[NORMATIVE AND LEGAL ASPECTS OF THE FORMATION OF THE BASIC PREREQUISITES OF PUBLIC HEALTH (PUBLICATIONS REVIEW)].

Preservation of public health is the main goal of social progress and development of the society. The search for potential opportunities to improve individual and public health indicators is a positive predictor of increasing the socio-economic efficiency of the society and increasing the healthy life expectancy of citizens. The scientific review provides arguments in favor of the need for professional collaboration of specialists from various industries in order to universally realize the most important right of citizens to protect their own and public health. Regulatory legal documents defining national and international policy in the field of health protection and forming the general vector of development of health care activities were used as the sources of information for the formation of the basis of the study. As a result of a logical generalization of global and national priorities and trends in the development of the healthcare sector, the main prerequisites (determinants) of health saving of citizens, adopted by the world community and reflected in domestic documents, are formulated. The main prerequisites (determinants) of health are defined as: promotion of activities that advantage health protection; creation of a single preventive space; specification of the concept of "responsible attitude to health"; coverage of the entire life cycle of a person and all spheres of his activity in the formation of a responsible attitude to health and motivation for its preservation; development of information technologies in the field of health protection; expansion of intersectoral and interdisciplinary cooperation in order to maintain and strengthen health; improvement of public health literacy; transformation of health services from the standpoint of health protection; development of human resources to ensure health-saving activities. The identified determinants of the preservation of individual and public health can act as a theoretical basis for the development of a scientific and practical methodology aimed at solving problems of improving health through the potential of interdisciplinary interaction of specialists in various fields of activity.

Effect of 4-Methyl-Phenyl Biguanide on Free Radical Homeostasis and Activity of Oxidative Metabolism Enzymes in Rats with Cardiovascular Pathology Developing against the Background of Rheumatoid Arthritis.

We studied the effect of 4-methyl-phenyl biguanide, a substance chosen by PASS software (Prediction of Activity Spectra for Substance), on oxidative status and activity of oxidation metabolism enzymes participating in limitation free radical processes (aconitate hydratase, glucose-6-phosphate dehydrogenase, and NADP-isocitrate dehydrogenase) in the heart and blood serum of rats with cardiovascular pathology developing against the background of experimental rheumatoid arthritis. Activity of cardiomyocyte cytolysis markers in rat blood serum was also measured. Normalization of the studied parameters under the influence of the test compound in animals with experimental pathology attests to its positive effects on metabolic and free radical processes.

Human beta-defensin-2 controls cell cycle in malignant epithelial cells: in vitro study.

AIM: In the present research we analyze the mechanism of human beta-defensin-2 (hBD-2) influence on cultured malignant epithelial cell growth. MATERIALS AND METHODS: The analysis of a concentration-dependent effect of recombinant hBD-2 (rec-hBD-2) on cell growth patterns and cell cycle distribution has been performed in vitro with 2 cell lines (human lung adenocarcinoma A549 cells and human epidermoid carcinoma A431 cells) using MTT test, flow cytometry and direct cell counting. To study intracellular localization of hBD-2 immunocytofluorescent and immunocytochemical analyses were applied, and effect of hBD-2 on signal cascades involved in cell cycle regulation has been studied by Western blotting. RESULTS: According to our data, rec-hBD-2 exerts a concentration-dependent effect on the viability of cultured A549 and A431 cells. It causes proproliferative effect at concentrations below 1 nM, significant suppression of cell proliferation at concentration range from 10 nM to 1 µM (p<0.05), and cell death at higher concentrations. Using flow cytometry we have demonstrated that hBD-2 dependent growth suppression is realized via cell cycle arrest at G1/S phase (p<0.05). Also, we have registered significant activation of pRB and decreased expression of Cyclin D1 in cells treated with the defensin compared to untreated control cells, while the expression of p53 remains unaffected. The study of intracellular localization of hBD-2 in these cells has revealed that exogeneously added defensin molecules enter the cells, are distributed throughout the cytoplasm and could be detected in cell nuclei. The model study using A549 cells treated with 1,25-(OH)(2)D(3) has shown similar cell growth suppression effect of native endogenously produced hBD-2. CONCLUSION: The results of our study suggest that in malignant epithelial cells hBD-2 may control cell growth via arrest of G1/S transition and activation of pRB.

