Category Archives: Uncategorized
Indoleamine 2,3-dioxygenase level and oxidative stress parameters in the serum of patients with chronic renal failure
F. M. Y. Saeed, R. F. Jasim*
College of Education for Girls, Department of Chemistry, University of Mosul, Iraq;
*e-mail: ra.fadhel@uomosul.edu.iq
Received: 13 April 2023; Revised: 02 June 2023;
Accepted: 07 September 2023; Available on-line: 12 September 2023
Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme belonging to the kynurenine pathway. IDO activity has been suggested as a biomarker for diagnosis of chronic kidney disease. The aim of the study was to estimate the level of IDO, urea, creatinine, uric acid, phosphate, calcium, albumin, MDA, GSH, and activity of peroxidase, catalase, arylesterase in the serum of chronic renal failure (CRF) patients treated with dialysis compared to the healthy control group. The results showed a significant increment in IDO level in patients compared with the control. Linear regression analysis using the Pearson correlation coefficient showed that increased IDO level correlates positively with urea, creatinine, uric acid, phosphate, MDA level and peroxidase activity whereas negatively with albumin, calcium, glutathione level, catalase activity and glomerular filtration rate. We concluded that IDO level might be a possible marker of oxidative stress and inflammation in patients with CRF.
Ser-Thr phosphatases in the rat brain that dephosphorylate phospho-Ser(1291)-GluN2A subunit of glutamate receptor
R. R. Prabhu1,2
1P. G. Department of Biotechnology, Government Arts College, Thycaud P. O, Trivandrum, India;
2Rajiv Gandhi Centre for Biotechnology, Poojappura, Thycaud P. O, Trivandrum, India;
e-mail: ramyarprabhu@gmail.com
Received: 04 June 2023; Revised: 06 July 2023;
Accepted: 07 September 2023; Available on-line: 12 September 2023
N-methyl-D-aspartate receptors (NMDARs), are one of the major ionotropic glutamate receptors found in excitatory synapses which play a key role in glutamatergic synaptic transmission. The receptors are regulated by post translational modifications such as phosphorylation. One of the major receptor subunits is GluN2A which is likely to get phosphorylated in vitro at a putative site Ser1291. However, the regulation of phosphorylation of this site by kinases and phosphatases is not yet completely understood. In the present study, we have used the fusion constructs of GluN2A tagged with glutathione S-transferase (GST) as substrate for phosphorylation, purified calcium/calmodulin dependent protein kinase type II (CaMKII) and radioactive P32. We demonstrated that the site phosphorylated by αCaMKII on GluN2A was Ser1291 and that protein phosphatases 1, 2A and 2C were able to dephosphorylate this phospho-GST-GluN2A-Ser1291 in vitro. In the rat brain tissue post synaptic density and cytosolic fraction the major phosphatase responsible for dephosphorylating phospho-GluN2A-Ser1291 was protein phosphatase 1.
Characterization of the blood coagulation system in morbidly obese patients
D. S. Korolova1, O. V. Hornytska1, A. S. Lavrik2,
N. M. Druzhyna1*, N. Prysyazhna3, T. M. Platonova1
1Palladin Institute of Biochemistry, National Academy of Science of Ukraine, Kyiv;
2Shalimov National Institute of Surgery and Transplantation,
National Academy of Medical Sciences of Ukraine, Kyiv;
3Shupyk National Healthcare University of Ukraine, Kyiv;
*e-mail: ndbiochem@gmail.com
Received: 18 April 2023; Revised: 05 May 2023;
Accepted: 7 September 2023; Available on-line: 12 September 2023
Obesity is a complex metabolic disorder that can be followed by blood coagulation disorders, atherosclerosis and atherothrombosis. In the present work, the levels of fibrinogen, soluble fibrin, D-dimer as well as protein C were measured in the blood plasma of 24 morbidly obese patients (the body mass index exceeds 40 kg/m2) to evaluate the risk of prothrombotic state. The study showed that near by 80% of patients had substantially increased fibrinogen concentration, 33% had increased concentration of soluble fibrin, 42% had increased level of D-dimer in blood plasma as compared to control. According to the results of individual analysis, the high level of fibrinogen and soluble fibrin while reduced protein C indicated the threat of thrombosis, which requires complex diagnostics to be identified. Therefore, simultaneous quantification of hemostatic system biomarkers in the blood plasma is the confident way to predict the risk of thrombotic complications in morbidly obese patients.
