[Role and place of ipidacrine in the therapy of diseases of the peripheral nervous system. The resolution of the expert council]. / Rol' i mesto ipidakrina v terapii zabolevanii perifericheskoi nervnoi sistemy. Rezolyutsiya Soveta ekspertov.

The resolution of the expert council is devoted to discussing aspects of the use of ipidacrine for the treatment of mononeuropathies, polyneuropathies and radiculopathies of various etiologies. Specialists prepared recommendations for ipidacrine's application in treating peripheral nervous system disorders.

[Shaping approaches to standardization of oropharynx mucous membrane assessment of immunological parameters]. / Formirovanie podkhodov k standartizatsii issledovaniya immunologicheskikh parametrov slizistoi obolochki rotoglotki.

Basis of acute pharyngitis pathogenesis is an inflammatory process at the entrance gate of the infection. Therefore, local immunity study proves to be the most informative. Difficulty in making that type of assessment is lack of generally accepted reference values and biological sampling techniques. OBJECTIVE: Validation of biological sampling techniques to study the parameters of local mucosal immunity in oropharynx acute inflammatory diseases. MATERIAL AND METHODS: 30 people with acute catarrhal pharyngitis with intoxication syndrome were examined. The sampling was carried out in 7 different ways. 1. Collect saliva samples using the passive drool collection method. 2. Collect saliva, using cotton swabs placed into the mouth for 3 minutes. 3. Cotton swabs wrapped around a metal probe was placed on palatine tonsils and lateral walls of the oropharynx. 4. Instead of a cotton swab, a disc of laboratory filter paper with a diameter of 0.7 cm was used. 5. Scrape by the mucous membrane of the palatine tonsils and lateral walls of the oropharynx were made with a cytobrush. 6. Using a cytobrush, scrapings were made from the mucous membrane of only the posterior pharyngeal wall, excluding the region of the palatine tonsils. 7. Using a cytobrush to make scrapings from the only palatine tonsils mucous membrane. RT-PCR was used to determine IL-1ß mRNA. RESULTS: Minimal IL-1ß mRNA values were detected in saliva collected by passive flow (0.095 [0; 3.45] units) and on a cotton swab (0.21 [0.1; 3.82] units). IL-1ß mRNA in the material collected by methods No. 3 and No. 4 on a cotton swab and a paper disk did not differ significantly from each other. Its level was higher than in saliva and lower than in scrapings. The maximum result was revealed with method No. 5 when simultaneously taking scrapings from the palatine tonsils and posterior pharyngeal wall mucous membrane (4.76 [0.92; 8.13] units). The expression of IL-1ß mRNA in the material obtained by methods No. 6 and No. 7 did not differ significantly from each other. CONCLUSION: Separated scrapings collecting from the palatine tonsils or posterior pharyngeal wall mucous membrane will allow assessing the inflammatory response autonomously in the lymphoid tissue and separately on the mucosa of the posterior pharyngeal wall. The mucosal scraping technique was the most effective for assessing cytokines in the oropharyngeal mucosal membrane.

Collagen Hydrolysis Products Reduce the Formation of Stress-Induced Ulcers by Regulating Stress-Associated Activation of the Neuroendocrine and Immune Systems.

We studied the effect of collagen fragments (PGP and AcPGP) on serum content of epinephrine, corticosterone, and IL-1ß in rats subjected to water-immersion stress. The degree of local inflammation accompanying ulceration was assessed by IL-1ß production by ln. gastricus caudalis cells. In 1 h, the sharp increase in hormone concentrations in the blood of stressed animals reflected the high stress intensity. Intranasal administration of PGP reduced the area of stress-induced ulcers by 63%, prevented the increase in the levels of stress hormones and the main proinflammatory cytokine in rat blood. The concentrations of IL-1ß in cell culture from regional lymph node of experimental animals returned to normal in 24 and 48 h after the stress. Acetylation of PGP prevents with gastroprotection, but does not abrogate other properties of the peptide.

Antiproliferative Effects of Modified Bioflavonoid in Ex Vivo Model.

We studied the effect of modified bioflavonoid and reference drug quercetin dihydrate on proliferation of mononuclears triggered by T- and B-cell mitogens. Lymphocytes were in vivo pretreated with the examined agents followed by their explantation and in vitro activation with T- and B-cell mitogens in cell culture. Intraperitoneal injection of modified bioflavonoid and quercetin dihydrate produced a dose-dependent inhibition of proliferation of the in vitroactivated splenocytes; modified bioflavonoid demonstrated higher antiproliferative activity.

[Effect of External Irradiation and Immobilization Stress on the Reproductive System of Male Rats].

