Direct and Indirect Neurological Signs of COVID-19.

Objective. To systematize the neurological manifestations of COVID-19. Materials and methods. A systematic computerized analysis of all currently available publications on the neurological manifestations of COVID-19 was undertaken (2374 reports in PubMed) by topological data analysis. Results. A set of interactions between infection with SARS-CoV-2, metabolic impairments affecting neurotransmitters (acetylcholine, dopamine, serotonin, and GABA), enkephalins, and neurotrophins, micronutrients, chronic and acute inflammation, encephalopathy, cerebral ischemia, and neurodegeneration (including demyelination) was described. The most typical neurological manifestations of COVID-19 were anosmia/ageusia due to ischemia, neurodegeneration, and/or systematic increases in proinflammatory cytokine levels. COVID-19 provoked ischemic stroke, Guillain-Barré syndrome, polyneuropathy, encephalitis, meningitis, and parkinsonism. Coronavirus infection increased the severity of multiple sclerosis and myopathies. The possible roles of the human virome in the pathophysiology of COVID-19 are considered. A clinical case of a patient with neurological complications of COVID-19 is described. Conclusions. In the long-term perspective, COVID-19 promotes increases in neurodegenerative changes, which requires special neurological rehabilitation programs. Use of cholinergic drugs and antihypoxic agents compatible with COVID-19 therapy is advised.

Surface characterization and biological assessment of corrosion-resistant a-C:H:SiOx PACVD coating for Ti-6Al-4V alloy.

The paper focuses on the SiOx-doped amorphous hydrocarbon (a-C:H:SiOx) coating on the titanium (Ti-6Al-4V) alloy substrate obtained by plasma-assisted chemical vapor deposition (PACVD) in a mixture of argon gas and polyphenylmethylsiloxane vapor using a bipolar substrate bias. It is shown that the a-C:H:SiOx coating deposition results in the formation of a negative surface potential important for application of this coating for medical implants. The a-C:H:SiOx coatings improve the corrosion resistance of Ti alloy to 0.5 M NaCl solution and phosphate-buffered saline. In particular, the corrosion current density of the a-C:H:SiOx-coated sample in a 0.5 M NaCl solution at 22 °C decreases from 1∙10-8 to 1.7∙10-10 A/cm2, that reduces the corrosion rate from 9∙10-5 to 15∙10-7 mm/year. The a-C:H:SiOx coating facilitates the surface endothelization of an implant located in the thoracic aorta of a mini pig, and reduces the risk of thrombosis and implant failure. This effect can be explained by the ability of the a-C:H:SiOx coating ability to reduce in vitro a 24-hour secretion of pro-inflammatory interleukins (IL-6, IL-12(p70), IL-15, and IL-17) and cytokines (IFN-g and TNF-a) by blood mononuclear cells (MNCs) and elevates the concentration of anti-inflammatory interleukin IL-1Ra. In vitro analysis shows no cytotoxicity of the a-C:H:SiOx coating for the human blood MNCs, suggesting a promising PACVD on Ti alloys for cardiovascular implants, including pumps for mechanical heart support systems.

[Direct and indirect neurological manifestations of COVID-19]. / O pryamykh i kosvennykh nevrologicheskikh proyavleniyakh COVID-19.

OBJECTIVE: To systemize the neurological manifestations of COVID-19. MATERIALS AND METHODS: A systematic computer analysis of all currently available publications on the neurological manifestations of COVID-19 (2374 publications in PUBMED) using algorithms of topological data analysis was performed. RESULTS: A complex of interactions between SARS-CoV-2 infection, metabolic disorders of neurotransmitters (acetylcholine, dopamine, serotonin and GABA), enkephalins and neurotrophins, micronutrients, chronic and acute inflammation, encephalopathy, cerebral ischemia and neurodegeneration, including demyelination, was described. The most common neurological manifestation of COVID-19 is anosmia/ageusia arising as a result of ischemia, neurodegeneration, and/or systemic elevation of proinflammatory cytokine levels. COVID-19 provokes ischemic stroke, Guillain-Barré syndrome, polyneuropathy, encephalitis, meningitis and parkinsonism. Coronavirus infection significantly aggravates the course of multiple sclerosis and myopathies. Possible roles of the human virome in the neuropathophysiology of COVID-19 are considered. A case of clinical management of a patient with neurological complications of COVID-19 is described. CONCLUSION: In the long term, COVID-19 stimulates neurodegenerative changes, which require specific programs of neurological rehabilitation. It is advisable to use choline drugs and antihypoxants that are compatible with COVID-19 therapy.

