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Fig. 2. Frequency of distributions of genotypes of gene C VEGFA G 634
Thus, during the comparative analysis of frequency of distribution of the alleles and genotypes of polymorphism of gene VEGFA C634G, between main and control groups the statistically reliable differences have been revealed. Thus the general predisposition to a pathology of cerebral vessels was associated with allele variant G. In the carriers of allele G the relative chance of development of a pathology of cerebral vessels was reliably increased in
more than in 2 times in comparison with carriers of alternative allele C. Besides the frequency of unfavourable state was defined by homozygotic genotype G/G, which was higher in group of the patients in comparison with the control (7.3 % against 2.3 %). So, the ratio of chances of the risk of development of pathology of the cerebral vessels in the carriers of this genotype was reliably high more than in 3 times, than in carriers of other genotypes.
References:
1.
Siervo M., Ruggiero D., Sorice R. et al. Angiogenesis and biomarkers of cardiovascular risk in adults with metabolic syndrome//J. Intern. Med. - 2010. - 268 (4). - P. 338-347.
Siervo M., Ruggiero D., Sorice R. et al. Body mass index is directly associated with biomarkers of angiogenesis and inflammation in children and adolescents//Nutrition. - 2012. - 28(3). - P. 262-266.
Coultas L., Chawengsaksophak K., Rossant J. Endothelial cells and VEGF in vascular development//Nature. - 2005. - 438, № 7070. -P. 937-945.
Tammela T., Enholm B., Alitalo K., Paavonen K. Thebiologyofvascularendothelialgrowthfa ctors//Cardiovasc. Res. - 2005. - 65: 550-563. Ferrara N. Vascularendothelialgrowthfactor: basicscienceandclinicalprogress//Endocrin. Rev. - 2004. - Vol. 25. - P. 581-611. Ferrara N., Gerber H. P., Le Couter J. The biology of VEGF and its receptors//Nat. Med. - 2003. - 9 (6). - P. 669-676. Tammela T., Enholm B., Alitalo K., Paavonen K. The biology ofvascular endothelial growth factors//Cardiov. Res. - 2005. - 65: 550-563. Li Y., Zhang F., Nagai N., Tang Z. et al. VEGF-B inhibits apoptosis via VEGFR-1-mediated suppression of the expression of BH3-only protein genes in mice and rats//J. Clin. Invest. - 2008. - 118 (3). - P. 913-923.
Trape J. C., Morales R., Molina X. et al. Vascular endothelial growth factor serum concentrations in hypercholesterolemic pa-tients//Scand.J. Clin. Lab. Invest. - 2006. - 663: 261-267.
Shen M., Gao J., Jianan Li J., Su J. Effect of ischaemic exercise training of a normal limb on angiogenesis of a pathological ischaemic limb in rabbits//Clinical. Science. - 2009. - 117: 201-208.
11. Kucukardali Y., Aydogdu S., Ozmen N. et al. The relationship between severity of coronary artery disease and plasma level of vascular endothelial growth factor//Cardiovasc. Revasc. Med. - 2008. - 9 (2): 66-70.
12. [Electronic resource]. - Available from: http://wbiomed.curtin.edu.au/genepop
9.
10.
Hamdamova Muhayo Tuhtasinovna, Bukhara state medical institute, Uzbekistan E-mail: gavhar72@inbox.ru
Indicators correlation among ferrokinetic performance, copper content in blood serum ceruloplasmin women with extended wear intrauterine device
Abstract: The aim was to evaluate the correlations between ferrokinetic indicators, copper and ceruloplasmin in serum of women with prolonged wearing intrauterine device (IUD). There was an inverse correlation relationship between transferrin and serum ferritin in women with IUDs, which increases with increasing duration of wearing the Navy. Within 12 months of the
correlation relationship between the content of copper and ceruloplasmin in the blood serum of women wearing the Navy has been positive, but weak. It has increased from the 18th month of wearing the Navy, but was of medium strength, and a strong, direct, positive relationship marked by 36 months of wearing a navy.
Keywords: Intrauterine device, honey, ceruloplasmin, ferrokinetic indicators, blood serum, correlations.
The control group (n = 40) have joined the women do not apply cop-
Exploring ferrokinetic parameters (serum ferritin and transferrin), the copper content and form of transport — cereloplazmin serum can judge the latent forms of iron deficiency that develops after prolonged wearing of an intrauterine device (IUD) in women [1; 2; 3].
