Endothelin Level in Menopausal Women with Comorbidity of the Acute Phase Middle Severity COVID-19 with Arterial Hypertension and Type 2 Diabetes Mellitus.

The levels of endothelins were assessed in menopausal women with arterial hypertension (AH) and type 2 diabetes mellitus (T2DM) in the acute phase of the moderate COVID-19. Women under observation (age 45-69 years) were divided into two groups. Control group consisted of women (n=16) who did not have COVID-19, were not vaccinated, and had no antibodies to SARS-CoV-2 (IgG). The main group included women (n=63) in the acute phase of the moderate COVID-19 accompanied by pneumonia. According to the clinical and anamnestic data analysis, the main group was divided into subgroups: without AH and T2DM (n=21); with AH and without T2DM (n=32); and with AH and T2DM (n=10). The parameters of clinical blood analysis, as well as endothelin-1, endothelin-2, and endothelin-3 levels were assessed. In women with a moderate COVID-19, the endothelin-1 and endothelin-2 levels were increased compared to the control regardless of AH and T2DM status. We found no statistically significant differences in the studied parameters of endothelial dysfunction between the subgroups of menopausal women in the acute phase of the moderate COVID-19.

[Neuroendocrine changes among 45-60 years old women with COVID-19 and 12 months after the disease.]

Climacteric women have the post-COVID period clinical features, which can lead to an acceleration of the aging. The study consists in assessing individual parameters of the neuroendocrine system in climacteric women with a moderate course of COVID-19 and 12 months after the disease. Under observation were women aged 45-69 years, who were divided into groups: women who did not have COVID-19, not vaccinated, with no antibodies to COVID-19 (IgG) - control group (n=16); women in the acute phase of COVID-19 with a moderate course, accompanied by pneumonia - main group (n=63); patients from the main group who agreed to be examined 12 months after COVID-19 (n=15). The prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, cortisol, testosterone, 17-OH-progesterone, dihydroepiandrosterone sulfate (DHEA-S) levels were assessed. In women with COVID-19 compared with the control the prolactin level was increased (p=0,0002) and the estradiol (р=0,032), testosterone (p=0,004), cortisol (p=0,009), 17-OH-progesterone (p=0,025) and DHEA-S (p=0,003) levels were reduced. Intragroup comparison of hormones showed a decrease in the prolactin level (р=0,041) and increase in the 17-OH-progesterone (р=0,011) and DHEA-S (р=0,0006) levels 12 months after the disease. With a personalized consideration of this group a decrease in the prolactin level is observed in 73,3% of these patients. In the same period, there was an increase in testosterone levels in 46,7% of women, cortisol - in 73,3% of women, 17-OH-progesterone - in 80% of women, DHEA-S - in 100% of cases. When comparing these hormonal parameters between the group of patients who recovered from COVID-19 12 months ago and the control, no statistically significant differences were found, however, patients were identified in whom prolactin and cortisol exceeded the reference values, although in the acute phase of COVID-19 the values of these indicators corresponded to the reference values.

Mutation Effect of Ionizing and Non-Ionizing Electromagnetic Radiation on Drosophila melanogaster.

The frequency of D. melanogaster embryonic death was estimated using the method of dominant lethal mutations after exposure to ionizing γ-radiation and non-ionizing pulsed magnetic field. γ-Radiation had a dose-dependent mutational effect on D. melanogaster. A pronounced increase in embryonic death was observed starting from a dose of 3 Gy and reaches a plateau at 60 Gy due to the maximum death of eggs. When D. melanogaster was exposed to pulsed magnetic field, the effect did not depend on the exposure time; a statistically significant genotoxic effect was detected after 5-h exposure.

Modifying Distant Effect of High Dilutions of Inorganic and Biological Substances.

It is known that highly diluted substances can exert a modifying effect on the initial substances without direct contact with them (distant interaction). The capability of high dilutions of IFNγ and Na2SO4 for the distant modifying effect was studied by the method of terahertz spectroscopy. Statistically significant differences were shown between terahertz characteristics of the initial solution of IFNγ protein and solution that had interacted with high dilutions of IFNγ; in case of sodium sulfate, no such differences were detected. Thus, high dilutions exert a distant modifying effect on the initial substances with complex spatial structure typical of biological molecules.

Length of Leukocyte Telomeres in Newborns of HIV-Infected Mothers.

