CC BY
31
Section 9. Medical science
Section 9. Medical science
Akhmedov Khalmurad, Tashkent Medical Academy Candidate of Science, assistant professor, Independent researcher, the department of training of the general practitioner
E-mail: khalmurad@rambler.ru Farrukh Khaydarov, Tashkent Medical Academy Independent researcher, the department of training of the general practitioner
E-mail: dr.farrux@gmail.com Noila Khudaybergenova, Tashkent Medical Academy Independent researcher, the department of training of the general practitioner
E-mail: hnoila9@mail.ru
Shifts immunological parameters in rheumatoid arthritis depending on the geographical and ecological zones of Uzbekistan
Abstract: The comparative analysis shows that the immunological parameters of RA differs in three zones of Uzbekistan, which does not exclude the probability of the impact of climatic and geographical factors of the environment on the course of disease.
Keywords: rheumatoid arthritis, immune status, geographic zone.
Introduction
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of connective tissue, characterized by destructive joint alterations, in the pathogenesis of which autoimmune mechanisms play a significant role [8, 317-334]. RA remains an urgent problem due to the widespread prevalence (up to 1% occurrence among the World population, with an annual incidence of new cases with 0.02%), affection of individuals mostly in young and middle-most working age [6, 1085]. Generalized immune inflammation with progressive dysfunction of the joints and internal organs in RA leads to a marked reduction in quality of life and in fact 50% ofpatients are become disabled within 5 years, and among them 10% losetheir working ability in the first two years of disease.
In recent years, there is dispute over a possible connection between the development as well as characteristics of the subsequent course of RA and environmental factors [5, 1081-1087]. RA is a multifactorial disease in which the interaction between the genetic component and environmental factors is responsible not only for the development of the disease, but also for its marked clinical polymorphism. The prevalence of RA. is determined by the environmental condition in a given region [5, 1081-1087], which determines the further prognosis.
It is believed that the determination of the impact of adverse environmental factors (air, soil, and groundwater) on patients with RA will contribute to the understanding of the new aspects of pathogenesis of the disease [1, 35].
To date, Uzbekistan is the subject of many studies of medical and geographic focus, as Republic is distinctive because of its geographical location, climate and nature of the industrial and agricultural development. Moreover, special attention should be paid to the environmental problem in certain areas of the Republic. As it is known, deterioration of the nature does not occur immediately or instantly, this process is observed for a long time, in other words, the environmental situation is gradually accumulated. One of thehuge environmental problems of Uzbekistan is the high degree soil salinity. A real threat to the intensive soil contamination is a various kinds of industrial and domestic waste [1, 36-37]. One of the major problems is the quality ofwater resources, the issue of the Aral Sea, and the threat of ecological security in the country and the pollution of air space. For Uzbekistan, that is located in the arid zone, the presence of major natural sources of dust atmosphere, as the Kara Kum desert and the KyzylKum with frequent dust storms are characteristic. Therefore, we believe that the current study in this area is urgent, particularly with regard to environmental
68
Shifts immunological parameters in rheumatoid arthritis depending on the geographical and ecological zones of Uzbekistan
rheumatology and specifically on RA course in different climatic and geographical areas of Uzbekistan. Our interest is on features of the development and course of RA associated with environmental factors.
It is known that the long-term effects of adverse factors accompanied by depletion of functional reserve, and even a slight increase in the degree of tension of regulatory systems in response to the external environment, can cause the disruption of homeostasis [1, 36-37]. It is proved that the immune cells are highly susceptible to various changes of homeostasis, including to exposure to various xenobiotics [2, 320]. Some studies show that the formation of secondary immunodeficiencies, which are the trigger mechanism for the development of RA affects complex adverse climatic conditions [2, 320]. Analysis of clinical material in different regions will enable to study and evaluate the pathogenetic role of environmental factors, expand understanding of the occurrence features and course of disease. Thus, the study of the distinctionsof the immune status in RA patients according to the residential areas in Uzbekistan is ofboth scientific practical interests.
Therefore, aim of this study was a comparative analysis of immunological parameters in RA. among residents of different zones of Uzbekistan.
Materials and methods
The study included 78 patients with a documented diagnosis ofRA between the ages of 35 to 44 years (mean age 39,6±4,2 years), the disease duration of9,3±2,4 years. The control group consisted of15 healthy volunteers who were matched for age and sex with the members of main group.
The studies were conducted on the residents with RA. of the following regions of Uzbekistan, representative for age, level of activity, and duration of the disease: the north — Tashkent city, I area (n = 25); Western — Khorezm region, II area (n = 25), as well as east — Namangan region, III area (n = 28).
A comparative analysis was conducted by comparing the parameters of the immune status of RApatients, residing in different regions of Uzbekistan.
