Научная статья на тему 'Changes in lipid peroxidation and antioxidant activity in pregnant women and women in labour with diffuse toxic goiter'

Changes in lipid peroxidation and antioxidant activity in pregnant women and women in labour with diffuse toxic goiter Текст научной статьи по специальности «Клиническая медицина»

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Ключевые слова
PREGNANCY / CHILDBIRTH / PEROXIDE OXIDATION OF LIPIDS / ANTIOXIDANT ACTIVITY / DIFFUSE TOXIC GOITER / ВАГіТНіСТЬ / ПОЛОГИ / ПЕРЕКИСНЕ ОКИСЛЕННЯ ЛіПіДіВ / АНТИОКСИДАНТНА АКТИВНіСТЬ / ДИФУЗНИЙ ТОКСИЧНИЙ ЗОБ / БЕРЕМЕННОСТЬ / РОДЫ / ПЕРЕКИСНОЕ ОКИСЛЕНИЕ ЛИПИДОВ / АНТИОКСИДАНТНАЯ АКТИВНОСТЬ / ДИФФУЗНЫЙ ТОКСИЧЕСКИЙ ЗОБ

Аннотация научной статьи по клинической медицине, автор научной работы — Payenok O.S., Payenok A.V., Pankiv I.V., Kostiv M.O.

In order to determine the dependence of lipid peroxidation activity on the severity of thyrotoxicosis as well as its effect on antioxidant defense in the mother-placenta-fetus system, 138 pregnant women with diffuse toxic goiter were examined, 65 patients had a mild form of diffuse toxic goiter, 64 a moderate form and 9 -a severe one. The control group consisted of 30 women with a physiological course of pregnancy. The research was carried out in the third trimester of pregnancy as well as during the process of childbirth. The concentration of the initial and final products of free radical oxidation and antioxidant defense enzymes was determined. The obtained results indicate that one of the leading causes of thyrotoxicosis is the lack of antioxidant protection of the body, the indicators of which can serve as criteria for the severity of the disease and they can be used for monitoring the onset of perinatal complications in pregnant women with diffuse toxic goiter.

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ИЗМЕНЕНИЯ ПОКАЗАТЕЛЕЙ ПЕРОКСИДАЦИИ ЛИПИДОВ И АНТИОКСИДАНТНОЙ АКТИВНОСТИ У БЕРЕМЕННЫХ И РОЖЕНИЦ С ДИФФУЗНЫМ ТОКСИЧЕСКИМ ЗОБОМ

С целью установления зависимости активности ПОЛ от степени тяжести тиреотоксикоза, а также влияния его на нарушение антиоксидантной защиты в системе мать-плацента-плод проведено обследование 138 беременных женщин с диффузным токсическим зобом, из которых 65 пациенток имели легкую степень диффузного токсического зоба, 64 среднюю, 9 тяжелую. Контрольную группу составили 30 женщин с физиологическим течением беременности. Обследования проводились в третьем триместре беременности, а также и во время родов. Определяли концентрацию начальных и конечных продуктов свободнорадикального окисления и ферментов антиоксидантной системы защиты. Полученные результаты указывают, что одной из ведущих причин развития тиреотоксикоза является недостаточность антиоксидантной защиты организма, показатели которой могут служить критериями тяжести течения заболевания и применяться для мониторинга возникновения перинатальных осложнений при диффузном токсическом зобе у беременных.

Текст научной работы на тему «Changes in lipid peroxidation and antioxidant activity in pregnant women and women in labour with diffuse toxic goiter»

4. Ovchynikova OV, Shchedrov AO, Lazarenko VV. Suchasni pidkhody do likuvannya vahitnykh iz zalizodefitsytnoyu anemiyeyu. V: Kamins'kyy VV, redaktor. Zbirnyk naukovykh prats' Asotsiatsiyi akusheriv-hinekolohiv Ukrayiny; Kyiv. Kyiv: Intermed; 2009, 418-21. [in Ukrainian!

5. Tatarchuk TF. Reproduktyvnoe zdorove zhenshchyny v XXI veke. Z turbotoyu pro zhinku. 2013 Noyab 9; 8(47): 6-8. [in Russian]

6. Kuznetsova IV, Kononova VA. Folievaya kislota i ee rol v zhenskoy reproduktsii. Ginekologiya. - 2014; 4: 17 - 23. [in Russian]

7. CRC Handbook of Chemistry and Physics/W.M. Haynes — Boca Raton: CRC Press, 2014. — P.3-278.

Реферат i

ПРОФ1ЛАКТИКА АКУШЕРСЬКИХ УСКЛАДНЕНЬ У Ж1НОК З ППОВ1ТАМ1НОЗОМ ГРУПИ В Мщенко В.П., Руденко 1.В., Л1хачов В.К., Голубенко М.Ю., 2Добровольська Л.М.

Представлен результати дослщжень в rpyni жшок репродуктивного вку з дефiцитом втмшв групи В, якi отримували у комплекснш профiлактицi та лiкуваннi гестацшних ускладнень вiтамiнну терапiю. Наведенi даш порiвняльноi характеристики клшко-лабораторних спостережень з групою жшок, що приймали стандартну тератю. Обгрунтовано ефективнiсть застосування запропонованого етюпатогенетичного пiдходу з метою профшактики i комплексно! терапп гестацшних ускладнень.

