Condition of the Right Heart in Patients With COVID-19­Associated Pneumonia: Follow-Up During Hospitalization.

Aim      Dynamic assessment of the right heart in patients with COVID-19-associated pneumonia of different severity during regression of the systemic inflammatory response (SIR).Material an methods    This single-center prospective study included 46 patients with the novel coronavirus infection COVID-19 and viral pneumonia according to chest multispiral computed tomography (CT). Laboratory and echocardiographic examinations of patients were performed.Results Based on the results of evaluation with the Clinical Condition Scale (CCS-COVID), patients were divided into two groups: group A, patients with a score from 6 to 9 and group B, patients with a score from 10 to 14. The study results of both groups were evaluated twice: on day 10±2.5 from the onset of symptoms (groups A10 and B10, respectively) and again on day 17±1.8 (groups A17 and B17, respectively). Patients of group B10 had more pronounced SIR (C-reactive protein, 111.38±52.5 mg / l) and a larger volume of ground-glass opacity (38.3±9.6 %). At the first stage, higher values of right ventricular global longitudinal strain (RV GLS) were detected in group B10 compared to group A10 (23.2±4.8 % vs. 19.9±3.5 %, р=0.048). During the regression of SIR intensity and the positive dynamics of CT, lower values of Е / А were observed in group B17 (1.0 [0.98; 1.2]) vs. group А17 (1.4 [1.18; 1.5, p=0.015), and е' / a' in group B17 (0.66 [0.58; 0.85]) vs. 0.95 [0.79; 1.12] in group B17 (p=0.010). Е / А and е' / a' ratios were correlated with total lactate dehydrogenase fraction (r= -0.452 and p=0.006; r= -0.334 and p=0.050, respectively).Conclusion      In patients with severe COVID-19-associated pneumonia during regression of SIR intensity, changes in the parameters that reflected RV diastolic dysfunction were observed.

[No Effect of the p.Arg230His Variant Of The VCL Protein on the Course of the Hypertrophic Cardiomyopathy In Russian Family Carrying The p.Gln1233Ter Pathogenic Variant In The MYBPC3 Gene].

Aim      To determine specific clinical characteristics caused by a combination of the rs397516037 pathogenic variant in the myosin-binding protein C (MTBPC3) and the rs749628307 polymorphic variant in the vinculin (VCL) gene in a Russian family of carriers and to evaluate the contribution of the rs749628307 polymorphic variant in the VCL gene to the development of hypertrophic cardiomyopathy (HCMP).Material and methods  The family under study included one healthy person and 3 patients with HCMP. A targeted analysis of proband's exome was performed. A structural alignment for both forms of the VCL protein, the canonical form and the form with p.Arg230His substitution, was performed.Results The pathogenic rs397516037 variant and the potentially pathogenic rs749628307 variant were detected in the proband and several family members. A possibly damaging variant rs749628307 was detected in the proband and several family members evaluated in this study. The structural alignment confirmed that the rs749628307 variant did not alter the protein structure significantly and could not cause an impairment or loss of the protein function.Conclusion      This study demonstrated that apparently the rs749628307 variant in the VCL gene does not affect the protein structure in a pathogenetically significant way, neither does it affect the severity and form of the clinical manifestations of HCMP; therefore, it cannot be considered as pathogenic.

Anti-SARS-CoV-2 Activity of a Polyphenolic Complex from Maackia amurensis.

We studied the ability of the polyphenolic complex from Maackia amurensis, the active substance of Maksar, to inhibit the cytopathogenic effect induced by the SARS-CoV-2 and to reduce the concentration of viral RNA in infected Vero E6 cells. Polyphenolic complex showed significant anti-SARS-CoV-2 activity and effectively inhibited viral replication by direct action on viral particles and the early stage of viral infection.

APPLICATION OF A COMPREHENSIVE APPROACH FOR EVALUATION OF TREATMENT EFFECTIVENESS OF MYCOPLASMA INFECTION IN CHILDREN WITH BRONCHIAL ASTHMA.

