Synthesis and Aminomethylation of 2-Amino-4-(2-chlorophenyl)-6-(dicyanomethyl)-1,4-dihydropyridine-3,5-dicarbonitrile N-Methylmorpholinium Salt.

Sequential reaction of 2-chlorobenzaldehyde, cyanothioacetamide, and malononitrile dimer in the presence of an excess of N-methylmorpholine resulted in the formation of N-methylmorphlinium salt of 2-amino-4-(2-chlorophenyl)-6-(dicyanomethyl)-1,4-dihydropyridine-3,5-dicarbonitrile. The resulting salt reacts under Mannich conditions with primary amines and an excess of formaldehyde to form substituted 2-alkylamino-4-(dicyanomethylene)-3,7-diazabicyclo[3.3.1]non-2-ene-1,5-dicarbonitriles. Structure of the key compound was confirmed by single crystal X-ray diffraction analysis.

N,N'-Diphenyldithiomalonodiamide: Structural Features, Acidic Properties, and In Silico Estimation of Biological Activity.

The spectral characteristics of dithiomalondianilide (N,N'-diphenyldithiomalonodiamide) were studied, and the dissociation constant was determined by potentiometric titration. Quantum-chemical methods at the B3LYP-D3BJ/6-311+G (2d,p) level were used to calculate the molecular geometry and vibrational spectra of the most stable tautomeric forms of dithiomalondianilide. The bioavailability parameters were calculated, and possible protein targets were predicted by the protein ligand docking method.

A new insight into mechanisms of interferon alpha neurotoxicity: Expression of GRIN3A subunit of NMDA receptors and NMDA-evoked exocytosis.

Neurological and psychiatric side effects accompany the high-dose interferon-alpha (IFNA) therapy. The primary genes responsible for these complications are mostly unknown. Our genome-wide search in mouse and rat genomes for the conservative genes containing IFN-stimulated response elements (ISRE) in their promoters revealed a new potential target gene of IFNA, Grin3α, which encodes the 3A subunit of NMDA receptor. This study aimed to explore the impact of IFNA on the expression of Grin3α and Ifnα genes and neurotransmitters endo/exocytosis in the mouse brain. We administered recombinant human IFN-alpha 2b (rhIFN-α2b) intracranially, and 24 h later, we isolated six brain regions and used the samples for RT-qPCR and western blot analysis. Synaptosomes were isolated from the cortex to analyze endo/exocytosis with acridine orange and L-[14C]glutamate. IFNA induced an increase in Grin3α mRNA and GRIN3A protein, but a decrease in Ifnα mRNA and protein. IFNA did not affect the accumulation and distribution of L-[14C]glutamate and acridine orange between synaptosomes and the extra-synaptosomal space. It caused the more significant acridine orange release activated by NMDA or glutamate than from control mice's synaptosomes. In response to IFNA, the newly discovered association between elevated Grin3α expression and NMDA- and glutamate-evoked neurotransmitters release from synaptosomes implies a new molecular mechanism of IFNA neurotoxicity.

[Line immunoassay for detection of IgG antibodies to hepatitis E virus (Hepeviridae, Orthohepevirus, Orthohepevirus A)].

