[Neurofilament light chain: a diagnostic potential for multiple sclerosis]. / Neirofilament legkikh tsepei: diagnosticheskie vozmozhnosti pri rasseyannom skleroze.

OBJECTIVE: To evaluate the influence of disease activity, the degree of patient disability and pathogenetic therapy on the concentration of neurofilament light chain (NFL) in the blood serum of patients with multiple sclerosis (MS). MATERIAL AND METHODS: One hundred and fourteen patients (84 women and 30 men) with definite MS were examined. The concentration of NFL in the blood serum of patients with MS was determined by enzyme immunoassay. The level of NFL was analyzed depending on the characteristics of the course and activity of the demyelinating process, the severity of neurological disorders as well as disease modifying drugs (DMDs). RESULTS: An NFL level equal to or greater than 4201 pg/ml was found to be associated with a higher risk of developing a clinical exacerbation in the next 4 months. In patients with progression of disability over the next 2 years, the initial concentration of NFL was significantly higher than in the group with a stable EDSS score. The NFL level (4943 pg/ml and higher), which may be a predictor of increased disability in the next two years, was established. CONCLUSION: The study demonstrates the possibility of using serum NFL levels as a diagnostic marker of possible exacerbation, as well as predicting disability in patients with MS.

Anti-Inflammatory Effect of Technologically Processed Antibodies to the Molecules of the Major Histocompatibility Complex in a Model of Acute Inflammation In Vivo.

The anti-inflammatory effect of technologically processed antibodies (TPA) to immune targets (MHC I and MHC II) was assessed in the carrageenan-induced rat paw edema model. The parameters "increase in edema" and "suppression of edema" significantly decreased (p<0.05) against the background of treatment with TPA and the reference drug indomethacin compared to the placebo group. The tested TPA produced an anti-inflammatory effect.

Female and Male Phenotypes of Iron Deficiency in CHF. Additional analysis of the «The Prevalence of Iron Deficiency in Patients With Chronic Heart Failure in the Russian Federation (J-CHF-RF)¼ study.

Aim    To evaluate the incidence of iron deficiency (ID) in men and women with chronic heart failure (CHF) and to compare clinical and functional indexes in patient with and without ID depending on the gender.Material and methods    An additional analysis of the study "Prevalence of Iron Deficiency in Patients With Chronic Heart Failure in the Russian Federation (ID-CHF-RF)" was performed. The study included 498 (198 women, 300 men) patients with CHF, in whom, in addition to iron metabolism, the quality of life and exercise tolerance (ET) were studied. 97 % of patients were enrolled during their stay in a hospital. ID was defined in consistency with the European Society of Cardiology (ESC) Guidelines. Also, and additional analysis was performed according to ID criteria validated by the morphological picture of the bone marrow.Results    ID was detected in 174 (87.9 %) women and 239 (79.8 %) men (p=0.028) according to the ESC criteria, and in 154 (77.8 %) women and 217 (72.3 %) men (p=0.208) according to the criteria validated by the morphological picture of the bone marrow. Men with ID were older and had more severe CHF. They more frequently had HF functional class (FC) III and IV (63.4 % vs. 43.3 % in men without ID); higher concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and lower ET. HF FC III increased the probability of ID presence 3.4 times (p=0.02) and the probability of HF FC IV 13.7 times (p=0.003). This clinical picture was characteristic of men when either method of determining ID was used. In women, ID was not associated with more severe CHF.Conclusion    Based on the presented analysis, it is possible to characterize the male and female ID phenotypes. The male ID phenotype is associated with more severe CHF, low ET, and poor quality of life. In females of the study cohort, ID was not associated with either the severity of CHF or with ET.

Prevention of the Genotoxic Effects of Doxorubicin with Anthocyanin-Containing Complex from Sorbus aucuparia L. Fruit.

We studied the effect of an anthocyanin-containing complex from the fruits of S. aucuparia L. on doxorubicin-induced genotoxicity in bone marrow cells of C57BL/6 mice. The complex reduced the genotoxic effect doxorubicin in metaphase plates of bone marrow cells in 24, 48 h, and 10 days after the administration of the cytostatic. The mean number of single fragments and the fraction of cells with gaps and aberrant metaphases also decreased.