[Choice of neuroprotective therapy regimens in patients with chronic cerebral ischemia, taking into account the synergy of drug interactions]. / Vybor neiroprotektivnoi terapii u patsientov s khronicheskoi ishemiei golovnogo mozga s uchetom sinergizma lekarstvennykh vzaimodeistvii.

OBJECTIVE: Optimization of the choice of neuroprotective treatment regimens in patients with chronic cerebral ischemia that takes into account the synergy of drug interactions gives the doctor an opportunity for personalized approach that increases the effectiveness of treatment. MATERIAL AND METHODS: Differential chemoreactomic analysis of the synergism of ethyl methyl hydroxypyridine succinate (EMHPS) and a number of monocomponent neuroprotective agents (piracetam, vinpocetine, citicoline, choline alfoscerate); proteomic analysis of polypeptide neuroprotectors (cerebrolysin, etc.); an expert analysis of multicomponent neuroprotector Cytoflavin. RESULTS: Piracetam, citicoline (Neupilept) and choline alfoscerate (Cereton) effectively enhance the pharmacological properties of EMHPS and vice versa. Expert assessments of the synergism between the properties of EMHPS, polypeptide neuroprotectors (cerebrolysin) and other multicomponent drugs (cytoflavin), which are also used in adjuvant therapy with EMHPS, are presented. CONCLUSION: In real clinical practice, of particular interest is the objectification of the appointment of combined therapy regimens. This study indicates that EMHPS can provide a favorable background for maximizing the effectiveness of therapy when used with other drugs.

[Experience with mexidol in neurological practice]. / Opyt primeneniia meksidola v nevrologicheskoi praktike.

Antihypoxic, antioxidant and nootropic effects of mexidol contribute to the improvement of patients with cerebrovascular pathology. The results of clinical studies show that the sequential scheme of using mexidol (first i.v. or i.m., then per os) is effective in the complex therapy of ischemic diseases of the brain, vascular surgery, therapy and rehabilitation of patients with degenerative-dystrophic changes of the spine, treatment of neurodegenerative pathology (including multiple sclerosis, Parkinson's disease and diabetic polyneuropathy), infectious neuropathies (ARVI, herpes, tick-borne encephalitis), neuropsychological and autonomic disorders.

[Deficit of Magnesium and States of Hypercoagulation: Intellectual Analysis of Data Obtained From a Sample of Patients Aged 18-50 years From Medical and Preventive Facilities in Russia].

The states characterized by pronounced hypercoagulable components (deep vein thrombosis, cardio- and cerebro-vascular pathologies) are caused by multiple pathophysiological factors, including insufficient supply of magnesium (Mg) and other micronutrients. AIM: to present results of analysis of the Institute of Microelements Data Base (IMDB) performed from point of view of interrelationships of Mg deficit and hypercoagulable states in adults treated in medico-preventive facilities of Central, Northwestern, Northern, and Siberian federal districts of Russia. METHODS: The analysis was realized as analysis of data obtained in a cross-sectional study. In the cohort of patients (n=1453) formed from the IMBD adequacy of Mg supply was assessed by magnesium levels in blood plasma (Mg BP) (0.69±0.15 mmol/L) and estimates of daily Mg consumption according to dietary diaries (Mg D) (185±90 mg/day). RESULTS: Mg supply was adequate (Mg BP >0.80 mmol/L, Mg D >300 mg/day) in not more than 6 % of patients. Presence of "Hypercoagulation" label in data base was associated with greater number of chronic diseases (2.3±2.1 and 0.83±0.8 with and without this label, respectively, р=0.0006) and elevated risk of the presence on 4 comorbid pathologies (odds ratio [OR] 18, 95 % confidence interval [CI] 10-25, р=0.0006). Mg deficit (Mg BP.

Decrease in Bcl-2 Protein Level during the Development of Lewis Carcinosarcome.

We studied the development of Lewis carcinoma and possible antitumor effect of preliminary administered antioxidant anphen. The tumor was intramuscularly transplanted to C57Bl×DBA mice (7×106 cells per mouse). According to immunoblotting results, the content of anti-apoptotic Bcl-2 protein steadily decreased starting from post-transplantation day 11. In few days, its content decreased by 15-20% and soon the animals died. After administration of anphen, the content of Bcl-2 decreased more rapidly than in the control. Atomic force microscopy revealed a decrease in the mean volume of erythrocytes and then increase in this parameter at the terminal stage of tumor growth. These findings suggest that anphen does not affect the tumor growth rate and mouse lifespan, but enhances apoptosis of blood cells of animals with Lewis carcinoma at the terminal stages of tumor growth.