Aim - improvement of efficiency assessment methods of therapy of mycoplasma infection in children with bronchial asthma. The effectiveness of treatment of mycoplasma infection in the period of exacerbation of bronchial asthma in 250 children, aged 1 to 7 years, was evaluated. The children were on basic therapy and received treatment with azithromycin: three courses at a dose of 10 mg/kg of weight for 3 days with an interval of 4 days 5-7 days. Microbiological (culturing), immunological (DIF, AHAA), and genetic (PCR) methods were used to identify mycoplasma markers. The main focus was on identifying two species - M. pneumoniae and M. hominis, most commonly found in mycoplasma respiratory infections, including bronchial asthma. In 250 children with bronchial asthma, antigens of Mycoplasma pneumoniae, Mycoplasma hominis, Ureaplasma urealyticum, Mycoplasma arthritidis and Mycoplasma fermentrans were detected in 62,8%, 42,8%, 46,8 %, 31,6%, 45,6% of cases, respectively. A detailed study of the presence of M. pneumoniae and M. hominis antigens in the blood of 83 children with bronchial asthma showed that before treatment, the detection rate of M. pneumoniae and M. hominis antigens was 67.5% and 50.6%, respectively, in the CIC - 65.1% and 61.5%, DNA in the blood serum - 4.8% and 16.9%, and in the CIC - 27.7% and 32.5%, respectively. From 7 CIC samples containing M. hominis DNA and 2 CIC samples containing M. pneumoniae DNA, atypical cultures of "mini-colonies" of M. hominis and M. pneumoniae were isolated, the specificity of which was confirmed not only by DIF and PCR, but also by the ability to grow on a solid medium for mycoplasmas. After treatment by azithromycin, the number of positive tests on antigens and DNA in free state and in structure of CIC significantly decreased. The identification of specific markers of mycoplasma cells in the comprehensive diagnostics of mycoplasma infection in children with exacerbation of asthma, increases the effectiveness of therapy control for mycoplasma infection and improves the prognosis of bronchial asthma in patients.

Comparative In Vitro Study of Antiherpetic Activity of Echinochrome A and Product of Its Oxidation Dehydroechinochrome.

The quinoid pigment echinochrome A isolated from the sea urchin Scaphechinus mirabilis, the product of its oxidation dehydroechinochrome, and structurally similar antiviral agent oxolin were tested for their ability to inhibit plaque formation induced by herpes simplex virus type 1 (HSV-1) in Vero cells. The tested compounds showed significant anti-HSV-1 activity, mainly due to their direct effect on viral particles and on virus attachment to cells. The antiviral efficacy of the test compounds increased in the following order: oxolin→echinochrome A→dehydroechinochrome.

[Cys-Flanked Cationic Peptides For Cell Delivery of the Herpes Simplex Virus Thymidine Kinase Gene for Suicide Gene Therapy of Uterine Leiomyoma].

Uterine leiomyoma (UL) is the most common benign tumor in women of reproductive age. Gene therapy using suicidal genes appears to be a promising approach for UL treatment. One of key factors for success of gene therapy is the right choice of genetic construct carrier. A promising group of non-viral carriers for cell delivery of expression vectors is cationic Cys-flanked peptides which form tight complexes with DNA due to electrostatic interactions and the presence of interpeptide disulfide bonds. The paper reports a comparative study of the physico-chemical, toxic, and transfectional properties of the DNA-peptide complexes obtained by matrix polymerization or oxidative polycondensation of Cys-flanked peptides using the chain growth terminator 2-amino ethanethiol. We have demonstrated the therapeutic effect of the delivery of the pPTK-1 plasmid carrying the herpes simplex virus type 1 (HSV-1) thymidine kinase gene into PANC-1, and HEK-293T cell culture as well as into primary UL cells. It has been shown that the carriers obtained by oxidative polycondensation transform primary UL cells more efficiently than those produced by matrix polymerization. Treatment with ganciclovir resulted in the death of up to 40% of UL cells transfected with the pPTK-1 plasmid. The perspectives of use of the polyR6 carrier produced by oxidative polycondensation as a tool for the development of modular peptide carriers for the purposes of UL gene therapy were discussed.

