Exacerbation Of Cytomegalovirus Infection Research Articles

Cyclooxygenase 2 and prostaglandin E2 in the genesis of pregnancy loss in cytomegalovirus infection

Prostaglandins (PGs), regulated by cyclooxygenase (COX) 2, play a significant role in the development of placental disorders in pathological pregnancy. A review of current literature reveals a lack of evidence demonstrating the involvement of PGs in the pathogenesis of early spontaneous miscarriages associated with cytomegalovirus (CMV) infection. The aim of this study was to investigate the levels of COX-2 and PG E2 in peripheral blood and determine their significance in predicting pregnancy loss during exacerbation of CMV infection at 7-8 weeks gestation.Materials and methods. The study involved 70 patients experiencing an exacerbation of chronic CMV infection at 7-8 weeks of gestation, with 36 patients presenting with a threatened miscarriage (main group) and 34 patients without signs of threatened miscarriage (comparison group). CMV infection was diagnosed based on the presence of M and G class antibodies using enzyme-linked immunosorbent assay (ELISA), as well as CMV DNA detected by polymerase chain reaction. COX-2 levels in mononuclear cell lysates were determined using the "Assay Designs, COX-2" (USA) test systems, and PG E2 concentrations in blood serum were measured using "Cloud-Clone Corp." (USA) kits.Results. Women with exacerbated CMV infection associated with spontaneous miscarriage at 7-8 weeks of gestation exhibited elevated concentrations of COX-2 (23.0±2.20 ng/mL) and PG E2 (850.10±35.0 pg/mL, p<0.001) compared to pregnant women without threatened miscarriage (12.75±1.35 ng/mL and 42.0±2.80 pg/mL, respectively).Conclusion. The findings of this study underscore the significant role of elevated COX-2 and PG E2 concentrations in the pathogenesis of pregnancy loss during exacerbation of CMV infection at 7-8 weeks of gestation. The assessment of COX-2 and PG E2 levels should be considered as a predictive measure for the risk of pregnancy loss during exacerbation of CMV infection.

Clinical and functional characteristics of cerebral ischemia in newborns from mothers with exacerbation of cytomegalovirus infection during pregnancy

Introduction. Despite the known role of antenatal virus-associated brain damage in the neurological status impairment of newborns, there is a lack of studies addressing the clinical features of cytomegalovirus (CMV) infection. Aim. To provide a clinical and functional characterization of cerebral ischemia in newborns from mothers with exacerbation of CMV infection in the second trimester of pregnancy.Materials and methods. Clinical and anamnestic data, Apgar scores, body weight, and resistance index in the anterior cerebral artery were studied in 30 newborns from mothers with uncomplicated pregnancies (control group) and 70 newborns from mothers who experienced an exacerbation of CMV infection in the second trimester of pregnancy (main group), including 38 with grade I cerebral ischemia (first subgroup) and 32 with grade II cerebral ischemia (second subgroup).Results. Newborns in the first subgroup exhibited signs of intrauterine hypoxia, characterized by a lower Apgar score at 1 (p<0.001) and 5 minutes (p<0.001) compared to the control group. Average body weight values were also reduced (p<0.01). Changes in neuro-reflex status manifested as hyperexcitability and motor disorders. The resistance index in the anterior cerebral artery did not differ significantly (p>0.05). In the second subgroup, Apgar scores at 1 (p<0.001) and 5 minutes (p<0.001), as well as average weight indicators (p<0.01 and p<0.001), were lower than in the control group and the first subgroup. The clinical picture was dominated by hypertensive-hydrocephalic syndrome and suppression syndrome, with some cases showing signs of hyperexcitability and convulsive syndrome. Doppler imaging revealed an increase in the resistance index in the anterior cerebral artery (p<0.001).Conclusion. Newborns from mothers with exacerbation of CMV infection in the second trimester of pregnancy exhibit hypertensive-hydrocephalic syndrome and suppression of neuro-reflex activity depending on the severity of cerebral ischemia, against a background of reduced blood flow in the anterior cerebral artery. Impaired cerebral hemodynamics in such newborns at birth may increase the risk of reduced adaptation in the postnatal developmental period.

The role of fatty acids in disturbance of energy processes in the early placenta with cytomegalovirus infection

Introduction. Cytomegalovirus (CMV) infection directly and indirectly can cause placental dysfunction. One of the reasons for its development may be a deficiency of energy supply due to changes in the level of fatty acids (FA) – the main sources of energy in the cell.Aim. Analysis of the fatty acids concentration and causes of its changes in the placenta during exacerbation of CMV infection in the first trimester of pregnancy.Materials and methods. Biosamples (venous blood, epithelium from the inner surface of the cheek, mucous membrane of the cervical canal, villous chorion) of 32 CMV-seropositive women with an exacerbation of CMV infection in the first trimester of pregnancy (main group) and 30 CMV-seronegative women (control group) were studied. Exacerbation of CMV infection was diagnosed by ELISA to detect IgM and IgG with avidity of 65% or more, PCR to detect CMV DNA. The profile and relative concentration of individual FA in villous chorion lipid extracts were studied by gas-liquid chromatography. The activity of pyruvate dehydrogenase, succinate dehydrogenase, NADP-dependent malate dehydrogenase, and glucose-6-phosphate dehydrogenase was determined by a histochemical method on sections of freshly frozen villous chorion tissues.Results. In the main group placentas, the concentration of medium-chain saturated fatty acids was statistically significantly lower: capric by 50%, lauric by 51%, unsaturated myristoleic by 44%; long-chain unsaturated acids: palmitoleic, oleic, linoleic and α-linolenic fatty acids by 52%, 55%, 57% and 64%, respectively; of polyunsaturated fatty acids with a very long chain: eicosapentaenoic and docosahexaenoic by 44% and 41%, respectively. The activity of enzymes: succinate dehydrogenase, pyruvate dehydrogenase, NADP-dependent malate dehydrogenase and glucose-6-phosphate dehydrogenase decreased.Conclusion. Thus, we found a decrease in energy supply in the placenta during exacerbation of chronic CMV infection in the first trimester of pregnancy. Disorders of placental energy metabolism can cause placental insufficiency, which has adverse consequences for fetal development.

