The problem of free radical pathology, the most important characteristic of which is the accumulation of toxic products of lipid peroxidation, is of exceptional scientific and practical importance. Radical oxidative processes are a significant pathogenetic factor in many diseases and pathological conditions (1,2,4,7,11). One of the important aspects of studying the pathogenesis of various diseases is the study of the state of lipid peroxidation and the antioxidant system. Violation of the stationary state of free-radical oxidation is considered one of the universal, non-specific indicators of the presence of damage and is characteristic of a wide variety of diseases: atherosclerosis, stress, neuroses, diabetes mellitus, inflammatory processes, autoimmune diseases, etc. (3,5,6,8,9 ,10).
Одним из факторов, способствующих развитию глаукоматозного процесса, по мнению ряда авторов, является нарушение баланса между процессами перекисного окисления липидов (ПОЛ) и состоянием антиоксидантной системы в камерной влаге глаза [1,4]. Усиление процессов ПОЛ ведет к угнетению адаптационных механизмов в структуре глаза [1,3], ухудшению микроциркуляции и кровоснабжения трабекулярной ткани глаза, способствующих снижению уровня секретируемого белка в слезной жидкости, зависящего от степени ПОУГ [2,3]. С интенсификацией ПОЛ связывают структурные и функциональные изменения глаза. Все это обусловливает необходимость коррекции нарушенного антиоксидантного статуса в глазном яблоке с использованием.
Subjects of the inquiry: 103 patients with rheumatoid arthritis, 20 healthy individuals.
Aim of the inquiry: To study therapeutic effect of low frequency physical factors on the cytokines and the processes of lipid peroxidation and to confirm scientifically the efficacy of their use based on the their effect on the clinical laboratory findings.
Methods of investigation: Clinical and laboratory investigations, immunological analyses of the blood scrum cytokine levels and synovial fluid, biochemical examinations of the lipid peroxidation and antioxidant system indicators, phospholipase-A2 activity, nonspecific phosphatases and free oxyprolinc in the blood serum of patients.
The results achieved and their novelty: There was studied clinical efficacy of ultraphonophoresis with benzketozon during treatment and rehabilitation of the patients with rheumatoid arthritis. It was proved that disbalance between inflammatory and anti-inflammatory cytokines as well as lipid peroxidation activation activity in the erythrocyte membranes and blood scrum destabilized cellular membrane structures, increase in phospholipase-A2 activity and, consequently, stimulating prostaglandines, inflammation mediators, synthesis. There was shown that complex therapy with inclusion of low frequency physical factors, particularly ultraphonophoresis with benzketozon, gave marked positive effect normalizing interrelation ship between inflammatory and anti-inflammatory cytokines reducing activity of phospholipase-A2, lipid peroxidation products and rising the levels of antioxidant system indicators.
Practical value: There has been shown rationality of inclusion of the physical-pharmacological method ultraphonophoresis with benzketozon into clinical practice. The differential indicators developed for application of low-frequency physical methods of therapy for rehabilitation of the patients with rheumatoid arthritis allow prolongation of the remission, improvement of the patients life quality.
Degree of embed and economic effectivity: The practical recommendation and guidelines have been applied in the clinical practice of the out-patient special course of arthrological treatment in the Republican Rhcumatological Center, Clinical Hospital N 1, Central Hospital of Zangiota district of Tashkent province. Sphere of usage: Rheumatology, physiotherapy.
В настоящее время установлено, что одним из ведущих механизмов повреждения мембран является активация перекисного окисления липидов (ПОЛ) на фоне снижения уровня антиоксидантной защиты (АОС), а эффективным средством для их восстановления являются антиоксиданты.
The goal of the research was to study the infringements of metabolizmes catecholami- nines and processes of peroxide oxidation of lipids (POL) at the patients with familial hypercholesterinemia. The subjects of the
study were 92 patients with familial hypercholesterinemia and 15 practically healthy individuals. The study condition sympaticadrenal system (SAS) (increase excretions of catecholaminines: adrenaline (A), noradrenaline (NA).dopamine (DA), DOPA), total cholesterol, cholesterol of low - density lipoproteins cholesterol of high - density lipoproteins, triglycerides, processes of peroxide oxidation of lipids and monoamoxydasa in plasma of blood . The study revealed that abnormalities activity of SAS
patients with familial hypercholesterinemia. low activity monoamoxydasa in plasma of blood and significantly higher level of POL, it was verified by increased level of malonic dialdehyde - final substance of peroxidation
In experiments on white rats it was established that administration of heliotrine during a month induced severe damage to the liver characterized by enhancement of lipid peroxidation, a decrease of enzyme activities - superoxide dismutase and catalase. Liquorice, immortelle flowers and mumie inhibited manifestation of heliotrine hepatitis and exerted antioxidant action. In combined use of natural compounds their antioxidant action increases.