The existence of different relationships between the features of living things (biological individuals) in nature and various phenomena in society has been known since ancient times. Changing one feature or phenomenon leads to a change in another trait or event [4]. It is known that the relationship is divided into functional and correlation. The functional relationship is observed mainly in the physical and chemical processes, and correlation with biological and medical processes. In 1806, J. Kove brought the first results of the study of materials on relations between the signs in nature and coined the term "correlation" (from the Latin «correlation — relationship).
Correlation is assessing the relationship and variability between two or more phenomena and signs [5] and better reflects the pattern of change between the features and phenomena. In this regard, the aim of the study was to study and evaluate the correlation relationships between ferrokinetic performance, copper and ceruloplasmin forms of transport in the blood serum of women with prolonged wearing an intrauterine device (IUD).
Materials and methods
All women using copper IUDs T-shaped Cu T380A (study group) were assigned depending on the duration of wearing the Navy: 1 year (n = 150); 2 to 3 years (n = 150); 3 to 5 years (n = 150).
per IUDs. All subjects were representative of age, living conditions, the number of pregnancies and births, permanent residence.
The criteria for inclusion in the main group of the study were: wearing a copper-bearing IUD T-shaped (Cu T380A), the absence of inflammatory diseases of the pelvic organs and cancer, the age of women from 20 to 49 years. IUD inserted according Muthal-Rathore A. (2004), which recommends the copper-bearing IUD T-shaped (Cu T380A) to insert at least 48 hours after the birth, taking into account the absence of infection and inflammation in the birth canal. Research carried out in the years 2009-2014 in Bukhara region.
Determining the level of ferritin and transferrin in the serum was performed by Buglanovu A. A. [6]. The content of copper and ceruloplasmin in blood serum were determined by photocolorim-etry on biochemical analyzer «Vitros Orto Clinical-diagnostics» Company "Johnson-Johnson" using special sets of the firm. For the correlation analysis of the material was used to determine the method of Spearman's rank correlation coefficient (p). The presence of significant association between the studied signs judged with a coefficient of correlation — p < 0.5 [7].
Results and discussion. In the first stage of the research was carried out to study and assess the relative variability in transferrin and ferritin (ferrokinetic figures) women to apply copper-containing IUD, depending on the length of wear (Fig. 1). Investigations were carried out every 6 months.
Fig. 1. Comparative parameters transferrin and ferritin levels in the serum of women, depending on the duration of wearing the IUD
The content of transferrin in serum initially (after the insertion of the IUD) was higher — 4.7 ± 0.3 g/l in comparison with normal (3.7 ± 0.05 g/l, P < 0.05) and timeI tended to increase. As serum ferritin observed the opposite picture — the original figure was 37.8 ± 2.3 pmol/l against 108.4 ± 1.7 pmol normal (P < 0.001).
The correlation analysis between the level of transferrin and ferritin in the serum of women shows that between these indicators there is a close inverse correlation. In early studies (baseline), this relationship is weak, negative (p = -0.3), but with increasing time of wearing the iron deficiency anemia it is amplified and over 6 months p = -0.5 (medium, negative correlation). Later (after 12 and 18 months), this relationship becomes strong, negative-respectively, p = -0.7. In other periods of observation revealed a negative relationship only intensified, reaching p = -0.8 (24 and
30 months). The most powerful, negative correlation is observed 36 months after insertion of the IUD, reaching p = -0.9. Strengthening the close, the negative correlation among the compared parameters indicates a clear relationship among the two women with IUDs. This fact proves the existence of a consistent relationship between these parameters that must be considered when choosing a method of contraception in this group ofwomen and the time of wear.
Thus, the detected correlation relationship between transferrin and serum ferritin in women, which increases with time. The close, the negative relationship between them indicates the development of iron deficiency in women is associated with prolonged wear IUD. The data obtained can be used as an additional diagnostic and prognostic criterion for clinical and laboratory criteria of iron deficiency in women wearing IUDs. Apparently,
development of an imbalance between the transport and the standby forms serum iron determines the formation of more stable bonds in the regulation of iron metabolism in women with prolonged use of IUDs.
The next stage of research was to study the content of copper and its transport form — ceruloplasmin in serum of women with IUDs. It is found that initially (after inserting the IUD) in women copper content in the serum was significantly reduced by 1.3-fold (P < 0.001) relative to standard values (respectively
65.6 ± 3.1 mg/dl vs. 83.7 ± 2.4 mg/dL). But, with the lapse of time (6 months later) there is a gradual increase in this parameter, which is 30 months comes to normal values, and after 36 months, 1.7 times higher than the permissible level — P < 0.001 (Fig. 2).