Pathomorphological characteristics of cotyledons with weak contrasting of the blood flow in the placenta of women who have undergone exacerbation of cytomegalovirus infection during the second trimester of pregnancy

Aim. To give pathomorphological characteristics of placental cotyledons with weakly contrasted bloodstream in women who had an exacerbation of cytomegalovirus infection (CMVI) in the second trimester of pregnancy.Materials and methods. A study was made of involutive-destructive processes in 153 cotyledons of the placenta with well and weakly contrasted bloodstream in women with pregnancy, uncomplicated and complicated by exacerbation of CMVI at 21-24 weeks of gestation. The first group included 36 cotyledon placentas from women with CMV-seronegative uncomplicated pregnancy with well contrasted blood vessels; the second group – 67 cotyledon placentas from patients with chronic compensated placental insufficiency (CCPI) and poorly contrasted vascular network; the third group – 30 cotyledon placentas from women with chronic subcompensated placental insufficiency (CSPI) with indistinctly visualized blood vessels; the fourth group – 20 cotyledon placentas from patients with chronic decompensated placental insufficiency (CDPI). Dosed introduction of red lead on drying oil (1:3) into the blood vessels of the placenta was carried out through the umbilical cord vein. Obtaining X-ray images of cotyledons with well and weakly contrasted blood vessels in the marginal part of the organ was carried out on the apparatus RUM-20M with X-ray image intensifier Sapphire (Russia). Cotyledon biopsy specimens for histometry and histochemical analysis were taken before their contrasting, and for survey microscopy – after injection of the contrast mass.Results. In the first group, the amount of fibrinoid in the stroma of the villi was 1.35±0.09%, perivillous fibrinoid − 1.02±0.08% in the absence of pseudonecrosis and calcifications. In the second group, unlike the first one, cotyledons prevailed, in which in 40-50% of cases weakly expressed contours of blood vessels were found, an increase in the specific volume of stromal fibrinoid by 1.82 times was observed (p<0.001), and fibrinoid around villi by 2.04 times (p<0.001); pseudonecrosis accounted for 2.29±0.13%, and calcificates − 1.50±0.12%. In the third group, in comparison with the second one, cotyledons were more common with 50-70% of indistinctly contoured vessels, villi with edematous changes and stromal collagenization; the concentration of stromal fibrinoid increased by 1.47 times (p<0.001), the proportion of perivillous fibrinoid – 1.46 times (p<0.001), pseudonecrosis – 1.41 times (p<0.001) and the accumulation of calcium salt – 1.57 times (p<0.001). In the fourth group, compared to the third one, cotyledons were more common, in which more than 70% of weakly contrasted blood vessels were determined, while the number of collagen fibers and acid glycosaminoglycans increased in the villi; there was an increase in the amount of fibrinoid around the villi by 1.24 times (p<0.01), pseudonecrosis – by 1.23 times (p<0.05) and calcificates – by 1.32 times (p<0.01).Conclusion. In women with an exacerbation of CMVI in the second trimester of gestation and CSPI, in contrast to patients with a similar infectious disease and CCPI, a decrease in the flow of contrast into the bloodstream of cotyledons is due to more pronounced edema, the formation of collagen fibers, fibrinoid and calcium salts in the stroma of the villi, as well as perivillous fibrinoid. In CDPI of cytomegalovirus etiology, compared with CSPI, weak contrasting of the vascular bed of cotyledons is associated with increasing changes in the stroma involved in the regulation of the resistance of draining veins and intracotyledon blood vessels.

Mechanisms of blood flow regulation in the uterine arteries during the formation of chronic placental insufficiency caused by exacerbation of cytomegalovirus infection during the second trimester of gestation

Aim. To evaluate the mechanisms of regulation of blood flow in the uterine arteries during the formation of chronic placental insufficiency caused by an exacerbation of cytomegalovirus infection (CMVI) in the second trimester of pregnancy.Materials and methods. The concentration of IL-1β, IFN-γ, IL-4, IL-2 and the systolic-diastolic ratio (SDR) in the right (RUA) and left uterine arteries (LUA) were determined in 90 women in the second trimester of pregnancy, uncomplicated and complicated by exacerbation of CMVI. Retrospectively, 2 groups were distinguished. Group 1 (control) was represented by 30 women with CMV-seronegative physiological pregnancy, group 2 (main) included 60 patients with acute phase of chronic CMVI and consisted of subgroups 1 and 2. Subgroup 1 included 30 women with exacerbation of CMVI, initiating the development of chronic compensated placental insufficiency (CCPI), subgroup 2 − 30 patients with acute phase of chronic CMVI, leading to the formation of chronic subcompensated placental insufficiency (CSPI) in the third trimester of gestation.Results. In women of the 1st group in the blood serum, the concentration of IL-1β (Me [Q1- Q3]) was 18.0 [13.4-36.3] pg/mL, IFN-γ − 134.4 [114.2-151.3] pg/mL, IL-4 − 26.2 [20.3-51.3] pg/mL and IL-2 − 27.9 [18.2-38.0] pg/mL; SDR in RUA – 1.95 [1.87-2.30] relative units and SDR in LUA – 1.84 [1.73-2.25] relative units. In patients of subgroup 1, in comparison with the control one, the concentration of IL-1β increased to 87.3 [55.6-98.2] pg/mL (p=0.000001), IFN-γ − up to 237.3 [191.4-318.6] pg/mL (p=0.000001) and IL-2 − up to 77.1 [58.6-92.3] pg/mL (p=0.000001) in the absence of statistically significant changes IL-4 level. There was an increase in SDR in RUA up to 2.45 [2.35-3.46] relative units (p=0.000001) and SDR in LUA up to 2.80 [2.31-3.05] relative units (p=0.000001). In subgroup 2, in comparison with subgroup 1, higher values of IL-1β were recorded (1.67 times, p=0.000001), IFN-γ (1.38 times, p=0.000015), IL-2 (1.36 times, p=0.00808), SDR in RUA (by 1.35 times, p=0.0105) and SDR in the LUA (by 1.08 times, p=0.0307), as well as a decrease in the level of IL-4 (by 1.84 times, p=0.000002). In women of subgroup 1, there was a direct relationship between the level of IL-1β, IFN-γ, IL-2 and SDR in the RUA (r=0.54, p<0.01; r=0.74, p<0.001 and r=0.58, p<0.001, respectively). The correlation between IFN-γ and SDR in the LUA was determined (r=0.40; p<0.05). In subgroup 2, there was a relationship between IL-4 and SDR in RUA (r=-0.59; p<0.001), as well as IL-2 and SDR in RUA (r=0.39; p<0.05). A correlation was recorded between the concentration of IL-1β, IFN-γ, IL-2 and the SDR value in the LUA (r=0.39, p<0.05; r=0.58, p<0.001 and r=0.57, p<0.001, respectively).Conclusion. Exacerbation of CMVI in women in the second trimester of gestation, leading to the formation of CSPI, in contrast to a similar viral infection that initiates the development of CCPI in the third trimester of pregnancy, is characterized by a more pronounced activation of the systemic inflammatory response, an increase in resistance to blood flow, as well as differences in immuno-hemodynamic relationships that determine the maintenance of vascular tone in the basin of the right and left uterine arteries.