Ключовi слова: гестацiйнi ускладнення, втмши, профiлактика.

Стаття надiйшла 12.12.17 р.

ПРОФИЛАКТИКА АКУШЕРСКИХ ОСЛОЖНЕНИЙ У ЖЕНЩИН С ГИПОВИТАМИНОЗОМ ГРУППЫ В Мищенко В.П., Руденко И.В., Лихачев В.К., Голубенко М.Ю., Добровольская Л.Н. Представлены результаты исследований в группе женщин репродуктивного возраста с дефицитом витаминов группы В, которые получали в комплексной профилактике и лечении гестационных осложнений витаминную терапию. Приведены данные сравнительной характеристики клинико-лабораторных наблюдений в опытной группе с группой женщин, которые получали стандартную терапию. Обоснована эффективность применения предложенного етиопатогенетического подхода з целью профилактики и комплексноой терапии гестационных осложнений

Ключевые слова: гестационные осложнения, витамины, профилактика.

Рецензент Катрушов О.В.

DOI 10.26724/2079-8334-2019-2-68-85-91

UDC 618.3+618.7)] - 06:616.441 - 008.61:612.015.11

O.S. Payenok A.V. Payenok \ I.V. Pankiv 2. M.O. Kosliv 1 'I.viv Nalional Medical I niversily named aller Danylo Malylskyi. I.viv 2llSl!l\ of I kraine "liukovinian Stale Medical I niversily". Chernivlsi

CHANGES IN LIPID PEROXIDATION AND ANTIOXIDANT ACTIVITY IN PREGNANT WOMEN AND WOMEN IN LABOUR WITH DIFFUSE TOXIC GOITER

e-mail: alex.payenok@gmail.com

In order to determine the dependence of lipid peroxidation activity on the severity of thyrotoxicosis as well as its effect on antioxidant defense in the mother-placenta-fetus system, 138 pregnant women with diffuse toxic goiter were examined, 65 patients had a mild form of diffuse toxic goiter, 64 - a moderate form and 9 -a severe one. The control group consisted of 30 women with a physiological course of pregnancy. The research was carried out in the third trimester of pregnancy as well as during the process of childbirth. The concentration of the initial and final products of free radical oxidation and antioxidant defense enzymes was determined. The obtained results indicate that one of the leading causes of thyrotoxicosis is the lack of antioxidant protection of the body, the indicators of which can serve as criteria for the severity of the disease and they can be used for monitoring the onset of perinatal complications in pregnant women with diffuse toxic goiter.

Keywords: pregnancy, childbirth, peroxide oxidation of lipids, antioxidant activity, diffuse toxic goiter.

The work is a fragment of the research project "The improvement of obstetric care monitoring in idiopathic miscarriage of pregnancy", state registration No. 0117U001080.

In recent years, there has been evidence that diffuse toxic goiter (DTG) causes significant metabolic and functional changes in the body, in pathogenesis of which the significant importance is paid to the violation of the lipid peroxidation (LPO) and antioxidant defense system (AODS) [2,10].

However, the mechanisms of activation of lipid peroxidation in pregnant women with DTG are not studied out. It is known that the increased lipid peroxidation in tissues is not the result of direct action of thyroxine, since the latter has antioxidant activity in vitro [5,12]. It is essential that during the inhibition of lipidperoxidation, thyroxine in vitro turns into the inactive form of hormone - reversed triiodothyronine [3,9].

Several ways of activating lipid peroxidation in DTG can be identified. First of all, this process can be related to the increased oxygenation of tissues due to the enhanced use of oxygen, the increase in the generation of hydrogen peroxide in cells as the result of the increased microsomal and mitochondrial oxidation [4,8], increasing the concentration of the LPO substrate- free fatty acids [1] The indicated changes lead to the restructuring of the spatial organization of the membrane protein-lipid complex. The

© O.S. Payenok, A.V. Payenok, 2019

latter is due to the fact that thyroxin not only enhances the synthesis of free fatty acids and increases the formation of monounsaturated fatty acids, but also contributes to the conversion of monosaturated to polyunsaturated fatty acids which are less resistant to oxidation [1,7].

The stimulation of LPO in tissues may be due to the decrease in the activity of the antioxidant defense system (AODS) in hyperthyroidism which occurs as a result of the decrease in the concentration of glutathione and the decrease in the number of SH-group proteins [6] as well as the deficiency of ascorbic acid in the body [7].

Constant monitoring of the contents of active forms of oxygen, free radicals and hydroperoxides, both enzymatic and non-enzymatic, clearly regulates lipid peroxidation reactions. The failure of such control leads to the increase in the processes of LPO and the accumulation of products of lipoperoxidationin the body, which is characterized by high reactivity. These products can systemically damage the cells [7].