We studied the relative length of telomeres in newborns with unrealized perinatal transmission of HIV (zero viral load according to PCR results). A cross-sectional survey of 62 newborns of HIV-infected mothers (Apgar score 8); the control group consisted of 80 healthy newborns (Apgar score 8). DNA extracted from whole venous blood samples was analyzed. In newborns of HIV-infected mothers, the relative length of telomeres was significantly lower (0.69 (0.66; 0.72)) than in newborns of the control group (1.1 (0.97; 1.22)) (p<0.001). No significant differences in the relative length of telomeres were found between newborns of mothers with a viral load at the time of delivery and with undetectable viral load: 0.69 (0.66; 0.73) and 0.69 (0.63; 0.72). These findings indicate that HIV-infection in mothers or exposure to antiretroviral therapy has an impact on the relative telomere length in leukocytes of newborns.

Features of the Free Radical Oxidation Process and Antioxidant System in Newborns Born to HIV-Infected of Mothers Who Received Antiretroviral Therapies to Prevent HIV Transmission.

The LPO processes and the state of the antioxidant system in perinatally HIV-exposed newborns were studied. Perinatally HIV-exposed (n=62) and healthy newborns (n=80; control) were examined retrospectively (Apgar score 8 in both groups). Blood plasma and erythrocyte hemolysate were used as the material for biochemical tests. Using spectrophotometric, fluorometric, and statistical methods, we found enhanced LPO processes insufficiently compensated by the antioxidant system with excessive accumulation of damaging metabolites in the blood of perinatally HIV-exposed newborns. These changes can be a consequence of oxidative stress during the perinatal period.

Pro-and Antioxidant Status in Newborn with COVID-19.

There is practically no information on the state of oxidative stress reactions in newborns with coronavirus infections. At the same time, such studies are extremely important and can contribute to better understanding of the process of reactivity in patients of different ages. The content of pro- and antioxidant status indicators was assessed in 44 newborns with confirmed COVID-19. It was found that the content of compounds with unsaturated double bonds, primary, secondary, and final LPO products were elevated in newborns with COVID-19. These changes were accompanied by higher SOD activity and retinol level and reduced activity of glutathione peroxidase. Contrary to popular opinion, newborns can be a COVID-19-susceptible age group and require more close monitoring of metabolic reactions during the period of neonatal adaptation that is an aggravating background during infection.

Study of the Effects of Highly Diluted Sodium Sulfate and Interferon-Gamma.

High dilutions of solutions containing extremely small amounts of the initial substance can modify the biological effects of the initial substance molecules. Using terahertz spectroscopy, we studied the possibility of modifying the physicochemical properties of the initial substance by adding high dilutions of high-molecular-weight (IFNγ) and low-molecular-weight (Na2SO4) compounds. In addition, the modifying effect produced by high dilutions of a low-molecular electrolyte (a solution of Na2SO4 salt) on the initial substance was confirmed by conductometry. This method allows measuring electrical conductivity that also depends on the physicochemical properties of the solution, namely, the number of ions and velocity of their movement. Statistically significant differences were shown between terahertz and conductometric characteristics of the initial solution (inorganic salt Na2SO4 or a protein IFNγ) and a solution, where high dilutions of the same substances were added in different concentrations. Interestingly, the differences were more pronounced for the biological molecule. Thus, it has been shown that high dilutions can change the properties of the initial solution; the effect is more pronounced for the protein solution.

Superoxide Dismutase Activity in Male and Female Patients of Different Age with Moderate COVID-19.

The study involved 271 patients (132 men and 139 women) with moderate COVID-19. Superoxide dismutase (SOD) activity in erythrocytes was measured spectrophotometrically. In total group of patients (divided into age groups of 18-35, 36-45, 46-60, and 61-90 years), higher SOD activity was found in the 18-35 age group in comparison with the groups 46-60 years (p<0.01) and 61-90 years (p<0.05). Then, the groups were additionally divided by sex. In men, no differences in enzyme activity were found between the age groups. In women of early reproductive age, SOD activity was higher than in groups 36-45, 46-60, and 61-90 years. The sex differences consisted in higher SOD activity in women aged 18-35 years in comparison with men of this age. These data should be taken into account when choosing the tactics of therapy for patients with moderate COVID-19 course.

[Withdrawal syndrome after tyrosine kinase inhibitors discontinuation in patients with chronic myeloid leukemia].

