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Clinical biochemical features in patients with undifferentiated connective tissue dysplasia
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Fig. 2. The correlation between the standardized incidence rate of breast cancer and divorce rates, fertility, mortality and middle-aged women
Although between these factors and SP were found in the incidence of correlation, they were not significant (p > 0.05). Therefore, these factors are not included in the linear regression model. To define measures of the identified relationships was regression analysis. The following multiple linear regression equation:
7 = -62.7 + 6.05*X1 + 2.25 *X2 + 0.46 *X3 - 0.78 *X4; R = 0.94, R 2 = 0.89, F = 18.1; p < 0.00025, where: Y — the incidence rate of breast cancer,
X1 — the divorce rates; X2 — the average age of women; X3 — fertility rate, X4 — coefficient of total mortality; R — coefficient of multiple correlation; R 2 — coefficient of determination, F — Fisher's criterion.
On the incidence ofbreast cancer in the population is strongly influenced by the average age of the women (59.6 %) and the odds of divorce rates (27.4 %), less mortality (11.5 %) and fertility (-9.5 %).
In conclusion it should be said that in areas where there is a low birthrate, high divorce rates, total mortality and the high average age of women we can expect an increased incidence of breast cancer. The average age, reproductive behavior of women, the divorce rate and overall mortality of the population, causing the state of the demographic situation in the territories and played a leading role in the incidence of breast cancer. The organizers of health in the development of preventive measures is necessary to consider the medico-demographic situation of the region.
References:
Uzbekistan Almanac 2013. - Tashkent, 2015.
Bershtein L. M. Hormonal carcinogenesis/L. M. Bershtein. - SPb., 2000. - 272 p.
Davydov M. I., Axel E. M. Statistics of malignant neoplasms in Russia and CIS in 2012. - Moscow, 2014.
Organization of oncological service in Russia (methodical recommendations, manuals for physicians). Part 2. Edited by V. I. Chissov, V. V. Starinsky, B. N. Kovalev. - Moscow, 2007. - 663 p.
Rebrova O. Y. Statistical analysis of medical data. The use of the STATISTICA software package. - M.: Mass Media, 2002. - 312 p. Tikhomirov N. P., Dorokhina E.J. Econometrics: A Textbook. - M.: Ekzamen, 2003. - 512 p.
Khudaykulov T. K., Khudaykulov A. T. Epidemiological aspects of breast cancer in Uzbekistan//Bulletin of the Tashkent medical Academy. - 2013. - No. 3. - P. 95-97. Lyon Geneva, 12 December 2013.pdf.
Shodikulova Gulandom Zikriyaevna, Samarkand State Medical Institute, Uzbekistan Toirov Erkin Sanatovich,
Babamuradova Zarrina Bahtiyarovna E-mail: Shodikulovagulandom@mail.ru
Clinical biochemical features in patients with undifferentiated connective tissue dysplasia
Abstract: The research objective is represented by the implementation of comparative performance analysis of NO-system, VEGF, expression indices of MMP-2, MMP-9, TIMP and magnesium level, GAG, HN in the blood of patients with congenital
Section 4. Medical science
MVP in UCTD. 86 patients were examined, including 36 (41.9 %) men and 50 (58.1 %) women aged from 15 to 25 (19.5 ± 1.42) with etiologic signs of primary (congenital) MPV. The first target group included 41 (47.7) patient with MPV and the I grade regurgitation, the second group comprised 45 (52.3 %) patients with the II grade. The conducted studies indicated that endothelial dysfunction was observed in patients with congenital MPV of the 1st and 2nd regurgitation grades, and which was conditioned by NO-system imbalance.
Keywords: mitral valve prolapse, undifferentiated connective tissue dysplasia, endothelial dysfunction.