The high content of lipid peroxidation products in biomembranes leads to the weakening of the barrier function and the increase in its permeability for organic matter and various ions. The products of lipoperoxidation cause a damaging effect on proteins, thiol compounds, deoxyribonucleic acid (DNA), nucleotide phosphates which ultimately negatively affect the vitality of a cell [1]. The leading factors in the disorganization of cellular metabolism in this case are the separation of oxidative phosphorylation in mitochondria, ion imbalance of a cell and the activation of lysosomal enzymes. The reduction of the activity of antioxidant enzymes and imbalance in this system can contribute to reducing the tissue resistance to LPO which, in turn, becomes a possible cause of the violation of the functional state of the thyroid gland [6,11].

The purpose of our study was to determine the dependence of the activity of free radical lipid oxidation on the degree of severity of thyrotoxicosis in pregnant women and women in labour, based on the determination of the malondialdehyde concentration (MDA), diene conjugates (DC), superoxide dismutase (SOD) enzymes and selenium-dependent glutathione peroxidase (GPO) which characterize the processes of glycolysis and the functional capacity of the antioxidant defense system.

Materials and methods. 138 pregnant women and a woman in labour with DTG (diffuse toxic goiter) were examined. The studies were conducted in women in the third trimester of pregnancy in the period of 37-40 weeks and during childbirth, examining lipid peroxidation and antioxidant defense system in the blood of women in labour and umbilical cord of newborns as well as the placental tissue were received immediately after delivery.

The group of pregnant women and women in labour with diffuse toxic goiter was distributed according to the severity of the disease, 65 patients of which had a mild form of DTG, 64 - moderate, 9 -severe. The control group included 30 women with a physiological course of pregnancy.

Clinical anamnestic, laboratory and statistical methods of examination were used in the course of the investigation.

The intensity of peroxide lipid oxidation (PLO) in the body of pregnant women was assessed by the content of malondialdehyde in blood plasma, which was determined by the reaction with tiabarbituric acid. This method determined the content of MDA in the blood of the umbilical cord of newborns and the placenta tissue.

The amount of diene conjugates of unsaturated fatty acids was determined in the blood plasma of a pregnant woman and venous blood of the umbilical cord and placenta tissue of newborns.

The status of antioxidant defense system in the body of pregnant women was assessed by the activity of selenium-containing glutathione peroxidase and superoxide dismutase in their blood, placenta tissue and umbilical cord blood of newborns.

The received data was processed by the method of variation statistics. The average value (M), the error of the arithmetic mean (m) were calculated. In order to assess the probability of the difference in the studied parameters which were compared by Student's t-test.

Results of the study and their discussion. As a result of the conducted research, it was found that the content of malondialdehyde (MDA) in erythrocytes and in blood plasma is significantly increasing at all degrees of severity of diffuse toxic goiter (DTG) (table 1).

It should be emphasized that more obvious changes in the content of MDA are observed in erythrocytes which causes the development of the hypoxic state of the tissues of both a mother and a fetus due to the harmful effect of peroxides on the erythrocyte membrane and the subsequent disintegration. The increase of MDA content in plasma may be due to its accumulation in the tissues of a mother and a fetus as well as with the disintegration of erythrocytes [1]. The characteristic feature is that the amount of MDA depends on the severity of the course of the disease - the more severe the course of diffuse toxic goiter, the higher its content in erythrocytes and plasma. In severe forms of diffuse toxic goiter, MDA in plasma

exceeds the control group indicators in almost 1.78 times, in erythrocytes in 2.86 times, respectively (table 1).

Table 1

The state of the oxidative stress of the lipid peroxidation - antioxidant defense system in the blood of women with the physiological course of pregnancy and in case of diffuse toxic goiter, M ± m

Examined groups Contents Activity

MDApi, ^mol / l MDArbc, ^mol / ml DCrbc, ^mol/1012er SODpl, units per mg of protein GPOpl, ^mol NADF / min 1 g protein

Control group, n=30 5,842±0,167 0,764±0,013 7,811±0,161 0,613±0,024 4,612±0,157

Degree of severity of the diffuse toxic goiter mild form, n=65 7,215±0,202 pk<0,05 1,263±0,030 pk<0,05 9,709±0,187 pk<0,05 0,463±0,009 pk<0,05 3,973±0,099 pk<0,05

moderate form, n=64 8,571±0,218 pk<0,05 pi<0,05 1,656±0,041 pk<0,05 pn<0,05 10,735±0,387 pk<0,05 pn<0,05 0,234±0,022 pk<0,05 pl<0,05 2,412±0,150 pk<0,05 pl<0,05

severe form, n=9 10,436±0,333 pk<0,05 pi<0,05 Pm<0,05 2,191±0,158 pk<0,05 pl<0,05 Pm<0,05 11,941±0,342 pk<0,05 pl<0,05 Pm<0,05 0,121±0,019 pk<0,05 pl<0,05 Pm<0,05 1,579±0,134 pk<0,05 pl<0,05 pm<0,05

Notes: probability of differences of the corresponding indicators relative to the control group of pregnant women; pk -

pl - probability of differences of the corresponding indicators relative to the group of pregnant women with a mild form

of diffuse toxic goiter;

pm - the probability of differences of the corresponding indicators relative to the group of pregnant women with a moderate form diffuse toxic goiter.