We studied the state of the reproductive system of male rats after irradiation at a dose of 2.0 Gy, immobilization stress (6 hours/day for 7 days) and their combined effects. On the 30th day after the combined treatment (37 days after irradiation) a decrease in the testicular weight by almost 50% compared with the control and lesions connected with the process of spermatogenesis are observed. In the remote period--on the 60th day (67th after irradiation) the effect of irradiation and irradiation in combination with immobilization stress leads to a sharp drop in the number of epididymal sperm (up to 18% of the control), and a reduction of their viability. The reaction ofthe reproductive system to the immobilization stress is expressed in a certain increase in the mass of the testes and epididymis, moderate imbalances in the composition of spermatogenic cells in the testis tissue, and in the long term--in the increased number of epididymal sperm and the decrease in their viability. Changes of testosterone in the blood serum, especially significant for the combined effect, reflect impairments of the regulation of the reproductive system of males under these conditions. With regard to individual indicators of the reproductive system of male rats in some cases, the- combined effects of radiation and stress had a synergistic, or, on the contrary, antagonistic character.

Evaluation of the Effect of Modified Bioflavonoid and Quercetin Dihydrate on Cytokine Secretion by Mitogen-Activated Mononuclear Cells.

An experimental study revealed the effect on modified bioflavonoid on the inhibition of secretion of IFN-γ and IL-2 by ConA-stimulated mononuclear cells. These changes were accompanied by an increase in the secretion of IL-17 and IL-6. Our results suggest the differentiation of CD4(+) T helper cells into Th1 and Th17 subpopulations. The reference drug quercetin dihydrate induced an insignificant change in the level of IL-2 and IL-6 and small increase in IFN-γ content. The content of IL-17 was shown to decrease above the detection limit.

Correlation analysis of cytokine gene expression changes and antiulcer effects of Pro-Gly-Pro and N-Acetyl-Pro-Gly-Pro in experimental models of ulceration.

Direct correlation of the cytokine gene expression level in peripheral blood mononuclear cells (BMNCs) and gastric mucosa (GM) cells with the development of gastric ulcers of various etiologies was shown for the first time. Ethanol-induced ulceration causes an increased transcription of IFNa, IL-8, and IL-12 mRNA in BMNCs. GM damages caused by water immersion stress were accompanied by an increased transcription of TNFa. The sizes of acetate-induced damages were positively correlated with the expression of IL-10 and IL-8 genes in BMNCs and with the expression of IFNa, IL-2, IL-12, and TNF genes in GM cells. Intranasal administration of Pro-Gly-Pro (PGP) reduced ethanol-induced ulceration, activating the transcription of IFNγ, IL-2, and IL-4 mRNA in BMNCs and prevents the formation of stress- and acetateinduced ulcers by inhibiting the expression of IL-8 and IL-10 genes, respectively.

Quantitative evaluation of learning and memory trace in studies of mnemotropic effects of immunotropic drugs.

Apart from restoration of disordered immunological parameters, tactivin and derinat exhibit a pronounced effect on the higher integrative functions of the brain. Experiments on Wistar rats have shown that these drugs accelerated conditioning of food and defense responses. New methods for quantitative evaluation of memory trace consolidation are proposed.

[Signal receptors of congenital immunity: a new molecular target for diagnostics and treatment of inflammatory diseases].

The discovery of signal receptors of congenital immunity (signal PRR) not only provided a novel view of basic aspects of pathogenesis of chronic inflammatory diseases but also created a basis for the development of additional diagnostic criteria for these pathologies and new pharmaceuticals for their treatment. Reduced expression and function of PRR due to mutations/polymorphisms or epigenetic disturbances of regulation can be regarded as immunodeficient conditions manifest as severe infectious inflammatory diseases. In contrast, excessive expression and activation of PRR as a rule leads to chronic autoinflammatory, autoimmune, and atopic diseases involving adaptive immunity and aggression against own tissues and cells. Assessment of certain mutations in PRR genes, their expression and activation provides a powerful tool for in-depth diagnostics of inflammatory diseases. Simultaneously, new lines of immunostimulating and anti-inflammatory therapy are developed based on the knowledge of molecular physiology of PRR with the use of synthetic agonists and antagonists of signal PRR.

[Various acute phase reactants in different types of proliferative diseases of the uterine appendages].

The authors examined serum in patients with ovarian cancer (OC; a disseminated process), ovarian cystadenoma (OCA), or external endometriosis (EM) before treatment and in apparently healthy females (a control) for the content of some acute-phase proteins and cytokines to clarify the specific features of changes in their concentrations in relation to the type of the proliferative process. It was shown that in OC, there were significant reductions in the levels of alpha2-macroglobulin (MG), plasmin (PL), alpha1-antitrypsin (AT) and statistically significantly increases in the content of lactoferrin (LF), interleukin (IL)-6, IL-8, Ig, and the regulatory transport complex of P--M. In M, the concentrations of AT were lower and those of IL-6, IL-8, and PL-MG were higher (to a lesser degree than those in OC). In OCA, the levels of MG and IgA were increased; those of IL-8 and PL-MG were decreased. The concentrations of interferon and IgM were unchanged in all groups. The findings suggest that difefrent proliferative processes initially provoke a number of changes of varying magnitude and even directions in the serum levels of inflammation reactants, which should be borne in mind when conducting clinical tests in the intraoperative and, probably, postoperative periods.