In an immunofluorescence test that used monoclonal antibodies for the revealing of a total pool of T-lympho-cytes, B-lymphocytes, an immunoregulatory subpopulation of T lymphocytes — CD4+ (helper) and CD8+ (suppressor) cells, natural killer cells, immunoglobulin G on у — positive B — lymphocytes, immunoglobulin M on p — positive B — lymphocytes was performed. An adhesion of molecules identified by a and ß chains of granulocytes, monocytes and natural killer cells were counted activated T lymphocytes, identifying interleu-
kin — 2 (CD25+ cells); revealed monomorphic determinant of HLA class I antigens (T-lymphocytes, mononuclear cells); — monomorphic determinant of class II histocompatibility antigens (B — cells, T — lymphocytes); — an antigen involved in cell apoptosis (CD95 + cells).
Statistical analysis of the results of research carried out by methods of parametric statistics with the calculation of the arithmetic mean values (M) and the mean square error (m). The significance of differences was assessed by Student’s T test with Bonferroni correction.
Results
Among the investigated patients females were predominant with the figure of 88.5%. Disability was found in the majority of the patients, i. e. 87.2%. Polyarthritis was the case in 98.7% of the patients. The first degree of inflammatory activity was detected in 3.8% of patients, the second — in 48.7%, and the third — in 47.5% of patients. In 78.2% of patients the seropositive form of RA. was determined. Radiographic changes of I-II grades were observed in 44.9% of patients, III-IV grades — in 55.1%. Systemic manifestations in the form of amyotrophy (70.5%), rheumatoid nodules (25.6%), fever (23.1%), lymphadenopathy (21.8%), hepatosplenomegaly (12.8%), digital arteritis (3.8%) were found in 47.4% of patients. The patients with II functional class disease was dominated — 38.5% and III functional class — 37.2%.
Besides the main complaints of patients to joint pain (98.7%) and morning stiffness (100%), the other most frequent complaints were general weakness (78.2%), irritability, sleep disorders and attention (55.1%), nervousness and anxiety (53.89%). Virtually all RA patients, regardless of the type of therapy, showedanemia signs of chronic inflammation.
Prospective studies illustrate that the indicatorsof RA patients in three different climatic and geographical zones have certain differences. So the comparison of the immune status of the three zones of monoclonal antibodies revealed significant T-cells differences. As can be seen from Table 1, there is a significant reduction in both the total pool of T lymphocytes (P <0.05) as well as their subpopulations — T-helper cells (P <0.05), and especially T-suppressors (P <0.02) in zone II. However, the results indicated that in the patients of I and III zon-esthe changes in T-cell immunity were absent. But, at the same time in patients ofzone I there was upward trend of T-suppressors.
As the result of study of B-mediated immunity it has been found that compared with healthy individuals there
69
Section 9. Medical science
is marked decrease tendency in RA patients in terms of total pool of B-lymphocytes and By-lymphocytes, and the content of Bp-lymphocytes had an increase trend. It should be noted that in patients of zone II (P <0.001) there was a significant increase in Bp-lymphocytes in comparison to the patients of other zones.
According to the literature [9, 223-224], natural killer cells are capable of enhancing the proliferation of T-cells forming colonies, to inhibit differentiation
of B lymphocytes and antibody synthesis. The study of the content in the peripheral blood of RA patients in regard tonatural killer cells showed their significant decrease in the I (P <0.01) and II (P<0.001) zones.
In RA. patients of all three zones compared with healthy individuals, there was a significant decrease in phagocytosis by neutrophils (p<0.02). The differences between the zones were not observed.
Table 1. - Indicators of the immune status
Investigated patients
Indicators Healthy Zone I Zone II Zone III
(n=25) (%) (n=25) (%) (n=28) (%)
T-lymphocytes 69,4±5,1 66,4±7,67 53,4±3,35* 67,8±5,67
B-lymphocytes 16,5±2,92 14,8±1,9 13,7±1,77 15,2±1,4
T-helpers 37,5±2,43 38,7±5,98 25,9±2,11* 39,7±3,26
T-suppressors 16,8±1,12 18,9±2,88 10,4±0,87** 14,8±3,22
NK 8,9±0,43 6,7±0,35*** 4,2±0,29**** 7,1±2,31
Phagocytosis 58,7±4,71 45,3±3,15** 44,4±3,61** 42,09±3,19**
B Y 9,1±2,4 8,4±2,27 7,2±1,55 7,9±2,34
B —i 4,4±0,25 6,5±0,88 6,6±0,28**** 6,1±0,57
Reliability indices are calculated in relation to the group of healthy volunteers (*Р<0.05, **Р<0.02, ***Р<0.01, ****Р<0.001).