Topicality and demand of the subject of dissertation. Researches of human population genomic variety and scenarios of its genetic pool formation arc one of perspective directions of modem genetics. Prompt progress in this field has allowed defining the basic routes of continents settlement. However the information about Central Asian (CA) populations even on «classical» genetic markers has accidental, fragmentary character, and requires additional large-scale investigations. Besides, according to historical, archeological, paleontological and some anthropogenetic studies, given region was playing certain role in ancient moving of modem human ancestors throughout Eurasian continent. Therefore it is extremely important to summarize and perform complex assessment of new and collected data on Central Asian populations as practically there arc no multivariate analyses studies of given region as a complex population system.
In studies of human population genetic structure arc usually used various approaches allowing understanding concept of populations subdivision and character of genetic relationships between them. Among these techniques the prominent place belongs to approaches based on an assessment of genetic distances between populations with their subsequent analysis by multivariate statistics methods. For even more compelling picture of the relationships between the populations on tree diagram we composed «the genetic landscape» of area, where the description of population genetic structure is presented by equally spaced figures consistently consolidating populations according to their genetic distances from each other and thus creating a genetic landscape. This approach is not only a tool for elementary population boundary detection, but also can be effectively used for identification of borders and sizes of population as naturalistic unit.
Multigcnctic landscape is a collection of different genetic systems which arc specific to the region and ethnic groups, which have their geographical areas, their geographical, historical and cultural boundaries. Gene flows arc run through these conventional boundaries, but they arc less intense than in the limits of area. These limits arc ambiguous and fluid, but it is real. You can identify them by studying, for example, the structure of marriage migration. Therefore anthropogenesis of different populations will inevitably differ from each other. Ethnogenetic composition tends to change over time, from generation to generation, and hence there is a need to understand the structure of the genepool, not only at a given time, but also in the study of genetic processes that form and reform the gcncpooL In this regard, the studying of multigcnctic landscapes is in close contact with the demographics, medical and genetic ecology, anthropology, ethnology, archeology and history of the peoples, that is, with a range of areas, not only natural, but also the humanities knowleges.
Study of genomic diversity is important not only to address questions of origin and genetic history of different ethnic groups, but is also the basis for molecular epidemiology of hereditary and multifactor diseases. Each region is characterized by a specific set of common genetically determined diseases. To understand the causes of the prevalence of disease in different regions, and to develop approaches to their early DNA diagnosis and effective prevention, initially it is necessary to conduct population-based studies, which determine the development of the disease.
Purpose of research is to implement a comprehensive description of the structure of indigenous Central Asian populations genetic pool, examine demographic, phylogenetic and evolutionary features of Central Asian populations through the analysis of genetic variety of mtDNA, Y-chromosomal (NRY), autosomal, X-chromosomal microsatcllites and immunogcnetic variants of Helicobacter pylori (H.pylori) and hepatitis В virus (HB V).
To achieve this goal the following tasks of research is solved:
specification of immunogcnetic variants of H.pylori and HBV, allocated at the patients in Central Asian region, with the subsequent comparative phylogenetic analysis of H.pylori and HBV regional versions with those in other regions of the world;
examination of genetic variety and degree of genetic differentiation of Central Asian populations according to classical population-genetic objects -polymorphisms of mtDNA, Y-chromosomal, autosomal and X- chromosomal STRs;
assessment of the Western and East-Eurasian lines of population inheritance contribution to Central Asian populations’ genetic pool at regional, ethnic, sub-cthnic levels and in a level of elementary populations;
reviewing of character of regional populations relationships by genetic variety of mtDNA, autosomal, X-chromosomal, Y-chromosomal STRs markers in view of ethnographic, social and linguistic data;
evaluation of sex-specific genetic structure and the social organization according to polymorphisms of mtDNA, autosomal, X-chromosomal, Y-chromosomal markers in the region;
determination of ancient ways of migrations and scripts of formation of Central Asian populations according to mtDNA, autosomal, X-chromosomal, Y-chromosomal STRs markers and immunogcnetic variants of H.pylori and HBV',
evaluation of ethnogenetic position of studied Central Asian populations in the system of genetic pools of Eurasia and the world in general through comparative analysis of all studied population-genetic parameters.