1,2,4-Triazoloazine derivatives as a new type of herpes simplex virus inhibitors.

A new class of inhibitors of herpes simplex virus replication was found. The compounds under study are derived from condensed 1,2,4-triazolo[5,1-c][1,2,4]triazines and 1,2,4-triazolo[1,5-a]pyrimidines, structural analogues of natural nucleic bases. Antiherpetic activity and cytotoxicity of the compounds were studied. The corresponding triphosphates of several active compounds were prepared and tested as inhibitors of DNA synthesis catalyzed by herpes simplex virus polymerase. The potential mechanism of their action is blocking of DNA dependent DNA polymerase, a key enzyme of viral replication.

Administration of vitamin D3 improves antimetastatic efficacy of cancer vaccine therapy of Lewis lung carcinoma.

AIM: To analyze antitumor efficacy of experimental cancer vaccine therapy combined with introduction of vitamin D3 (VD3) for treatment of Lewis lung carcinoma (3LL). MATERIALS AND METHODS: Cancer vaccines composed from recombinant murine beta-defensin-2 (mBD-2) and 3LL cell lysate, or DNA, coding for mBD-2-Muc1 fusion construct cloned in pcDNA3+ vector, were prepared and used for intradermal vaccination. Experimental cancer vaccines introduced i. d. at therapeutic and prophylactic regimens to 3LL-bearing C57Bl mice, were applied alone or in combination with VD3 (administered per os) and/or low-dose cyclophosphamide (CP, administered intraperitoneal). Efficacy of treatments was analyzed by primary tumor growth dynamics indexes and by metastasis rate in vaccinated animals. RESULTS: As it has been shown, administration of the protein-based vaccine composed from mBD-2 and 3LL cell lysate in combination with VD3 and CP, but not in VD3 free setting, led to significant suppression of primary tumor growth (p < 0.005) and had significant antimetastatic effect. Introduction of VD3 with or without CP in the scheme of treatment with mBD- 2-Muc1-DNA vaccine at therapeutic regimen has led to significant suppression of primary tumor (p < 0.05) and metastasis volumes (p < 0.005), while in the groups of animals treated with DNA-vaccine + VD3 with or without CP at prophylactic regimen, significant antimetastatic effect (p < 0.05) and elevation of average life-span (p < 0.05) have been registered. CONCLUSION: The results of this pilot study have shown promising clinical effects of VD3 administration in combination with cancer vaccinotherapy in vivo.

Immunohistochemical analysis of beta-defensin-2 expression in human lung tumors.

AIM: The present research was directed on analysis of the expression patterns of human beta-defensin-2 (hBD-2) in human lung tumors. MATERIALS AND METHODS: Specimens of surgically resected human lung tumors (n = 31) of different histological type (1 case of small cell lung cancer, and 30 cases of non-small cell lung cancer (1 case of clear cell carcinoma, 9 cases of squamous cell carcinoma (SCC), and 20 cases of adenocarcinoma (AC)) were analyzed for expression of hBD-2 with the use of immunohistochemical analysis. RESULTS: Immunohistochemical analysis has revealed that all lung tumor samples independently on their histological type express hBD-2 peptide, however at different levels (from < 5% to 100% cells). According to our observations, low-differentiated AC differs from moderately differentiated AC by significantly lower hBD-2 expression levels (p < 0.05). No correlation between hBD-2 expression patterns and PCNA or Bcl-2 expression has been found. CONCLUSION: Human beta-defensin-2 expression levels may depend on differentiation grade of lung adenocarcinoma.

Expression patterns of murine beta-defensin-2 mRNA in Lewis lung carcinoma cells in vitro and in vivo.

