Tag Archives: pregnancy

Validation of the diagnostics algorithm to monitor coagulation parameters in pregnant women

D. S. Korolova1, A. O. Pavlenko1, A. Altorjay2, S. I. Zhuk3,
I. V. Us3, Y. Tsaryk1, A. Suranyi2, V. O. Chernyshenko1*

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
2Albert Szent-Györgyi Medical School, University of Szeged, Hungary;
3P. L. Shupyk National Medical Academy of Postgraduate Education, Kyiv, Ukraine;
*e-mail: bio.cherv@gmail.com

Received: 19 May 2023; Revised: 05 June 2023;
Accepted: 07 June 2023; Available on-line: 11 July 2023

Thrombotic events are among the most dangerous complications of pregnancy. Therefore, selection of appropriate tests and standardization of techniques used for accurate diagnostics of blood coagulation system state is of great importance. In this present study, we monitored several molecular markers of the dangers of intravascular thrombus formation and estimated the platelet function in pregnant women during­ gestation. We performed independent measurements using the same methodology for different cohorts of patients recruited in Kyiv (Ukraine) and in Szeged (Hungary). D-dimer and soluble fibrin were measured using ELISA. Protein C (PC) level was estimated using chromogenic substrate assay. Fibrinogen concentration was measured by spectrophotometry using thrombin-like enzyme. Platelet function was estimated by aggregometry­. Statistical data analysis was performed using the Kruskal-Wallis test. Statistically significant increases of fibrinogen concentration from first to third gestational trimester was shown for both studied cohorts of patients (5-6 mg/ml at third trimester on average). Applied methods allowed us to detect the same tendencies of decreases in PC level as well as the appearance of moderate amounts of D-dimer (up to 300 ng/ml) and SF (up to 10-15 ug/ml). Platelet function was increased on the first trimester of pregnancy and decreased during­ following trimesters slightly. Results indicated the changes in the blood coagulation system of pregnant women during gestation with the same effectiveness independently of the selected cohorts, time and place of measurements. The application of the proposed diagnostics algorithm may allow estimating the risk of thrombotic complications during pregnancy.

Common mechanisms of placental dysfunction in preeclampsia, gestational diabetes, and COVID-19 in pregnant women

S. G. Vari1*, O. Shevchuk2, A. Boychuk3, S. Kramar4,
Z. Nebesna4, Y. Yakymchuk5, L. Kobylinska6, V. Chernyshenko7,
D. Korolova7, A. Gaspar-Suranyi8, T. Altorjay8, R. Gaspar9

1International Research and Innovation in Medicine Program, Cedars-Sinai Medical Center, Los Angeles, California, USA;
2Department of Pharmacology and Clinical Pharmacology, I. Horbachevsky Ternopil National Medical University, Ukraine;
3Department of Obstetrics and Gynecology, I. Horbachevsky Ternopil National Medical University, Ukraine;
4Department of Histology and Embryology, I. Horbachevsky Ternopil National Medical University, Ukraine;
5Department of Therapeutics and Family Medicine, I. Horbachevsky Ternopil National Medical University, Ukraine;
6Department of Biochemistry, Danylo Halytsky Lviv National Medical University, Ukraine;
7Department of Protein Structure and Function, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
8Department of Obstetrics and Gynecology, Albert Szent-Györgyi Medical School, University of Szeged, Hungary;
9Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, Hungary;
*e-mail: sandor.vari@cshs.org

Received: 13 June 2023; Revised: July 2023;
Accepted: July 2023; Available on-line: 11 July 2023

COVID-19 infection, preeclampsia and gestational diabetes mellitus in pregnancy cause similar changes in the placenta and influence development of the fetus between conception and birth in gestation. Proper uterine and placental vascularization is essential for normal fetal development. The transplacental exchange is regulated and maintained by the placental endothelium. During placental implantation, the trophoblast differentiates into two distinct layers, the inner cytotrophoblast and outer syncytiotrophoblast, which are key elements of the human placental barrier. Proinflammatory cytokines exacerbate ischemic events and create an upward spiral of an inflammatory reaction in the placenta. Placental pathology in gestational COVID-19 shows desquamation and damage of trophoblast and chronic histiocytic intervillositis. Similar lesions also occur in gestational diabetes mellitus and preeclampsia. The systemic inflammatory response of the mother, the increased inflammation in the placenta and cytokine production by placental trophoblasts should be monitored throughout pregnancy. Placental angiogenesis can be evaluated by serum vascular endothelial growth factor, Annexin A2, placental growth factor or sclerostin. Tissue damage can be assessed by measuring levels of serum lactate dehydrogenase and myeloperoxidase. Blood flow can be monitored with three-dimensional Doppler and pathological changes can be documented with paraffin-embedded tissue sections stained with hematoxylin and eosin, and electron microscope images as well as immunohistochemistry tests for vascular endothelial growth factor, placental growth factor, sclerostin and Annexin A2. The damage of maternal and fetal vascular perfusion (villitis and fibrin deposition) is a common mechanism of gestational diseases. The placenta lesions liberate anti-endothelial factors that lead to anti-angiogenic conditions and are the common mechanism of maternal placental vascular malperfusion in gestational diseases.

