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During the economic instability, crisis processes in economic relations, and the growing prospects of a new “step” of the global economic crisis, theoretical and applied research in the field of legal support for strengthening and supporting economic development, small and medium-sized businesses, and digital technologies in the Russian Federation plays a great role. The purpose of the study: A legal study of the current legislation in order to apply the concept of synergy of family business and social entrepreneurship for the effective implementation of economic processes and solving technological problems, identify the problems of family business development in the new economic realities and propose some ways to solve them at the legislative level. The object of the study is a set of economic, entrepreneurial, civil-legal relations that arise in the implementation of family business and social entrepreneurship in modern economic realities based on new technologies. Methods: General scientific and private scientific methods of scientific cognition were used in the study: systematic, historical, logical, comparative-legal, formal-legal, and others. Novelty: It is proved that social entrepreneurship and family business should be a system-forming link in economic relations, linking the state with small and medium-sized businesses. The introduction of such form of business (social and family entrepreneurship) should eliminate many economic problems and gaps in the legal regulation of issues that arise while conducting economic activities by family members. The necessity of separating social entrepreneurship and family business into a separate economic and legal category is justified, and the expediency of consolidating the concept of social entrepreneurship and family enterprise at the federal level is proved.

The purpose of the study is to show the necessity to integrate the Corporate Social Responsibility course into the educational process. The methodological basis of the study are such methods of scientific knowledge as a historical method, method of logical unity of analysis and synthesis, systematic method, and others. The questions of necessity to reflect CSR in educational programs of economists training programs are discussed. The author substantiates the reasons for the growing interest in this issue. A review of relevant practices in the field of CSR knowledge dissemination is given. It was found that the introduction of the proposed educational product in the learning process allows to strengthen main vocational training programs in many areas of training, to improve their efficiency, to have a significant impact on improving the quality of students’ knowledge, and contribute to the development and the formation of a fundamentally new professional competencies.

Memory acquisition is accompanied by many cellular and molecular processes, and it is not always clear what role they play. Fatty acids (FAs) are known to be important for cognitive functions, but the details of their involvement in memory processes remain unknown. We investigated FAs in the prefrontal cortex and hippocampus of rats trained to perform a task with food reinforcement. The learning consisted of two training sessions, each of which included 10 trials. The results showed that such training altered individual FAs in the brains. The most significant changes were in the prefrontal cortex, where an increase in the level of many FAs occurred, especially after the second training session: palmitic (16:0), stearic (18:0), docosahexaenoic (22:6, n-3), arachidonic (22:4, n-6), docosapentaenoic (22:5, n-6) acids. Changes in the fatty acid level after training in rats were detected only in the left hippocampus, where the levels of palmitic, docosapentaenoic, and docosahexaenoic acids changed. The changes in the right hippocampus were not significant. In both the prefrontal cortex and the left hippocampus, 72 h after training, all FAs returned to control levels. We believe that the main role of a reversible increase in FA levels during memory acquisition is to support and protect cellular processes involved in memory acquisition. Consolidation of memory traces, which occurs mainly in the neocortex, requires protection from external influences, to which FAs makes a significant contribution. They are able to improve neuronal plasticity, enhance local blood flow, improve mitochondrial processes, and suppress pro-inflammatory signals., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The goal of this study was to evaluate the effects of anti-inflammatory cytokine, interleukin-10 (IL-10), and calpain inhibitor, PD150606, on the expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits in rat hippocampal slices exposed to repeated brief hypoxic episodes. We studied both individual and combinatory effects of PD150606 and IL-10 on the expression of AMPA receptor subunits under hypoxic conditions for GluA1 and GluA2 as well as their phosphorylated forms - pSer831-GluA1 and pSer880-GluA2. Additionally, we studied whether brief hypoxic episodes and IL-10 may affect mRNA expression of transcriptional factors such as hypoxia-inducible factor-1α and nuclear factor κB (NF-κB). Western blotting analysis of hippocampal slice homogenates revealed that IL-10 and PD150606, both individually and in combination, ameliorate hypoxia-induced decrease in the expression of GluA1 and pSer831-GluA1, with different level of efficiency measured at 10, 50, and 90 min after hypoxia induction. Interestingly, brief hypoxic episodes did not induce any changes in the expression of GluA2 and pSer880-GluA2 subunits, whereas PD150606 showed biphasic effect, decreasing the expression of GluA2 and pSer880-GluA2 at 10 min and potentiating it at 90 min after hypoxia induction. IL-10 alone did not show any effect but was able to reverse PD150606 action on the expression of pSer880-GluA2 at 10 min and further potentiated it for GluA2 at 90 min after hypoxia. Finally, PCR analysis revealed that modulation of GluA1 and GluA2 expressions by hypoxia, and IL-10 was not associated with changes in the expression of hypoxia-inducible factor-1α and nuclear factor-κB (NF-κB) transcriptional factors.