[Myocardial ischemia in patients with hypertrophic cardiomyopathy].

Authors present is comprehensive clinical and instrumental evaluation of patients with HCM with myocardial ischemia. 104 patients (38.4% of men) with HCM were examined, mean age 58.2±14.7. The examination included risk factors assessment for CAD, ECG, Echo, stress ECG test, 24-hour ECG monitoring. In the presence of myocardial ischemia, CAG (n=66) and MSCT of the coronary arteries (CA) (n=4) were performed. All patients were split up on 2 groups: I - 70 HCM patients with myocardial ischemia, 67.3%, and II (the control group) - 34 HCM patients without myocardial ischemia, 32.7%. The group I was divided on 2 subgroups: 1 - 29 patients with coronary atherosclerosis (41.4%), 2 - 41 patient without coronary atherosclerosis (58.6%). Age (p=0.046), family history (p=0.037), higher systolic and diastolic arterial pressure, long-term arterial hypertension (p<0.05) were determined as significant risk factors for CAD. Smaller diameter of LAD (p=0.008), higher LV mass index, greater LV diastolic function disorder (p<0.05) were detected in group 2 compared to group II. The decrease in myocardial perfusion (MBG scale) was associated with high LV mass index and cardiac arrhythmias. The frequency of concomitant coronary atherosclerosis among HCM patients with myocardial ischemia was determined as 41.4%. Analysis of traditional risk factors for CAD in patients with HCM revealed the strong relation to age, aggravated by a family history of CAD, blood pressure level and duration of hypertension. Smaller diameter of LAD, higher LV mass index, greater LV diastolic function disorder were observed in HCM patients with myocardial ischemia without CAD.

Cytotoxic and antiproliferative effects of thymoquinone on rat C6 glioma cells depend on oxidative stress.

Thymoquinone (TQ) is a highly perspective chemotherapeutic agent against gliomas and glioblastomas because of its ability to cross the blood-brain barrier and its selective cytotoxicity for glioblastoma cells compared to primary astrocytes. Here, we tested the hypothesis that TQ-induced mild oxidative stress provokes C6 glioma cell apoptosis through redox-dependent alteration of MAPK proteins. We showed that low concentrations of TQ (20-50 µM) promoted cell-cycle arrest and induced hydrogen peroxide generation as a result of NADH-quinone oxidoreductase 1-catalyzed two-electron reduction of this quinone. Similarly, low concentrations of TQ efficiently conjugated intracellular GSH disturbing redox state of glioma cells and provoking mitochondrial dysfunction. We demonstrated that high concentrations of TQ (70-100 µM) induced reactive oxygen species generation due to its one-electron reduction. TQ provoked apoptosis in C6 glioma cells through mitochondrial potential dissipation and permeability transition pore opening. The identified TQ modes of action on C6 glioma cells open up the possibility of considering it as a promising agent to enhance the sensitivity of cancer cells to standard chemotherapeutic drugs.

[A Case of Apical Hypertrophic Cardiomyopathy With Rare Anomaly of Coronary Arteries Origin].

A clinical case of apical hypertrophic cardiomyopathy (HCM) in 44­years old man is presented. In this patient exercise ECG testing and 24­hour ECG monitoring revealed exercise-induced ST depression in the angiographically confirmed absence of coronary atherosclerosis. The uncommonness of this observation was the combination of HCM with a rare anomaly of coronary arteries origin.

Mechanisms of Antiviral Activity of the Polyphenol Complex from Seagrass of the Zosteraceae Family against Tick-Borne Encephalitis Virus.

Antiviral activity of the polyphenol complex from seagrass of the Zosteraceae family against highly pathogenic strain of the tick-borne encephalitis virus was studied on passaged culture of porcine embryo kidney cells. The antiviral effect of the test compound manifested in a decrease in the infectious titer of the virus and depended on the concentration and application schemes. Polyphenol complex in a concentration of 100 µg/ml suppressed accumulation of the pathogen in the cell culture: pretreatment of the virus reduced its titer by 4 log, pretreatment of cells by 1.4 log, and application of the compound 1 h after cell infection by 2.8 log. Antiviral action of the test compound is determined by direct inactivation of the virus and inhibition of virus replication at the early stage, which attests to potential of this compound in the treatment of tick-borne encephalitis.