BACKGROUND: Withdrawal syndrome (WS) a musculoskeletal pain after discontinuation of tyrosine kinase inhibitors (TKI) in patients with chronic myeloid leukemia (CML) has been described in the treatment-free remission (TFR) studies. The pathophysiological mechanisms and predisposing factors of WS have not been well established. AIM: Our aim was to evaluate clinical features and factors associated with WS in the Russian cohort of CML patients who discontinued TKI therapy. MATERIALS AND METHODS: WS was evaluated in total of 183 CML patients with chronic phase and sustained deep molecular response (DMR). WS was defined as a musculoskeletal pain newly observed after TKI cessation or as a worsening of previously observed symptoms. RESULTS: DMR loss free survival at 36 months was 49% and 43% in prospective and retrospective groups respectively (p=0.96) with mеdian (Me) time of observation 33 months (range 1136). WS was observed in 49 (27%) patients: grade 12 was in 45 (92%) patients, grade 3 in 4 (8%) patients. Me time to WS occurrence was 2 months (range 17), Ме duration of WS was 5 months (range 135). WS was resolved in 14 of 15 patients with molecular relapse after 13 months of TKI re-initiation and was decreased in 1 patient. WS was completely resolved in 31 of 34 patients who continued remained in TFR and decreased in 3 patients. WS was resolved spontaneously or with nonsteroidal anti-inflammatory drugs in 14 (45%) and 17 (55%) patients accordingly. Older age (p0.0001), longer duration of TKI therapy (p0.0001) and presence of locomotion system diseases (p=0.022) were observed in patients with WS. No WS was observed in pregnant patients (р0.001). Survival without DMR loss at 12 months after TKI stop was 66 and 42% in patients with and without WS accordingly (р=0.095). CONCLUSION: The rate of WS was 27% that is in a good concordance with the data of the other TFR studies. A longer period of TKI exposure, older age and the history of locomotion system diseases were associated with the development of the WS. We found for the first time that WS was not observed in patients with pregnancy. There was no association of WS development and the rate of molecular relapses.

THE EFFECTIVENESS OF MELATONIN IN THE COMPLEX TREATMENT OF HYPERTENSION IN PATIENTS WITH STAGE 5 CHRONIC KIDNEY DISEASE.

In recent years, there has been a progressive increase in the number of patients with chronic kidney disease (CKD), whose mortality risk is significantly higher than in general patients, which is associated with cardiovascular risks.In patients with CKD stage 5D before the start of replacement renal therapy for hypertension exceeds 90%. The aim -to analyze the efficacy and safety of the use of melatonin in the complex treatment of arterial hypertension (AH) in patients with CKD of 5 stage with impaired melatonin-forming function of the epiphysis (MFE). 60 people (35 women and 25 men) with a chronic kidney disease of 5 stage, which have violated MFE and AH were examined. For all patients in addition to antihypertensive therapy were prescribed the drug melatonin at a dose of 3 mg, which was taken once a day at 22:00 for 8 weeks. For all examined, before and after the course of treatment, were measured blood pressure (BP), Ambulatory Blood Pressure Monitoring (ABPM) and determination of the concentration of melatonin in the salivaby immunosorbent method. The examined patients showed a high frequency of MFE disturbance both in the daytime and at night - respectively, in 52,4% (p<0,001) and 82,6% (p<0,001). The dynamics of the diurnal BP on the background of treatment was due to changes in the degree of nocturnal decrease of BP, the number of patients in the main group with the "non-dipper" profile, decreased from 44,5% to 27,6% (p<0,05%), the proportion of patients with a daily profile of BP "night-peakear" from 22,4% to 4,8% (p<0,05%). Besides, a statistically significant of the number of persons with a daily profile of BP "dipper" increase in 30,2%. Against the background of complex treatment, there was a decrease in the patient's need for the dose and amount of antihypertensive drugs to achieve BP targets. Our data show a high incidence of MFE disorders in patients with CKD stage VD, and adding to the antihypertensive therapy of the drug melatonin in patients with CKD of 5 stage is effective and safe.

Fluorescence analysis of polyaromatic hydrocarbon photodegradation in the presence of polypropylene microfibers.

In this study, degradation of naphthalene and anthracene in water using ultraviolet (UV) light in the presence of polypropylene microfibers (PPM) modified with TiO2 was investigated using fluorescence analysis. KrCl (λrad  = 222 nm) and XeCl (λrad  = 308 nm) excilamps were used in a photoreactor. Phototransformation was studied for compounds in the presence of PPMs modified with TiO2 particles. The results indicated that the toxicants concentration was reduced by two orders of magnitude in the presence of PPMs. This reduction was due to effective adsorption of naphthalene and anthracene from water onto the surface of the PPMs. Exposure to the toxicant-water-PPM system to UV light led to the formation of fluorescent photoproducts.