Scientific novelty of dissertational research consists in the following:
for the first time was performed a study of genetic pool structure of 26 Central Asian populations from 6 ethnic groups as complete population systems using a wide range of genetic objects;
for the first time was made an assessment of informativeness of each type of genetic subjects. For the first time was received detailed characteristic of genetic pool structure of indigenous Central Asian population on the basis of variability lines of the spectrum of genetical objects;
for the first time was defined the ratio of Westem-and the East-Eurasian lines in a genepool of Central Asian population and were made an assessments of genetic variety level and genetic differentiation degree of regional populations as a whole;
for the first time phylogenetic analysis of major haplogroups of investigated genetic subjects was conducted;
for the first time the position of Central Asian population in population genetic pool system of surrounding regions and Eurasia in the whole was studied;
for the first time the evolutionary-adaptable mechanisms, necessary in the forecast of formations of multigenic pathologies in region were studied at 6 ethnoses of Central Asian.
CONCLUSION
1. H.pylori from Central Asian territory is similar to Western Europe isolates, and shaped by two ancestral populations genotype Ancestral Europe 1 (dominant) and Ancestral Europe2 and for AE1-genotype Central Asian region probably is the source. H.pylori from the territory of Central Asia form a separate cluster group: close relationship of Tadjik, Uzbek strains and Iranian isolates from the north of Iran is established. Kirghiz isolates were found to be closer to populations from territory of Siberia.
2. High diversity of HBV genotypes in Central Asia was found -4 genotypes (A, C, D, and G). Phylogenetic analysis of Central Asian genotype HBV-with options for other regions of the world showed a close relationship between the dominant genotype D (0,78), the D1-subtype with variants of the virus in Europe, the Middle East and Africa.
3. The rates of genetic affinity for STR-NRY in Kazakhs, Turkmens, Karakalpaks Turtkul at the level of the same lineage were high: 0,58 (p<0,001); 0,34 (p<0,01) and 0,77 (p<0,001), respectively. The coefficients of relationship at the level of clan for Kazakhs, Turkmens, Uzbeks and Karakalpaks from Kungrad and Turtkul were lower: 0,30 (r<0,01); 0,21 (p<0,001) and 0,40 (r<0,001); 0,07 (p<0,05) and 0,09 (p<0,05), respectively. At the level of the tribe, the indicators were negative for all Turkic populations: -0,02 (r<0,05);-0,04 (r<0,001);-0,07 (p<0,01); -0,0011 (r<0,1) and -0,10 (r<0,01), respectively.
4. The analysis of mtDNA HVS-1 showed that total rate of differentiation level for all populations was low: FST=0,013; p<0,0001. Level of diversity between groups was 0,6% (p<0,001) of the total variability. Parameter of genetic differences between Turkic and Indo-Iranian populations made 0,55% (p<0,0283) of the total genetic variability. The rate of genetic differentiation on a sub-ethnic level was significantly expressed in Indo-Iranian group (FST=0,0197;r<0,001) than among the Turkic-speaking (0,3%; p=0,10). In all populations, in general, wasn‟t detected the correlation between genetic and geographic distances at the global level on mtDNA HVS-1: r=0,00682; p=0,502.
5. Analysis of STR-NRY showed that the level of the genetic differentiation between ethnic groups was 5,6% (p<0,02); general differentiation between populations made RST=0,186 (p<0,001). Combined analysis, taking into account the language and way of life of Turkic and Indo Iranian populations, showed the general differences between the two groups – 9,1% Value of genetic differentiation when comparing the ethnos-ethnos was slightly lower than the level within ethnos: 5,6% among ethnic groups, 18,6%, and 13,7%-between populations within the ethnic group.
