MANIFESTATIONS OF DISEASES OF THE ORAL MUCOSA OF PATIENTS IN THE ADJARA REGION DURING THE COVID-19 PANDEMIC.

The aim of this study was to describe manifestations of diseases of the oral mucosa of patients in the Adjara region during the COVID-19 pandemic. We recruited 55 patients, 25 women (45.5%) and 30 men (54.5%), aged between 18 and 89 years with confirmed COVID-19 at different stages of severity. After obtaining informed consent, we examined their mouths and recorded clinical findings. Forty percent of the patients had at least 1 oral lesion. The most common lesions were candidiasis and ulcers (7 patients each); 2 patients had enanthems. Geographic tongue and caviar tongue were also observed. Altered taste, dry mouth, and painful/burning mouth were noted in 60%, 27.3%, and 36.4% of patients, respectively. Oral mucosal alterations and lesions were prevalent in this series of COVID-19 patients. An altered taste and a painful/burning mouth were common symptoms. For the first time, we performed a description of the oral cavity of patients diagnosed with COVID 19 in the Adjara region. Data were analyzed using descriptive statistics. The variable "age" was compared using the Student's t-test and P-values <0.05 were considered statistically significant.

ALTERATIONS OF RBC MEMBRANE PROTEINS IN DIABETIC PATIENTS WITH AND WITHOUT PERIODONTITIS.

The RBC membrane is considered as a key element in their rheology. The rheological properties of RBCs significantly depend on their membranes properties - deformability. The essential contribution of integral membrane proteins in establishing/maintaining membrane stability is due to their ability to anchor the membrane skeleton to the lipid bilayer, their capacity to bind and stabilize membrane lipids, and their ability to influence and regulate local membrane curvature. The goal of the research was investigation the alterations in RBC membrane protein component in diabetic patients with or without periodontitis. We examined peripheral blood samples from type-1 diabetic patients with and without variable severity periodontitis and healthy volunteers. Freshly drawn blood samples from type 1 diabetes with and without periodontitis were obtained from the Railway Hospital (Tbilisi, Georgia). The blood samples from healthy volunteers were obtained from the the Blood Bank of the Institute of Hematology and Transfusiology (Tbilisi, Georgia). Individuals often consume alcohol addicts, pregnant women and patients with other chronic diseases were excluded from the study. The study protocol was approved by Ethical Committee of the Dabid Aghmashenebeli University of Georgia. RBCs membrane proteins have been extracted from human heparinized blood and studied by electrophoresis method. In patients with diabetes type-1 decreased of RBCs membrane low molecular weight proteins (18-22 kDa) content was detected, whereas their electrophoretic mobility (and hence their charge) does not change significantly compared to the control. In patients with diabetes type-1, suffering from periodontitis RBCs membrane low molecular weight (45-29 kDa) and high molecular weight (200, 116, 97, 55 kDa) proteins content reduced as compared with those in diabetic patients not suffering from periodontitis. In this group the electrophoretic mobility of membrane proteins reduces (especially with increasing severity of periodontitis). Reducing the negative charge (apparently caused by a decrease in the carring negative charge glycophorin C and band 3 protein content) and high molecular fraction (weight of 200, 116, 97, 55 kDa) proteins (due to a low content of Band 4.1, band 4.2, band 3 proteins, adducin and ankyrin, actively involved in the regulation of RBCs mechanical stability, deformability and shape) in RBCs membrane in patients with diabetes type-1 suffering from periodontitis, contributes to violation of RBC-RBC interactions as well disorders of their deformability and may induce adhesion of RBCs to the endothelium and disorders of blood circulation. Thus in patients with diabet-1 suffered by periodontitis alterations of the content and the mobility of RBCs membrane proteins were detected (this alterations corelated with severity of periodontitis but was not related with patients sex and age). Changes in the protein composition of the RBCs membranes promote disorder of RBCs membrane deformability and their adherence to the endothelium, pathogenetically related to the disorders of the microcirculation. So that alterations of the content and the mobility of RBCs membrane proteins may be considered as a predictor of microcirculation disturbance during periodontitis.