[Problems of diagnostics and treatment of transtiretinum amyloidosis with destruction of the heart in the elderly: Clinical experience.]

The article presents a modern understanding of the treatment of cardiac amyloidosis, provides data on the frequency of occurrence, classification and variants of clinical manifestations of transthyretin amyloidosis. This pathology is a slowly progressive disease, the symptoms of which usually appear in the elderly and senile age. This diagnosis may become more common in the future as the population ages and diagnostic methods improve. As an illustration, a description of the clinical case of transtritin amyloidosis of the heart in a 77-year-old patient, which occurred with a primary lesion of the heart and symptoms of chronic heart failure, is given. It shows the difficulties in the lifetime diagnosis of transthyretin amyloidosis.

Ergoferon Increases IL-2 Production by Activated Lymphocytes.

We studied the effects of Ergoferon on the production of antiviral cytokine IL-2 by type 1 CD4+T cells. Preincubation of Jurkat cells with Ergoferon increased IL-2 secretion by these cells after stimulation with phorbol 12-myristate 13-acetate/ionomycine in comparison with the placebo group. The data prove that Ergoferon is capable of activating cell cascades involved in the realization of the antiviral immune response.

Multipotent Mesenchymal Stromal Cells in Patients with Chronic Myeloid Leukemia before Discontinuation of Tyrosine Kinase Inhibitors.

We analyzed changes in multipotent mesenchymal stromal cells of patients with chronic myeloid leukemia before discontinuation of tyrosine kinase inhibitors. Withdrawal syndrome was significantly more common in patients who have been taking tyrosine kinase inhibitors for a longer time and in patients of older age and with lower body weight. In patients with withdrawal syndrome, the total production of mesenchymal stromal cells and expression of FGFR2 and MMP2 genes were significantly lower; loss of deep molecular response was also less frequent in this group of patients. At the same time, the expression of genes important for the maintenance of stem cells (SOX9, PDGFRa, and LIF) was significantly lower in the mesenchymal stromal cells of patients with withdrawal syndrome and loss of deep molecular response. We observed a clear-cut relationship between the development of withdrawal syndrome and the loss of deep molecular response. The decrease in the expression of FGFR2 and MMP2 genes in the mesenchymal stromal cells of patients with chronic myeloid leukemia before discontinuation of treatment can be a predictor of withdrawal syndrome, while simultaneous decrease in the expression of SOX9, PDGFRa, and LIF in these cells attests to undesirability of therapy discontinuation at the moment.

[The intraoperative prophylaxis of local ischemical brain damage in neurosurgical patients with cerebral aneurysm]. / Intraoperatsionnaia profilaktika lokal'nogo ishemicheskogo povrezhdeniia golovnogo mozga u neirokhirurgicheskikh patsientov s tserebral'noi anevrizmoi.

AIM: To study the effectiveness of intraoperative administration of Cytoflavine for the prevention of ischemic brain injury during cerebral aneurysm (CA) clipping with temporary occlusion of the leading artery under general anesthesia. MATERIAL AND METHODS: The prospective cohort single-center study included 40 patients with CA ( the main group - 27 patients with intraoperative administration of cytoflavine; the comparison group -13 patients without use of cytoflavine), who underwent aneurism clipping with temporary occlusion of the afferent artery. We assesed the intraoperative state of the brain, the time of awakening and extubation of patients after surgery, neurological deficit and local ischemic changes in the area of surgery according to the CT of the brain in the early postoperative period, resuscitation bed-day and the relationship of these indicators with the duration of temporary occlusion of the afferent artery in the selected groups of patients. RESULTS: In intergroup comparison, patients of the main group treated with intraoperative cytoflavin showed a reduction in the time of awakening (p=0.013) and the time of extubation (p=0.01) both with temporary occlusion of the afferent artery and in patients without temporary occlusion (p<0.05). The duration of resuscitation bed-day decreased in the main group of patients receiving intraoperatively cytoflavine (p=0.01), as well as in patients in the comparison group without temporary occlusion (p<0.05). CONCLUSION: Temporary occlusion of the afferent artery with short intervals of vessel occlusion in combination with intraoperative intravenous administration of cytoflavine expands the tolerability to artery occlusion in patients operated in the 'cold' period, reduces the possibility of neurological deficit, reduces the recovery period and resuscitation bed-day after surgical clipping CA.

Redox-Dependent Expression of Genes Encoding NADPH Oxidase 5 and the Key Antioxidant Enzymes during Formation of Drug Resistance of Tumor Cells to Cisplatin.

