation of fresh-frozen plasma infusions and plasma exchange (80% of patients) and subsequent eculizumab treatment (40% of patients). Maternal mortality was high (35%) as was foetal mortality (25%). Conclusions: Obstetric-aHUS is a serious condition characterized by multiple organ failure (MOF) and a high mortality rate. Presentation of obstetric-aHUS is preceded by various precipitating factors, suggesting pregnancy complications, and not the pregnancy per se, often induce aHUS in women with a genetic predisposition to its development. A delay in the correct diagnosis and initiation of the most effective treatment can have serious consequences, reinforcing the need to raise awareness of obstetric-aHUS.

© 2018 Dynasty Publishing House. All rights reserved. The article presents a clinical case of severe preeclampsia, HELLP syndrome in a 39-year-old woman, who became pregnant after IVF using donor oocytes. Conclusion: donor egg recipients, irrespective of age, should be viewed as having a higher risk for obstetric complications.

© Bionika Media Ltd. The paper presents current generalized data on the immunological aspects of preeclampsia development and progression and emphasizes the role of immunological maladaptation of the mother to pregnancy with the participation of key factors of the immune system in response to the formation of a semi-allogenic fetus and placenta. The results of recent studies allow us to take a fresh look at therapeutic approaches to managing patients with preeclampsia, by taking into account targeted exposure methods against the most important component of its pathogenesis, in particular to prevent excessive activation of the complement system.

© 2018 Izdatel'stvo Meditsina. All rights reserved. The right drug at the right dose administered to a patient in time is the goal which all medical specialists aim at when prescribing medicines to patients. Pregnancy is a condition when the principle of personalized pharmacotherapy is especially relevant. Due to the developing fetus and the occurring changes in the maternal organism, the selection of drug therapy during pregnancy is especially difficult for a clinician. This issue is tightly intertwined with clinical pharmacogenetics since the genetic code of a woman that determines the activity of the liver cytochrome, the fetus-placental barrier, and renal clearance contributes to the peculiarities of the drug metabolism during pregnancy. Additional data provides the opportunities to form therapeutic models and to determine the ways of personifying pharmacotherapy in pregnancy. The purpose of this review is to summarize the available data on the pharmacogenetics of antihypertensive drugs used during pregnancy.

© Bionika Media Ltd. Objective. To study the most important aspects of maternal mortality from preeclampsia, eclampsia, the current clinical features of the most severe forms of this complication of pregnancy, as well as main defects in rendering qualified medical care, including those in the development of complications. Subjects and methods. A confidential audit of maternal mortality was conducted in different regions of the Russian Federation in 2013-2015. A total of 270 anonymous copies of primary medical records were analyzed. Results. The features of development and progression of the most severe forms of preeclampsia and eclampsia were identified. The development of preeclampsia in the presence of previous extragenital diseases was seen in most clinical cases. Early clinical manifestation is characteristic in the vast majority of women; and the non-classical (atypical) clinical picture of the disease is also common. Conclusion. Practical activities are proposed, which are aimed at reducing maternal mortality from preeclampsia in Russia.

© Bionika Media Ltd. Objective. To present an analysis of the data available in the literature on the role of extracellular fetal DNA (fDNA) in predicting the great obstetric syndromes. Material and methods. Literature sources published in databases, such as Pubmed and Scopus, were sought. Results. There is evidence indicating that increased maternal blood DNA levels can be used as a predictive marker for pregnancy complications, such as preeclampsia, preterm birth, and fetal growth retardation. The most likely mechanism for increasing maternal blood fDNA is the strengthening of apoptotic, necrotic, and inflammatory processes in the placenta. However, not all studies confirm that there is a relationship between the development of the great obstetric syndromes and higher fDNA concentrations. Conceivably, the contradictions are due to the use of a number of procedures to determine fDNA, which limit sampling by sex and rhesus factor. Also, there is no consensus on the time when its concentration starts to increase; the influence of confounding factors has not been investigated. Conclusion. Maternal blood extracellular fDNA is a promising marker for predicting the great obstetric syndromes. There is a need for further investigations, by using the procedures that do not limit sampling and by taking into account the factors that influence the maternal blood concentration of extracellular fDNA.