Extragenital and infectious factors may provoke miscarriage
T. G. Gutor1, N. F. Timchenko1*, O. I. Matsyura2
1Department of Social Medicine, Economics and Organization of Health Care,
Danylo Halytsky Lviv National Medical University, Lviv, Ukraine;
2Department of Pediatrics №2, Danylo Halytsky Lviv National
Medical University, Lviv, Ukraine;
*e-mail: timchenkonataliaf@ukr.net
Received: 08 May 2023; Revised: 05 June 2023;
Accepted: 11 June 2023; Available on-line: 11 July 2023
Adverse reproductive outcome before term is a polyetiological pathology associated with demographic crisis. Some adverse outcomes include perinatal and neonatal infant mortality, major morbidity and mortality of children under two years, violation of psychomotor and physical development, cognitive disturbances and disability of children under age five. Finding ways to solve these issues remain a priority. The research involved two female groups. The experimental group included 403 women after the involuntary termination of pregnancy, premature birth or in case of threat of miscarriage; the control group included 402 women with physiological course of pregnancy and parturient with full-term pregnancy. The study required the application of systemic approaches and methods including structural, logical, medical and statistical analyses. The survey revealed more than 20 infectious risk factors and more than 70 factors of extragenital origin. The most significant infectious pathologies included COVID-19 (36.23 ± 2.29% and 14.93 ± 1.78%), herpes type 1 (5.96 ± 1.18% and 1.0 ± 0.50%), toxoplasmosis (4.22 ± 1.0% and 1.0 ± 0.50%) and chlamydial infection (4.22 ± 1.0% 0.50 ± 0.35%) in the experimental and control groups, respectively (P < 0.01). The most significant extragenital pathologies involved autoimmune thyroiditis (8.68 ± 1.40% and 0.75 ± 0.43%), type 1 diabetes mellitus (2.23 ± 0.74% and 0%) and allergic rhinitis/sinusitis (3.97 ± 0.97% and 0.50 ± 0.35%) in the experimental and control groups, respectively (P < 0.01). Obtained results will be used in the development of a personified risk-oriented model for the prevention of preterm pregnancy loss.
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.
Risk factors of preterm infants with CPAP intubated for mechanical ventilation
O. Borysiuk1,2*, O. Matsyura1, L. Besh1, Y. Dubrovna2
1Department of Pediatrics No. 2, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine;
2LRC CNE “Lviv Regional Clinical Hospital,” Lviv, Ukraine;
*e-mail: olenabora@gmail.com
Received: 09 May 2023; Revised: 07 June 2023;
Accepted: 11 June 2023; Available on-line: 11 July 2023
Early use of continuous positive airway pressure (CPAP) is equal to the prophylactic administration of a surfactant to prevent neonatal respiratory distress syndrome (nRDS) in high-risk infants. However, almost half of the smallest infants still require intubation and mechanical ventilation in the first 72 hours after birth. It is known that ineffective initial CPAP is associated with a poorer prognosis. Therefore, the search for reliable prognostic risk factors for ineffective CPAP in very preterm neonates whose respiratory support is started with CPAP is still relevant today. The results of a retrospective cohort study conducted at the Lviv Regional Clinical Hospital (Ukraine), which included 151 children with birth weight <1500 g and gestational age <32 weeks, showed that CPAP failure occurred at a median age of five hours in 31% of infants initially treated with CPAP and average (SD) FiO2, while the failure point was 0.48 (0.15). The prevalence of the main risk factors for severe nRDS did not differ significantly between two groups (CPAP success and CPAP failure). The risk of CPAP failure was significantly associated with surfactant treatment (OR – 7.46; 95% CI: 2.3–24.2), severe RDS (OR – 12.17; 95% CI: 3.8–39.3), requirement in resuscitation after birth (OR – 3.10; 95% CI: 1.2–8.1), initial CPAP pressure (OR – 0.38; 95% CI: 0.15–0.99). Earlier administration of exogenous surfactant to children at high risk of developing severe RDS could prevent the need for mechanical ventilation.