Hypolypidemic Activity of L-Rhamnopyranosyl-6-O-Methyl-D-Galacturonan, a Polysaccharide Isolated from Birch Leaves (Betula pendula L.).

In male Syrian hamsters fed a synthetic high-fat diet enriched with cholesterol (0.3%), administration of a polysaccharide from birch leaves L-rhamnopyranosyl-6-O-methyl-D-galacturonan (3 g/100 g of diet) resulted in a decrease in total cholesterol levels, mainly due to the LDL fraction, triglycerides, and bile acids in blood serum; the content of triglycerides and cholesterol in the liver also decreased, while excretion of bile acids with feces increased. Thus, the lipid-lowering effect of L-rhamnopyranosyl-6-O-methyl-D-galacturonan is related to its ability to bind bile acids in the intestine and interrupt their enterohepatic circulation.

Restructuring of the Optokinetic Reflex during Metamorphosis in Pelobates fuscus Laur.

The restructuring of the gaze stabilization system in Pelobates fuscus was investigated by quantitative analysis of the optomotor response using video imaging. Gaze stabilization is an important component in the system of neural mechanisms of visual depth perception. It was shown that the optomotor response in aquatic tadpoles of P. fuscus is similar to that of fish (movement of the animal in the direction of the visual background movement and eye nystagmus consisting of a fast and a slow phase). During metamorphosis (transition from the aquatic to the terrestrial lifestyle), froglets of P. fuscus responded to the movement of the visual background by eyes and head movements. One year after metamorphosis, P. fuscus responded to movement of the visual background as adult Anura: only by head movements (a slow and a fast phase), while eye movements were absent. Possible causes of the loss of active eye movements by Anura amphibians in the process of evolution are discussed.

Erythropoiesis-Stimulating Properties of Anthocyanin-Containing Complex from Sorbus aucuparia L. in Cytostatic Anemic Syndrome in Mice with Lewis Lung Carcinoma.

The results of studying the effect of the anthocyanin-containing complex from Sorbus aucuparia L. on the main indicators of erythropoiesis in the blood and bone marrow of mice with Lewis lung carcinoma against the background of doxorubicin administration were presented. It was shown that administration of the anthocyanin-containing complex from S. aucuparia L. to animals with the tumor prevented the development of anemic syndrome by promoting regeneration of the erythropoiesis after its depletion caused by single administration of a cytostatic agent.

[Iron deficiency in Russia heart failure patients. Observational cross-sectional multicenter study].

Aim    To evaluate the prevalence of iron deficiency (ID) in Russian patients with heart failure (HF).Material and methods    Iron metabolism variables were studied in 498 (198 women, 300 men) patients with HF. Data were evaluated at admission for HF (97 %) or during an outpatient visit (3 %). ID was determined according to the European Society of Cardiology Guidelines.Results    83.1 % of patients had ID; only 43.5 % of patients with ID had anemia. Patients with ID were older: 70.0 [63.0;79.0] vs. 66.0 years [57.0;75.2] (p=0.009). The number of patients with ID increased in parallel with the increase in HF functional class (FC). Among patients with ID, fewer people were past or current alcohol users (p=0.002), and a greater number of patients had atrial fibrillation (60.1 vs. 45.2 %, p=0.016). A multiple logistic regression showed that more severe HF (HF FC) was associated with a higher incidence of ID detection, whereas past alcohol use was associated with less pronounced ID. An increase in N-terminal pro-brain natriuretic peptide (NT-proBNP) by 100 pg/ml was associated with an increased likelihood of ID (odds ratio, 1.006, 95 % confidence interval: 1.002-1.011, p=0.0152).Conclusion    The incidence rate of HF patients is high in the Russian Federation (83.1 %). Only 43.5 % of these patients had anemia. The prevalence of ID in the study population increased with increases in HF FC and NT-proBNP.

The impact of the Hsp67Bc gene product on Drosophila melanogaster longevity, fecundity, and acute heat stress tolerance.