AIM: To evaluate the anti-tumor activity of murine beta-defensin-2 (mBD-2) expression in vitro and in vivo. MATERIALS AND METHODS: Based on pcDNA3 vector, constructs containing mBD-2 cDNA coding mature defensin molecule (pcDNA3-mBD2), and Igk-mBD-2 insertion, coding secretory sequence plus mature defensin molecule (pcDNA3-Igk-mBD-2) were generated. Lewis lung carcinoma (3LL) cells were transfected in vitro with these plasmids and with blank pcDNA3 vector, and the proliferative rate and clonogenic ability of obtained cell lines cultivated in vitro were analyzed using (3)H-incorporation technique and colony formation in semi-soft medium, respectively. Expression of mBD-2 mRNA was studied by semiquantative RT-PCR analysis. Also, transfected cells were transplanted to C57B mice, and the patterns of tumor growth in vivo were analyzed by routine techniques. RESULTS: We have found out that in the 3LL cells transfected with pcDNA3-mBD-2 and pcDNA3-Igk-mBD-2, the expression of mBD-2 mRNA is significantly down regulated compared to wild-type cells and 3LL cells transfected with blank vector. The cells with suppressed mBD-2 expression differed from parental cells and cells transfected with blank vector by higher proliferation rate (p < 0.001) and higher clonogenic ability. The 3LL-mBD-2 and 3LL-Igk-mBD-2 cells that are transplanted to C57B mice gave rise to more aggressive tumors that possessed significantly higher growth rate (p < 0.01) than those that arise from wild-type 3LL cells. CONCLUSION: The obtained results indicate the relation between mBD-2 expession in 3LL cells and their proliferation rate and malignant phenotype, and also allow to hypothesize the possibility of regulation of mBD-2 mRNA expression in these cells by a feedback mechanism.

Expression of human beta-defensins-1, 2 and 4 mRNA in human lung tumor tissue: a pilot study.

AIM: To analyze the patterns of human beta-defensin-1, 2, 4 (hBDs) expression in human lung tumors. MATERIALS AND METHODS: Tissue samples of surgically resected human lung tumors (squamous cell carcinoma (SCC), n=10; adenocarcinoma (AC), n=10) paired with conditionally normal tissue samples were analyzed for expression of hBD-1, 2, 4 mRNA by semiquantitative RT-PCR. RESULTS: In a number of studied lung cancer tissue samples, overexpression of defensin mRNA was registered: hBD-1 mRNA (50% of SCC and 60% AC), hBD-2 mRNA (60% of SCC and 50% of AC) or hBD-4 (40% of SCC and 20% AC). No correlation was detected between the levels of hBD-1, hBD-2 and hBD-4 mRNA and histological type, differentiation grade of the tumor, and the stage of the disease, as well as the content of hBD-2 peptide in blood serum of lung cancer patients. CONCLUSION: Human beta-defensins-1 and -2 are often up-regulated in human lung tumors.

Regulated expression of human beta-defensin-2 leads to altered phenotype and growth patterns of cultured human embryonal kidney cells.

AIM: To create cell line with regulated expression of human beta-defensin-2 (hBD-2) and evaluate the influence of expressed peptide on its phenotypic and growth patterns. MATERIALS AND METHODS: Using cloning techniques, on the base of human embryonic kidney cells of HEK293T line, stable T-rex HEK-hBD2-m cell subline expressing mature biologically active hBD-2 molecule upon the presence of tetracycline in culture medium was generated. The morphological patterns, growth characteristics and colony forming activity of these cells were studied using routine techniques. RESULTS: T-rex HEK-HBD2-m cell subline was shown to express both mRNA and hBD-2m protein upon the presence of 1 mug/ml tetracycline in culture medium as it was demonstrated by RT-PCR and immunocytochemical approach. Upon prolonged expression of hBD-2, the cells acquired special features: they lost ability to grow in monolayer in vitro and to form colonies in soft agar, characteristic to parental HEK293T cells, but possess higher growth rate and longer survival in FBS-free medium than wild type cells. CONCLUSION: Expression of hBD-2 in T-rex HEK-HBD2-m cell subline results in specific biological consequences that favor cell survival.

[Efficiency of iodine prophylaxis in pregnant women with nontoxic diffuse goiter in a mild iodine-deficiency area].

Thirty-four pregnant women with nontoxic diffuse goiter (NDG), living in a mild iodine-deficiency area, were examined. The absence of iodine prophylaxis causes a higher than normal increase in thyroid-stimulating hormone levels by the end of pregnancy and a high frequency (87.5%) of hypothyroxinemia In the second half of pregnancy. These unfavorable events are prevented by the administration of iodine in a daily dose of 150-200 g; the early initiation of iodine prophylaxis is most effective. In women with NDG, pregnancy is most commonly complicated as threatening miscarriage, particularly in those who have not received iodine prophylaxis. Smoking during pregnancy enlarges the thyroid, which is not prevented by iodine prophylaxis.