[Hypertrophic cardiomyopathy and ischemic heart disease: the problem of pathology combination].

Hypertrophic cardiomyopathy (HCM) is a disease with left ventricular hypertrophy caused by mutations in the genes of myocardial contractile proteins, whose frequency is about 0.5 %. Due to the high incidence of anginal pain and marked changes in ECG with HCM, the problem of diagnosing the combination of HCM and coronary artery disease (CAD) presents a rather difficult task for the clinician. The complexity of this diagnosis is due to the ability of standard methods of instrumental examination (ECG, a test with physical activity, stress tests in conjunction with visualization of the myocardium) to detect myocardial ischemia in both СAD and HCM. In such cases, the coronary angiography, or multispiral computed tomography of coronary arteries (in patients with low СAD risk) remains the gold standard for detecting atherosclerotic lesions of the coronary arteries. The possibility of combining HCM and СAD in patients of older age groups raises the question of the features of the course of diseases and the prognosis of such patients.

Carbon Nanotubes as A High-Performance Platform for Target Delivery of Anticancer Quinones.

BACKGROUND: In spite of considerable efforts of researchers the cancer deseases remain to be incurable and a percentage of cancer deseases in the structure of mortality increases every year. At that, high systemic toxicity of antitumor drugs hampers their effective use. Because of this fact, the development of nanosystems for targeted delivery of antitumor drugs is one of the leading problem in nanomedicine and nanopharmacy. OBJECTIVE: To critically examine the modern strategies for carbon nanotubes (CNTs)-based delivery of anticancer quinones and to summarize the mechanisms which can provide high effectiveness and multifunctionality of the CNT-based quinone delivery platform. RESULTS: Quinones, including anthracycline antibiotics - doxorubicin and daunorubicin, are among the most prospective group of natural and syntetic compounds which exhibit high antitumor activity against different type of tumors. In this review, we focus on the possibilities of using CNTs for targeted delivery of antitumor compounds with quinoid moiety which is ordinarily characterized by high specific interaction with DNA molecules. Quinones can be non-covalently adsorbed on CNT surface due to their aromatic structure and π-conjugated system of double bonds. The characteristic features of doxorubicine-CNT complex are high loading efficiency, pH-dependent release in acidic tumor microenviroment, enough stability in biological fluid. Different types of CNT functionalization, targeting strategies and designs for multifunctional CNT-based doxorubicine delivery platform are disscussed. CONCLUSION: Nanosystems based on functionalized CNTs are very promising platform for quinone delivery resulting in significant enhancement of cancer treatment efficiency. Functionalization of CNTs with the polymeric shell, especially DNA-based shells, can provide the greatest affinity and mimicry with biological structures.

[Enteral tube feeding in adult patients with cystic fibrosis and respiratory failure]. / Énteral'noe zondovoe pitanie u vzroslykh bol'nykh mukovistsidozom s dykhatel'noi nedostatochnost'iu.

AIM: To evaluate the efficiency of nocturnal hyperalimentation in adult patients with cystic fibrosis (CF) and respiratory failure. SUBJECTS AND METHODS: The investigation enrolled 17 patients older than 18 years (mean age, 25.6±4.2 years) diagnosed with very severe CF (forced expiratory volume in one second (FEV1), < 30%; body mass index (BMI), < 18.5 kg/m2); all the patients were on the waiting list for lung transplantation. Nutritional status and pulmonary function parameters, such as body weight, height, BMI, and FEV1, were measured at baseline, before and 6 and 9 months after tube feeding. RESULTS: The study group showed a considerable increase in body weight and BMI after 6 and 9 months. The change in lung function was statistically insignificant. Lung transplantation was successfully conducted in 5 patients; 4 died while on the waiting list; the cause of death was respiratory failure. CONCLUSION: Supplemental PEG tube feeding improves the nutritional status (BMI, body weight) of patients with very severe CF.