The severity level assessment of UCTD in patients with congenital mitral valve prolapse (MVP) is classified among the complex issues in current clinics of internal diseases. It is reasoned by the variety of clinical implications of different organs and systems, primarily in cardiovascular system. The principal causes of UCTD progression in patients with congenital MVP include the development of endothelial dysfunction associated with the imbalanced polymorphism of extracellular matrix gene proteins [1, 14-23]. Endothelial dysfunction on the molecular level is conditioned by the local NO-production disorders and high oxidative stress [2, 40-44]. Vascular endothelial growth factors (VEGF) are instrumental in this process [3, 48-51]. The reduction of VEGF level determines endothelial apoptosis that leads to luminal obstruction and vascular regression. At the present time, it is established that MMP are the key effectors in tissue remodeling. Polyfunctional MMP proteins participate in the process of apoptosis and angiogenesis. The alteration ofMMP level and its tissue inhibitor (TIMP) are considered as the possible prospective biological markers of differential diagnostics, CTD prognosis and treatment [4, 4-8]. The important peculiarities of impaired cardiac valve comprise the structural rearrangement of connective tissue elements, extracellular matrix, collagen and elastin fiber, glucosamineglucan (GAG) and hyaluronidase (HN) amorphous substance [5, 76-81], which during the last decade are rigorously studied by the scientists. Low Mg+2 concentration effects the performance of cardiac valve, dysplastic disorders of cardiac valve, prolapse deepening of mitral valve, mitral regurgitation grade, left atrial dimension and mucoid regeneration rate ofvalve, cardiac arrhythmia [6, 10-16].
In connection therewith, the research objective is represented by the implementation of comparative performance analysis of NO-system, VEGF, expression indices of MMP-2, MMP-9, TIMP and magnesium level, GAG, HN in the blood ofpatients with congenital MVP in UCTD.
Material and methods. 86 patients were examined including 36 (41.9 %) men and 50 (58.1 %) women aged from 15 to 25 (19.5 ± 1.42) with etiologic signs ofprimary (congenital) MPV. The diagnosis were established based on the classification of T. I. Kadu-rina [1, 14-23] and confirmed by echocardiography. Upon studying anamnestic data and instrumental examination, the patients with recurrent MVP and patients with cardiovascular diseases were not included to the target groups. The target group included 41 (47.7 %) patients with MPV and the 1st grade regurgitation and 45 (52.3 %) patients with the 2nd grade. There was performed the assessment of nitric oxide (NO) value in blood based on its stable metabolites (NO2-and NO3-), endothelial (eNOS) and inducible (iNOS) — synthase, peroxynitrite (ONO2), endothelin-1 concentration (ET-1), vascular endothelial growth factor (VEGF), matrix metalloprotease level (MMP-2 and MMP-9) and its tissue inhibitors (TIMP-1 and TIMP-2), glucosaminoglycans (GAG) and hyaluronidase (GH) in blood plasma. Statistical data processing was conducted by the use of variation statistics method with Student's t-test.
The performed studies figured the high stable NO metabolites that grew by 1.12 (p < 0.05) and 1.34 (p < 0.05) times in patients with the 1st and 2nd grade of regurgitation. The identified changes, obviously, represent the compensatory response of patient's
organism to definite chronic myocardial ischemia. It coincides with the high level of VEGF in patient's blood serum that leads to some myocardial vascularization. The performed investigations have found the growth of VEGF in the blood serum of patients with MVP based on the grade of regurgitation. Thus, if for patients with MVP of the I grade it raised by 1.1 times, then for patients with II grade this indicator increased by 1.27 (p < 0.05) times. It is approved by receptor reinforcement in the blood serum of experimental patients. In that way, the rate of VEGF-R1 increases by 1.2 (p < 0.05) and 1.59 (p < 0.01) times, and VEGF-R2 rises by 1.08 and 1.24 (p < 0.05) times, in accordance with the regurgitated intensity ofMVP of the I and II grade. The eNOS analysis established the regressive trend in patients with MPV and the 1st grade of regurgitation, whereas in patients