[The biological characteristics of Shigella flexneri strains circulating in Saint Petersburg in 1992-1994]. / Biologicheskaia kharakteristika shtammov Shigella flexneri, tsirkulirovavshikh v Sankt-Peterburge v 1992--1994 gg.

S.flexneri 2a strains isolated in 1992-1994 from 371 patients in sporadic cases, from 90 patients and their contacts in cases of group diseases and from 71 lethal cases of Flexner's dysentery, were studied in comparison with strains isolated in 1980s. The study revealed the biological heterogeneity of S.flexneri 2a strains. The circulation of 3 enzymatic variants and 11 variants differing in their sensitivity to colicins from Frederick's collection was established. The overwhelming majority of strains circulating in 1990s were resistant to 6-7 antibiotics, while the strains isolated in 1980s were resistant only to 4 of these antibiotics. The strains under study possessed antilysozyme activity, as well as pronounced invasive properties. The circulation of the population of multiresistant strains in the city could affect the course of present-day Flexner's dysentery and their domination in the ecological structure of Shigella infections.

[Creatine phosphokinase in the cerebrospinal fluid of patients with acute meningitis]. / Kreatinfosfokinaza v spinnomozgovoi zhidkosti u bol'nykh ostrymi meningitami.

A study is presented of the general activity and isoenzymatic spectrum of creatine phosphokinase (CPK) in the cerebrospinal fluid (CSF) in patients with acute meningitis of different etiology. The enzymatic activity proved to be increased due to the cerebral (CPK-BB) isoform. Liberation of CPK-BB from the brain tissue and its penetration into the intercellular fluid and then into the CSF was related to the functional-structural changes in the cellular membranes of the brain in meningitis.

[Analysis of recording of cardiac rhythm and myocardial function after exercise test]. / Analiz izmereniia serdechnogo ritma i funktsional'nogo sostoianiia miokarda pri vypolnenii fizicheskikh nagruzok.

A continuous telemetric registration of the cardiac contraction rate was made in 534 persons performing various physical exertions. The ensuing epxerimental graphs of changes in the rhythm obtained under the effect of physical loads are described by mathematical formulas. Three types of changes in the rhythm in effort have been established, viz. linear, exponential and logarithmic. To determine cardiac function quantitative coefficients, reflecting the rate of the cardiac rhythm coming up to the working level and relationship between the areas of the steady state cardiac contractions frequency phase and that of its rapid increment, are proposed.

[Mnestic disorders in tumors of the temporal lobe]. / Mnesticheskie narusheniia pri opukholiakh visochnoi doli

The paper contains some results of a neuropsychological study of memory in 32 patients with tumors of the temporal lobe. The authors distinguished syndromes of disturbed speech memory (mainly--auditory-verbal) in tumors of the medial, posterior and, to a less degree, frontal areas of the left temporal lobe. In tumors of the right temporal lobe changes of memory were less expressed and had prevalently a visual-image character. An involvement into the process of the hyppocampus leads to a model nonspecific drop of short-time memory, while the expansion of the tumor towards the diencephalo-mesencephalic structures--to a formation of the Korsakoff syndrome. The results of the study demonstrate a certain correlation of disturbed memory with degree of emotional changes. It is being assumed that the defect of a retarded reproduction is due to an inertia of the nervous processes.

[Memory disorders in epileptic children with temporal psychomotor seizures]. / Narushenie pamiati u bol'nykh épilepsiei s psikhomotornymi visochnymi pripadkami

The authors demonstrate the results of experimental psychological examination of memory in 57 patients with epilepsy in psychomotor temporal seizures. It was possible to show that in such cases there was a total decline of short-time memory. In bilateral foci and a long-term development of the disease there was a formation of an amnestic syndrome. The most distinct changes were seen in a delayed reproduction. In an electrostimulation of the structures of the temporal lobe by means of implanted electrodes the experiments displayed an intactness of direct reproduction during a stimulation of the neocortex, a moderate decrease in a stimulation of the hypocampus and a grave -- when stimulating the amygdalar complex.