The indication of the intensification of all links of lipid peroxidation (LPO) is to enhance the formation of diene conjugates (DC), one of the initial products of this process. The number of the latter naturally increases depending on the degree of severity of the course of diffuse toxic goiter (DCc = 7,811 ± 0,161; DCvT = 11,941 ± 0,342 ^mol / 1012rbc), however, as compared with MDA their number is much smaller (in 1.52 times). This is probably due to the fact that DC is an initial product which further is used to form MDA, one of the final products of LPO.

Interesting were the results of the study of LPO during the childbirth which was complicated by DTG (table 2). In this case, the content of MDA during the childbirth in all forms of thyrotoxicosis greatly exceeds the control indicators and in some mild forms of DTG MDArbc.lT = 1,965 ± 0,052; in a moderate form - MDArbc.cT = 1,95 ± 0,165; in a severe form - MDArbc.vT = 3,426 ± 0,288 ^mol / ml. In blood plasma, respectively, in a mild form of diffuse toxic goiter MDApl.lT = 7,308 ± 0,154; in a moderate form - MDApl.lc = 8,955 ± 0,322; in a severe form - MDApl.m = 13,164 ± 0,817 ^mol / l.

Table 2

The state of the system of lipid peroxidation - antioxidant defense system in the blood of pregnant women

during childbirth in the physiological course of pregnancy and in case of diffuse toxic goiter, M ± m

Examined groups Contents Activity

MDApl, ^mol / l MDArbc, ^mol / ml DCrbc, ^mol /1012er SODpl, units per mg of protein GPOpl, ^mol NADF / min 1 g protein

Control group, n=30 6,745±0,118 0,935±0,025 8,113±0,214 0,718±0,024 6,107±0,235

Degree of severity of the diffuse toxic goiter mild form, n=65 7,308±0,154 pk<0,05 1,195±0,052 pk<0,05 9,025±0,229 pk<0,05 0,654±0,019 pk<0,05 5,562±0,104 pk<0,05

moderate form, n=64 8,995±0,332 pk<0,05 pl<0,05 1,950±0,165 pk<0,05 pl<0,05 11,659±0,440 pk<0,05 pl<0,05 0,408±0,040 pk<0,05 pl<0,05 4,621±0,198 pk<0,05 pl<0,05

severe form, n=9 13,164±0,817 pk<0,05 pl<0,05 Pm<0,05 3,426±0,288 pk<0,05 pl<0,05 Pm<0,05 15,362±0,638 pk<0,05 pl<0,05 Pm<0,05 0,172±0,010 pk<0,05 pl<0,05 Pm<0,05 3,551±0,349 pk<0,05 pl<0,05 Pm<0,05

Notes: probability of differences of the corresponding indicators relative to the control group of pregnant women; pk -

pl - probability of differences of the corresponding indicators relative to the group of pregnant women with a mild form

of diffuse toxic goiter;

pm - the probability of differences of the corresponding indicators relative to the group of pregnant women with a moderate form diffuse toxic goiter.

It is likely that such intense formation of LPO products in the body of a woman with various forms of thyrotoxicosis negatively affects the state of a fetus, since in the venous blood of the umbilical cord

which enters a fetus in all forms of thyrotoxicosis, DC and MDA are significantly increasing. This determines the critical situation of vital processes in the body of a fetus. Thus, in the mild form of diffuse toxic goiter in cord venous blood, the content of MDA in erythrocytes is 1,102 ± 0,054 ^mol / ml and, accordingly, the content of DC in erythrocytes is 7,447 ± 0,204 ^mol / 1012 rbc; in a moderate form the MDA is 1,441 ± 0,063 ^mol / ml, and DC is 8,959 ± 0,285 ^mol / 1012rbc, in the severe form the MDA is 2,197 ± 0,014 ^mol / ml, and DC is 13,419 ± 0,888 ^mol / 1012rbc (table 3).

The confirmation of this is the change in the products of the LPO in the placenta. Thus, in a mild form of DTG the MDA in the placenta is 114,070 ±4,544 ^mol / ml, and DC is 918,543 ± 31,097 ^mol / 1012rbc, in a moderate form the MDA is 140,188 ± 3,639 ^mol / ml, and DC 1165,32 ± 31,95 ^mol / 1012rbc, while in a severe form the MDA is 231,966 ± 18,495 ^mol / ml while DCis 1557,272 ± 61,252 ^mol / 1012rbc (table 4).

Thus, the obtained results indicate that LPO is one of the leading links in the pathogenesis of DTG development. At the same time peroxidation syndromeis developing, which promotes destructive changes in the biological membrane cells of both a mother and a fetus, the violation of the biosynthesis of nucleic acids, protein, changes in the structure and function of many enzymes, which is a negative prediction for the subsequent occurrence of the postpartum period and the period of a newborn's birth.