The study of a number of differentiation antigens: CD 11b+, CD 18+, CD 25+ and CD 95+ in RA patients according to the residential areas in Uzbekistan was carried out for the first time. Besides, a detection of histocompatibility antigens ofclass I and II was examined. It was found, as illustrated in Table 2, in II zone patients with RA there is a decrease of CD 11b+, CD 18+, CD 25+ cells (P <0.05) versus indicators ofhealthy individuals. It is known that the molecule CD 11b (adhesion molecule — alpha chain) serves as a receptor for C3 bi-component of complement. The CD 18 is set of integrin alpha subunits: CD 11a, CD 11b, CD 11c. CD 25 molecule is a receptor
and the IL-2 is detected on activated T lymphocytes [4, 438-443], whereas these indices had no apparent changes in patients of other zones.
The study of determination of monomorphic determinants of class I histocompatibility antigens (HLA-1) showed a significant decrease in the patients of I and III zones (P <0,05) in comparison to healthy subjects. Concerning the detection of monomorphic determinants of class II histocompatibility antigens (HLA DR) may be noted that in patients with RA II zone marked improvement of their parameters, unlike in healthy volunteers (P <0,05).
Table 2. - Indicators of the immune status
Indicators Investigated patients
Healthy Zone I (n=25) (%) Zone II (n=25) (%) Zone III (n=28) (%)
CD11b+ cells 39,4±3,4 35,7±2,77 29,4 ± 2,22* 34,1±3,13
CD18+ cells 98,8±6,5 91,7±6,75 78,3 ± 4,51 * 86,4±5,147
CD25+ cells 45,9±4,3 39,9±4,5 31,2 ± 4,54 * 36,2±5,26
CD95+ cells 59,1±4,2 55,1±3,75 44,4 ± 4,83 * 48,8±5,9
HLA — 1 64,1±5,9 42,2±3,1* 59,7 ± 5,45 47,3±3,14*
HLA DR 60,7±4,3 62,1±6,55 74,6 ± 4,11 * 64,6±4,93
Reliability indices are calculated in relation to the group of healthy volunteers (*Р<0,05).
Discussion cytokine systems. In recent years, a significant progress,
It is known that an important role in the develop- in the study of the pathogenesis of RA, as well as in the
ment and progression of RA is given to lymphocyte and development of modern means of diagnosis and treat-
70
Shifts immunological parameters in rheumatoid arthritis depending on the geographical and ecological zones of Uzbekistan
ment, is reached. However, the study of molecular receptors lymphocytic system during RA remains urgent and under-investigated issue. This is due to the fact that the views on the content of the T-lymphocytes subpopulations in peripheral blood and their role in RA are limited and conflicting. According to the researchers, patients with RA compared with healthy subjects have the T-lymphopenia-a reduction in the relative content of CD3 + lymphocytes [8, 317-334]. In the peripheral blood of patients with RA, some authors found no significant alterations in the content of CD4+ T lymphocytes [8, 317-334], whereas others have revealed a significant increase ofthese cells [7, 1666-1672]. According to some researchers, in the peripheral blood of RApatients there is a marked reduction of CD8+ T lymphocytes as a result of balance violation of the immune response [3, 1677-1684]. According to others, in patients with RA content of CD8+ T-lymphocytes is normal or elevated [4, 438-443]. According to the literature, in the peripheral blood of RA patients there is increased content of CD8+ T-cell memory cells and reduced content of the effector cells, which is associated with accelerated differentiation of memory T cells with the phenotype CD4+ and CD8+ [10, 335-353]. In our opinion, this is due to the fact that the authors did not take into considerationthe environmental factors, which, as mentioned above, have an impact on the immune system. The results of our studies in a certain extent show, this phenomenon for the particular zone. Thus, in zone II the deficit of T-cell-mediated immunity is dominated, whereas in other zones the obvious changes are not expected. Moreover in the zone I there was an upward tendency of T-suppressors.
It is known that in RA patientsthere is an activation of humoral immune system, characterized by an increase in the content of B-lymphocytes in peripheral blood, which is accompanied by a raising ofIg and circulating immune complex [10, 335-353]. However,
our results showed a decreasetrend of the total pool of B-lymphocytes, which is probably due to the migration of B-lymphocytes from peripheral blood in the area of inflammation and this observation is consistent with the results ofseveral other authors [3, 1677-1684]. The results also had a number of distinctive features in regards to the content of subpopulations according to the area of residence, such as RA patients from the Kharezm region demonstrated marked elevation of the Вр-lymphocytesin the peripheral blood.
The study of a number of differentiation antigens presented on immunocompetent cells of RA patients revealed changes in their expression depending on the residential areas. Thus, the course of RA has a close relationship with the state of immunological shifts, which-presented with changes of cellular, humoral and non-specific immune deficiency parameters as well as indicators of a number of differentiation antigens (CD 11b +, CD 18+, CD 25+, CD 95+ cells and HLA-1) depending on the residential areas in Uzbekistan.