Anatomical characteristics of the placental cotyledon bloodstream in women with exacerbation of cytomegalovirus infection during the second trimester of gestation

Aim. To give an anatomical description of the placental cotyledon bloodstream in women who had an exacerbation of cytomegalovirus infection (CMVI) in the second trimester of gestation. Materials and methods. A study was conducted on 117 placentas, of which 101 were from women with full-term pregnancy and 16 from women with premature birth. In all cases, CMVI led to the development of chronic compensated (CCPI), subcompensated (CSPI) and decompensated placental insufficiency (CDPI). 5 groups were identified: the first group consisted of 30 placentas from women with full-term pregnancy seronegative for cytomegalovirus (CMV); the second – 27 placentas from patients who had an acute phase of chronic CMVI, initiating the development of CCPI; the third – 23 placentas from women with exacerbation of CMVI, leading to the formation of CSPI; the fourth – 21 placentas from patients with an exacerbation of CMVI, which caused the development of CDPI and prolongation of pregnancy to the term of delivery; the fifth – 16 placentas from women with an acute phase of chronic CMVI, initiating the formation of CDPI and miscarriage. The assessment of the bloodstream of cotyledons of the placenta was carried out by injection of contrast (red lead-paint on dryingoil) through the vein of the umbilical cord. To obtain X-ray phlebograms, the apparatus RUM-20M “Sapphire” was used. Results. It was shown that the total number of cotyledons did not differ in the studied groups. In the first group, anatomical forms with a well-contrasted bloodstream were 21.4±2.17, with weakly contrasted vessels – 9.3±0.47, and with no contrast in the veins, arteries and capillaries of the villi – 2.9±0.22. In the placentas of the second group, in comparison with the first one, no differences were found in the number of cotyledons, in which blood vessels were clearly visualized and not detected. However, the number of anatomical forms with poorly contrasted vessels increased by 1.51 times (p<0.05). The placentas of the third group in comparison with the second one were characterized by a decrease by 1.97 times (p < 0.001) in the proportion of cotyledons with a clear contouring of the vascular network and an increase in anatomical forms with a poorly contrasted bloodstream by 2.34 times (p<0.001). In the fourth group, in comparison with the third group, the number of cotyledons with clear visualization of vessels decreased by 2.05 times (p<0.001), and the number of anatomical forms increased by 1.44 times (p<0.01), in which X-ray phlebography did not determine the vasculature. In the fifth group compared to the fourth one, cotyledons with a well-contrasted bloodstream were found 2.83 times less frequently (p < 0.01). Conclusion. With an exacerbation of CMVI in the second trimester of gestation, leading to the formation of CDPI, in comparison with CCPI and CSPI in the placenta, a reduction of blood flow in cotyledons is more often detected as a result of direct endotheliotropic and mediated effects of CMV. This is the anatomical basis of placental ischemia and one of the pathogenetic mechanisms for the development of miscarriage.

Fetal inflammatory response and endothelial dysfunction in newborns from mothers with exacerbation of cytomegalovirus infection during the second trimester of pregnancy