GLIOMA CELL PROLIFERATION MEDIATED BY COENZYME Q10 AT SERUM DEPRIVATION IN VITRO.

Mechanisms of coenzyme Q10 effect on serum-deprived glioma cell proliferation have been studied. Our results have shown that the addition of coenzyme Q10 into serum-free culture medium leads to increase in cell viability, stimulation of cell growth, as well as restoration of mitochondrial potential and increase of quantity of energized mitochondria. It has been found out that coenzyme Q10-induced glioma cell proliferation under serum deficiency is a result of intracellular reduced glutathione concentration decrease with subsequent activation of proteinkinase C, ERK1/2 and phosphoinositol-3-kinase.

[Antiviral activity of various drugs with different mechanisms of action in patients with experimental tick-borne encephalitis].

A possible approach to effective, pathogenetically valid treatment of patients with the tick-borne encephalitis (TBE) is a complex therapy with the immunotropic preparations isolated from natural objects. This work is devoted to the comparative study of the antiviral activity of the tinrostim (immunoactive peptide from the optical ganglia of the squid Berritiuthis magister) and some officinal drugs used for prevention and treatment of the TBE (ribavirin, reaferon-EC, cycloferon, 4-jodantipyrin, immunoglobulin human against encephalitis ixodicum) in the experimental models of the TBE. All tested drugs significantly inhibited the proliferation of the highly virulent strain of the TBEV in the sensitive PK cell cultures: ribavirin and immunoglobulin against TBE completely inhibited viral replication (by 100%); cycloferon - by 75%; tinrostim, reaferon-EC, and jodantipyrin - by 50-60%. Therapeutic efficacy of the compounds was evaluated on a model of acute lethal TBE in mice: treatment with cycloferon and immunoglobulin against TBE prevented the mortality in 35-45% of infected animals; tinrostim - in 25%; ribavirin, reaferon-EC, and jodantipyrin - in 5-10%. The combination of the immunoactive peptide, tinrostim, with officinal drugs (ribavirin, cycloferon) was more effective than the treatment with a single drug, thereby indicating the prospects of the use of this therapy for treating TBE.

Antioxidants as Potential Antiviral Agents for Flavivirus Infections.

The review considers potential opportunities of certain antioxidants as antiviral agents for flavivirus infections. Currently flavivirus infections represent a significant public health problem for various regions of the world, since they result in high morbidity and mortality. Oxidative stress induced by viruses, including the flaviviruses, not only interferes with the body's important metabolic processes, but also regulates replication of the virus. A broad spectrum of antiviral activity of the natural phenolic antioxidants, i.e. rosmarinic acid and luteolin as components of the polyphenol complex isolated from the seagrass family Zsteraceae is decribed. The antiviral activity of rosmarinic acid and luteolin is shown to be due to their high antioxidant, antiinflammatory and neuroprotective potential. Particular attention is paid to the analysis of the activity of the polyphenol complex and its components against the tickborne encephalitis virus. The antiviral properties of the compounds with a broad spectrum of the biological action provide an oppor- tunity to consider them as promising candidates for combined therapy of tick-borne encephalitis.

Redox regulation of mitochondrial functional activity by quinones.

Quinones are among the rare compounds successfully used as therapeutic agents to correct mitochondrial diseases and as specific regulators of mitochondrial function within cells. The aim of the present study was to elucidate the redox-dependent effects of quinones on mitochondrial function. The functional parameters [respiratory activity, membrane potential, and reactive oxygen species (ROS) generation] of isolated rat liver mitochondria and mitochondria in intact cells were measured in the presence of eight exogenously applied quinones that differ in lipophilicity and one-electron reduction potential. The quinones affected the respiratory parameters of mitochondria, and dissipated the mitochondrial membrane potential as well as influenced (either decreased or enhanced) ROS generation, and restored the electron flow during electron transport chain inhibition. The stimulation of ROS production by juglone and 2,5-di-tert-butyl-1,4-benzoquinone was accompanied by a decrease in the acceptor control and respiration control ratios, dissipation of the mitochondrial membrane potential and induction of the reverse electron flow under succinate oxidation in isolated mitochondria. Menadione and 2,3,5-trimethyl-1,4-benzoquinone, which decreased the mitochondrial ROS generation, did not affect the mitochondrial potential and, vice versa, were capable of restoring electron transport during Complex I inhibition. In intact C6 cells, all the quinones, except for coenzyme Q10, decreased the mitochondrial membrane potential. Juglone, 1,4-benzoquinone, and menadione showed the most pronounced effects. These findings indicate that quinones with the reduction potential values E1/2 in the range from -99 to -260 mV were effective redox regulators of mitochondrial electron transport.