Conclusion
Overall, it was found that the development and course of RA is accompanied by disturbances in im-munoregulation, especially by changes of T-immunity, as well as the indices of a number of differentiation antigens (CD 11b+, CD 18+, CD 25+, CD 95+ cells and HLA-1).
A comparative analysis shows that the indicators of the immune status of RA. distinguish in three zones of Uzbekistan, which does not exclude the probability of the impact of climatic and geographical factors on the flow of disease. This calls for a more focused and detailed study of the influence of environmental factors on the development and progression of RA., which allow to mark possible ways of impact on the pathologic process, i. e. to develop a more rational basis for adequate therapy for improving the course of RA., and thus enhancing the quality of life of the patients.
References:
1. Малхазова С. М. Медико-географический анализ территорий: картографирование, оценка, прогноз. Изд. Научный мир. 2001, С. 35-37.
2. Хаитов Р. М. Иммунология: учебник/Р. М. Хаитов. - М.: ГЭОТАР-Медиа, 2009. - 320 с.
3. Adriaansen J., Tas S. W., Klarenbeek P. L. et al. Enhanced gene transfer to arthritic joints using adeno-associ-ated virus type 5: implications for intra-articular gene therapy//Ann. Rheum. Dis. - 2005. - 64, N 12. - P. 16771684.
4. Bank I., Coheu L., Monallem M. T cell subsets in patients with arthritis and chronic neutropenia//Ann Rheum Dis. - 2002. - Vol.61, № 5. - Р. 438-443.
5. Carmona L., Ballina J., Gabriel R., Laffon A. The burden of musculoskeletal diseases in the ge^ral population of Spain: results from a national survey. Ann.Rheum.Dis., 2001, 60, 11, 1040-1045.
71
Section 9. Medical science
6. Hakoda M. Absolute risk for fracture and WHO guideline. Epidemiology of rheumatoid arthritis/M. Hako-da//Clin. Calcium. - 2007. - Vol. 17, N 7. - P. 1081-1087.
7. Klimiuk P.A., Sierakowski S., Latosiewicz R et al. Mistological patterns of synovitis and serum chemokines in patients with rheumatoid arthritis // J Rheumatol. - 2005. - Vol. 32, №9. - P. 1666-1672.
8. Panayi G.S., Corrigall V.M., Pitzalis C. Pathogenesis of rheumatoid arthritis - The role of T cells and other beasts // Rheum. Dis. Clin. N. Am. - 2001. - 27. - P. 317-334.
9. Proffitt F., Bagla P. (2004) Ecology: Circling in on a vulture killer. Science, 306 (5694): 223-224.
10. Zhang Z.X., Bridges S.L. Pathogenesis of rheumatoid arthritis - Role of B lymphocytes // Rheum. Dis. Clin. N. Am. - 2001. - 27. - P. 335-353.
Belik Svetlana Nikolaevna, Rostov State Medical University, Candidate of medical sciences, Associate professor, the Faculty of general hygiene E-mail: superbelik@mail.ru Zhukova Tatyana Vasilyevna, Rostov State Medical University, Doctor of medical sciences, professor,
the Faculty of general hygiene Haragurgieva Irina Martirosovna, Rostov State Medical University, Candidate of medical sciences, Associate professor, the Faculty of general hygiene Kryuchkova Vera Vasilyevna, Don State Agrarian University, Doctor of Engineering Sciences, professor, the Faculty of Commodity Research and Examination of Goods
E-mail: kverav@yandex.ru Avetisyan Zita Ervandovna, Rostov State Medical University, Candidate of medical sciences, Associate professor, the Faculty of hygiene
Hygienic characteristics of the sensory parameters of the pork with the intensive method of the production
Abstract: The comparative analysis ofsensory characteristics of pork from the animals receiving the protein-vitaminmineral additive (PVMA) containing synthetic amino acids and antibacterial preparations at sagination and using a traditional protein additive — sunflower meal is carried out. It is established that introduction to a diet ofpigs of BVMD has no essential impact on organoleptic characteristics ofbroth, boiled meat and fat, but authentically improves sensory parameters of meat at culinary processing by frying on such indicators as appearance, taste, rigidity and juiciness. Keywords: sensory (organoleptic) characteristics, pork, pork fat, feed additives, antibiotics.
Белик Светлана Николаевна, Ростовский государственный медицинский университет,
доцент кафедры общей гигиены E-mail: superbelik@mail.ru Жукова Татьяна Васильевна, Ростовский государственный медицинский университет, профессор кафедры общей гигиены Харагургиева Ирина Мартиросовна, Ростовский государственный медицинский университет,
доцент кафедры общей гигиены
72