Aim. To study the fetal inflammatory response and endothelial dysfunction in newborns from mothers with an exacerbation of cytomegalovirus infection (CMVI) in the second trimester of pregnancy. Materials and methods. We examined 90 newborns with an antenatal history, uncomplicated and aggravated by the acute phase of chronic CMVI, diagnosed in their mothers at 21-24 weeks of gestation. The concentration of TNFα, IL-6, and endothelin-1 was determined in cord blood serum. The control group consisted of 30 newborns whose intrauterine development proceeded against the background of physiological pregnancy seronegative for cytomegalovirus (CMV). The main group included 60 newborns, which were divided into 2 subgroups. Subgroup 1 included 30 newborns from mothers who had an acute phase of chronic CMVI, leading to the development of chronic compensated placental insufficiency, subgroup 2 consisted of 30 newborns from mothers with exacerbation of CMVI, initiating the formation of chronic subcompensated placental insufficiency. Results. In the control group, DNA of CMV, IgM antibodies to CMV and IgG antibodies to CMV were not detected. In the main group, in newborns of subgroup 1, compared with the control, DNA of CMV, both in the cord blood and in the nasopharyngeal aspirate, was isolated in 3.3 % of cases, and was not detected in scrapings of the buccal epithelium. The titers of IgG antibodies to CMV were determined in the ratio of 1: 100 in 36.7 %, 1: 200 in 43.3 %, 1: 400 in 13.3% and 1: 800 in 6.7 % of cases. At the same time, in mother-newborn pairs, higher titers of IgG antibodies to CMV in pregnant women, compared with those in their offspring, were detected in 18 cases, and equal titers of IgG antibodies to CMV were detected in 12 dyads. In the control group, the concentration of TNFα was equal to (Me) 16.2 (12.9-32.7) pg/ml, IL-6 – 1.93 (1.65-2.21) pg/mL, endothelin-1 – 0.52 (0.45–1.21) fmol/mL. In subgroup 1 of the main group, in comparison with the control one, there was an increase in the concentration of TNFα by 2.6 times (p=0.000001), IL-6 – by 2.1 times (p = 0.000001) and endothelin-1 – by 2.1 time (p = 0.000002). In newborns of subgroup 2, compared with subgroup 1, CMV antigens were identified in the blood in 6.7 % (p > 0.05), and in nasopharyngeal aspirate – in 10% (p>0.05) in the absence of identification of the CMV genome in the buccal epithelium. In 6.7%, IgM antibodies to CMV were detected. IgG antibodies to CMV 1:800 were detected more often (in 33.3%, p<0.05), as well as equal titers of IgG antibodies to CMV in 20 mother-offspring pairs (p<0.05). There was an increase in the concentration of TNFα by 1.47 times (p=0.0076), IL-6 - by 1.33 (p = 0.0016) and endothelin-1 - by 1.5 times (p = 0.0161), respectively. Conclusion. In the offspring of mothers who had an exacerbation of CMVI in the second trimester of pregnancy and with the presence of chronic subcompensated placental insufficiency, compared with newborns from women with the acute phase of chronic CMVI at similar gestation periods and formed chronic compensated placental insufficiency, higher levels of pro-inflammatory cytokines and endothelin-1 are recorded, indicating activation of the fetal immune system as a result of viral aggression and penetration of IgG to CMV of maternal origin.

Interrelation of immunological and hemodynamic parameters of the fetoplacental system in exacerbation of chronic bronchitis of cytomegalovirus etiology

Aim. To establish the relationship of immunological and hemodynamic parameters of the fetoplacental system during exacerbation of chronic bronchitis of cytomegalovirus etiology. Materials and methods. A study was carried out of the concentration of TNFα, IgA, IgM in the blood serum and the systolic-diastolic ratio (SDR) in the right uterine artery (RUA) in 80 women in the second trimester of pregnancy, uncomplicated and complicated by exacerbation of cytomegalovirus infection (CMVI). Three groups were retrospectively distinguished. The first group included 30 patients with CMV seronegative physiological pregnancy, the second group included 25 women with exacerbation of chronic bronchitis caused by CMVI reactivation, initiating the development of chronic compensated placental insufficiency (CCPI), in the third group – 25 pregnant women with chronic bronchitis in the acute stage, induced by CMVI, leading to the formation of chronic subcompensated placental insufficiency (CSPI) in the third trimester of gestation. Results. In the first group, the concentration of TNFα in the blood serum was Me 16.4 (13.1–33.8) pg/mL, IgA – Me 2.5 (2.23–2.62) mg/mL, IgM – Me 0.99 (0.87–1.56) mg/mL, and SDR in RUA – Me 1.95 (1.87–2.30). In the second group, compared with the first one, there was an increase in the concentration of TNFα by 4.95 times (p=0.000001), IgM − by 2.51 times (p = 0.000001) and SDR in RUA by 1.25 times (p = 0.000001) with a 1.49-fold decrease in the IgA level (p = 0.000001). In the third group, compared with the first one, there was an increase in TNFα by 6.12 times (p = 0.000001), IgM − by 2.98 times (p = 0.000001) and the value of SDR in RUA by 1.70 times (p = 0.000001) against the background of a 2.31-fold decrease in IgA concentration (p = 0.000001). In patients of the third group, in comparison with the second group, higher levels of TNFα (by 1.23 times, p = 0.000001), IgM (by 1.18 times, p = 0.000001) and SDR in the RUA (by 1.35 times, p = 0.000001), as well as lower values of the IgA concentration (1.54 times, p = 0.000001). Conclusion. In women with exacerbation of chronic bronchitis caused by CMVI reactivation, leading to the formation of CSPI, in contrast to patients with a similar bronchopulmonary pathology of cytomegalovirus origin and the development of CCPI, a more pronounced activation of the systemic inflammatory response and an imbalance in the humoral component of immune system lead to an increase in vascular resistance in the RUA pool.

Changes in the concentration of endothelin-1 and the state of blood flow in the uterine arteries of women in the third trimester of gestation with exacerbation of cytomegalovirus infection in the second trimester of pregnancy