SARS-CoV-2 infection and thyroid dysfunction in children
K. V. Kozak1*, H. A. Pavlyshyn1, I. Y. Avramenko2,
O. M. Dyvonyak3, O. O.Shevchuk1, K. T. Hlushko1
1I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine;
2Danylo Halytsky Lviv National Medical University, Lviv, Ukraine;
3Ternopil Municipal Children’s Hospital, Ternopil, Ukraine;
*e-mail: kozakk@tdmu.edu.ua
Received: 08 May 2023; Revised: 28 May 2023;
Accepted: 29 May 2023; Available on-line: 11 July 2023
The problem of thyroid dysfunction related to SARS-CoV-2 infection remains unclear in children. Therefore, the study aimed to reveal the interrelationship between thyroid dysfunction and COVID-19 severity as well as to determine optimal cut-off values for screening for thyroid disorders in children. A total number of 90 children aged from 1 month to 17 years were involved in the study. Patients with known thyroid disease were not recruited for the research. A thyroid panel was assessed for all participants that included: free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH) and anti-thyroid peroxidase (ATPO) antibodies. Statistical analysis was done using the computer software Statistica 13.0. Research has revealed euthyroid sick syndrome (ESS) in 14.10% of SARS-CoV-2 infected children more often among patients with severe COVID-19 and multisystem inflammatory syndrome (33.33%) compared to mild COVID-19 course (6.67%) and moderate disease severity (8.89%) (P < 0.05). Significant correlation relationships were revealed for next values – FT3 and erythrocyte sedimentation rate (ESR) (rs = -0.22; P < 0.05); FT3 and C-reactive protein (CRP) (rs = -0.33; P < 0.05); FT3 and procalcitonin (rs = -0.43; P < 0.05). The next cut-off values for ESS determination were revealed: ESR 18.5 mm/h (AUC 0.803); CRP 11.5 mg/l (AUC 0.763); ferritin 84.8 ng/ml (AUC 0.733). Results suggest that pediatricians should pay attention to the endocrine disruptions by COVID-19 in children.
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.
Healing Ukrainian Wounded Soldiers
Sandor G. Vari
International Research and Innovation in Medicine Program,
Cedars-Sinai Medical Center, Los Angeles, California, USA;
e-mail: sandor.vari@cshs.org
Received: 30 June 2023; Revised: 10 July 2023;
Accepted: 10 July 2023; Available on-line: 11 July 2023
The Regional Cooperation for Health, Science and Technology (RECOOP HST) Association, led by Cedars-Sinai Medical Center was formed in 2012 that includes 17 universities and academic organizations from eight countries in Central and Eastern Europe (Croatia, Czech Republic, Hungary, Poland, Romania, Slovakia, and Ukraine), and USA. The brutal Russian invasion of Ukraine changed the life of many families in Ukraine. The brave Ukrainian soldiers protecting their homeland, and now advancing into the occupied territories. During their heroic fight, many soldiers died, and many were wounded. RECOOP HST Association with Cedars Sinai Medical Center provided and provides continuous support for the wounded soldiers. RECOOP helped to purchase the electric gene¬rators at Lviv (LNMU), Ternopil (TNMU), and Kyiv (Palladin Institute), therefore, RECOOP donated 1,500 USD in humanitarian aid for each of our Ukrainian partners who have RECOOP Research Grants. RECOOP (350) and the author (200) purchased 550 one-handed Combat Application Tourniquet C-A-T® (30 USD/tourniquet) tested by U.S. Army’s Institute of Surgical Research and proved that C-A-T® completely occluded blood flow of an extremity in the event of a traumatic wound with significant hemorrhage. RECOOP already produced 2,400 Hemostatic Kits (9 USD/kit), and continuously producing the kits in Grant # 032: 2022–2023 Rostyslav Bilyy, Lviv, Ukraine, Improved Hemostatic Device with Chitosan Powder for Combat Injury Dressing. The Volunteer Centre of TNMU works around the clock to provide medical supplies and first aid kits for the Ukrainian soldiers and civilians distributing Hemostatic Kits and Combat Application Tourniquet C-A-T® to the frontline.
RECOOP HST Association with Cedars-Sinai Medical Center will start a project to help Ukrainian wounded soldiers. We would like to assist in the development of a grassroots organization of wounded soldiers and organize a network of Ukrainian medical universities. Ternopil National Medical University will assist in organizing the network to manage the Ukrainian Wounded Soldiers’ health problems online and offline. The posttraumatic stress disorder (PTSD) assessment will begin using a self-screen on the web. We will use the International Trauma Questionnaire (ITQ), an 18-question self-report measure focusing on the core features of PTSD and Complex PTSD (CPTSD). It was developed to be consistent with the organizing principles of the ICD-11 (https://novopsych.com.au/assessments/diagnosis/international-trauma-questionnaire-itq/). RECOOP Grant# 38 Ukrainian Wounded Soldier Project (UWSP) will involve volunteering wounded soldiers with PTSD would complete the online PTSD questionnaire that has already been tested in three Ukrainian projects [1 3]. We will train volunteer medical doctors to help the wounded soldiers online. Also, if the online consulting doctor realizes the severity of the health problems, soldiers should be referred to the nearby university hospital mental health unit. If you are interested in participating as a wounded soldier or medical professional, please contact Dr. Sandor G Vari, MD via Facebook Messenger or e-mail: vari@cshs.org.