Changes in the fatty acid composition of the hippocampal dentate gyrus in Krushinsky-Molodkina rats with hereditary predisposition to audiogenic seizures were studied in 1, 3, and 14 days after 1 or 5 seizures. Seizure activity changed the content of saturated and monounsaturated as well as polyunsaturated fatty acids at different terms after seizures. After seizures, the content of individual fatty acids changed in different directions. Similar shifts after 1 and 5 seizures were observed only for eicosapentaenoic acid at all observation terms. More pronounced changes in fatty acid composition were observed after 5 seizures. These results can be useful for the development of new approaches to correction of seizure activity.

We found small but statistically significant increase in the number of stable to peroxide oxidation saturated and monounsaturated fatty acids in the auditory cortex of KM rats in comparison with control Wistar ones. The levels of fatty acids in the cells of the auditory cortex of KM rats were studied at different times (1 h, 1 day, 3 days and 14 days) after a single audiogenic seizure. The changes in fatty acids composition in auditory cortex of KM rats were found already in time point 1 h after convulsion, the maximal decrease of fatty acids levels was observed at 3 days after convulsion. These data suggest that the fatty acids pool in this time was depleted. Finally, we found the recovery of the better part of fatty acids in the auditory cortex of KM rats to 14 day after convulsion. These results can be used for development of new approaches to eliminate brain damage after seizures.

The goal of this study is to evaluate the effects of anti-inflammatory cytokine interleukin-10 (IL-10) on the repeated brief hypoxia-induced changes in expressions of AMPA receptor subunit GluA1 and α- and β-subunit of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). The hypoxia-induced changes in the rat hippocampal slice CA1 neuronal activities were investigated by the method of field potentials recording. Subunit-specific antibodies staining of Western blots of hippocampal slice homogenates to characterize the receptor subunit GluA1 and α- and β-subunit of CaMKII were used. IL-10 (1ng/ml) abolished the development of posthypoxic hyperexcitability in the CA1 pyramidal neurons induced by repeated brief hypoxia. This neuroprotective effect of IL-10 was rapidly developed within 10min after hypoxic episodes and accompanied by reversions of the hypoxia-induced decreases in expressions of AMPA receptor subunit GluA1 and α-subunit of CaMKII. These findings provide some evidence about existence of the novel mechanism underlying the rapid neuroprotective effect of anti-inflammatory cytokine IL-10 against hypoxia-induced neurological deteriorations., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Administration of anticonvulsant sodium valproate alleviated audiogenic seizures in Krushinskii-Molodkina rats, which was accompanied by a decrease in cAMP-dependent phosphorylation of microtubule-associated protein MAP2 in the hippocampus ex vivo. In contrast, audiogenic kindling resulted in a marked increase in MAP2 phosphorylation at cAMP-dependent protein kinase-specific sites. These changes in the state of MAP2 phosphorylation providing restructuring of dendrites in response to specific influences modulate neuronal activity and are the important mechanisms of neuronal plasticity.

Using a Western blot method it was been shown that a aontent of beta-CaMKII subunit was decreased on 40 % in hippocampus of Krushinskii-Molodkina rats (rats, genetically prone to audiogenic seizures) in comparison with normal Wistar rats. Additionally, we have investigate the temporal modifications of alpha/beta-CaMKII subunits in dependent from number audiogenic fits (n = 1 or n = 5). The level of beta-CaMKII in hippocampus of naive KM rats and KM rats in 24 h after single audiogenic seizure was not different, but it was increased on 56 % through 72 h after convulsion fit. In contrast, both 5-fold seizures and 20-fold seizures (audiogenic kindling) reduced the beta-CaMKII levels in comparison with naive group. The levels of alpha-subunit protein kinase in hippocampus these experimental groups of animals were not different. We suggest a hypothesis, that modifications alpha/beta ratio can be viewed as specific "homeostatic mechanism", which provide for neuronal function in hippocampus, thereby changing the rules governing synaptic plasticity in dependence from preliminary neuronal activity.

Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) and protein phosphatase 2B (calcineurin) play a critical role in modulation responses of nerve cells to Ca(2+)-signal. Here we asked the question, whether and how these enzymes may become affected by single seizure activity. Male epilepsy-prone Krushinsky-Molodkina rats were exposed to single sound stimulation (80 dB, 12-15 kHz). Biochemical studies carried out two days after the sound exposure. Immunoblots of hippocampal and cortical (from sensomotor area) homogenates reacted with monoclonal antibodies to neurospecific alpha-subunit CaMKII showed an increased presence of this protein in seizured animals in comparison with naive controls. The level of the calcineurin catalytic subunit was increased in the hippocampus only. Additionally, studies of CaMKII activity revealed that the total enzyme activity from hippocampus and cortex of seizured rats was increased as compared with controls. However, it was no differences in functional (Ca(2+)-calmodulin-independent) CaMKII activity between experimental and control groups. It was suggested that observed long-lasting changes in rats brain induced by seizure activity may be a one in a number adaptative mechanisms against neuronal exitability.