Aim. To assess the change in the concentration of endothelin-1 (ET-1) and the state of uteroplacental blood flow in women in the third trimester of gestation with exacerbation of cytomegalovirus infection (CMVI) in the second trimester of pregnancy.Materials and methods. A comprehensive examination of 120 women with pregnancies uncomplicated and complicated by exacerbation of CMVI in the second trimester of gestation was carried out. The first group consisted of 30 women with a seronegative CMVI normal pregnancy, the second group – 30 patients with a latent course of CMVI and the development of chronic compensated placental insufficiency (CCPI), the third – 30 women with exacerbation of CMVI and CCPI, and the fourth – 30 patients with exacerbation of CMVI and chronic subcompensated placental insufficiency (CSPI).Results. With the development of CCPI at 30-34 weeks of gestation in women of the second group, compared with the first, the concentration of ET-1 in blood serum increased to 1.16±0.09 fmol/L (in the control – 0.86±0.08 fmol/L, p<0,05). There was an increase in the systolic-diastolic ratio (SDR) in the right uterine artery (RUA) by 1.40 times (p=0.000001) and in the left uterine artery (LUA) by 1.46 times (p=0.000001), which illustrated the important role of endothelial activation in increasing resistance in the uterine artery basin. In the third group, in comparison with the first and second ones, an increase in the concentration of ET-1 was recorded to 1.57±0.13 fmol/L (p<0.001 and p<0.05, respectively), reflecting a more pronounced activation of the endothelium. In women of the third group, in comparison with the first and second groups, there was an increase in SDR in the RUA by 1.43 times (p=0.000001) and 1.01 times (p=0.046), respectively. Comparison of blood flow in the LUA in women in the third group in comparison with that in the first and second groups showed an increase in SDR by 1.47 times (p=0.000001) and 1.01 times (p=0.0462), respectively. At the same time, a strong positive correlation was recorded between the SDR in the RUA and the level of ET-1 (r=076; p<0.001), which is a marker of an endothelium-dependent increase in vascular resistance. In women of the fourth group, the level of ET-1 was 2.15±0.17 fmol/L, which is significantly higher compared with group 1 (5.08 times, p=0.000001), with the second group (4.08 times, p=0.000001) and in comparison with the third group (1.23 times, p=0.0029). SDR in RUA in the fourth group compared to the first one increased by 1.62 times (p=0.000001), and compared to the second – by 1.15 times (p=0.00002). At the same time, in patients of the fourth group in comparison with the third group, SDR in RUA increased by 1.13 times (p=0.024). In the fourth group, in contrast to the first one, there was an increase in SDR in LUA by 1.58 times (p=0.000001), and in comparison, with the second group, SDR in LUA was 1.07 times higher (p=0.00021). Patients of the fourth group, in comparison with the third one, had higher SDR indices in the LUA (1.06 times, p=0.0207). There was a stronger relationship between the SDR value in RUA and the concentration of ET-1 (r=0.86; p<0.001) and a weak correlation between SDR in LUA and ET-1 (r=0.47; p<0.01), which reflects the influence of endothelial dysfunction in response to an increase in the tone of the uterine arteries.Conclusion. The development of CSPI in the third trimester of gestation in women who underwent an exacerbation of CMVI in the second trimester of pregnancy, in contrast to CCPI with a similar infectious pathology in pregnant women, is characterized by a more pronounced increase in vascular resistance in the uterine artery basin against the background of endothelial dysfunction.

Phospholipid profiles and annexin V content in villous chorion from women with spontaneous miscarriage associated with cytomegalovirus infection

Aim. To carry out a comparative analysis of the phospholipid profiles and annexin V content in the villous chorion obtained from women with spontaneous abortion associated with exacerbation of cytomegalovirus infection (CMVI) and the physiological course of pregnancy.Materials and methods. 66 patients were randomly selected at a gestational age of 6-8 weeks. A control group was identified in the amount of 32 healthy pregnant women with medical abortion. The main study group consisted of 34 women with spontaneous abortion associated with exacerbation of cytomegalovirus CMVI. The material for the study was the villous chorion, peripheral blood and urine. Type-specific antibodies to CMV immunoglobulins M and G class and the avidity index were determined in blood serum by the method of enzyme-linked immunosorbent assay. Lipids in the villous chorion homogenate were extracted with a chloroform-methanol mixture, phospholipids were fractionated by thin layer chromatography. The quantitative determination of annexin V was carried out by the method of enzyme immunoassay.Results. The phospholipid profile of the villous chorion in the main group was characterized by a decrease in the fraction of phosphatidylcholine to 22,39±0,04% (control group – 28,50±0,052%; p<0,001), phosphatidylethanolamine to 27,63±0,011% (control group – 30,11±0,073%; p<0,001), phosphatidylinositol up to 14,24±0,021% (control group – 16,17±0,018%; p<0,001), an increase in lysophosphatidylcholine up to 2,25±0,032% (control group – 1,07±0,022%; p<0,001), phosphatidylserine up to 14,57±0,075% (control group – 10,02±0,012%; p<0,001), sphingomyelin up to 18,92±0,012% (control group – 14,13±0,012%; p<0,001). At the same time, an increase in the content of annexin V was revealed up to 43,12±0,50 U/mL (control group – 20,21±0,50 U/mL; p<0,001).Conclusion. The results of the study showed that in the villous chorion from women with spontaneous abortion associated with exacerbation of CMVI, there was a change in the profile and ratio of phospholipids, as well as in the concentration of annexin V. The established increase in the content of phosphatidylserine and the associated annexin V in the villous chorion indicates a violation of the hemostatic system and microcirculation due to increased thrombus formation, which supports local inflammation and apoptosis of the trophoblast, which leads to embryonic demise and spontaneous abortion.

Changes in the immunomorphological indicators of the placenta in women with exacerbation of cytomegalovirus infection in the second trimester of pregnancy complicated by chronic placental insufficiency