Table 3

The state of the system of lipid peroxidation - antioxidant defense system in the blood of a newborn's

umbilical cord in mothers with diffuse toxic goiter, M ± m

Examined groups Contents Activity

MDApi, ^mol / l MDArbc, ^mol / ml DCrbc, ^mol /1012er SODpl, units per mg of protein GPOpl, ^mol NADFN / min 1 g protein

Control group, n=30 5,691±0,148 0,749±0,013 6,036±0,161 0,602±0,019 2,726±0,079

Degree of severity of the diffuse toxic goiter mild form, n=65 6,571±0,150 pk<0,05 1,102±0,054 pk<0,05 7,447±0,204 pk<0,05 0,489±0,021 pk<0,05 2,239±0,085 pk<0,05

moderate form, n=64 8,046±0,230 pk<0,05 pi<0,05 1,441±0,063 pk<0,05 Pl<0,05 8,959±0,285 pk<0,05 Pl<0,05 0,343±0,037 pk<0,05 Pl<0,05 1,853±0,068 pk<0,05 Pl<0,05

severe form, n=9 11,614±0,71 pk<0,05 pi<0,05 Pm<0,05 2,197±0,14 pk<0,05 pl<0,05 Pm<0,05 13,419±0,888 pk<0,05 pl<0,05 Pm<0,05 0,101±0,005 pk<0,05 pl<0,05 Pm<0,05 0,658±0,069 pk<0,05 pl<0,05 Pm<0,05

Notes:pk probability of differences of the corresponding indicators relative to the control group of pregnant women;

pl - probability of differences of the corresponding indicators relative to the group of pregnant women with a mild form

of diffuse toxic goiter;

pc - the probability of differences of the corresponding indicators relative to the group of pregnant women with a

moderate form diffuse toxic goiter.

Thus, the complex of conducted studies shows that the intensity of the LPO can serve as a test for determining the severity of DTG and is used for the diagnosis of thyrotoxicosis, the prognosis of the course of the childbirth, postpartum and the period of a newborn's birth, for the application of adequate tactics and therapy in this pathology of pregnancy.

The investigation of enzymes of antioxidant defense system at DTG has shown that superoxide dismutase (SOD) activity in plasma is depleted in accordance with the severity of DTG, and especially during the childbirth, and in the severe form of SOD is 0,121 ± 0,019 units/ mg of protein, in the moderate form of SOD - 0,234 ± 0,023 units / mg of protein, in a mild form of SOD - 0,463 ± 0,009 units / mg of protein (table 1).

In the study of the venous cord blood of a fetus, a significant decrease in the plasma enzyme was detected in accordance with the severity of the pathological process. In a severe form of DTG SOD is 0,101 ± 0,005 units / mg of protein, in a moderate form SOD is 0,343 ± 0,037, while in the mild form SOD is 0,489 ± 0,021 (p<0,05). These data suggest the intensification of the pathological process in the mother-placenta-fetus system and the correction of adaptive processes is carried out at the expense of the antioxidant system of a fetus in the progressive pathology of the placental system (table 3).

Similar data were obtained in the study of glutathione peroxidase (GPO) activity, the content of which in the blood plasma of pregnant women is depleted according to the severity of the process, which is due to the increased hemolysis in erythrocytes when the patient's condition deteriorates. Thus, in a mild form of DTG GPO in the blood plasma makes up 3,973 ± 0,079 ^mol of NADF / min 1 g of protein, in a

moderate form it is 2,412 ± 0,1136 ^mol of NADF / min 1 g of protein, in a severe form 1,579 ± 0,134 ^mol of NADF / min 1 g protein (table 1).

Table 4

The state of the system of the lipid peroxidation - antioxidant defense system in the placenta during physiological pregnancy and in case of diffuse toxic goiter, M ± m

Examined groups Contents Activity

MDApl, ^mol / l MDArbc, ^ / ml DCrbc, ^mol /1012er GPOpl, ^mol NADFN / min 1 g protein

Control group, n=30 79,328±3,527 681,625±33,828 210,567±10,123 789,270±31,373

Degree of severity of the diffuse toxic goiter mild form, n=65 114,070±4,544 pk<0,05 918,543±31,097 pk<0,05 179,755±2,138 pk<0,05 704,098±13,448 pk<0,05

moderate form, n=64 140,188±3,639 pk<0,05 pl<0,05 1165,32±31,95 pk<0,05 pl<0,05 168,095±2,765 pk<0,05 pl<0,05 635,853±16,405 pk<0,05 pl<0,05

severe form, n=9 231,966±18,495 pk<0,05 pl<0,05 Pm<0,05 1557,272±61,251 pk<0,05 pl<0,05 Pm<0,05 104,449±1,640 pk<0,05 pl<0,05 Pm<0,05 372,408±19,066 pk<0,05 pl<0,05 Pm<0,05

Notes:

pk - probability of differences of the corresponding indicators relative to the control group of pregnant women;

pi - probability of differences of the corresponding indicators relative to the group of pregnant women with a mild form

of diffuse toxic goiter;

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pm - the probability of differences of the corresponding indicators relative to the group of pregnant women with a moderate form diffuse toxic goiter.