with the 2nd grade of regurgitation these changes are statistically significant, decreasing by 1.23 (p < 0.05) times related to the state of almost healthy men. It is considered that the other form of NO-synthase — iNOS is accountable for the progression of inflammatory process. In that way, if in patients with MVP of the 1st grade of regurgitation the iNOS activity increases by 1.2 (p < 0.05) times, then in patients with the 2nd grade of regurgitation this rise comprised by 1.36 (p < 0.01) related to the state of almost healthy men. The iNOS activation, that conditions the NO hyperexpression, is stimulated by the activated forms of oxygen and proinflammatory cytokines [7, 50-53]. While analyzing the results of ONO2 determinations in the blood serum of patients with MVP, we have revealed the rise of its level by 1.15 (p < 0.05) and 1.31 (p < 0.01) times. The NO excess and the intensified formation of cytotoxic ONO2- by type of feedback suppresses to a greater degree the basal rate of eNOS activity and initiates the pathologic isoform NOS — iNOS. Under these circumstances, the hyperexpression of NO and ONO2- has high vasopressor effect, that can be associated with its inducing influence on the activity of ET-1 [10]. With the progression of UCTD, the growth of ET-1 rate becomes statistically significant and equals to 0.780 ± 0.043 pg/ml (p < 0.01) in patients with the 2nd grade regurgitation, when this indicator in the almost healthy men is 0.611 ± 0.031 pg/ml. These indices exceeded the characteristics of the almost healthy men by 1.1 and 1.28 (p < 0.01) times, correspondingly. The conducted studies showed that in patients with MVP and the 1st grade regurgitation, the activity of MMP-2 tends to increase, while in patients with the 2nd grade of regurgitation we could observe its evident rise by 1.16 (p < 0.05) times. The value of MMP-9 activity in patients with the 2nd degree of regurgitation reliably raised by 1.13 times compared with the indices of almost healthy men. The content analysis of TIMP-1 in blood serum demonstrated the trend towards the decrease of its concentration in patients with the 1st grade of regurgitation and its evident decrease by 1.16 (p < 0.05) times in patients with the 2nd grade of regurgitation. At the same time we could observe the increasing trend for TIMP-2 in patients with the 1st degree of regurgitation, and it reliable growth by 1.36 (p < 0.01) times in patients with the 2nd grade of regurgitation. Considering that its level increases in systemic sclerosis, we can assume that the revealed rise of TIMP-2 in blood serum represents one of the predisposing causes in the formation of CTD. We have studied the magnesium level, GAG
Significance of mid mass molecules in cytokine cascade of oral fluid in patients with oral lichen planus
and HN in the blood serum of patient with MVP considering the grade of regurgitation. The related studies demonstrated the decreasing trend of the magnesium level in patients with the 1st grade of regurgitation. The reliable decrease of the magnesium level was observed in patients with the 2nd grade, its level in blood serum decreased by 1.2 times (P < 0.05) related to the parameters of almost healthy people. We have conducted Pearson's correlation analysis in order to validate the importance of MMP-2 and MMP-9 increase with TIMP-1 in angiogenesis and conjunction with the content reduction of Mg+2, GAG and HN. Thus, in patients with the 1st grade of regurgitation we could observe the certain relation between the growth of MMP-2 and MMP-9, and the drop of TIMP-1, the ions ofMg+2 (r = -0.22-0.28, p > 0.05) and the growth of GAG level and HN activity (r = +0.24-0.31, p > 0.05) as compared to the control data. Along with that, in patients with the 2nd grade of regurgitation the expression of MMP-2 and MMP-9 had the invert correlation with the activity of TIMP-1 (r = -0.83-0.82, p < 0.01), and also after the statement of relation with the drop of the ion parameters for Mg+2 (r = -0.69-0.80, p < 0.02 and p < 0.01), and the direct correlation with the parameters of GAG (r = -0.80-0.832, p < 0.01) and HN (r = -0.77-0.81, p < 0.01). The expression of TIMP-1 correlated with the drop of the level of Mg+2 ions in blood (r = -0.75, p < 0.01)
and inversely with the GAG indicators (r=-0.84, p < 0.01) and HN activity (r = -0.86, p < 0.01).