Aim. To assess the change of immunomorphological parameters in the placenta in women with exacerbation of cytomegalovirus infection (CMVI) in the second trimester of pregnancy, complicated by chronic placental insufficiency.Materials and methods. The concentration of TNF-α in the homogenate of 120 placentas and the histometric parameters of chorionic villi were determined in patients who underwent latent CMVI and exacerbation of CMVI in the second trimester of gestation. Group 1 included 30 placentas from seronegative women with a physiological course of pregnancy, group 2 included 30 placentas from patients with latent CMVI and chronic compensated placental insufficiency, group 3 – 30 placentas from women with exacerbation of CMVI and chronic compensated placental insufficiency; and group 4 – 30 placentas from pregnant women with exacerbation of CMVI and chronic subcompensated placental insufficiency.Results. In the 1st group in the placenta homogenate the concentration of TNF-α was 16.8±1.86 pg/mL; the number of villi with a diameter of 30-50 microns was 25.4±2.08%, with a diameter of 60-90 microns – 64.4±2.43% and with a diameter of more than 90 microns – 10.2±0.88%; the number of terminal villi with 1-3 capillaries was 27.0±2.29%, with 4- 6 capillaries – 42.1±2.02%, with 7-10 capillaries – 23.9±1.58% and villi with more than 10 capillaries – 7.0±0.79%. In group 2, the concentration of TNF-α in the placenta homogenate was amounted to 22.1±2.06 pg/mL (p>0.05); among the villi, anatomical forms with a diameter of 30-50 μm (p<0.01) were found 1.41 times more often, and villi with a diameter of 60-90 μm (p<0.01) were 1.19 times less common; the number of villi with 4-6 capillaries decreased by 1.21 times (p<0.05) and the number of villi with 7-10 capillaries increased by 1.43 times (p<0.001). In the placentas of group 3, compared with group 2 in the homogenate, there was an increase in the concentration of TNF-α to 60.2±3.47 pg/mL (p<0.001) against the background of a decrease in the concentration of villi with a diameter of 30-50 μm to 26.4±2,61% (p<0.05), villi with 7-10 capillaries up to 20.7±1.53% (p<0.001) and an increase in the number of villi with 1-3 capillaries up to 34.8±3.05% (p<0.05). In the placental homogenate of group 4, compared with group 3, the concentration of TNF-α (p<0.05) increased 1.31 times, the number of villi with a diameter of 60-90 μm increased to 70.2±1.59%, (p<0,01) and villi with 1- 3 capillaries to 46.8±3.76% (p<0.05) with a decrease in the number of villi with a diameter of 30-50 μm to 18.9±1.69% (p<0,05), with 7-10 capillaries up to 13.3±1.36% (p<0.001) and with 10 or more capillaries – up to 3.9±0.43% (p<0.01).Conclusion. In women with exacerbation of CMVI in the second trimester of pregnancy and the development of chronic subcompensated placental insufficiency, inhibition of the growth and angiogenesis of terminal villi is observed against the background of the maximum concentration of TNF-α in the medium.

State of the immune system in women with exacerbation of cytomegalovirus infection in the third trimester of pregnancy

Aim . To study the state of the immune system in women with exacerbation of cytomegalovirus infection (CMVI) in the third trimester of pregnancy. Materials and methods . The study involved 120 women in the third trimester of pregnancy, uncomplicated and complicated by CMVI. The first group was represented by 30 seronegative women with physiological pregnancy, the second − 30 pregnant women with latent CMVI, leading to the development of placental insufficiency, the third − 30 patients with exacerbation of CMVI and placental insufficiency, and the fourth − 30 women with exacerbation of CMVI, initiating the development of placental insufficiency and the threat of miscarriage. The concentration of immunoglobulins (sIgA, IgA, IgG and IgM) and circulating immune complexes (CIC) in blood serum was studied. Results . It was shown that in women of the first group the concentration of sIgA in the blood serum was 5.0 (4.10-7.10) mg/ml, IgA − 2.32 (2.09-2.48) mg/ml, IgG – 13.8 (13.0-14.4) mg/ml, IgM − 1.08 (0.98-1.19) mg/ml and CIC − 0.097 (0.076-0.113) AU. In the second group, compared with the first one, the IgG concentration increased to 14.3 (13.3- 15.3) mg/ml (p=0.0284), at the same time there were no statistically significant changes in the sIgA level (p=0.697), IgA (p=0.085), IgM (p=0.197) and CIC (p=0.476). In the third group, in contrast to the second one, an increase in IgG concentration was recorded by 1.09 times (p=0.0016), IgM – by 1.88 times (p=0.000001) and CIC – by 1.70 times (p=0.000001) against the background of a 1.24-times decrease in IgA levels (p=0.000001) and no difference in sIgA concentration (p=0.208). In patients of the fourth group, in comparison with the third one, a decrease in the level of sIgA was diagnosed by 1.66 times (p=0.0000089) and IgA − by 1.41 times (p=0.00048) with an increase in IgG by 1.26 times (p=0.000001), IgM − 1.21 times (p=0.0011) and CIC − 1.09 times (p=0.0199). Conclusion . With exacerbation of CMVI in the third trimester of pregnancy, complicated by placental insufficiency, severe dysimmunoglobulinemia and autoimmune changes in the female body lead to the development of symptoms of the threat of miscarriage.

Indicators of vascular-endothelial growth factor and docosahexaenoic acid in pregnant women with threatening course of early pregnancy associated with cytomegalovirus

Aim . To determine the indices of vascular endothelial growth factor and docosahexaenoic acid in women with threatened early pregnancy associated with cytomegalovirus infection exacerbation. Materials and methods . The study included 74 women at a gestation period of 7-12 weeks, of which 38 women with exacerbation of cytomegalovirus infection and the onset of spontaneous miscarriage (main group) and 36 without such pathology (control group). The material for the study was peripheral blood, urine, and scraping of the buccal epithelium. Antibodies IgM and G to cytomegalovirus, low avidity IgG (avidity index) were determined by enzyme-linked immunosorbent assay. Cytomegalovirus DNA was detected by real-time PCR analysis. Indicators of vascular endothelial growth factor were established by enzymelinked immunoassay. The concentration of docosahexaenoic acid was analyzed using capillary gas-liquid chromatography. Results . The concentration of vascular endothelial growth factor in the blood serum in pregnant women in the main group was 1.7 times (p<0.001) lower than in the control group. A similar dynamics of changes was established for docosahexaenoic acid, the concentration of which was 1.4 times lower than that of the control group (p<0.001). Conclusion . The data obtained indicate that the exacerbation of cytomegalovirus infection in early pregnancy is associated with a significant decrease in vascular endothelial growth factor and docosahexaenoic acid, which has adverse effects on angiogenesis and growth of placenta, and pregnancy outcome.