6. Analysis of heterozygosity (H) and the average number of pairwise differences (p) of mtDNA, were high in nomadic populations (av.H=0,99; av.p=5,29) and farmer populations (av.H=0,99; av.p=5,32). Heterozygosity (H) on Y- chromosome was lower in nomadic groups than in the agrarian – 0,86 and 0,99,respectively (p<0,01). Nomadic populations exhibit a higher level of population differentiation (RST) in comparison with farmers - 0,19 and 0,06, respectively (p<0,01). Indicators of population growth (r) were lower in nomadic populations compared with farmers - 1,004 and 1,008, respectively (p=0,056).
7. The level of genetic differentiation in all ethnic groups was higher on the Y chromosome in comparison with mtDNA. The farming populations showed no significant difference in the genetic differentiation FST (Y)=0,069 and FST (mtDNA)=0,034, while among patrilineal nomadic population the level of genetic diversity was higher in the male line of inheritance - FST(Y)=0,177 and FST (mtDNA)=0,010. Genetic diversity of population structure in patrilineal nomads on autosomal and X-linked markers were: FST (A)=0,008 (0,006-0,010) and FST (X)=0,011 (0,001-0,004) (H0: FST(A)=FST(X); H1: FST(A)>FST(X); p=0,02). In bilinear farmer populations the differences of autosomal and X-chromosomal markers were insignificant: FST (A)=0,014 (0,012-0,016) and FST (X)=0,013 (0,008-0,018 at p=0,36).
8. Analysis of mtDNA indicated that the age of expansion on the territory of Eurasia (τw) declined significantly from East to West (r=0,72; p<0,001). The age of expansion had a pronounced tendency to decrease from 30 thousand years in China to 17 thousand years in Western Europe. Age of expansion in Central Asia amounted to 26 thousand years. Results of expansion analysis on NRY also show a decrease in genetic diversity from the East to the West of Eurasia (r=0,49; p<0,001). In Central Asia this age was 16 thousand yrs. According STRs-NRYBatwing analysis of the minimal age of Uzbek population origin was 1232,71 yrs old (Ne=14088 (6765-23942); α=0,0108 (0,0065-0,0155)).
9. The apportionment of multilocus genetic variations among ethnic and linguistic groups of Central Asian populations showed that more than 98% of all variations were within the population (p<0,0001). Evaluation of the ethnic and linguistic affiliations in the observed variations showed reliable conformity - FST=0,007; p<0,0001 and FST=0,011; p<0,0001, respectively. We didn‟t find evidence of geographical isolation within each of the Turkic and Indo Iranian groups of populations (p=0,363 and p=0,772, respectively).
10. Analysis of multilocus allelic diversity (AR) and heterozygosity (He) showed differences among the Central Asian and other populations in allelic variety (χ2 =105,29; d.f.=25; p<0,0001) and heterozygosity (χ2=67,98; d.f.=25; p<0,0001). Population differentiation at multilocus analysis at populations of Central Asia is more pronounced than in the other regions of Eurasia: in European and Middle Eastern groups pairwise estimation of FST ranged from 0,011 to 0,015 and -0,008-0,021, respectively; in East-Asian groups from -0,011 to 0,046; and finally, in Central Asia these rates ranged from -0,004 to 0,056. Heterozygosity was significantly higher in the group of the Indo-Iranian populations than among Turkic-speaking (He=0,818 and He=0,787, respectively; Z=-4, 55; p<0,0001). According to multilocus analysis all 26 Central Asian populations slightly but significantly differed (FST=0,015; CI99%=0,011-0,018; p<0,01).
An increased tendency towards high morbidity of liver diseases requires a detailed study of the pathogenesis of the liver and the search for effective hepatoprotectors that can eliminate pathobiochemical changes in hepatocytes: increased lipid peroxidation against the background of a decrease in the activity of antioxidant defense enzymes and a violation of the lipid composition of membranes.
Liver pathology leads to a violation of lipid metabolism, because it plays a leading role in this metabolism. The synthesis of bile is disrupted, hydrolytic enzymes are activated, the synthesis of phospholipids decreases, the digestion of lipids in the gastrointestinal tract and the absorption of fat breakdown products, as well as fat-soluble vitamins, including the antioxidant vitamin E are disrupted.