The same trend as we have observed, and the level of ceruloplasmin, with the only difference that the original content of this parameter was increased with respect to the norm (P < 0.05) and gradually continued to grow, reaching to the last observation interval (36 months) to a maximum value — 747.2 ± 11.3 pmol/L (P < 0.001).
Fig. 2. Comparative parameters of copper and ceruloplasmin in serum of women, depending on the duration of wearing the IUD
Correlation analysis between the copper content and form of transport — ceruloplasmin shows that between these parameters have a direct, positive correlation, that is an increase of one indicator is closely linked to an increase in other settings. Initially determined weak, direct, positive relationship between the compared parameters (p = 0.2) is the same weak, a direct link is maintained and after 6 and 12 months of wearing the IUD (respectively, p = 0.3). Only from the 18th month revealed the relationship is strengthened and reaches p = 0.5 (average, direct, positive relationship). Eventually (after 24 months), this relationship is enhanced reaches p = 0.6, but after 30 months of wearing the IUD this relationship is weakened and reduced to p = 0.4. This coincides with the normalization of the copper content in the blood serum of women in the period of observation. But after 36 months of correlation between these indices increased sharply and there is a strong, direct, positive correlation (p = 0.7).
Furthermore, the study and evaluation of related options between copper and ceruloplasmin in blood serum shows that the baseline and within 12 months of correlation between the studied parameters was positive, but weak, that is the connection between the increase in their contents were insignificant. The relationship has intensified since the 18th month of wearing the IUD, but was of medium strength, and a strong, direct, positive relationship observed only after 36 months of wearing the IUD. This fact indicates a lack of related laws between copper and ceruloplasmin serum of
women with IUDs within 2-2.5 years. Main abrupt changes observed after 3 years of wearing the IUD, therefore, the presence of strong, direct, positive correlation between the compared parameters indicates a negative prognostic sign of wearing the IUD 3 years.
Conclusions:
1. An inverse correlation relationship between transferrin and ferritin serum from women with IUDs, which increases with increasing duration of wearing the IUD.
2. The presence of the close, the negative correlation relationship between transferrin and ferritin serum indicates the formation and development of iron deficiency in women associated with extended wear IUD.
3. Relationship between ferrokinetic parameters and duration ofwearing the IUD can be used as an additional diagnostic and prognostic criterion for clinical and laboratory criteria of iron deficiency in women wearing IUDs.
4. At baseline and 12 months the correlation relationship between copper and ceruloplasmin in serum of women wearing the IUD has been positive, but weak. The relationship has intensified since the 18th month of wearing the IUD, but was of medium strength, and a strong, direct, positive relationship observed after 36 months ofwearing the IUD.
5. Having a strong, direct, positive correlation between copper and ceruloplasmin in serum indicates a negative prognostic sign of wearing the IUD 3 years.
References:
1. Jabbarov J. K., Malikova G. B. Iron deficiency anemia in obstetrics and gynecology//Guidelines. - Tashkent, 2011. - 27 p.
2. Kuznetsova I. V. Intrauterine contraception//Gynecology. - Moscow, 2008. - Vol. 10, № 2. - S. 32-37.
3. Saidkariev B. K. Advantages of the Navy - as a reliable method of contraception//Bulletin GP doctor. - Samarkand, 2009. - Part II. -№ 3. - S. 334-335.
4. Mamatkulov B. Jamoat salomatligi sogliqni saqlash boshqarish//textbook for students of medical universities. - Tashkent, Knowledge and science, 2013. - 574 p.
5. Iskandarov T. I., Mamatkulov B. Sanitation statistics. - Tashkent, 1994. - 201 p.
6. Buglanov A. A. Clinical and diagnostic value of indicators ferrokinetics serum//Clinical Laboratory. - Moscow, 2001. - № 7. - S. 14-16.
7. Nuraliev N. A. Collection of scientific works "Actual issues of infectious diseases". - Tashkent, 2001. - S. 264-267.
Hamdamova Muhayo Tuhtasinovna, Bukhara state medical institute, Uzbekistan E-mail: gavhar72@inbox.ru
Prognostic significance of transcription factor HiF-1 a in the regulation of NO — system in women wearing lUDs
Abstract: Women with IUDs is marked in red blood cell lysates synchronous oscillations HIF level — 1 a and NO options — system (NO content, eNO activity and iNOS, ONO concentration — 2); decrease in HIF-1a is associated decrease in the level of NO, inhibition of eNOS activity, overexpression of iNOS and concentration of ONO-2. Keywords: intrauterine device, system of oxide, of transcription factor HiF-1 a.
tion of the IUD). Regularly, during the periods of wearing the IUD conducted clinical examination, we found the presence of pain,
Among the protective factors at the cellular and systemic level of importance is given to anti-hypoxic protein HIF- 1 (hypoxia — inducible factor — 1) [1]. It is found that HIF-1 a coordinates the processes of proliferation, differentiation, and cell survival, as in stage of embryonic development and postnatal [3,4].