Changes in the systemic inflammatory response in women in the third trimester of pregnancy complicated by exacerbation of cytomegalovirus infection

Aim . To study the change in the systemic inflammatory response in women in the third trimester of pregnancy complicated by exacerbation of cytomegalovirus infection (CMVI). Materials and methods. The study involved 120 women with a physiological course of gestation and with a pregnancy complicated by CMVI. The first group was represented by 30 seronegative women at 31-34 weeks of gestation, the second – by 30 pregnant women with a latent course of CMVI and placental insufficiency, the third – 30 women with exacerbation of CMVI and placental insufficiency; and the fourth – 30 patients with exacerbation of CMVI, initiating the development of placental insufficiency and threatened miscarriage. Results. In the blood serum of women in the first group, the TNF-α content was 14.7 (12.1-32.0) pg/mL, IFN-γ – 128.7 (117.0-172.5) pg/mL, IL-1β – 20.3 (13.8-35.3) pg/mL, IL-6 – 2,57 (2,10-2,73) pg/mL, IL-4 – 37,8 (30,0- 55,4) pg/mL and IL-2 – 34,3 (29,4-41,3) pg/mL. The patients of the second group, in comparison with the first one, were diagnosed with an increase in the median TNF-α to 29.5 (14.4-43.1) pg/mL (p=0.0168) and IL-2 – 40.7 (33.2-47.9) pg/mL (p=0.0169) against the background of the absence of significant differences in the concentration of IFN-γ, IL-1β, IL-6 and IL-4. In the third group, compared with the second one, the concentration of TNF-α increased by 2.74 times (p=0.000001), IFN-γ – by 1.69 times (p=0.000001), IL-1β – by 3.16 times (p=0.000001), IL-6 – 2.17 times (p=0.000001), IL-2 – 2.2 times (p=0.000001) and there were no differences in the concentration of IL-4 (p=0.994). In the fourth group, compared with the third one, an increase in TNF-α level was diagnosed by 1.03 times (p=0.028), IFN-γ – by 1.18 times (p=0.017), IL-1β – by 1.64 times (p=0.000001), IL-6 – by 1.49 times (p=0.0035), IL-2 – by 1.32 times (p=0.000001) against the background of a drop in IL-4 level by 1.52 times (p=0.00031). Conclusion. Increase in serum concentration of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, IL-6 and IL-2) against the background of a decrease in the level of anti-inflammatory cytokine (IL-4) in women with exacerbation of CMVI in the third trimester of gestation, complicated by placental insufficiency, plays an important role in the pathogenesis of threatened preterm labor.

Cyclooxygenase 2 as a Marker of Early Pregnancy Loss in Cytomegalovirus Infection

Background. Increased expression of cyclooxygenase 2 in the placenta plays a significant role in the formation of placental disorders in the pathological course of pregnancy. It was shown that a high level of expression of cyclooxygenase 2 leads to excessive synthesis of prostaglandins, which stimulate the contractile activity of the uterine myometrium and trigger the abortion mechanism. An analysis of modern literature has shown a lack of data proving the involvement of cyclooxygenase 2 in the pathogenesis of early miscarriages in cytomegalovirus infection. Objective. To establish the pathogenetic role of cyclooxygenase 2 in early pregnancy in the course of miscarriage during exacerbation of cytomegalovirus infection. Materials and methods. The study included 86 women with a gestational age of 8–12 weeks, of which 46 women with spontaneous abortion (O03) and exacerbation of cytomegalovirus infection (main group) and 40 women with medical abortion (O04) without cytomegalovirus infection (control group). The material for the study was peripheral blood serum, urine, homogenate of the villous chorion of the placental tissue. The content of cyclooxygenase 2, the level of IgM and IgG antibodies to cytomegalovirus, low-type IgG antibodies to cytomegalovirus (avidity index) were analyzed by enzyme-linked immunosorbent assay; the content of arachidonic acid – by capillary gas-liquid chromatography. Results. During the study, women of the main group found an increase in the concentration of arachidonic acid by 59 % (p < 0.001) and the activity of the lipolytic enzyme cyclooxygenase 2 – by 58 % (p < 0.001) in the placenta villous chorion homogenate. Conclusion. With an exacerbation of cytomegalovirus infection in the homogenate of the villous placenta chorion of pregnant women with spontaneous abortion, an increase in the content of arachidonic acid and the level of cyclooxygenase 2 is observed. An increased level of cyclooxygenase 2 indicates the development of pregnancy complications and can be used as a non-specific marker predictor of pregnancy termination during exacerbation of cytosis.

The role of lipid peroxidation products in the development of iron deficiency anemia in cytomegalovirus infection in pregnant women of the first trimester

Aim. To establish the role of lipid peroxidation (LPO) products in the development of iron deficiency anemia in pregnant women of the first trimester during exacerbation of cytomegalovirus infection. Materials and methods . A prospective case-control study included 60 women in the first trimester of pregnancy (8-12 weeks), of which 35 were cytomegalovirus-positive with mild iron deficiency anemia (main group) and 25 - cytomegalovirus-seronegative (control group). Antibodies of IgM and IgG to CMV, low avid IgG (avidity index), and serum ferritin concentration were determined by enzyme-linked immunosorbent assay. In order to assess the intensity of LPO processes in blood serum spectrophoto-metric method was used to measure the levels of molecular products of oxidation: diene conjugates and active products of thiobarbituric acid. The concentration of arachidonic acid in blood serum was analyzed by means of the method of capillary gas-liquid chromatography. The concentration of total hemoglobin in red blood cells was measured by photometry. The study of iron metabolism included: evaluation of serum iron by spectrophotometric method, the total iron binding capacity of serum using commercial kits of the company “Lachema” (Czech Republic), transferrin saturation coefficient by means of calculation method. Results . Activation of LPO processes was noted in women of the main group, as evidenced by an increase in the concentration of diene conjugates by 1.54 times (p<0.001), active products of thiobarbituric acid by 2.4 times (p<0.001) and arachidonic acid by 1.3 times (p<0.001) compared with similar indicators of the control group. It has been found that hemoglobin levels were reduced by 1.2 times (p<0.001), serum iron and ferritin, respectively, by 1.4 (p<0.001) and 2 times (p<0.001), in the setting of an increase in the total iron binding capacity of serum while reducing the coefficient of iron saturation with transferrin. Conclusion . The data obtained indicate the important role of LPO products in the pathogenesis of iron deficiency anemia during exacerbation of cytomegalovirus infection in the first trimester of gestation.