The authors analyze 143 cases of extrapulmonary and generalized tuberculosis in HIV-infected patients. There is a steady increase in the number of patients with multiple organ tuberculosis that frequently acquires the pattern of an acute generalized septic process. Generalized tuberculosis predominantly develops in HIV-infected patients with a considerable reduction in immunological parameters and it is, in these cases, of primary generalized nature. The efficiency of treatment is very low in patients with multiple organ tuberculosis. Despite therapy, the progression of the disease results in early death. However, the prospects for further inclusion of highly active antiretroviral therapy in multimodality treatment for comorbidity give hope for the solution of this problem.

Extrapulmonary tuberculosis mainly afflicted females over 60 years of age; males aged 20-29 years suffered from this disease concurrent with HIV infection. The major site of extrapulmonary tuberculosis was the urogenital tract; however, the incidence of tuberculosis of the nervous system considerably increased. At the same time abdominal tuberculosis was prevalent in HIV-infected patients. The rate of concomitant pulmonary and extrapulmonary tuberculosis was on the rise. In extrapulmonary tuberculosis, the common cause of death was nervous system tuberculosis. Disseminated and complicated extrapulmonary tuberculosis requires that the problems associated with personnel, organization, and finance be solved.

Experiments on Krushinskii-Molodkina rats with hereditary predisposition to audiogenic seizures showed that chronic consumption of aqueous solution of melatonin (50 mg/liter) had no effect on the pattern of seizures induced by 20-fold acoustic stimulation. Sodium valproate (50 mg/liter) insignificantly decreased the seizure response. Combined treatment with sodium valproate and melatonin produced a potent anticonvulsant effect, i.e. increased the latency and decreased the severity of audiogenic seizures. However, myoclonus in animals receiving combined treatment with these drugs developed much more rapidly compared to rats receiving melatonin or sodium valproate monotherapy.

Rats Krushinsky-Molodkina inbred strain (KM) genetically prone to audiogenic seizures were injected with pineal hormone melatonin (50 mg/kg, s.c.) within the period 7th to the 14th posnatal days (PND). The remote effects of this injection adult KM rats consisted in a decrease in the latency and increase in severity of myoclonic seizures produced by audiogenic kindling (20 sound stimuli, 100 dB and 12-15 kHz). As compared to the control, in the cortex and hippocampus of rats of melatonin group, we also found a significant reduction of both total and functional activity of Ca2+/calmodulin-dependent protein kinase II (CAMK II) after audiogenic kindling. On the contrary, melatonin administration within the 1st to 7th PND and the 14th to the 21st PND resulted in a decrease in seizure activity. In the first case, both the total (cortical) and functional (hippocampal) CAMK II activities in melatonin-injected rats were increased as compared to control, whereas in the second case, only a slight increase in Ca2+-independent CAMK II activity in the hippocampus of melatonin-injected rats was observed. Probably, the melatonin administration in the period of early postnatal development changes the features of expression and/or regulation of CAMK II activity, and this could be one of the mechanisms of audiogenic seizure modulation in KM rats.

It has been shown that modification of microtubule (MT) ultrastructure are accompanied by functional changes in microtubule-associated protein MAP2 in the hippocampus of Krushinsky--Molodkina rats (KM), which are prone to autogenic seizures. The morphogenetic analysis revealed that contrary to Wistar rats, which are insensitive to sound stimulation, in KM the middle length of microtubule fragments in the apical dendrites of pyramidal neurons in CA3 hippocampal area was reduced. Using immunoblot and autoradiography methods, we found that the level of MAP2 and the rate of its cAMP = and Ca(2+)-calmodulin-dependent phosphorylation were increased in hippocampus of KM, in comparison with Wistar rats. Daily repeated sound stimulation for 20 days (audiogenic kindling) induced a further decrease in length of MT fragments, and an increase of their density in the proximal part of apical dendrites of KM. Moreover, audiogenic kindling induced additional increase in MAP2 phosphorylation state, but did not change the level of MAP2 in KM hippocampus. We suppose that the obtained alteration of MAP2 phosphorylation state exerted influence on kinetic parameters of microtubule assembly, serving as part of genetically determined predisposition of KM to audiogenic epilepsy.

The paper presents the results of follow-up of 894 patients in 1983 - 1993. The increasing topicality for physiology and the potentialities of making the diagnosis of the disease better are defined, based on the data on the pathogenesis and pathomorphism of tuberculous lymphadenitis and on the results of testing new diagnostic techniques, including cytological and histological studies of sections and imprints, enzyme immunoassay, and polymerase chain reaction.

Basing on the results of their studies, analysis of 894 patients with tuberculosis of the lymph nodes and nonspecific lymphadenopathy treated in 1983-1993, medical literature, the authors investigate the place of lymphadenopathies in medical practice: new data on the patients, pathogenesis and pathomorphosis of tuberculous and nonspecific lymphadenopathies, diagnostic techniques. Updated approaches to this disease led to a 17.8% decrease in the percentage of cases with unclear etiology.