Drosophila melanogaster Hsp67Bc is a heat- and cold-inducible small heat shock protein that participates in the prevention of aggregation of misfolded proteins and in macroautophagy regulation. Overexpression of the Hsp67Bc gene has been shown to enhance macroautophagy in Drosophila S2 cells, and the deletion of this gene leads to the formation of a slightly increased number of autophagic vacuoles in the fruit f ly brain neurons. Recently, we found that Hsp67Bc-null D. melanogaster f lies have poor tolerance to cold stress (0 °C) of various durations. In the present work, we investigated how the Hsp67Bc gene deletion affects the f itness of fruit f lies under normal conditions and their tolerance to elevated temperatures at different developmental stages. Larvae and pupae were not adversely affected by the Hsp67Bc gene deletion, and adult Hsp67Bc-null f lies showed an extended lifespan in comparison with the control at normal (24-25 °C) and elevated temperature (29 °C), and after acute heat stress (37 °C, 2 h). At the same time, the fecundity of the mutant females was lower by 6-13 % in all tested environments, except for permanent maintenance at 29 °C, where the mean numbers of eggs laid by the mutant and control f lies were equal. We explain this phenomenon by a reduced number of ovarioles in Hsp67Bc-null females and enhanced macroautophagy in their germaria, which promotes the death of forming egg chambers. In addition, short heat stress (37 °C, 2 h), which increased the control line's longevity (an effect common for a wide range of organisms), had a negative impact on the lifespan of Hsp67Bc-null f lies. Therefore, Hsp67Bc-null D. melanogaster have an extended lifespan under normal and elevated temperature conditions, and reduced fecundity and thermal stress tolerance.

Antinociceptive Effect of Ethowurtzine, a New Compound from the Class of Hexaazaizowurzitane.

Analysis of specific pharmacological activity evaluated high antinociceptive efficacy of the first synthesized compound 10-di(ethoxyacetyl)-2,6,8,12-tetraacetyl-2,4,6,8,10,12-hexaazatetracyclo[5,5,0,03,11,05,9]dodecane (ethowurtzine) in models of somatogenic pain of different genesis (thermal, visceral pain, mechanical compression of paw).The new molecule from the class of hexaazaisowurtzitane effectively blocks nociceptive reactions at the supraspinal and peripheral levels of pain sensitivity organization. The effect of ethowurtzine was comparable or exceeded the effect of tramadol. The obtained results prove the possibility of creating new pharmacologically active molecules based on the high-energy substance hexaazaisowurtzitane.

[Study of the structure and microflora of urethral tissues in urethral pain syndrome].

Urethral pain syndrome (UPS) is characterized by the occurrence of persistent or recurrent pain in the urethra in the absence of a confirmed infection and other obvious local pathological changes. The study of its pathogenetic aspects is important first of all for understanding the causes of the disease, to prescribe effective treatment, specific recommendations for the prevention and treatment of this disease are also absent. This paper presents the advanced experience of our research group on the study of the urethral state by the in vivo cross-polarization optical coherence tomography (CP OCT) method, and also the results of the microbiota analysis in the urethral tissues. The purpose of the study is to search for the risk factors for UPS and the character of changes in the urethral tissues, using the data of: 1) concomitant pathology, 2) structural changes in the urethral wall in UPS in comparison with chronic cystitis of bacterial etiology 3) studying the microbiota of urethral tissues. MATERIALS AND METHODS: The condition of the urethra was studied in 109 patients: 55 of them with UPS (group "US"), without clinical manifestations of inflammation; 41 - with chronic inflammation of the lower urinary tract of various origins (group "Inf"); in 14 patients with stones of the upper urinary tract without pyelonephritis, the urethra was taken as the norm (group "N"). All performed a clinical minimum of studies, also cystoscopy with the study of the bladder triangle, the neck of the bladder and the urethra by the method of in vivo tissue imaging - CP OCT. The device "OCT-1300U" with wavelength of 1300 nm is used. To determine the possible role of UPS disease background, the analysis of concomitant pathology preceding the development of UPS was performed. To analyze the relationship of changes in the urethral tissues with the composition of its microbiota, a PCR study of biopsies from the proximal segment of the urethra was performed in 13 patients with UPS. RESULTS: Qualitative comparison of the thickness and character of the OCT signal of the urethral wall layers observed using CP OCT in the studied groups of patients allowed us to establish that the state of the epithelium and connective tissue structures of the mucous membrane in patients with UPS is not the norm, changes are similar to those in chronic inflammation. Changes in the character of the OCT signal were recorded in all parts of the urethra, but in the middle third they are most pronounced and most critical. In UPS, there is a brightly pronounced reorganization of the connective tissue stroma components. Pronounced fibrosis of subepithelial structures (increased signal brightness in the cross-channel compared to the norm) with their thickening was recorded in 48.2% of cases, and thinning/lack of visualization of the epithelial layer was detected in 20.5%, and in chronic inflammation 55.5% and 40.6% of cases, respectively. According to the results of PCR, only one patient had significant total bacterial contamination of the biopsy (TB=104.7). In all other cases, the total bacterial mass of the biopsies was at the level of negative control. CONCLUSIONS: In patients with UPS, the presence of several concomitant, often chronic, diseases was revealed, which may be a premorbid background and one of the risk factors for the occurrence and maintenance of UPS. Pilot PCR studies of biopsies from the proximal segment of the urethra indicate that low values of bacterial contamination in the majority of patients with UPS do not exclude the possible role of bacteria in the development of the disease in some patients. The CP OCT method used in this study is currently the only one in vivo method of visualization of the urethral mucosa, which provides real-time images of structural changes in the epithelial (atrophy or hyperplasia) and connective tissue (active or latent inflammation with cellular infiltration or fibrosis) layers of the urethra, allowing better understanding of the pathogenesis of the disease and monitoring of therapy.