[Nutritional status in patients with cystic fibrosis: Possibilities of correction]. / Status pitaniia u bol'nykh mukovistsidozom: vozmozhnosti korrektsii.

The major risk factor for death in cystic fibrosis (CF) is a progressive lung injury; however, low nutritional status (NS) remains an important and underestimated problem in the management of these patients. The NS of a patient with CF is impaired by many factors, such as chronic malabsorption, pancreatic failure, chronic inflammation, and recurrent pulmonary infection - they all lead to higher energy demand in the presence of lower intake of nutrients. The NS of those with CF plays an important role in maintaining lung function. The patients with higher NS have longer life expectancies. According to the Russian National Registry, both pediatric and adult patients with CF have shorter life expectancies. The article discusses various nutritional support regimens and their impact on lung function parameters.

[Tissue Doppler imaging and ultrasonic methods for evaluating myocardial deformation in the diagnosis of hypertrophic cardiomyopathy].

Hypertrophic cardiomyopathy (HCM) is a genetic cardiovascular disease caused by mutations in genes that encode components of the sarcomere. Standard echocardiography is not always capable to identify regional systolic dysfunction of the left ventricle (LV), and to detect the disease on its preclinical stage. Genetic testing allows identifying sarcomere gene mutations in less than 50% of patients due to difficulty of screening all genes responsible for hypertrophic cardiomyopathy. Modern innovative methods of echocardiography - tissue Doppler, strain and strain rate, speckle tracking have been widely used for quantification of regional ventricular motion. Work of recent decades has proven the ability of these techniques to detect regional systolic and diastolic dysfunction of the LV, to diagnose HCM early, to differentiate it from other pathological and physiological hypertrophies. These modes can be used for prediction of cardiovascular complications in patients with HCM. In clinical practice the use of innovative technologies in combination with standard echocardiography allows to obtain more accurate and extensive information on the severity and prognosis of the disease.

[Use of high-frequency chest wall oscillation in an exacerbation of chronic pyo-obstructive bronchitis in adult patients with cystic fibrosis].

AIM: To evaluate the efficiency of high-frequency chest wall oscillation in the treatment of an exacerbation of chronic pyo- obstructive bronchitis in adult patients with cystic fibrosis (CF). SUBJECTS AND METHODS: A simple open-label comparative study enrolled 31 patients with CF. C-reactive protein (CRP), spirometric indicators (forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow), hemoglobin oxygen saturation, anthropometric data, six-minute walk test, and dyspnea rating by the MRC scale were assessed before treatment and on the last day of hospitalization. All the patients received conventional drug therapy; the study group patients (n=15) had the latter in combination with vibration-compression therapy for 15 minutes twice daily at a vibration frequency of 9-12 Hz and at an amplitude of 6-9 bars; the treatment cycle lasted 12-14 days. RESULTS: Both groups showed significant changes in spirometric and pulsometric readings, 6-minute walk test results, and MRC score. Body mass index increased and CRP decreased in the majority of patients in both groups. There were significant group differences in functional and anthropometric changes: 10.0 ± 4.6 and 6.9 ± 3.6% for FEV1 (p = 0.04) and 9.5 ± 4.8 and 5.9 ± 3.8% for FVC (p = 0.03) in the study and control groups, respectively. CONCLUSION: Incorporation of vibration-compression therapy (Vest vibro drainage) into the combination treatment of adult patients with CF results in significantly improved bronchial patency and more effective abolishment of an exacerbation.