INTRODUCTION: The diagnostic efficacy of methods for hepatitis E serodiagnostic varies over a wide range; therefore, the combined use of tests of various formats is recommended. The aim of the research was to develop a test system for the detection of IgG antibodies to hepatitis E virus (HEV) in human serum by linear immunoassay (LIA). MATERIAL AND METHODS: Serum samples from patients with hepatitis and healthy individuals were tested using commercial enzyme-linked immunosorbent assay systems for the presence of IgG antibodies to viral agents causing hepatitis and other infections associated with liver pathology. Recombinant antigens ORF2 and ORF3 of HEV genotypes 1 and 3 were used. The "RecomLine HEV IgG/IgM" reagent kit (Mikrogen GmbH, Germany) was used as a comparison test system. RESULTS: The first Russian diagnostic kit "Blot-HEV", designed to detect IgG antibodies to individual HEV proteins in human serum using LIA, was developed. The antigenic base is represented by strips of a nitrocellulose membrane with immobilized recombinant antigens ORF2 (aa 406-660) and ORF3 (aa 1-113) of HEV genotypes 1 and 3, and control antigens in the form of discrete lines. The conjugate was mouse monoclonal antibodies to human class G immunoglobulins labeled with horseradish peroxidase. The chromogen solution contained the 3,3',5,5'-tetramethylbenzidine. A visual and digital recording of results was provided. The analytical sensitivity of the test kit was 0.625 IU/ml for ORF2 antigens and 2.5 IU/ml for ORF3 antigens. The absence of the influence of endogenous interfering substances on the results of the analysis and the absence of cross-reactions with antibodies to hepatitis pathogens of the other etiologies had been shown. The sensitivity of the test system compared to the "RecomLine HEV IgG/IgM" kit was 92%, specificity 97%. Shelf life in condition of storage was determined to be 12 months. CONCLUSIONS: The developed test can be used to confirm the results of ELISA in laboratory diagnosis of hepatitis E.

[The estimation of the hepatitis E proportion in the etiological structure of acute viral hepatitis in certain regions of of Kyrgyzstan.]

Despite the fact that the Kyrgyz Republic (KR) belongs to the highly endemic regions of the world for hepatitis E, the true extent of the spread of this infection in the country remains poorly understood. It was estimated the prevalence of serological markers of hepatitis E virus (HEV) infection among patients with acute viral hepatitis (AVH) from the regions of the Kyrgyz Republic with a high level of seroprevalence previously established by us. Blood sera samples of hepatitis patients who were admitted to hospitals of Kyrgyzstan in the period 2018-2019 were examined by the enzyme immunoassay method using the kits «DS-ELISA-Anti-HEVIgG¼ and «DS-ELISA-ANTI-HEV-IgM¼ (RPC Diagnostic Systems, Russia). IgG and IgM antibodies to HEV were detected in 103 of 344 studied samples (29.9%). Most often, seropositive specimens were detected among people of age groups under 20 and over 40 years old. Hepatitis with the fecal-oral mode of transmission was dominated in the structure of AVH: the specific gravity of hepatitis E was 47.9%, hepatitis A - 35.32%. Markers of mixed infections with other hepatitis viruses have been detected in 40.4% IgM-positive individuals. Thus, high prevalence of serological markers of HEV infection in the territory of Kyrgyzstan during the interepidemic period had been shown. The necessity of including the determination of serological markers of hepatitis E into the algorithm for the comprehensive diagnosis of AVH in patients of all age groups with liver pathology had been confirmed.

[The analysis of sero-prevalence of virus of hepatitis E among patients with HIV-infection and syphilis.]

The infection with hepatitis E virus is one of causes of liver diseases in patients with secondary immunodeficiency, including HIVinfected ones. The study was carried out concerning analysis of rate of detection of serological markers of infection with hepatitis E virus in samples of blood serums of HIV-infected patients and other group of patients with expressed immuno-suppression - patients with syphilis. The sero-prevalence of hepatitis E virus on IgM-antibodies among HIV-infected patients in Moscow made up to 21.7% and 2.9% correspondingly. In the examined group from the Far-East region the highest sero-prevalence of hepatitis E virus on specific IgE-antibodies (73%) is established in the group of patients infected with HIV subtype B. The most frequently IgG and IgM antibodies to hepatitis E virus were detected in HIV-infected patients at the stage of disease 4B. The examined group of patients with syphilis the sero-prevalence of hepatitis E virus made up to 14.7% that significantly surpasses the given indicator in the group of healthy persons (1.7%). The increasing of the level of sero-postivity is demonstrated in the groups of patients with latent syphilis and on the second stage of disease. Therefore, the highest values of sero-prevalence of hepatitis E virus is observed in the groups of HIV-infected patients and patients with syphilis at late stages of disease. In the Russian Federation, the identification of antibodies to hepatitis E virus in HIV-infected patients depends of the region of residence.