© 2018, Bionika Media Ltd.. All rights reserved. Objective. To investigate the relationship of the levels of preactivated (primed) neutrophils in the peripheral blood of pregnant women with preeclampsia. Subjects and methods. The investigation enrolled 14 women with preeclampsia (a study group, Group 1), 15 women with physiological pregnancy (a control group, Group 2), and 11 non-pregnant women (to obtain normative values). Formyl peptide, Ficoll-Hypaque (1.077 and 1.119 g/ml) gradients, lucigenin, Roswell Park Memorial Institute (RPMI) 1640 medium, Hanks medium, and fetal calf serum (Sigma-Aldrich) were determined in the peripheral blood. Neutrophils were isolated from the blood samples obtained from the ulnar vein (the anticoagulant heparin 35 IU/ml) using a two-step Ficoll-Hypaque gradient. Red blood cells were destroyed by hypotonic lysis. Neutrophils in the suspensions were at least 96%. The live cells tested with trypan blue were 94%. Suspensions containing 1×106 сells/ml were prepared. Formyl-methionyl-leucyl-phenylalanine (fMLP, 2 µM) was used as a stimulant. The formation of oxygen radicals was recorded in imp/sec, by using the luminophor lucigenin (30 µM) on a Biotox-7 chemiluminometer (Russia). The maximum radical formation amplitude, the time of its achievement, and the light sum were determined for a fixed time period. Results. The cell suspensions from non-pregnant women showed a monotonic spontaneous increase in oxygen radical formation at a very low rate. The rate increased by 1.3 times in healthy pregnant women (p > 0.05). The rate of spontaneous oxygen radical generation rose sharply in pregnant women with preeclampsia. In this group, the formation of oxygen radicals reached maximum values and plateaued at 24±7 min. The spontaneous radical formation might be due to the stimulation of initially primed neutrophils as a result of their adhesion on the cell walls. To test this assumption, the standard stimulant fMLP that strongly stimulates the neutrophil generation of oxygen radicals were added to the suspensions from the women with preeclampsia. It should be noted that in both non-pregnant women and healthy pregnant women, fMLP significantly increased the level of radicals compared to the responses of neutrophils in women with preeclampsia. Conclusion. The potentiated response to formyl peptide due to spontaneous neutrophil stimulation in pregnant women with preeclampsia suggests that their peripheral blood contain primed cells. This total response may suggest that the mechanism of stimulation of neutrophils due to their adhesion on the cell wall and to fMLP stimulation is different, additive in nature, and is carried out by different processes.

© Bionika Media Ltd. Objective. To determine the expression level of the genes encoding the paraoxonase family enzymes (PON1, PON2, and PON3) in the placentas of women with uncomplicated pregnancy and in the development of preeclampsia Materials and methods. The investigation enrolled 26 pregnant women aged 24 to 35 years, including 14 women with normal pregnancy and 12 with preeclampsia. The expression of the PON1, PON2, and PON3 genes was analyzed by real-time PCR using the primers specific to these genes. Results. Women whose pregnancy was complicated by preeclampsia showed a significant decrease in the placental expression of the PON2 gene. The lowest PON2 gene expression was found in the placentas of women with severe preeclampsia. There were no significant differences in the placental expression level of the PON1 and PON3 genes in women with preeclampsia compared to healthy women. Conclusion. In women with preeclampsia, the placental PON2 gene expression decreases; however, the expression level of the PON1 and PON3 genes does not differ from that of the PON1 and PON3 genes in the placentas of patients with physiological pregnancy. The placental expression of the PON2 gene depends on the severity of preeclampsia; is lower in severe preeclampsia than in moderate preeclampsia.