Changes in the enzymes of the selenium-dependent glutathione anti-oxidant system in the venous blood of the umbilical cord have a characteristic dependence that is suppressed by the severity of the DTG course: in a severe form of DTG the LPO in the venous blood of the umbilical cord is 0,658 ± 0,069, in a moderate form it is 1,853 ± 0,068, and in a mild form - 2,239 ± 0,085 microns per mole of NADF / min 1 g of protein (table 3).

Changes in superoxide dismutase and glutathione peroxidase are also noted in the placental tissue. Thus, SOD in the placenta in a severe form of DTG is 104,449 ± 1,64 units / mg protein; in a moderate it is 168,095 ± 2,765, in a mild form it makes up 179,755 ± 2,138 units/ mg of protein (table 4).

The LPO in the placenta in a severe form is 372,408 ± 19,066; in a moderate form it is 635,853 ± 16,405; in a mild form - 704,098 ± 13,448 micron NADF / min 1 g protein (table 4).

Thus, the presented results of researches indicate that the state of patients with DTG corresponds to the peculiarities of the increasing changes of free radical processes and the depletion of the antioxidant defense system. [11]

It should be emphasized that free radical processes continue to grow rapidly in accordance with the severity of the course of the pathological process. There is the suppression of the intensification of antiperoxide enzymes, which is probably due to the overload of their substrates (peroxides, hydroperoxides, cycloperexides).[7, 11]

The object of the action of oxygen-active compounds in the conditions of reducing the buffer capacity of the antioxidant system of defence of the body of a pregnant woman are proteins, nucleic acids, substrates of lipid nature, the intensive oxidation of which leads to their modification, and as a result - to the violation of the biological activity of the synthesis and transport of enzymes, hormones, vitamins, changes in receptor functions of membrane permeability, energy deficiency, the violation of tissue respiration. Such violences lead to radical changes in the biological function of the tissues of the body as a whole. [4]

The activation of the LPO during the physiological pregnancy is thought to be due to the increase in the need for oxygen, which does not lead to irreversible damage, because it is ensured by the increase in the antioxidant defense system (AODS) which partially neutralizes the links of LPO, preventing the formation of MDA, the final metabolite of free radical lipid oxidation. The physiological pregnancy is accompanied by stable persistent oxidative stress, which can be explained by the parallel increase in the activity of tissue antioxidant enzymes that have an adaptive nature and are the main factor in stabilizing oxidative stress in such pregnant women. [7]

In the course of the physiological course of pregnancy, the increase of AODS intensification is determined, however, it does not exceed 5-10 % of the level in non-pregnant women, which is the result of

the compensation of the overall increase in metabolism and the physiological response to the intensification of LPO. As the progression of pregnancy has been observed, we have noted further increase of all investigated AODS indicators. [11]

The indicated changes, in turn, cause the violation of the system of homeostasis, vascular reactivity, microcirculation, cardiac activity. Further on, these changes, combined with the tissue and cell hypoxia, lead to profound changes in the organs and systems of life support for both a mother and a fetus.

The obtained metabolic disorders are characterized by the accumulation in the body of undocociated products such as ketones, aldehydes, semi-solids, free radicals, peroxide leads to the development of metabolic acidosis, which contributes to the decrease in the buffer capacity of AODS in pregnant women, which can lead to the development of severe encephalopathies in diffuse toxic goiters. [1] The development of metabolic disoders in severe forms of thyrotoxicosis is characterized by the pathological activation of LPO in the context of the decrease in the antioxidant activity, which significantly affects the degree of degradation of protein molecules, and the free radicals thus occur, violate the permeability of the biomembrane cells, reduce the synthesis of endogenous phospholipids, increase the viscosity of the lipid bilayerof cells.[12]

Paying attention to the biological significance of the dynamic equilibrium of these processes in the life of the cells, one can not ignore this mechanism, in examining the causes of the development of obstetric and perinatal pathology, which are so typical for thyropathies.

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Thus, based on the data obtained, we can state that one of the leading causes of thyrotoxicosis is the lack of antioxidant defense of the body, which plays a leading role in its adaptation during pregnancy, childbirth and in the postpartum period.

The indicator of LPO and oxidative stress may be criteria for the severity of thyrotoxicosis, as well as a marker for predicting the course of pregnancy, both for a mother and a fetus in women with diffuse toxic goiter. The study of AODS and its resistance to toxic LPO products allow the development of adequate programs for the treatment of hyperthyroidism and the prevention of fetoplacental complications in pregnant women with diffuse toxic goiter.