Luminescence study of nanosized Al2O3:Tb3+ obtained by gas-dispersed synthesis.

Terbium-doped Al2O3 samples were obtained by gas-dispersed synthesis. It was shown that the resulting powders, with particle sizes of 10-70 nm, consist of a mixture of transition aluminas, among which the δ *-polymorph is dominant. The luminescence properties of Al2O3:Tb3+ have been studied upon excitation in the UV-visible range of the spectrum. It was found that Tb3+ ions cause several groups of inhomogeneously broadened emission bands in the range of 470-640 nm, which are characteristic for disordered materials. In addition, the emission spectra contain a broad band at about 450 nm and several narrower ones in the 680-720 nm region. These features are attributed to surface defects and impurity Cr3+ ions occupying Al3+ octahedral positions, respectively.

[Features of consumption of vitamins and foods enriched with biologically active substances by Petersburgers].

Purpose. To study and evaluate the use of vitamins and products enriched with biologically active substances by the residents of St. Petersburg. The study was conducted with the use of the questionnaire survey method of 1200 Petersburgers. Results. A third of residents (35.5 per cent) never used enriched food products in nutrition. The majority of St. Petersburgers (59.3%) when cooking do not use iodized salt or do it rarely. While the use of salt increases with the age. Inclusion of vitamins in the diet fails to be widely distributed among the citizens: monthly they are used by only 20.3% of citizen, 2 times a year - 28.2% and only during illness - 17.7%. One third of the population (33.8 percent) never takes vitamins in the form of tablets, syrups, solutions, etc. Conclusion. The analysis indicates the need to improve the nutrition of Petersburgers to reduce risk factors for diseases by improving health literacy in organized units for healthy nutrition on the base of Health Centers or clinics in St. Petersburg.

Critical Casimir forces in the presence of random surface fields.

We study critical Casimir forces (CCFs) fC for films of thickness L which in the three-dimensional bulk belong to the Ising universality class and which are exposed to random surface fields (RSFs) on both surfaces. We consider the case in which, in the absence of RSFs, the surfaces of the film belong to the surface universality class of the so-called ordinary transition. We carry out a finite-size scaling analysis and show that for weak disorder, CCFs still exhibit scaling, acquiring a random field scaling variable w that is zero for pure systems. We confirm these analytic predictions by Monte Carlo (MC) simulations. Moreover, our MC data show that fC varies as fC(w→0)-fC(w=0)∼w2. Asymptotically, for large L, w scales as w∼L-0.26→0, indicating that this type of disorder is an irrelevant perturbation of the ordinary surface universality class. However, for thin films such that w≃1, we find that the presence of RSFs with vanishing mean value increases significantly the strength of CCFs, as compared to systems without them, and it shifts the extremum of the scaling function of fC toward lower temperatures. But fC remains attractive.

[Monitoring the nutritional status of the residents of St. Petersburg].

The purpose of the study was to analyze the diet of the population of St. Petersburg from different social and age groups and justify organizational-methodological ways to improve it. 1200 inhabitants 18 years old and over (674 women, 526 men) were interviewed using questionnaires. One-third of St. Petersburg population did not adhere to the recommended 3-4 meals per day, taking meal 2 times per day or less (21.7%) or 5 times per day or more (11.3%). The young (18-29 years old) and socially active residents 1.5-2fold more likely than pensioners (13.8%) fed 2 times per day. Women 2.2 fold more frequently than men fed 5 times per day. Young people (20%) and socially active persons (24.4%) prefer not to have breakfast or take it 2-3 times per week compared with 9.6% pensioners. Supper as the main mealtimes called 27.8% women, that is 1.4 fold more likely than men. Thus, a great part of the population in the young and socially active adulthood violates proper diet, and women more often as compared to men. This can lead to disruption of the metabolic processes, increasing the risk of nutrition-related diseases, a decrease of efficiency and reduced life expectancy. This raises the feasibility of establishing of healthy eating offices based on health centers or clinics in St. Petersburg.