Systemic inflammatory response in exacerbation of cytomegalovirus infection in women in the second trimester of pregnancy

Systemic inflammatory response in exacerbation of cytomegalovirus infection in women in the second trimester of pregnancy

Structural organization of the umbilical cord vascular connective tissue in cytomegalovirus infection in the third trimester of pregnancy

Aim. To study the structural organization of the connective tissue of the vein wall of the umbilical cord vessels from seropositive to cytomegalovirus (CMV) women with an exacerbation of infection in the third trimester of pregnancy. Materials and methods . There was done the study of the activity of glycosaminoglycans in the connective tissue of the vascular wall of the vein and the content of elastase in the umbilical cord homogenate obtained during childbirth at 38-39 weeks of pregnancy from 35 CMV-seropositive women with an exacerbation of infection in the third trimester of pregnancy (the main group), and from 32 CMV-seronegative women (the control group). The material for the histo-chemical study was the sections of the venous wall of the umbilical cord vessels adjacent to the placenta. The activity of glycosaminoglycans was studied by Steedman, the content of elastase was studied by enzyme immunoassay. Results. The study of umbilical cord tissue extracts revealed a 1.3-fold increase in immune enzyme elastase indices (p&lt;0.001) in the group of CMV-seropositive women with an exacerbation of infection in the third trimester of pregnancy. Histochemical examination of the same umbilical cords revealed an increase in the intensity of the reaction to acidic glycosaminoglycans located in the subendothelial layer, in the intermuscular layers of connective tissue, in the cytoplasm of fibroblasts and in the smooth muscle cells of the inner layer of the umbilical vein muscles. The most pronounced reaction to glycosaminoglycans was detected in the collagen fibers of the subendothelial layer of the umbilical vein. In addition, areas of pronounced destruction and desquamation of endothelial cells were detected. The connective tissue of the subendothelial layer was characterized by the disappearance of the tortuosity of collagen fibers with signs of atrophy and a decrease in the number of cell elements in the vascular wall. Conclusion. Based on the results of the study, it was shown that the exacerbation of CMV infection in the third trimester of pregnancy is characterized by an increase in the enzymatic activity of elastase and the production of acid glycosaminoglycans in the connective tissue of Wharton’s jelly, which leads to the destruction of collagen fibers and disturbance of the framework and elasticity of the vascular wall of the umbilical vein.

Relative Risk Assessment of Intrauterine Infection of the Fetus During Cytomegalovirus Infection in Early Pregnancy

Background. Intrauterine fetal infection (IUI), the common cause of which is the cytomegalovirus (CMV), occupies one of the first places in the structure of perinatal morbidity and mortality. There are no data on the relative risk assessment of IUI at the exacerbation of CMV infection and its delitescent course in first trimester of pregnancy in the literature.Aim: to calculate the relative risks of fetal IUI in pregnant women with exacerbation of CMV infection in the first trimester of pregnancy.Methods. A retrospective review of the labor and delivery medical records and prenatal records of 104 CMV-seropositive women was carried out. Fifty of these women had an exacerbation of CMV infection in the first trimester of pregnancy – main group and 54 of them were with delitescent course of the disease (comparison group).Results. A comparative analysis of ultrasound and morphological markers of IUI with risk assessment depending on the course of CMV infection in the first trimester of pregnancy has been carried out. A high risk of placental structure abnormalities, as well as amniotic fluid and fetal membranes, fetal and placental blood flow pathology, onset of choroid plexus cyst and fetal growth restriction was found, with a statistically significant difference in the group of pregnant women with exacerbation of CMV infection in the first trimester of pregnancy.Conclusion. The findings suggest that the exacerbation of CMV infection in early pregnancy is a risk factor for IUI.

МЕТАБОЛИТ ПРОГЕСТЕРОНА 11-ДЕОКСИКОРТИКОСТЕРОН В ПЛАЦЕНТЕ ПРИ ОБОСТРЕНИИ ЦИТОМЕГАЛОВИРУСНОЙ ИНФЕКЦИИ

The aim of the work is to study the content of 11-deoxycorticosterone in the placenta during pregnancy complicated by exacerbation of cytomegalovirus infection. Histochemical method was used to determine the content of 11-deoxycorticosterone in 72 placentas, including 37 cases from women with acute cytomegalovirus infection and simultaneously diagnosed moderate preeclampsia, and 35 placentas from women with exacerbation of chronic cytomegalovirus infection without concomitant diseases. The control group consisted of 30 placentas from mothers with chronic cytomegalovirus infection in the latent stage. It was found out that an increase in the content of 11-deoxycorticosterone in placenta by 25% in comparison with the control group occurred during gestation with an exacerbation of cytomegalovirus infection. A significant increase (by 40%) in the content of this hormone in the placenta was noted during the reactivation of the viral process accompanied by preeclampsia. We believe that an increase in the production of 11-deoxycorticosterone with mineralocorticotropic effect in the placenta could contribute to the development of hypertensive disorders in pregnancy complicated by cytomegalovirus infection.