[In vitro migration activity of human peripheral blood neutrophils in the normal state and in immunopathology]. / Migratsionnaia aktivnost' in vitro neitrofilov perifericheskoi krovi cheloveka v norme i pri immunopatologii.

Methodological approaches to evaluation of the migration activity of human peripheral blood neutrophils into a collagen matrix were worked out. The migration of neutrophils in healthy donors and in patients with severe bronchial asthma was studied. In the normal state there was practically no migration of intact neutrophils into the collagen matrix (1.1 +/- 0.4%). Following their stimulation by formyi peptide about a quarter of their population was drawn into the matrix in avalanche (22.0 +/- 5.9%). In the acute phase of severe bronchial asthma an increase in both spontaneous (3.3 +/- 1.5%, P < 0.01) and stimulated (35.6 +/- 4.6%, P < 0.001) cell migration occurred. Changes in the migration characteristics of the neutrophils of patients and those of the cells of healthy donors, treated with the polycytokine preparation at concentrations exceeding 100 g/ml, followed similar trends. In case of the standard asthma treatment along with positive disease dynamics further increase in spontaneous neutrophil migration (5.8 +/- 2.9%, P < 0.001) in combination with deficiency in cells reaction to formyi peptide (11.8 +/- 3.8%, P < 0.01) was registered. At the same time dexamethasone did not change the character of the in vitro migration of neutrophils into the collagen matrix. Thus the dynamics of the peripheral blood neutrophil migration during treatment of severe bronchial asthma was demonstrated; this dynamics could be indicative of the pathogenetic role of neutrophils in the development of this pathology.

Dynamics and Mechanisms of Interaction of Mouse Spleen Lymphocytes with 3D Collagen Matrix in vitro.

Interaction of immunocompetent cells with extracellular matrix is one of the main stages in their homing and circulation. In this connection we investigated quantitative and dynamic parameters of interaction between splenocytes and 3D collagen matrix in vitro. It was found out that, about 20% of mouse spleen lymphocytes exhibited ability to bind to type I collagen that reflected as their adhesion to and/or migration in collagen matrix. The number of lymphocytes capable of the interaction with collagen gained successively as far as the time of their incubation on collagen matrix was increased and reached maximum by 24 h. The lymphocyte-collagen interaction was energy-dependent and engaged collagen receptors, which probably have been already expressed on cells before spleen lymphocytes were isolated. The series of intracellular interchanges as activation of protein kinase C, assembly of actin filaments and depolymerization of tubulin microtubules were critical for lymphocytes to adhere to and further to migrate in collagen matrix. Long lasting incubation (24 h and more) of lymphocytes in adhesion excluding conditions did not reduce the number of cells able to interact with collagen, but to a great extent changed mechanisms providing their adhesion and/or migration.

[Reactions between protease inhibitors in blood plasma and collagen]. / Izuchenie reaktsii mezhdu ingibitorami proteinaz plazmy krovi i kollagenom.

The interaction of three macroglobulins and three serpines, as well as inter-alpha-trypsin inhibitor (ITI) with alpha 1- and alpha 2-chains of collagen I which were immobilized on nitrocellulose. All seven proteinase inhibitors were shown to have a certain affinity for collagen. The binding of alpha 2-macroglobulin and gestation-associated protein A with collagen chains is largely determined by the conformational state of these macrophages. alpha 2-Antiplasmin, proteinase alpha 1-inhibitor, antithrombin III and ITI with collagen yield complexes that are resistant to urea, sodium dodecylsulfate, and Trilon B.

[T-lymphocyte induced normalization of transformed malignant fibroblasts: lymphokine with normalization factor activity]. / Indutsirovannaia T-limfotsitami normalizatsiia transformirovannykh zlokachestvennykh fibroblastov: limfokin s aktivnost'iu faktora normalizatsii.

Normalizing influence of different lymphocyte populations and their soluble factors on L-929 transformed malignant fibroblasts (L cells) has been examined. It was demonstrated that splenic T-lymphocytes caused stable (heritable) normalization of receptor apparatus, biophysical and proliferative characteristics of L cells. Lymphokine with the activity of normalization factor (NF) was purified from 24-hour immunocyte conditioned medium. Stability of the normalization phenomenon was caused by NF induced synthesis of functionally analogous factor in L cells. The results obtained indicate the existence of non-cytotoxic mechanisms of tumour growth immunological control. The isolated lymphokine possessed also the activity of early embryonal cell differentiation factor. It is suggested that lymphokines with the activity of NF are physiological regulators of nonlymphoid cell differentiation.