Expression of genes that plays a significant role in the control of cellular redox homeostasis was studied during the development of drug resistance of human ovarian adenocarcinoma SKOV-3 cells to cisplatin. It was found that the development of drug resistance was accompanied by enhanced expression of the genes encoding the key antioxidant enzymes (SOD2, CAT, GPX1, and HO-1) and transcription factor Nrf2, as well as reduced expression of the gene encoding NOX5 isoform of NADPH oxidase. The results testify to redox-dependent development of the adaptive antioxidant response as an important process in the mechanism of formation of resistance to cisplatin.

Electron Transfer through the Acceptor Side of Photosystem I: Interaction with Exogenous Acceptors and Molecular Oxygen.

This review considers the state-of-the-art on mechanisms and alternative pathways of electron transfer in photosynthetic electron transport chains of chloroplasts and cyanobacteria. The mechanisms of electron transport control between photosystems (PS) I and II and the Calvin-Benson cycle are considered. The redistribution of electron fluxes between the noncyclic, cyclic, and pseudocyclic pathways plays an important role in the regulation of photosynthesis. Mathematical modeling of light-induced electron transport processes is considered. Particular attention is given to the electron transfer reactions on the acceptor side of PS I and to interactions of PS I with exogenous acceptors, including molecular oxygen. A kinetic model of PS I and its interaction with exogenous electron acceptors has been developed. This model is based on experimental kinetics of charge recombination in isolated PS I. Kinetic and thermodynamic parameters of the electron transfer reactions in PS I are scrutinized. The free energies of electron transfer between quinone acceptors A1A/A1B in the symmetric redox cofactor branches of PS I and iron-sulfur clusters FX, FA, and FB have been estimated. The second-order rate constants of electron transfer from PS I to external acceptors have been determined. The data suggest that byproduct formation of superoxide radical in PS I due to the reduction of molecular oxygen in the A1 site (Mehler reaction) can exceed 0.3% of the total electron flux in PS I.

[Results of following up patients with chronic myeloid leukemia and a deep molecular response without tyrosine kinase inhibitor therapy]. / Rezul'taty nabliudeniia bol'nykh khronicheskim mieloleikozom s glubokim molekuliarnym otvetom bez terapii ingibitorami tirozinkinaz.

AIM: To assess the results of following up patients with chronic myeloid leukemia (CML) and a deep molecular response (MR) without tyrosine kinase inhibitor (TKI) therapy. SUBJECTS AND METHODS: The reasons for TKI discontinuation in 70 patients with CML and a deep MR of more than 1 year's duration were adverse events, pregnancy, and patients' decision. Information was collected retrospectively and prospectively in 2008-2016. RESULTS: The median follow-up after TKI therapy discontinuation was 23 months (2 to 100 months). At 6, 12 and 24 months after TKI therapy discontinuation, the cumulative incidence of major MR (MMR) loss was 28, 41 and 48%, respectively; the survival rates without TKI therapy were 69, 50, and 39%, respectively. MMR loss was noted in 28 (88%) patients at 12 months; it was not seen without TKI therapy at 2-year follow-up. Deaths due to CML progression were absent. The Sokal risk group was a reliable factor influencing MMR loss (p ≤ 0.05). The cumulative recovery rate for deep MR after resumption of TKI use was 73 and 100% at 12 and 24 months, respectively, with a median follow-up of 24 months (1 to 116 months). Deep MR recovered at a later time when the therapy was resumed more than 30 days after MMR loss. CONCLUSION: Safe follow-up is possible in about 50% of the patients with CML and stable deep MRs without TKI therapy. The introduction of this approach into clinical practice requires regular molecular genetic monitoring and organizational activities. Biological factors in maintaining remission after TKI discontinuation need to be separately studied.

[The use of SPECT-CT for visualization of sentinel lymph nodes and lymph drainage pathways in prostate cancer patients].

There was studied the use of SPECT-CT for visualization of sentinel lymph nodes and lymph drainage pathways in 35 patients with localized prostate cancer (cT1-T2 N0 M0). Sentinel lymph nodes were imaged in 31 (89%) patients. There were advantageously detected drainage pathways to exterior (77%) and internal iliac (58%) lymph nodes. Visceral (29%) lymph nodes (paraprostatic, paravesical and mesorectal) were less determined. There was established high informative value of SPECT-CT for imaging sentinel lymph nodes, determining their location as well as identification of lymph drainage pathways in patients with prostate cancer.