Deficit of Magnesium and States of Hypercoagulation: Intellectual Analysis of Data Obtained From a Sample of Patients Aged 18-50 years From Medical and Preventive Facilities in Russia.

The states characterized by pronounced hypercoagulable components (deep vein thrombosis, cardio- and cerebro-vascular pathologies) are caused by multiple pathophysiological factors, including insufficient supply of magnesium (Mg) and other micronutrients. AIM: to present results of analysis of the Institute of Microelements Data Base (IMDB) performed from point of view of interrelationships of Mg deficit and hypercoagulable states in adults treated in medico-preventive facilities of Central, Northwestern, Northern, and Siberian federal districts of Russia. METHODS: The analysis was realized as analysis of data obtained in a cross-sectional study. In the cohort of patients (n=1453) formed from the IMBD adequacy of Mg supply was assessed by magnesium levels in blood plasma (MgBP) (0.69±0.15 mmol/L) and estimates of daily Mg consumption according to dietary diaries (MgD) (185±90 mg/day). RESULTS: Mg supply was adequate (MgBP >0.80 mmol/L, MgD >300 mg/day) in not more than 6% of patients. Presence of "Hypercoagulation" label in data base was associated with greater number of chronic diseases (2.3±2.1 and 0.83±0.8 with and without this label, respectively, р=0.0006) and elevated risk of the presence on 4 comorbid pathologies (odds ratio [OR] 18, 95% confidence interval [CI] 10-25, р=0.0006). Mg deficit (MgBP.

[INTERACTION OF GLUTAMATE AND GABA RECEPTORS IN THE CENTRAL NERVOUS SYSTEM].

The article provides an overview of postsynaptic interaction of GABA and glutamate receptors in central neurons. Co-localization of GABA and glutamate in synapses, structure and function of their receptors and interaction of both ionotropic and metabotropic glutamate and GABA receptors are being discussed.

Effect of Monocyte-Like THP-1 Cells on the Formation of Vascular Tubes by EA.Hy926s Endothelial Cells in the Presence of Cytokines.

The interaction of endothelial cells with cells of the microenvironment, including monocytes/ macrophages, and extracellular matrix during angiogenesis is controlled by cytokines. The stimulating effect bFGF, IL-8, and VEGF on the formation of capillary-like structures by endothelial cells was demonstrated in both monoculture and in co-culture with THP-1 cells; in the latter case, the effects of bFGF and VEGF were more pronounced. IL-8 reduced branching of vascular tubes in co-culture in comparison with monoculture of endothelial cells. Placental growth factor PlGF had no effect of tube formation by endothelial cells in monoculture, but in co-culture with THP-1 cells this cytokine in high concentrations exhibited proangiogenic activity. TGFb inhibited the formation of vascular tubes by endothelial cells and its antiangiogenic potential was more pronounced in co-culture with THP-1 cells.

[Diagnostics of magnesium deficiency and measurements of magnesium concentrations in biosubstrates in norm and in various pathologies].

In accordance with the evidence from large-scale studies magnesium deficiency has a significant negative impact on the cardiovascular system, carbohydrate and fat metabolism. Diagnosis of magnesium deficiency should be based on clinical symptoms of magnesium deficit and confirmed by additional diagnostic methods--ECG myography, bone densitometry, and quantitative determination of magnesium in various biosubstrates (whole blood, red blood cells, plasma, serum, saliva, urine, nails, hair). It is also desirable to estimate dietary intake of magnesium according to food frequency questionnaires verified by measurements of magnesium in blood. Analysis of magnesium content in blood and other biosubstrates allows to establish those perturbations of compartmentalization of magnesium in tissues that are typical for a particular pathology. It is important to emphasize that one should not confuse values of magnesium levels measured in serum and in plasma as it leads to serious errors in the diagnosis of magnesium deficiency and results in underdiagnosis of magnesium deficiency (code E61.2 of ICD-10).

[Diagnosis of mixed tick-borne encephalitis and tick-borne borreliosis in the early stages of the disease].

The paper describes a method of prognosis for the possible development of mixed tick-borne encephalitis and borreliosis based on a comparison of clinical manifestations of the disease and results of laboratory tests.

[Effect of oregano essential oil on the engraftment and development of Lewis carcinoma in F1 DBA C57 black hybrid mice].