Therefore, the study of the mechanism of cardiac hemodynamics disorders showed that in the patients with MVP and regurgitation we can observe the inadequate endothelial production of antiangiogenic factors, which results in the decrease of response relaxation, and determines the drop of responsiveness index and the risk of hypertensive state, in particular induced by physical exercises. The development of these changes is conditioned by the rise of VEGF in blood serum; it determines the risk of angiogenesis stimulation in patients with MVP, the expression of which is related with the regurgitation grade. In patients with congenital MVP of the 1st and 2nd grade of regurgitation, we can diagnose endothelial dysfunction, caused by the imbalance of NO-system. The other factors that lead to the MVP formation includes the drop of magnesium level, HN activation, which promotes the increased degradation of extracellular matrix components followed by the growth of its debris excretion, this is associated with the activation of MMP-2 and HN. It can be expected that the reason for the progression of mitral regurgitation in patients with congenital MVP lies in the drop of TIMP-1 inhibiting action, the content of Mg+2 ions, HN activation.
References:
1. Kadurina T. I., Gorbunova V. N. Connective tissue dysplasia. - St. Petersburg: ELBI, 2009. - 714 p.
2. Gnusaev S. F. Connective tissue cardiac dysplasia syndrome in children//Consulting physician. - 2010. - No. 8. - P. 40-44.
3. Pereskalskaya M. A., Makarova L. I., Vereshchagina G. N. Neuroendocrine dysfunction in women with systemic connective tissue dysplasia//Clinical medicine. - 2002. - V. 80, No. 4. - P. 48-51.
4. Komissarova L. M., Karachaeva A. N., Kesova M. I. Gestation and partus course in CTD//Obstetrics and Gynec. - 2012. - No. 3. - P. 4-8.
5. Domnitskaya T. M., Diachenko A. V., Kupriyanova O. O., Domnitskiy M. V. Clinical relevance of Magnesium orotate administration in adolescents with connective tissue cardiac dysplasia syndrome//Cardiology. - 2005. - V. 45(3). - P. 76-81.
6. Kadurina T. I., Abbakumova L. N. Rehabilitation principles for patients with connective tissue dysplasia//Consulting physician. -2010. - V. 40. - P. 10-16.
7. Basaragina E. N. Connective tissue cardiac dysplasia syndrome in children//Issues of modern pediatrics. - 2007.- V. 6(6). - P. 50-53.
Shukurova Umida Abdurasulovna, PhD, Tashkent State Dental Institute, Uzbekistan, Faculty Dental Therapeutics department E-mail: shua1981@mail.ru Bekjanova Olga Esenovna, PhD, MD, DDS, Faculty Dental Therapeutics department E-mail: bekjanovaolga@mail.ru
Significance of mid mass molecules in cytokine cascade of oral fluid in patients with oral lichen planus
Abstract: Taking into consideration that severe disturbances in metabolism accompanying by tissue destruction occur in the organism along with accumulating of toxic metabolites in biologic environment, the study of the problem is seen as endotoxicosis. The analysis of such a correlated interconnection certifies various influence of MMM on the immune system of the organism.
This influence is complicated and specific and is reflected in immune imbalance response and obviously in the structural disturbances of oral mucous membranes epithelium.
Keywords: oral lichen planus (OLP), pro- inflammatory cytokines, mid mass molecules (MMM), nuclear derivative, toxic derivative, aromatic derivative.
Oral lichen planus (OLP) is one of the most common diseases of mucous membrane of the oral cavity (MMOC). In the structure of MMOC diseases OLP composes 35 %. It is known that in OLP of MMOC main changes take place in the epithelium of mucous membranes [1, 156-166; 10, 13-14].
At present, main metabolic chains responsible for cellular damage and damage of tissues in the pathology have been noted. They are: high level of peroxide oxidation of lipids and the lack antioxidant defense, unbalanced cytokine level with prevailed level of pro- inflammatory cytokines [1, 160-162; 4, 14-16; 8, 89-90; 9, 134-135; 10, 11-12].