1. Bakhareva I V. Rol antioksidantov pri beremennosti vysokogo riska. Ginekologiya. 2014; 1:90-6. [in Russian]

2. Dedov II, Melnichenko GA. Endokrinologiya: natsionalnoye rukovodstvo. M.: GEOTAR-Media; 2013. 1072 s. [in Russian]

3. Zayduyeva YAZ. Beremennost pri zabolevaniyakh shchitovidnoy zhelezy (obzor literatury). Meditsinskiy alfavit. 2017;1(3):31-8. [in Russian]

4. Korovay SV. Nekotoryye pokazateli svobodnoradikalnogo okisleniya i lipidnogo obmena u beremennykh s prezhdevremennymi rodami i endotelialnoy disfunktsiey. Ukrayinskyi zhurnal klinichnoyi ta laboratornoyi medytsyny. 2012; 7(4):32-6. [in Ukrainian]

5. Lovkova YuS, Potin VV, Tkachenko NN, Shelayeva YeV. Lecheniye diffuznogo zoba vo vremya beremennosti. Zhurnal akusherstva i zhenskikh bolezney. 2017; 66(3):89-96. [in Russian]

6. Prokopenko VM, Pavlova MG. Znachenie glutation-zavisimykh fermentov antioksidantnoy zashchity v funktsionalnoy aktivnosti placenty cheloveka. Akusherstvo i ginekologiya, 2014. 11: 62-67. [in Russian]

7. Shalina RI, Kanzapetov MR. Antioksidanty i ikh rol v akusherskoy praktike. Ginekologiya. 2013; 15(5):3-7. [in Russian]

8. Shcherbakov AYu, Melikova TA. Kliniko-patogeneticheskoye znacheniye narusheniy v sisteme gemostaza u beremennykh s autoimmunnym tireoiditom. Mezhdunarodnyi meditsinskiy zhurnal. 2017; 23(1):39-42. [in Russian]

9. Fadeev VV. Po materialam klinicheskikh rekomendatsiy po diagnostike i lecheniyu zabolevaniy shhitovidnoy zhelezy vo vremya beremennosti i v poslerodovom periode Amerikanskoy tireoidnoy assotsiatsii. Perevod i kommentarii VV. Fadeeva. Klinicheskaya i eksperimentalnaya tireoidologiya. 2012; 8(XI):7-18. [in Russian]

10. Kholodova EA. Clinical endocrinology: a guide for physicians. M.: Medical Information Agency LLC; 2011. 736 s. (in Russian)

11. Knuppell RA, Hassan MI, McDermott JJ, Tucker JM, Morrison JC. Oxidative Stress and Antioxidants: Preterm birth and Preterm Infants, preterm birth - mother and child [Internet]. 2012[cited 2011 Aug 18]. p. 126-150. Available from: https://www.intechopen.com/books/preterm-birth-mother-and-child/oxidative-stress-and-antioxidants-preterm-birth-and-preterm-infants.

12. Krassas GE, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr. Rev. 2010;5(31): 702-55.

Illlll1!яи1И1!!!!И

ЗМ1НИ ПОКАЗНИК1В ПЕРОКСИДАЦП Л1П1Д1В ИЗМЕНЕНИЯ ПОКАЗАТЕЛЕЙ ПЕРОКСИДАЦИИ ТА АНТИОКСИДАНТНО! АКТИВНОСТ1 ЛИПИДОВ И АНТИОКСИДАНТНОЙ

У ВАГ1 ТНИХ ТА РОД1ЛЬ I З ДИФУЗНИМ ТОКСИЧНИМ ЗОБОМ Паенок О. С., Паенок А.В., Паньюв I.B., Коспв М.О.

З метою встановлення залежност активност пероксидацп лшвдв вщ ступеня важкост тиреотоксикозу, а також впливу його на порушення антиоксидантного захисту в системi мати-плацента-плщ проведено

АКТИВНОСТИ У БЕРЕМЕННЫХ И РОЖЕНИЦ

С ДИФФУЗНЫМ ТОКСИЧЕСКИМ ЗОБОМ Паенок А. С., Паенок А.В., Панькив И.В., Костив М.А.

С целью установления зависимости активности ПОЛ от степени тяжести тиреотоксикоза, а также влияния его на нарушение антиоксидантной защиты в системе мать-плацента-плод проведено обследование 138

обстеження 138 ваптних жшок iз дифузним токсичним зобом, iз яких 65 пащенток мали легкий стутнь дифузного токсичного зобу, 64 - середнш, 9 - важкий. Контрольну групу склали 30 жшок iз фiзiологiчним перебiгом вагiтностi. Обстеження проводилися в третьому триместрi вагiтностi, а також та тд час пологiв. Визначали концентрацiю початкових та кiнцевих продукпв вiльнорадикального окислення та ферментiв антиоксидантно! системи захисту. Отриманi результати вказують, що однiею з провiдних причин розвитку тиреотоксикозу е недостатшсть антиоксидантного захисту оргашзму, показники якого можуть слугувати критерiями важкостi перебiгу захворювання та застосовуватися для монiторингу виникнення перинатальних ускладнень при дифузному токсичному зобi у вагiтних.

Ключовi слова: ваптшсть, пологи, перекисне окислення лшвдв, антиоксидантна активнiсть, дифузний токсичний зоб.

Стаття надшшла 26.10.18 р.