ß2-adrenergic regulation of T lymphocites function (in vitro study).

The aim of our study was to establish the influence of ß2AR agonists and antagonists on Th1/Th2 subpopulation balance in intact and activated CD4+ T lymphocyte. Jurkat leukemic T cell line was used as a model for studying T cell activation conditions under the influence of ß2AR ligands. As follows from the results of our studies, after the influence of ß2AR agonist isoproterenol on intact Jurkat cells expression of IL-2 was not changed in comparison to control level. Under the PHA-stimulation level of IL-2 production in Jurkat cells increased significantly; isoproterenol caused decrease level of IL-2 expression in the PHA-stimulated Jurkat cells. Adding of ß2AR antagonist propranolol to the Jurkat cells pre-incubated with isoproterenol didn't change expression of IL-2. ß2AR antagonist propranolol induced slight increase of IL-2 expression in PHA-stimulated Jurkat cells pre-incubated with isoproterenol. Neither isoproterenol nor propranolol didn't change intensity of IL-10 expression in intact Jurkat cells. In the PHA-stimulated Jurkat cells level of IL-10 production decreased in comparison to control level. Isoproterenol induced sharp intensification of IL-10 expression in these cells. Propranolol prevented increase of IL-10 expression in the PHA-stimulated Jurkat cells pre-incubated with ß2AR agonist. It was concluded that ß2ARs in dose-dependent manner regulate cytokine profile in intact and mitogen activated CD4+ T lymphocyte and by this way induce dose-dependent alterations of lymphocyte proliferation and immune response. This indicated existence of a link among immune response and sympathetic nervous system activity.

[The role of neuroendocrine mediators in regulatory activity of T-cells].

The aim of the study was to establish the role of some neuroendocrine mediators (agonists and antagonists of ß-adrenergic receptors, progesterone) in regulating T-cells activity. Studies conducted on the culture of leukemiatransformed T-cells (Jurkat cells) (DSMZ-Deutshe Sammulung von Mikroorganismen und Zellkulturen (Germany)). Jurkat Cells (4 x 105 cells/ml) stimulated with 50 µg/ml fitogemaglutinin A (PHA) at 370С for 5 minutes and then incubated for 24 hours alone, or together with ß- adrenergic receptors agonist izopretonolom (at dose of 10-5 M, 10-6 M), an antagonist, propranolol (dose of 10-5 M, 10-6 M) and progesterone (dose 0,07 µl, 0,7 µl) added to the incubation medium. The viability of Jurkat cells was determined by MTT test. It was shown that ß-adlenoretseptors agonist, izoprotenol didn't affect the activity of mitochondrial dehydrogenases in intact and contributed to their low activation (12%) in the mitogen-activated Jurkat cells. ß-adrenergic receptors antagonist, propranolol, promotes a significant reduction in activity of mitochondrial dehydrogenases, and hence the viability of both intact (40-60%) and mitogen stimulated Jurkat cells (20-40%). Viability of intact Jurkat cells didn't change, and dose-dependently increased in PHA-stimulated Jurkat cells during progesterone exposure. It was concluded that viability of the T-cells and hence their functional activity is largely sensitive to the influence of the ß-adrenoceptor antagonists and progesterone. These data should be considered in the clinical application of appropriate drugs.

Inflammatory markers of gallstones disease in menopausal women.