Biochemical and molecular-physiological aspects of the nitric oxide action in the utera

H. V. Danylovych, Yu. V. Danylovych

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: danylovych@biochem.kiev.ua

Received: 18 May 2021; Accepted: 12 November 2021

The sources of the nitric oxide (NO) formation in the uterus and the dynamics of changes in its content in different periods of organ functioning in human and animals are analyzed. The biochemical mechanisms of NO action on the myometrium contractile activity, the significance of NO in the physiological processes during pregnancy and labor, the importance of mitochondria as a reliable NO source in the smooth muscle and the possible ways of NO influence on Ca2+ transport and bioenergetic processes in mitochondria are considered. The authors’ data concerning ionic and membrane mechanisms of NO action on Ca2+-homeostasis of uterine myocytes, identification of nitric oxide in uterine smooth muscle mitochondria, biochemical characteristics of the NO-synthase reaction and the possible role of NO in the regulation of Ca2+ transport in these subcellular structures and in the electron transport chain functioning are presented and discussed.

Inflammation is the common mechanism of diseases (CMD) in COVID-19 disease during pregnancy and in gestational diabetes mellitus

Sandor G. Vari

Cedars-Sinai Medical Center, International Research and Innovation in Medicine Program, Los Angeles, California, United States

The Regional Cooperation for Health, Science and Technology (RECOOP HST) Consortium, led by Cedars-Sinai Medical Center was formed in 2006, was transformed into an Association in 2012 and includes 17 universities and academic organizations from eight countries: seven in Central and Eastern Europe (Croatia, Czech Republic, Hungary, Poland, Romania, Slovakia, Ukraine) and the United States. RECOOP builds multinational, multidisciplinary collaborations, and assists as well as coordinates the research activities of the sixteen research groups that are the Cedars-Sinai Medical Center – RECOOP Research Centers (CRRCs). https://www.cedars-sinai.org/research/administration/recoop.html.
Implementations of RECOOP’s strategic goals enable diverse talents geared towards integration of new knowledge derived from multiple specialties to investigate Common Mechanism of Diseases (CMD). While some may consider RECOOP’s CMD research strategy unorthodox, recent and timely scientific evidence shows that inflammation is the triggering event in the change of vascularization and it is the common mechanism of these two diseases: COVID-19 Disease during pregnancy and gestational diabetes mellitus (GDM).
Binding of the SARS-CoV-2 virus to the ACE2 receptor and its entrance into endothelial cells plays a role in vascular thrombosis but has a lesser effect placental endothelial dysfunction. The latter is induced by inflammation and exacerbated by proinflammatory cytokines, resulting in ischemic events and creating an upward spiral of an inflammatory reaction in pregnant women, accompanied by similar conditions in the placenta that will ultimately affect fetal development. In mild or moderate COVID-19 disease, changes in placental vascularization and blood flow have similarities to comorbidities in pregnancy such as GDM. However, during severe or critical stages of COVID-19 Disease, the changes could be harsher than those observed in GDM.
In COVID-19 Disease and GDM the immune status of pregnant women and consequently the newborn is altered due to inflammation and characterized by changes in levels of C-reactive protein (CRP), immunoglobulins (IgG, IgM, IgA) and proinflammatory cytokines that are detectable in maternal and umbilical cord blood and in mother milk.
To examine changes and monitor placental angiogenesis it is necessary to measure Vascular Endothelial Growth Factor (VEGF), Placental Growth Factor (PLGF), and Umbilical Cord Blood Sclerostin (UCBS) in maternal and umbilical cord blood serum. The angiogenic activity of sclerostin must be validated with the well-known marker VEGF, which is a proven indicator for changes in vascularization. The morphology of the vascular tree and blood flow in the placenta could be evaluated with three-dimensional power Doppler. The proinflammatory and ischemic effects in the placenta should be quantified with histopathology and immunohistochemistry. Changes in blood flow in the placenta and the morphology of the vascular tree in COVID-19 Disease during pregnancy may have similarities to those observed in GDM.
In summary, to improve maternal and fetal outcomes it is imperative to formulate better strategies for managing pregnancies during COVID-19 Disease and comorbidities like GDM. VEGF, PLGF and UCBS could be predictors of placental weight, birth weight, and fetal outcomes. In addition, further studies are needed to investigate the effects, if any, of proinflammatory and anti-inflammatory cytokines on postnatal development.

Immunosuppression under pregnancy and risks under viral infections

O. I. Kiselev

Scientific-Research Institute of Influenza, Ministry of Health
and Social Development, Russian Federation, St.-Petersburg

The paper is devoted to studying the mechanisms of combined immunosuppression in pregnant women with influenza infection to develop arrangements for controlling these processes and for decreasing mortality from this infection. In this connection the author is dwelling on the following problems:
– How are the fetus immune privilege and tolerance development provided?
– What mechanisms do underlie the functional immunosuppresion under pregnancy?
– Why are the infections especially dangerous for pregnant women?
– Is there the code of the immune system control, and do viruses use this code?
The paper deals with the problem of influence of endogenic viruses, which have penetrated the human genome more than 25 million years ago, on the great number of risks of development of various kinds of human pathologies: from infertility to pregnancy diseases; from development of malignant tumors to system pathology and autoimmune diseases.