[Pathomorphological peculiarities of hemomicrocirculatory bed of the small and large intestine in acute peritonitis].

Experimental comparative morphological investigation of hemomicrocirculation bed (HMCB) of the small and large bowel wall was performed in dynamics of an acute serous peritonitis. Spreaded aseptic peritonitis was simulated using injection of 5 ml of gamma-caraginen (Sigma, USA) in 1 ml of isotonic solution of sodium chloride. On the early stage of peritonitis (in 12 h from beginning of the experiment) in mucosa of small bowel nonsignificant venuls dilatation and the capillary lumen reduction were observed. In 1 day (reactive stage of peritonitis) in mucosa the quantity of capillars have had reduced significantly, comparing with such observed previously. On the 2-nd day (toxic stage of peritonitis) some capillary dilatation in intestinal villi and crypts coexistant with the blood rheology disorders in a form of stasis, change in permeability of the vessels walls, predominantly of the venous, was noted. On the 3-d day (late stage) the arteriol's spasm have had reduced, capillary paralytic dilatation was revealed. The staged course of experimental peritonitis with the HMCB changes, characteristic for every stage, was confirmed, basing on analysis of the investigation result.

[Immune status of patients after splenectomy, performed for the spleen traumatic injury in remote terms and choice of preparations for its correction].

Immune status was analyzed in 28 patients in remote period after splenectomy. In accordance to immunological data obtained in splenectomy patients, inhibition of cellular chain of speciphic and natural immunity was noted on background of hyperactivation of its humoral chain with signs of autoimmune processes. In such patients, while immunomodulators selection, the mostly pronounced stimulating impact was noted in immunoglobulin; of sorbents the most binding capacity has rheopolyglukin. This opens further perspectives of postsplenectomy patients treatment, using immunomodulating and elimination correction of the disorders revealed. Expediency of application of rheopolyglukin and immunoglobulin in contents of eliminating amed immunomodulating therapy was substantiated. Studying of peculiarities of immune status constitute a perspective way in the patients, in whom various variants of organpreserving tactics while surgical interventions on spleen were applied.

[A new type of bread in the diet of healthy and sick person].

In the study the hygienic assessment of a new type of bread in terms of quality and safety was performed. The results of the study showed that a new type of corn bread has a high nutritive and biological value, it is safe for human health. The glycemic index of bread was determined by the method described by FAO, WHO in 1998, "Carbohydrates in Human Nutrition." A new type of bread has a low glycemic index. This makes it possible to use the bread in dietary nutrition for persons who are overweight, suffers from the cardiovascular disease and type 2 diabetes, as well as for preventive nutrition for healthy individuals with risk factors for these diseases.

[Dietary correction of nutrition status in patients with irritable bowel syndrome].

Hygienic and dietology estimation of cereal breakfast (oat muesli and crispbread) were carried out on 137 irritable colon syndrome (SRK) patients with functional chronic constipation. It is established that inclusion of cereal breakfast in a diet of such patients positively influences on motor-evacuation function of digestive tract and promotes improvement of indicators of carbohydrate and lipid metabolism. It is important for patients with overweight and type 2 diabetes. Positive improvements of research allow making a cereal breakfast use recommendations: muesli in number of 50 g/days (with milk or kefir), crispbread and crunchy snacks in number of 100 g/days in SRK patients with functional chronic constipation dietary nutrition.

[Effectiveness of dietary supplements--biologically active substances in patients with obesity].