The effect of a low uptake dose of oregano essential oil with drinking water for three months (Origanum vulgare L.) on the degree of Lewis carcinoma engraftment and some parameters of oxidative stress has been studied in vivo using F1 DBA C57 Black hybrid mice. Oregano essential oil has been established to possess an anticancer activity. The degree of tumor engraftment decreased by 1.8 times, its size decreased by 1.5 times, and the development of tumor was significantly suppressed in sick mice under the effect of oregano essential oil. It was found that the uptake of essential oil did not affect the intensity of lipid peroxidation in the brain of mice and resulted in a significantly (by 36%) decreased content of secondary lipid oxidation products in the liver as shown in a reaction with thiobarbituric acid as compared to control subjects. The activity of antioxidant enzymes was found to increase after three months of essential oil uptake (by 1.5-3 times) as compared to the control group. This effect of essential oil supports the presence of bioantioxidant properties in this essential oil.

High-power picosecond laser pulse recirculation.

We demonstrate a nonlinear crystal-based short pulse recirculation cavity for trapping the second harmonic of an incident high-power laser pulse. This scheme aims to increase the efficiency and flux of Compton-scattering-based light sources. We demonstrate up to 40x average power enhancement of frequency-doubled submillijoule picosecond pulses, and 17x average power enhancement of 177 mJ, 10 ps, 10 Hz pulses.

Isotope-specific detection of low-density materials with laser-based monoenergetic gamma-rays.

What we believe to be the first demonstration of isotope-specific detection of a low-Z and low density object shielded by a high-Z and high-density material using monoenergetic gamma rays is reported. The isotope-specific detection of LiH shielded by Pb and Al is accomplished using the nuclear resonance fluorescence line of L7i at 478 keV. Resonant photons are produced via laser-based Compton scattering. The detection techniques are general, and the confidence level obtained is shown to be superior to that yielded by conventional x-ray and gamma-ray techniques in these situations.

[The effect of volatile antioxidants of plant origin on leukemogenesis in mice].

The effect of savory essential oil added with drinking water (150 ng/ml) or with feed (2.5 microg/g) on the lifetime of AKR mice and the parameters of oxidative stress in animal blood were investigated. It was found for the first time that long-term administration of an essential oil in low doses increased the average lifetime of mice by 20-35% and was accompanied by a decrease in the hemolysis level and the content of lipid peroxidation products in erythrocytes of mice, as well as alteration in the structural state of their membranes and stabilization of polyunsaturated fatty acids level in mice liver cells.

[Effect of antioxidant beta-(4-hydroxy-3,5-ditertbutylphenyl) propionic acid (phenosan) on the development of malignant neoplasms].

The effect of different doses of synthetic antioxidant beta-(4-hydroxy-3,5-ditertbutylphenyl)propionic acid (phenosan) on the development of spontaneous leukemia in AKR mice was studied. The drug efficiency was determined from the survival curves, animal life spans, and the incidence of leukemia. Phenosan exhibited a pronounced antitumor activity at therapeutic (10(-4) mol/kg, 4 administrations) and ultra-low (10(-14) mol/kg, 4 administrations) doses. The dose of 10(-4) mol/kg proved most efficient to increase the life span of the shortlived subpopulation, while the dose of 10(-14) mol/kg increased the life span of the long-lived subpopulation. The ultra-low dose of the drug seems promising as a prophylactic agent.

[Diagnosis, prevention and treatment of renal lesion in extracorporeal shock wave lithotripsy].

The diagnosis and treatment of 120 patients with urolithiasis were made. The following examinations were made: the study of immune status and lipid peroxidation, detection of selective proteinuria, leukocyte migration inhibition reaction with autoantigens obtained from the tissues of the renopelvic segment providing additional information about renal parenchyma and immune system. The patients were divided into two groups: 70 patients of the study group received pre-, intra- and postoperative preventive pharmacotherapy, while 50 patients of the control group received standard therapy. It is shown that preventive measures in the patients of the study group aimed at raising resistance of the kidney to the shock wave and prevention of infectious-inflammatory process evidence for necessity of the above measures not only before extracorporeal shock wave lithotripsy, but also in intra- and postoperative periods.

[Effect of low-level irradiation on incidence rate and development of malignant neoplasms].

Low-level irradiation (1.2-2.4 cGy, dose-rate 0.6 cGy/day) leads to a significant acceleration of the development of spontaneous leukosis in AKR mice: decrease in the average and the maximum life-span of animals leukosis-carriers (by 20 and 120 days, respectively) and an increase in the leukosis incidence rate (%). The introduction of antioxidant phenozan (beta-(4-hydroxy-3,5-ditertbutylphenyl) propionic acid) results in a considerable antileukosis effect: the average life-span increases by more than 40 days and the leukosis incidence rate decreases by 6%.