Among the factors contributing to the gallstones formation an important role belongs to the inflammation. The goal of our research - determination alterations of the redox balance and cytokines (IL-1α, IL-6, IL-8, TNF-α) content in the blood postmenopausal women with gallstone disease. 58 menopausal women with gallstone disease, who had been admitted to the LTD "1-st Clinic" (Tbilisi, Georgia) during 2009-2011 were studied. Gallstone disease was proved by Ultrasonography method. The control group consisted of 25 menopause aged women without gallstone disease. The Local Ethics Committee approved the protocol, and informed consent was obtained from all participants or their surrogates. Patients was conducted for blood redox status (EPR signals of superoxide (O2-) and lipoperoxide (LOO.) radicals) and citokins (IL-1α, IL-6, IL-8, TNF-α) content. It was revealed increase production of oxygen and lipoperoxide free radicals, macrophage inflammatory cytokines (IL-6, IL-1α, TNF-α) in blood of menopausal women with gallstone disease. It was concluded that macrophages play a dominant role in the inflammatory and oxidative response during gallbladder stones disease in postmenopausal women.

Alteration in viability and proliferation activity of mitogen stimulated Jurkat cells.

The aim of our study was the establishment of mechanisms of alterations in viability and mitogen stimulated T lymphocyte proliferation activity. In PHA-stimulated Jurkat cells along with increased proliferation level the reduction of mitochondrial dehydrogenases activity (by 20%) and rising number of cells with low mitochondrial membrane potential (ΔΨm) was revealed. It was concluded that interaction of mitogen (PHA) with T cells receptors (TCR) contributes reduction activity of mitochondrial NADH-dehydrogenase (via phospolipasa C-diacilglicerol (PLC-DAG)-induced PKCs (PKCα, PKCθ) activation pathway). Supression activity of I complex (NADH-dehydrogenase) of mitochondrial respiratory chain and reduction of mitochondrial membrane potencial (ΔΨm) is accompanied with intensification of superoxide radicals production. Superoxide radicals as secondary messengers involve in the induction of T cells viability and proliferative activity regulating genes (CD95L and IL-2) and by this way contribute modification of cell proliferation and apoptosis intensity.

[Influence of antioxidant phenovin and immunomodulator Una de gato on free radical oxidation at parodontitis].

The aim of the research: detection of changes in free radical oxidation at treatment of parodontitis with combination of preparations - antioxidant Phenovin and immunomodulator Una de gato. Reactive compounds of nitrogen, oxygen and lipids in saliva, blood and gingival tissue of patients suffering from moderate form of parodontitis has been studied by means of the electronic paramagnetic resonance (EPR) method and spin-traps (DETC, DMPO, PBN - Sigma). In patients with parodontitis content of free NO in saliva and blood increases, while in gingival tissue - decreases. In saliva, blood and gingival tissue of patients intense EPR signals of superoxidradicals (O2(-)) and lipoperoxides (LOO(-)) has been revealed indicating intensification of processes of lipid peroxidation in oral cavity, as well as in whole organism of patient. Exaggerated synthesis of NO in saliva and blood of patient is determined by high- expression of inducible NO-synthase triggered by oxidative stress, and increased activity of neuronal NO-synthase in saliva as a result of high concentrations of metacholine and P substance intensely secreted at parodontitis. Decreased content of free NO in gingival tissue of patients with parodontitis compared to control is the result of biological degradation of nitric oxide (conversion of NO into peroxinitrite on the background of intense oxidative stress in oral cavity) and nitrosylation of mitochondrial electron transport proteins of gingival tissue (characteristic for parodontitis) with further decrease in content of free oxide, suppression of intensity of mitochondrial respiration, energogenesis, development of ischemia in oral tissue leading to further initiation of destructive processes and progression of parodontitis. Treatment with combination of preparations - Phenovin and Una de gato decreased intensity of oxidative stress in organism of patients and reduced destructive processes of tissues in oral cavity. Relative normalization of oxidative metabolism in organism, restoration of NO-synthase system activity (intensity of EPR signals of spin-trapped nitric oxide and lipoperoxide radicals approach to control data) has been observed. It is concluded that combined treatment of patients suffering from parodontitis using preparations of antioxidant and immunoregulatory activity results in long-term remission of disease.

[Microbiological investigations and studies of phagocytic activities of peripheral neutrophils during the treatment of parodontitis by Unimag].