Effect of Surgical Technique on the Microstructure and Microcirculation of the Small Intestine Stump during Delayed Anastomosis: Multimodal OCT Data.

The aim of the study was to use multimodal optical coherence tomography (MM OCT) to evaluate microstructure and microcirculation in the proximal and distal sections of the intestine relative to the resected area in acute mesenteric ischemia. MATERIALS AND METHODS: The study was carried out using three groups of male Wistar rats weighing 270-435 g (n=18). Acute occlusive arterial ischemia of the small intestine was initiated in all animals. After 80-90 min, the ischemic non-viable part of the intestine was resected, and the operation was completed by stoma exteriorization (group 1, n=6), by applying purse-string sutures (group 2, obstructive resection, n=6), or by internal drainage of the proximal and distal ends of the small intestine (group 3, bypass, n=6). Relaparotomy and anastomosis formation were performed 2 days later.With the help of MM OCT at each stage of the surgical intervention, images were obtained from the serous membrane side: the intestinal wall microstructure (layers) was viewed using cross-polarization OCT (CP OCT) and the intramural circulation - using optical coherent angiography (OCA). The MM OCT images obtained from the terminal intestine sections immediately after resection and 2 days later (before the anastomosis formation) were compared between the experimental groups, as well as with the pre-ischemic data (norm). All resected sections of the intestine were then histologically examined. The MM OCT data were compared with the histological and intravital macroscopy data. RESULTS: As a result of studying the intestinal wall microstructure by in vivo CP OCT, it was found that during ostomy (group 1) and obstructive resection (group 2), the images showed signs of tissue edema and destructive changes in the mucous membrane that were confirmed histologically, while with bypass surgery (group 3), there were minimal changes as compared with the norm.According to the OCA data, on day 2 of ostomy in the proximal and distal segments of the intestine, there was a noticeable disappearance of small and medium blood vessels; mainly large arteries and veins could be visualized. Following obstructive resection (purse-string suturing) or bypass surgery, the most noticeable changes (a decrease in the number of visualized blood vessels) were observed in the distal part of the intestine. The L index calculated from OCA images and characterizing the total length of the intramural perfused vasculature, showed a statistically significant decrease during ostomy: 12.18 [10.40; 14.20] µm - in the proximal and 10.67 [7.98; 13.05] µm - in the distal section; for comparison, the L index before ischemia was 18.90 [17.98; 19.73] µm and 18.74 [17.46; 19.90] µm, respectively (p=0.0001). In obstructive resection (group 2), statistically significant differences in the L parameter were found only for the distal bowel section: 16.39 [12.37; 18.10] µm compared with 18.74 [17.46; 19.90] µm before ischemia (p=0.041). After bypass surgery (group 3), there were no significant deviations in the L index. CONCLUSION: By using MM OCT, we found that in treating the remaining sections of the intestine after its emergency resection for acute mesenteric ischemia, the type of surgical technique determines the tissue structure in the period before the delayed anastomosis is applied.The least pronounced and most balanced changes occur in the proximal and distal segments of the intestine when operated using the bypass technique. However, to recommend this type of surgery, the development of reliable, safe, and effective bypass instruments is needed.

