Effect of Glycyrrhetic Acid Derivatives on Regulation of Thymocyte Volume.

We studied the effects of glycyrrhetinic acid (bioactive aglycone of glycyrrhizin) and its ester derivatives at positions C-3 and C-30 on the cell volume regulation in rat thymocytes under conditions of hypoosmotic stress. Native glycyrrhetinic acid completely suppressed this process with half-maximal concentration of 12.7±1.4 µM and Hill coefficient of 3.1±0.6. Formation of esters at C-3 (esters with the acetic, cinnamic and methoxi-cinnamic acid) and at C-30 (methyl ester) drastically decreased the inhibitory activity of the molecule, suggesting that intact hydroxyl group at C-3 and carboxyl group at C-30 are structurally important determinants of biological activity of glycyrrhetinic acid towards volume regulation of thymic lymphocytes.

DISEASES OF THE ORAL MUCOSA IN PATIENTS IN THE POST-COVID PERIOD.

The impact of SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus-2) on the entire human body causes irreversible changes in all organs and systems. Complications in the form of chronic diseases require the treatment of clinicians in various fields of medicine. Dentists are faced with diseases of the oral mucosa in apparently healthy patients who are not predisposed to them but have undergone COVID-19. Purpose of the study - to assess the impact of the coronavirus infection (COVID-19) on the course of diseases of the oral mucosa. We examined 51 patients aged 20 to 75 who had undergone COVID-19 with various diseases of the oral mucosa. The study used clinical and laboratory methods. The features of the clinical course of certain diseases of the oral mucosa were revealed, the dynamics of the local immune defense of the oral cavity in the post-covid period was determined.

[The synergistic action of lipopolysaccharide and muramyl dipeptide in the immunotherapy of DBA/2 mice with mastocytoma P815]. / Sinergichnoe deistvie lipopolisakharida i muramildipeptida pri immunoterapii myshei DBA/2 s mastotsitomoi P815.

The intratumoral administration of lipopolysaccharide (LPS) and muramyl dipeptide (MDP) in combination, but not separately, resulted in necrosis and rejection of subcutaneous P815 mastocytoma nodules in DBA/2 mice with 30 to 40% survival. Previous sensibilization of animals by LPS + MDP, treatment by indomethacin, cyclophosphamide or syngeneic lymphocytes did not augment the immunotherapeutic action of LPS + MDP combination. Reinoculation of P815 cells into cured DBA/2 mice 8 months after the disappearance of the primary tumor led to rejection of new nodules with 50% survival rate. In LPS + MDP immunotherapy of these tumors two stages may be distinguished by a thrombo-necrotic stage and that of development of immunity.

[Immunostimulating properties of synthetic derivatives of muramyl dipeptide and glucosaminyl muramyl dipeptide in vitro]. / Immunostimuliruiushchie svoistva sinteticheskikh proizvodnykh muramildipeptida i gliukozaminilmuramildipeptida in vitro.

Production of tumor necrosis factor (TNF) and interleukin-1 (IL-1) by macrophages of the spleen and peritoneal exudate of mice as well as cytotoxic factors (CFs) by murine splenocytes after in vitro activation was estimated. All the derivatives of muramyldipeptide (MDP) and glucosaminylmuramyldipeptide (GMDP) were able to induce production of TNF and CFs. In the presence of lipopolysaccharide (LPS), the effect was always higher. The response of the spleen macrophages to the effect of the preparations was higher than that of the peritoneal ones and ++non-fractionated splenocytes. GMDP and GMDP4 especially in the presence of LPS had the highest effect on induction of IL-1 by the murine peritoneal macrophages. On the contrary, MDP induced higher IL-1 synthesis by the spleen macrophages. The most active substances with respect to production of TNF, CFs and IL-1, i.e. MDP3 and GMDP4, might be recommended for immunotherapy of syngeneic tumors in animals.

[Increasing the sensitivity of murine splenic cells to interleukin-2 after in vivo exposure to lipopolysaccharide, muramyl dipeptide and concanavalin A]. / Povyshenie chuvstvite'lnosti kletok selezenki myshei k inter- leikinu-2 pri deistvii lipopolisakharida, muramildipeptida ikonkanavalina A in vivo.

Changes in sensitivity of the murine spleen cells to interleukin-2 (IL-2) after exposure to lipopolysaccharide (LPS), muramyldipeptide (MDP) and their combinations were studied. The possible effect of concanavalin A (Con A) administered in vivo on increasing sensitivity of the lymphoid cells to IL-2 was also studied. Exposure to LPS, MDP and their combinations led to an over 2-fold increase in responses of the spleen cells to the effect of IL-2 as compared to the controls. When Con A was administered to mice intravenously in a high dose, sensitivity of their spleen cells to IL-2 markedly increased in 18 hours.

[Immunostimulating effects of muramyl dipeptide, glucosaminyl muramyl dipeptide and their synthetic derivatives in vitro]. / Immunostimuliruiushchee deistvie muramildipeptida, gliuko- zaminilmuramildipeptida i ikh sinteticheskikh proizvodnykh v sisteme in vitro.

The effect of muramyldipeptide (MDP), glucosaminylmuramyldipeptide (GMDP) and their six synthetic derivatives on production of tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-2 (IL-2) by murine spleen cells in vitro was studied. MDP induced insignificant TNF production and did not stimulate production of IL-1 by the murine splenocytes within a 24-hour cultivation period whereas in combination with lipopolysaccharide (LPS) it induced significant production of both the cytokins. GMDP induced marked production of TNF (54 per cent cytotoxic index) and IL-1 (stimulation index 8). Addition of LPS in an amount of 10 ng/ml increased production of TNF by the murine splenocytes under the effect of GMDP but had no effect on production of IL-1. Neither MDP nor GMDP even in combination with LPS induced production of IL-2 by splenocytes of mice DVA/2 and C57B1/6 at activation for 24 hours. All the synthetic derivatives of MDP and GMDP except the MDP polymer activated TNF production by the murine spleen cells. GMDP lysine had the highest effect: 67 per cent cytotoxic index. In combination with LPS its cytotoxic index amounted to 87 per cent. The TNF activity was always higher when LPS in an amount of 10 ng/ml was added to the glycopeptides.

[Activation of the production of cytotoxic factors by mouse spleen cells exposed to the combined action of lipopolysaccharide and muramyl dipeptide in vitro]. / Aktivatsiia produktsii tsitotoksicheskikh faktorov kletkami selezenki myshei pri sochetannom deistvii lipopolisakharida i muramildipeptida in vitro.

Lipopolysaccharide (LPS) and muramyl dipeptide (MDP) stimulated murine splenocytes in vitro to produce cytotoxic factors (CF) that killed target cells L-929. This effect was synergic at LPS dose of 10 ng/ml and MDP dose of 10 micrograms/ml. CF production started 2 hours after spleen cell activation and was maximum in 6 hours. CF were produced by macrophages as well as by lymphocytes stimulated by LPS, MDP or their combination. However, synergic effect of immunomodulators was registered only if nonfractionated spleen cells were stimulated during 24 hours. Lymphocytes depleted on T cells did not lack the ability to generate CF upon activation. In addition, LPS and MDP activated synergically the production of interleukin-I by spleen cells in vitro.