During the treatment by Unimag (UN), quantity of microbes in the mouth cavity of patients with periodontitis (PD), significantly decreases in comparison with the patients treated by traditional scheme. That is due to direct and indirect influence of UN on the pathogenic microorganisms. During the treatment of patients with PD by UN, quantity of Gram-negative microbes gradually decreases and their substitution by Gram-positive microbes, typical for mouth cavity, takes place. On the background of the treatment by UN, phagocytic activity (PA) of polynuclear cells (PC) increases. In comparison with the patients treated by traditional scheme, increases both phagocytic number and number of active neutrophils. On 14-15 days after beginning of treatment of patients with PD by traditional scheme, PA of PC does not change significantly. Reduction of the microbial number in the mouth cavity and the active substitution of Gram-negative microbes by Gram-positive microorganisms during the treatment of patients with PD by UN, have prognostic importance and together with the reinforcement of PA of PC indicate to the improvement of the therapeutic effect and shortening of the duration of the treatment.

Some opinions about matter and material substances: from inanimate system -- to living according to A. Einstein general theory of relativity.

During transformation from inanimate to living, change of the space position of the matter causes the change of the field, as the space does not exist without the field, therefore the time-space as the properties of material substances, should undergo certain changes. The outside inanimate system, in this case a matrix, has its own time. The living system, in this case a cell, where the matter undergoes space conformation with the change of field and space-time, has its own time and it has begun to flow more rapidly than in matrix. From the surface of the body, from different energetic reservoirs oppositely charged matter substances following from special transport systems from the life system transmitted into lifeless one and change their matter space conformation, create transmission gradient that is the gradient border of time from lifeless system into live. In the case of a human, hypothetically, the gradient system of time must be of a complex scheme counting the inter-transformation and interaction gradients of outer and inner abdominal systems. Subconscious and consciousness by means of special links and messages, information selection interact and form unique connection between the systems. Subconscious serves for accelerated time system. Conscious by means of permanent contact with the environment collects and reacts in matrix time system By interconnection of these two systems ideal adaptation with the environment takes place. Time difference gradient system is an additional energy factor, by means of which respective ordered geometrical structures special for the given types are formed. The living organism is an inter-regulated interconnection global system resulting from the changes of matter and material substances space configuration.

[Changes of local resistance of oral cavity and humoral immunity among workers of metallurgical and chemical production during parodontitis].

On the basis of the data of immunological investigations of 142 workers of metallurgical (melting shops of Zestaphoni's Farroalloy Plant) and chemical (electrolytic shops of manganese and dioxide manganese of Farroalloy Plant and "Azoti") production it was found that during parodontitis among studied contingent local resistance of mouth cavity and humoral immunity are changed, the compound of lysozyme and amylase in saliva is lowered, in the layers of saliva and blood is revealed the misbalance of immunoglobulin's system. First of all was established, that during parodontitis among the studied workers autoimmune processes are developed directed against the I-st type collagen and the tissue of gum. Changes of local and common homeostasis as well as the changes of intensity of autoimmune process are in direct correlation with the severity of parodontitis and the pollution of production environment with the spray of manganese dioxide.

[Dynamics of leukocytes' migration degree in oral cavity and parameters of INFgamma and TNFalpha in blood serum of patients suffering from parodontitis on the background of treatment with Unimag].

In the oral cavity of patients with parodontitis before treatment the quantity of migrated leukocytes (ML) was increased. Among them number of living cells was sharply reduced. In the process of treatment on the background of immune modulation with Unimag, the concentration of migrated leukocytes decreases and number of living leukocytes increases. The above-mentioned quantitative and qualitative parameters of migrated leukocytes were normalized after 1-1.5 months. The analogical dynamics has been detected in patients suffering from parodontitis and treated with traditional scheme. However, despite reduced concentration of migrated leukocytes and increased percentage of living leukocytes' content, normalization of the mentioned parameters has not been detected. In the blood serum of patients suffering from parodontitis increased concentration of INFgamma and TNFalpha have been revealed. In the process of treatment, concentration of the mentioned cytokines was decreased, however, in patients treated with Unimag on the background of immune modulation, decrease in concentration of INFgamma and TNFalpha was much more expressed.