With the help of clinical, anthropometric and anthropometric method examination the study estimation of the effectiveness of a new food additives "Vita-Plant-herbal tea N16"--with overweight and obesity. Components of a new herbal tea rich in biologically active compounds, flavonoids, phenolic acids, vitamin C and B, carotenoids, trace elements iodine, zinc, molybdenum, manganese, iron, etc. The studies were conducted on 53 patients with overweight and obesity, which were divided into two similar groups of patients were on standard low-calorie diet. The main group (28 patients) received a glass of analyzed herbal tea two times a day for 4 weeks. The control group (25 patients) were in similar conditions, but did not receive this herbal tea. Comprehensive clinical and laboratory evaluation of patients included a study of the dynamics of clinical symptoms, anthropometric data and blood biochemical parameters. Studies have shown a beneficial effect of herbal tea components on metabolism, anthropometric parameters and clinical symptoms in patients with overweight and obesity. This gives us grounds to recommend a new kind of herbal tea in the dietary of patients with this pathology.

[Estimation of the results and quality of life indices in patients with gastroduodenal ulcer depending on the method of operative treatment].

The results of operative treatment of 261 patients, suffering perforative gastroduodenal ulcer, are analyzed. In 159 patients the ulcer excision with pyloroplasty and without vagotomy was performed and in 102--the ulcer excision with vagotomy. In all the patients the chronic ulcer perforation was noted. In operated patients gastric mucosa have had morphologic peculiarities, characteristic for chronic atrophic gastritis with complete intestinal metaplasia foci. In surgical treatment for perforative gastroduodenal ulcer its excision with pyloroplasty conduction and medicinal correcting therapy are recommended.

[Physiological nature and diagnostic implications of rotational nystagmus].

The authors provide a rationale for clinical studies of four types of rotational nystagmus, true vestibular, cervico-vestibular, opto-vestibular, and cervico-optovestibular. A physiological concept of nystagmus during active head rotation is formulated. Negative consequences of vestibular nystagmus as a pathophysiological reaction are discussed. The main criteria for nystagmometric differential diagnosis of peripheral vestibular and central disorders are proposed. Diagnostic potential of the new <> system is demonstrated.

[New methodology for the stabilometric diagnosis of equilibrium dysfunction].

The necessity of studying the dynamic stabilization of the human body vertical position is substantiated. New capacities of a stabilometric vector analysis in diagnosing equilibrium dysfunction, evaluating the efficiency of treatment, and determining the statistical significance of differences in the results in a patient rather than in a group of subjects are shown.

[A computerized method for the combined evaluation of otoneurological and non-pharmacological correction of vestibulo-sensory and oculomotor disturbances].

Methodology and a new <> hard/software complex (HSC) have been developed jointly by the Institute of Biomedical Problems, <> and <> Companies to be used in vestibulometric, otoneurological, and psychophysiological tes-ting with synchronous registration and in the analysis of head movements, various types of nystagmus, and all forms of visual pursuit. The complex is intended for the expert/diagnostic evaluation, prognosis, and monitoring of the vestibular function, intersensory interactions, and eye pursuit movements as well as for teaching correction and elimination of unfavourable perceptive and vestibular-sensorimotor responses by developing a fixation reflex during exposure to visual and dynamic stimuli. The <> HSC was tested during pre- and post-flight observation of astronauts, under simulated and clinical conditions, as well as in monitoring the functional status of athletes engaged in various sports. The study has demonstrated that the use of special computerized stimulation programs allowing (by irritating visual and vestibular sensory inputs) to produce perceptive and sensorimotor responses provides a promising tool for the evaluation of the state of the vestibular and related sensory systems, stability of static and dynamic spatial orientation in the presence of separate and combined visual and vestibular stimuli or without them.

[Organization dietological help for population in clinics and hospitals institution Saint-Petersburg].

Experience of dietological help for population in Saint-Petersburg has shown in this article. Efficiency of dietological help in clinics and hospitals depends on completeness of investigation of fundamental bases of patient's nutrition.