It was revealed that HIF-1 a regulates angiogenesis, erythro-poiesis, glycolysis, vascular tone through stimulation of nitric oxide production mechanisms (NO) [7]. However, until now the role of NO and the HIF- 1 a in the prevention of ischemic and reperfusion (IR) injury of the reproductive organs in their pathology is not fully understood. Some studies have shown that inhibition of NO synthesis prevents the formation of adaptive protection against IR uterine tissue damage [2,9].
Considerable interest in this regard is the work associated with wearing the IUD [6]. The protective effects of NO are related to its dilatation of vessels of internal organs, increased microcirculation, activation of antioxidant enzymes, stimulation of HIF- 1 a [7], and damaging — TS overexpression of NO, an increase peroxynitrite (ONO-2), the activation of the pathological isoform of NOS — an inducible NO- synthase (iNOS) [5,7,8].
Given the above it can be assumed that as a result of wearing the IUD and the development of various complications (expulsion, inflammatory diseases of the uterus, irregular menstruation, heavy bleeding prolonged intrauterine), which occurs in 11-24% of women [2,10,13], an important factor in favor — endothelial dysfunction and hypoxia. At the same time, not only on a local level within the impaired microcirculatory bed of the uterus, but also at the system level.
In connection with the above, the purpose of the study was to evaluate the effect of extended wear IUD hypoxic transcription factor of HIF-1 a and NO Activity — system in erythrocytes.
Research methods. The study involved 150 women of reproductive age who use copper-bearing IUD for 3 years. The control group consisted of 40 apparently healthy women without IUDs. The criteria for inclusion in the survey group were women of reproductive age from 20 to 43 years (33,6 ± 2,15 year) with the absence of inflammatory diseases of the pelvic organs and cancer.
In the history of the women surveyed were from 1 to 7 pregnancies and from 1 to 4 genera transferred from 1 to 5 abortions. According to the recommendations [3,4,11,13], copper-containing IUD T — shaped (Cu T 380A) is inserted after the birth in the absence of infection and inflammation. Studies conducted in the dynamics (in 3,6,12,24 and 36 months from the start of the inser-
discomfort, volume and number of days of menstruation, and others.
The determination of HIF-1a [9,11,12] prepared erythrocyte lysate. Proteins were separated on 8% polyacrylamide gel (Puggy). Transfer proteins PAGE nitrotsellyuznuyu membrane electroelu-tion was performed for 60 minutes. Western preincubated — blots were performed 60 min in PBS, containing 0,5% Twin — 20 and 5% skim milk. Then, Western — blots were incubated for 14 hours at 4 °C in a solution of polyclonal antibodies (Santa Cruz Biotech no logy) against HIF — 1a in a dilution of1:1000.
After washing, blots were incubated for 60 minutes in a solution of secondary antibodies conjugated with peroxidase N (Santa Cruz Biotech no logy) diluted 1:5000. Detection HIF — 1a reaction was performed with ECL — calculations on Kodak company film followed by densitometry on penetrating densimeter DM — 1 (Russia). The results are expressed as% of total number of densito-mogramm.
Activity markers NO — system was assessed by the content amount of stable NO metabolite (ONO-2-ONO-3) [9], eNOS activity [11], iNOS and ONO-2 [1]. NO — the system was evaluated by spectrophotometry using dvuluchego Spectrophotometer UV VIS — 2100 (LTD, China).
The obtained data were processed using the computer program Statistika v.6. the reliability of differences counted. The original content of HIF-1a, NO, activity of enzymes eNOS, NOS significant at p <0,05.
Results and discussion. The concentration of ONO-2 in the lysate of erythrocytes in women in the control group, and prior to insertion of the IUD were quite comparable. In the control group, as well as in women with IUD without complications up to 36 months of follow up were slight fluctuations of the studied parameters and did not differ from baseline (before ICH).
However, the Group WMC with anemia after 6 months there is a significant decrease in the concentration of HIF-1a compared to the control — by 20,1% (p <0,05), after 12 months was maintained in the same range as after 6 months observation. After 24 months, the level of HIF-1a is practically no different from those in the controls, and then after 36 months was again reduced by 18,9% (p <0,05).
It is believed that the decrease in HIF-1a reflects the state of women>s adaptability to the conditions of the observed groups