[Humoral mechanisms of autoimmune process against type I collagen in psoriasis].

Psoriasis represents disease with the involvement autoimmune mechanism against type I collagen, and its degree depends on the form of the disease and its clinical course. There is direct association between the autoantibody titres against type I collagen and the severity of the disease. As developed autoimmune process against type I collagen is specific in traditional treatment process, in spite of definite clinic effectiveness, without usage of specific factors there is no involution in autoimmune process against type I collagen. 134 patients with psoriasis have been investigated. 94 of them had vulgar psoriasis, 20 had erythrodermal form and 20 had arthropatic form. 50 healthy subjects were included in the control group. The age of patients varied from 20 to 70 years. It is confirmed that by treatment using miolophid immunomodulation autoantibody against type I collagen has decreased and treatment was relatively effective. It should be mentioned that despite immunomodulation therapy and achieved effect, there is no complete involution of autoimmune process, as in the case of psoriasis clinical and biological recovery periods do not coincide and thus after discharging from hospital prognosis must be controlled by measuring of autoantibody titres.

[Correlation of local immune system indices of patients with tuberculous and serous meningitis]. / Vzaimosviazi pokazatelei mestnoi immunnoi sistemy bol'nykh tuberkulezom i seroznym meningitom.

The method of discrete-dynamic analysis was used for studying the immunity system state in 60 patients with tuberculous meningitis (TM) of various degree of severity and in 35 patients with serous meningitis of nontuberculous etiology (SMNE). A significant difference was established of the correlation between parameters in the combinations comprising lymphocytes immune to Mycobacterium tuberculosis which enables TM and SMNE differentiation. TM was characterized by a sharp increase in the number of correlations (intensity) in the parameters as compared with SMNE. Intensity significantly declines in the fatal outcome of TM as compared with this parameter in the survived patients. In SMNE local immunity state normalizes (intensity decline) in 1.5-2 months, in TM of moderate severity in 3 months and in a serious course (during the follow-up) intensity does not decline.

[Immunologic aspects of the pathogenesis of latent and seroresistant forms of syphilis]. / Immunologicheskie aspekty patogeneza skrytykh i serorezistentnykh form sifilisa.

Studies of the cellular and humoral immunity in patients with latent and seroresistant syphilis have revealed decreased content of T-lymphocytes and elevated levels of B- and antigen-reactive lymphocytes. Reduced T-cell level is due to a decrease of the T-suppressor subpopulation. Unlike latent syphilis, seroresistant form is associated with a complete disappearance of the theophylline-sensitive subpopulation, whereas T-lymphocytes are represented mainly by the theophylline-resistant (helper) subpopulation. Effective therapy of patients with seroresistant syphilis has normalized the counts of T- and B-antigen-reactive lymphocytes, and theophylline-sensitive cells appear in the blood. These data give grounds to prescribe immunostimulating therapy to patients with seroresistant syphilis.

[NK cells in patients during complex therapy of destructive pulmonary tuberculosis]. / NK-kletki u bol'nykh v protsesse kompleksnoi protivo-tuberkuleznoi terapii destruktivnym tuberkulezom legkikh.

Functional activity of peripheral blood NK-cells was studied in 85 patients aged 18 to 72 years with active destructive tuberculosis of the lungs. There was detected a significant decrease in the activity of the NK-cells them. The most pronounced decrease was observed in the patients over 50 years. The changes in the functional activity of the NK-cells during chemotherapy correlated with the time course of the tuberculosis process. The results of the study provided the use of the NK-cell activity index in addition to the other indices in estimation of the patients immunity status and control of the treatment efficacy. For correction of immunodeficiency detected by the NK-cell activity early use of immunostimulating agents in the combined therapy of the patients with destructive tuberculosis of the lungs was required.