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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
Prognostic significance of transcription factor HiF-1 a in the regulation of NO — system in women wearing lUDs
forming the urgent and long-term adaptation to the WMC. This is confirmed by the fact that we have found at least three groups: high- HIF-1a — from 170 to 185% 7 (14.0%) patients, moderate between 140 and 170% — 33 (66.0%) patients and low — from 120 to 140% — 10 (20.0%) patients. 3 cases (30%), — That in patients with low levels of HIF -1a the highest frequency of complications, such as inflammatory diseases of the uterus 1a marked, excessive bleeding — 5 (50%), pain in the pelvis — 5 (50%). While in the whole group of the total number of examinees with expulsion and pain syndrome was diagnosed in 6 (12%), abundant uterine bleeding — in 9 (18%) patients, and inflammatory diseases of the uterus in 7 (14.0%).
Reducing the concentration of HIF-1a simultaneously associated decrease in comparison with those in the control, such indicators NO — system as NO and eNOS expression on iNOS background and ONO-2. NO changes — the system in the lysate of erythrocytes were synchronous nature of the quantitative content of HIF-1a. At the same time revealed correlation between the index of HIF-1a with NO, eNOS, iNOS and ONO-2 and that amounted to an average of 6 months after wearing the IUD — r = 0,61; 0.72-0.72 and — 0.74.
After 12 months of wearing the IUD r -0,63; 0.70-0.71 and 0.76. After 24 months of wearing the IUD r = 0,55; 0.60; -0.86 And 0.77. And after 36 months of use of the IUD is r = 0,64; 0.76, 0.78 and 0.78 (p < 0.05-0.01), respectively. The high correlation between the parameters of HIF-1a and indicators of NO — the system indicates that the women adaptation mode to the WFC strengthens the processes of endothelial dysfunction and primarily due to stimulation of the pathological isoform of NOS — iNOS, and giperekpressii ONO-2 — has a high cytotoxic, tsitostatisticheskim and suppressive effects [7,8,13].
However, attention is drawn to the fact that after 24 months indicator HIF — 1a, NO, the eNOS activity, despite the high content of ONO-2. This, in — apparently caused by the activity of iNOS, were within the control that confirms by what mechanisms are formed in women with IUD and long -term resistance, is an adaptation of indicators.
It should be emphasized that women with high HIF — 1a adaptability to the WFC, manifested in the practical absence of clinical complaints wearing a contraceptive, they do not have complications.
The absence of inflammation and bleeding in this group was due, on — apparently, that the tolerance of uterine vessels, its mucosa to the IUD.
However, long wearing IUD to 36 months reduces the possibility of adaptation HIF — 1a, thus appears that the NO reduction, eNOS activity increasing reaction rate iNOS, cytotoxic form ONO-2. According to the literature, the high concentration of ONO-2 may be the cause ofwomen's uterus, ovaries [5,12].
Thus, studies have shown that wearing dynamics IUD fluctuations observed in the lysate of erythrocytes HIF-1a and indicators NO — system. Fluctuations of HIF-1a and indicators NO — system are synchronous, which can be assumed to reflect the adaptation and reaction of the female body in the IUD, the availability of oxygen to tissues, regulation of vascular tone, which is essential for the functioning of the uterus.
Reducing HIF — 1a, and the imbalance in the NO — system is characterized by increased damage to cellular systems on the level of the uterus, which manifests the development of complications. At the same time it revealed a clear relationship between the degree of NO — system, reducing HIF — 1a and severity of wear IUD complications. Identify patterns depending of complications from HIF- level changes — 1a and NO — the system allows them to be used as markers for the prediction and evaluation of the tactics of preventive and curative measures, depending on the length of stay in the uterus IUD.
Conclusions
1. 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.
2. Revealed in the dynamics of increase in terms of women wearing IUDs statistically significant correlation between the levels of HIF-1a and NO options — system.
3. There are three groups ofwomen carriers of the IUD — high, moderate and low levels of HIF-1a and functional activity of NO system that determines the nature and severity, the prognosis of complications. Women with IUDs high HIF — 1a and functional activity of the system tolerance to NO IUDs, the complication rate is higher than in women with low levels of these parameters.
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Honkeldieva Hurmathon Kamchievna, Andizhan State medical institute, assistant chair of hospital and outpatient pediatrics, scientific competitor, Uzbekistan
Alimdzhanov Ibrahim Inamovich, Andizhan State medical institute, professor chair of hospital and outpatient pediatrics
Abdullaeva Mavjuda Ergashevna, docent of chair of hospital and outpatient pediatrics
Tojiboev Temur Topvoldiygli, Student of Andizhan State medical institute
Mamatkhyjaev Mirhojiddin Sadriddinkhoji ygli, Student of Andizhan State medical institute E-mail: evovision@bk.ru
Functional state of the autonomic nervous system in bronchial asthma in children
Abstract: These shifts vegetative status have undoubted positive effect on the microcirculation and the rhythm of the circulatory system, facilitating a more rapid liquidation of clinical manifestations of autonomic dysfunction and create psi-hoemotsinalnogo patient comfort mode.
Keywords: nervous system, bronchial asthma, children.
As is known, autonomic tone has significant impact on the clinical manifestations of asthma (BA) [1; 4; 5; 7; 11]. Identified psychovegetative violations necessitate further development ofAD therapies in terms of vegetative homeostasis correction using vegetotropic drugs [6; 8; 9; 10]. The purpose of the study. Was to examine the influence of a tranquilizer Phenibutum on vegetative status and clinical manifestations of asthma in children with initial sympathicotony.
Material and methods. All observed patients with initial sympathicotony divided into 2 groups. Patients of the first group (n = 40) ssceived standard therapy alone (control group), and the second group ofpatients (n = 37) along with conventional methods
therapy plus Phenibutum. For greater reliability of observation and treatment of these children were held over the pair factor. Indicators reflecting the state the vegetative status of patients before and after one month of treatment are shown in Table I.
Results
Studies have shown that prior to the appointment of complex therapy in patients of both groups on the studied parameters revealed no significant differences. On the background of generally accepted standard therapy in patients of group 1 was observed a tendency to a decrease in heart rate, the number ofbreaths intersystem index. But after a month of therapy, none of the indicators were not significantly different from those on admission.
Table 1. - Dynamics of some vegetative parameters in patients with asthma (M ± m)
Index Patients in group 1 Patients in group 2 P1 P2 P3
Hr 108.01 ± 2.21 104.34 ± 2.23 105.82 ± 2.34 90.48 ± 3.04 > 0.05 < 0.001 < 0.001
Number of breaths 19.12 ± 0.96 18.23 ± 0.78 18.85 ± 0.64 16.61± 0.83 > 0.05 > 0.05 > 0.05
Intersystem index 5.68 ± 0.17 5.67 ± 0.16 5.58 ± 0.15 5.01± 0.14 > 0.05 < 0.01 < 0.01
Sbp 91.45 ± 1.89 91.29 ± 1.29 92.01 ± 1.78 95.34 ± 1.13 > 0.05 > 0.05 < 0.05
Dbp 60.42 ± 2.42 60.26 ± 2.62 61.76 ± 2.78 60.71 ± 2.29 > 0.05 > 0.05 > 0.05