[The social health of citizen of the Eurasian Economic Union in conditions of COVID-19 pandemic].

The article considers, on the basis of results of sociological research, consequences of pandemic impact on social health of citizens of the Eurasian Economic Union states. The comparative analysis was applied to two groups of labor migrants from the EAEU states in Moscow and Russian citizens of the same age. The measures taken by the EАEU to maintain population social health in conditions of COVID-19 pandemic are considered.

[Homocysteine and markers of endothelial dysfunction in multiple sclerosis]. / Gomotsistein i markery endotelial'noi disfunktsii pri rasseyannom skleroze.

OBJECTIVE: To identify hyperhomocysteinemia and to assess its possible association with the course and other markers of endothelial damage in multiple sclerosis. MATERIAL AND METHODS: Analysis of blood serum for homocysteine, for the content of adhesion molecules sPECAM-1, matrix metalloproteinase 9, blood plasma test for von Willebrand factor antigen in patients with multiple sclerosis. The values of these indicators were analyzed depending on the course and activity of the demyelinating process, the severity of neurological disorders, as also depending on the therapy received. RESULTS: Hyperhomocysteinemia was found in more than half of patients with multiple sclerosis. A significantly higher homocysteine level was found in male patients, and hyperhomocysteinemia was associated with the activity of the process in patients with highly active multiple sclerosis. CONCLUSION: The results of the study suggest a possible association of hyperhomocysteinemia with high process activity and disease progression, as well as with mechanisms of neurodegeneration. Determination of homocysteine concentration may be one potential marker for predicting the course of the disease.

[Social health of the citizens of the States of the Eurasian Economic Union in the context of the COVID-19 pandemic].

Based on the results of sociological research, the article considers the consequences of the pandemic on the social health of citizens of the Eurasian Economic Union (EAEU) states. A comparative analysis is carried out between groups of labor migrants from the EAEU states in Moscow and Russian citizens of the same age. The paper discusses the measures taken by the EАEU, for the maintenance of social health in terms of the COVID-19 pandemic crisis.

Erythropoesis-Stimulating Properties of Anthocyanin-Containing Complexes in Cytostatic Anemic Syndrome.

We studied the effect of an anthocyanin-containing complex from Sorbus aucuparia L. on the main indicators of erythropoiesis in the blood and bone marrow of mice against the background of doxorubicin treatment. It was shown that administration of an anthocyanincontaining complex from S. aucuparia L. prevented the development of anemic syndrome by stimulating regeneration of the erythroid lineage of hematopoiesis after its devastation by single administration of the cytostatic.

[Thrombosis of the inferior vena cava and right portions of the heart in a relapsing retroperitoneal malignant tumour]. / Tromboz nizhnei poloi veny i pravykh otdelov serdtsa pri retsidivnoi zabriushinnoi zlokachestvennoi opukholi.

Presented herein is a clinical case report regarding successful treatment of a female patient with a relapsing malignant retroperitoneal tumour complicated by disseminated thrombosis of the inferior vena cava, right atrium and right ventricle of the heart. A relapse of the malignant uterine tumour had developed 3 years after the primary operation and was represented by a large-size mass ingrowing into the infrarenal segment of the inferior vena cava, aorta, as well as jejunum. Additional examination revealed the presence of a tumorous thrombus extending from the primary tumorous node in the lumen of the inferior vena cava to the right atrium and ventricle. The procedures performed consisted in removal of the tumour with resection of the inferior vena cava, aorta, and jejunum, followed by thrombectomy from the right portions of the heart under extracorporeal circulation. The postoperative period turned out uneventful, with no complications observed. The woman was discharged on POD 15. Twelve-month postoperative follow up revealed neither relapse nor progression of the disease. Currently, the patient continues undergoing specific treatment (second-line chemotherapy). Also discussed in the article are current challenges concerning both the classification of tumour thrombosis of the inferior vena cava in retroperitoneal sarcomas, and the choice of optimal strategy and policy of treatment.