беременных женщин с диффузным токсическим зобом, из которых 65 пациенток имели легкую степень диффузного токсического зоба, 64 - среднюю, 9 - тяжелую. Контрольную группу составили 30 женщин с физиологическим течением беременности. Обследования проводились в третьем триместре беременности, а также и во время родов. Определяли концентрацию начальных и конечных продуктов свободнорадикального окисления и ферментов антиоксидантной системы защиты. Полученные результаты указывают, что одной из ведущих причин развития тиреотоксикоза является недостаточность антиоксидантной защиты организма, показатели которой могут служить критериями тяжести течения заболевания и применяться для мониторинга возникновения перинатальных осложнений при диффузном токсическом зобе у беременных.

Ключевые слова: беременность, роды, перекисное окисление липидов, антиоксидантная активность, диффузный токсический зоб.

Рецензент Лiхачов В.К.

DOI 10.26724/2079-8334-2019-2-68-91-96 УДК 614.2:616-082.3

В.Д. Марш1. С.М. I |>М111> к2. 11.М. Коришчу к2. А.М. I ар.шкыкг. Л.В. I орохова2 111;ммона. imiiiü метчнимупвериисч iMeiii О.О. Бшомо.ii.iiu. К'мТи :Ж'мюммрськмм державммм уиверсмич i\ieiii 1вама Франка. Житомир

РЕЗУЛЬТАТИ АУДИТУ ДОТРИМАННЯ УН1Ф1КОВАНОГО КЛ1Н1ЧНОГО ПРОТОКОЛУ НАДАННЯ МЕДИЧНО1 ДОМОМОГИ МАЦ1СНТАМ З 1ШЕМ1ЧНИМ 1НСУЛЬТОМ

У ГОСТРОМУ ПЕР1ОД1

e-mail: zamlkzt@gmail.com

Метою роботи було провести аудит вщповщност надання спeцiалiзованоI медично! допомоги в стацiонарних умовах пащентам з iшeмiчним iнсультом у гострому nep^i положенням галузевого кйшчного протоколу на прикладi закладiв охорони здоров'я Житомирсько! областi. Дослiджeння проводилося шляхом суцшьно! вибipки та ретроспективного аналiзу медичних карт стацiонаpних хворих з дiагнозом «Iшeмiчний шсульт», яю отримували спeцiалiзовану медичну допомогу у 26 закладах охорони здоров'я Житомирсько! област у першому пiвpiччi 2018 року. За спещально розробленою «Картою аудиту», яка включала 21 шдикатор за 4 роздшами, було здшснено аналiз 508 випадкiв лiкування. Ушфкований клiнiчний протокол надання медично! допомоги при iшeмiчному iнсультi (протокол) в частиш дiагностики та обстеження за 5 кpитepiями був повнiстю дотриманий у 25,0±1,9% випадкiв, в частинi призначення лiкаpських засобiв за 11 шдикаторами - при лiкуваннi лише 7,9±1,2% пацiентiв. Рання мобiлiзацiя в гострому пepiодi iшeмiчного iнсульту проводилася в 59,8±2,2% випадкiв, iндивiдуальний план реабштацп наявний в 54,7±2,2% випадюв лiкування. Заходи з пpофiлактики повторного шсульту вiдповiдали протоколу у 59,8±2,2% випадкiв. За результатами оцiнки 21 шдикатора у 2018 pоцi повне дотримання протоколу встановлено при лкуванш лише 15 пащенив (3,0±0,8% випадюв), хоча за окремими кpитepiями в частиш обстеження i лiкування поpiвняно з даними 2014 року вiдмiчeна достовipно позитивна динамiка. Встановлено низький piвeнь стандартизацп медично! допомоги при iшeмiчному iнсультi, що зумовлено недостатньою вepифiкацiею дiагнозу, призначенням лiкаpських засобiв з недоведеною eфeктивнiстю, вiдсутнiстю сучасних пiдходiв до peабiлiтацiI пацiентiв та профшактики повторних iнсультiв.

Ключов! слова: аудит, ¡шем1чний ¡нсульт, протокол, шдикатор, медична допомога.

Дане дождження е фрагментом НДР «Oco6nneocmi переб^у та натдки шсульту у хворих pi3Hux вжових груп з урахуванням генетичних та шфекцшних чиннитв i коморбiдноl патологи (номер державно!реестрацн 0118U003695).

Проблема цереброваскулярних захворювань е одшею ¡з найбшьш актуальных у сучаснш медициш, зокрема для системи охорони здоров'я Укра!ни, де основною причиною смертносп е хвороби системи кровообпу. Серед них особливо небезпечним е шем1чний шсульт (II) [3,5]. Захворювашсть на II становить 270—280 випадюв на 100 тисяч населення i перевищуе середнш показник у кра!нах Евросоюзу (200 на 100 тисяч населення). В Украш щороку рееструють майже 100 тис. випадюв первинного II, вщ нього помирають 10-12% пащенпв, близько 60% стають швалщами [1,2,6]. За даними Ыституту по вишрюванню показниюв здоров'я та оцшщ стану здоров'я (IHME), в Укра!ш шсульти е другою (тсля 1шем1чно! хвороби серця) причиною передчасно! смертносп й швалщносп. У загальнш структур1 глобального тягаря хвороб у нашш держав1 у 2017 рощ частка шсульт1в становила понад 8% [8].

© В.Д. Парш, С.М. Грищук, 2019

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