Semaphorin-3A Inhibits Proliferation, but Does Not Affect Apoptosis of Mouse Thymocytes In Vitro.

Neuronal factor semaphorin-3A is viewed as immune suppressant of peripheral T lymphocytes, but it can also negatively affect activity of the thymus, the central organ of the immune system. The study examined the effects of this factor on proliferative activity and apoptosis of mouse thymocytes in vitro. Semaphorin-3A inhibited spontaneous and mitogen-stimulated proliferative activity of thymocytes producing no effect on the development of apoptosis in these cells. Flow cytometry revealed expression of semaphorin-3A receptors neuropilin-1 and plexin-A1 on thymocyte membranes. Approximately 13% thymocytes simultaneously expressed both receptors. The study suggests that semaphorin-3A, which is constitutively synthesized in thymic stroma in vivo, can play the role of inhibitory factor during thymocyte maturation.

Trans-Serosal Multimodal Optical Coherence Tomography for Visualization of Microstructure and Blood Circulation of the Small Intestine Wall.

The aim of the study was to evaluate the performance of trans-serosal multimodal OCT (MM OCT) in in vivo detecting of changes in microstructure and blood circulation of the small intestine wall caused by arteriovenous ischemia resulted from intestine strangulation. MATERIALS AND METHODS: In experiments on Wistar rats (n=22), we examined the small intestine wall in vivo using MM OCT; the access to the intestine was reached through laparotomy. The microvasculature and microstructure of the wall were studied before and after acute arteriovenous ischemia created by ligation of a small bowel segment. The results were then added with data obtained from histological and intravital microscopic examination. RESULTS: Trans-serous MM OCT allowed us to visualize the bowel wall to its entire thickness, distinguish between the serous-muscular and mucous-submucosal layers, and detect the villi and functioning blood vessels. The structures were best seen after a fat emulsion had been administered into the bowel lumen. In OCT images made in the optical coherent angiography (OCA) mode, large paired vessels (arteries and veins) and micro-vessels with a diameter of >15 µm could be seen. Most of the blood vessels were imaged in the depth range of 80-300 µm from the surface. Capillaries with a diameter of 7-10 µm were not seen, but they produced an overall bright background. In the OCA images reconstructed from a volume of 2.4×2.4×1.8 mm, the total length of the vascular bed before ischemia was 18.3 [16.6; 19.8] mm.Strangulation of the intestinal loop was associated with changes in the CP OCT picture: the villi-associated vertical pattern and shadows of blood vessels disappeared and the depth of tissue visualization in the cross-channel decreased. The optical equivalents of the serous-muscular layer were preserved; after 180±12 min of ischemia, their proportion in the intestinal wall thickness increased from 25 [18; 32] to 42 [31; 55]% (p=0.031). At that time-point, OCA images of the strangulated bowel loop looked all similar: a uniform dark background with isolated fragmentary large vessels and no signs of blood flow in the microvascular network. CONCLUSION: Trans-serous MM OCT provides for in vivo visualization of microstructures critical for surgical gastroenterology: the intestinal wall layers including villi and blood vessels of each layer, as confirmed by histological analysis. Destructive processes in the intestinal wall resulting from bowel ligation bring about optical changes, which can be detected using real-time MM OCT.

Analgesic Activity of Hexaazaisowurtzitane Derivatives.

Pronounced analgesic activity of the innovative compound 4-(3,4-dibromthiophencarbonyl)-2,6,8,12-tetraacethyl-2,4,6,8,10,12hexaazatetracyclo[5,5,0,03, 11,05, 9] dodecane (thiowurtzine) was observed in the thermal nociceptive hot plate test and in the acute visceral and somatic deep pain model (acetic acid writhing test). In these experimental models, naloxone-sensitive thiowurtzine-induced analgesia was revealed. The absence of tropism to peripheral opioid receptors in the acetic acid writhing test was demonstrated using naloxone methiodide. Course administration of low-toxic thiowurtzine in effective doses was not associated with ulcerogenic damage to the gastric mucosa in experimental animals.