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

2020 ◽  
Vol 5 (3) ◽  
pp. 7-12
Author(s):  
N. A. Ishutina ◽  
I. A. Andrievskaya ◽  
M. N. German

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.

Author(s):  
N. A. Ishutina ◽  
I. А. Andrievskaya ◽  
I. V. Dovzhikova ◽  
N. N. Dorofienko

Introduction. It is now generally acknowledged that cytomegalovirus infection (CMVI) is one of the main causes of miscarriage. However, the mechanism of this effect has not been sufficiently studied. At the same time, the influence of acids of the ɷ-3 family and α-tocopherol (αTP) on the placentation process through a pro-angiogenic action is shown.Aim. To study the concentration of αTP and ɷ-3 family acids in the peripheral blood and establish their role in miscarriage in CMV-seropositive women with CMVI reactivation.Materials and methods. A case-control study included 64 women in the first trimester of pregnancy (7-10 weeks), of which 36 were CMV-seropositive with CMVI reactivation (main group) and 28 were CMV-seronegative (control group). CMVI was diagnosed by the determination of class M and G antibodies by ELISA, as well as CMV DNA detected by PCR. The concentration of ɷ-3 acids of the family (eicosapentaenoic – EPA, docosahexaenoic – DHA) in blood serum was studied by capillary gas-liquid chromatography (J.P.Carreau, J.P.Dubacq). The αTP concentration was determined by the fluorometric method (L.G.Hansen, W.I.Warwich).Results. In women of the main group, a significant (p<0.001) decrease in the concentration of αTP to 1.32±0.025 μg/mL was observed in the peripheral blood compared to the same indicator in the control group (1.49±0.029 μg/mL). At the same time, the levels of EPA and DHA were also statistically significant (p<0.001) lower than the same indicator in the control group and amounted to 1.09±0.012 and 6.09±0.015%, respectively (in the control, 1.29±0.071 and 8.80±0.071%, respectively). Conclusion. The obtained results of the study allow us to establish the important role of disorders in the content of α-TF, EPA and DHA in the pathogenesis of miscarriage during reactivation of CMVI in the early periods of gestation, which can serve as a basis for expanding diagnostic and therapeutic measures in this pathology of pregnant women.


2021 ◽  
Vol 12 ◽  
Author(s):  
Chiara Mazziotta ◽  
Giulia Pellielo ◽  
Mauro Tognon ◽  
Fernanda Martini ◽  
John Charles Rotondo

Merkel cell polyomavirus (MCPyV) is a small DNA tumor virus ubiquitous in humans. MCPyV establishes a clinically asymptomatic lifelong infection in healthy immunocompetent individuals. Viral infections are considered to be risk factors for spontaneous abortion (SA), which is the most common adverse complication of pregnancy. The role of MCPyV in SA remains undetermined. Herein, the impact of MCPyV infection in females affected by SA was investigated. Specifically, an indirect enzyme-linked immunosorbent assay (ELISA) method with two linear synthetic peptides/mimotopes mimicking MCPyV antigens was used to investigate immunoglobulin G (IgG) antibodies against MCPyV in sera from 94 females affected by SA [mean ± standard deviation (SD) age 35 ± (6) years] and from 96 healthy females undergoing voluntary pregnancy interruption [VI, mean (±SD) age 32 ± (7) years]. MCPyV seroprevalence and serological profiles were analyzed. The overall prevalence of serum IgG antibodies against MCPyV was 35.1% (33/94) and 37.5% (36/96) in SA and VI females, respectively (p &gt; 0.05). Notably, serological profile analyses indicated lower optical densities (ODs) in females with SA compared to those undergoing VI (p &lt; 0.05), thus indicating a reduced IgG antibody response in SA females. Circulating IgGs were identified in sera from SA and VI females. Our immunological findings indicate that a relatively reduced fraction of pregnant females carry serum anti-MCPyV IgG antibodies, while SA females presented a more pronounced decrease in IgG antibody response to MCPyV. Although yet to be determined, this immunological decrease might prompt an increase in MCPyV multiplication events in females experiencing abortive events. The role of MCPyV in SA, if present, remains to be determined.


2016 ◽  
Vol 1 (60) ◽  
pp. 75-79
Author(s):  
Дорофиенко ◽  
Nikolay Dorofienko

Due to the broad spectrum of influence of polyunsaturated fatty acids of ω-6 family on the development of the fetus and newborn child, the composition of arachidonic fatty acid and its predecessor linoleic fatty acid were studied in blood of the umbilical cord blood of newborns from mothers with chronic reactivation of cytomegalovirus infection. 82 newborns were examined; among them there were 42 infants (the main group) from mothers who had cytomegalovirus infection (titer of IgG antibodies to cytomegalovirus was 1:1600) in the III trimester. The control group included 42 newborns from healthy women. In the umbilical cord blood of newborns the contents of arachidonic and linoleic fatty acids were identified with gas-liquid chromatography. The study found out that the reactivation of cytomegalovirus infection in the mother (titer of IgG antibodies to cytomegalovirus 1:1600) leads to an increase in the content of linoleic acid by 56% (p&#60;0.001) and of the predecessor of pro-inflammatory eicosanoids - arachidonic acid by 34% (p&#60;0.001) in the cord blood of newborns; it is one of the causes of disturbance of the structural and functional organization of the umbilical artery vessels. Identified changes in umbilical cord blood and umbilical artery endothelium can cause disturbances of the elastic properties of vessels, stagnation and thrombosis of blood vessels and, consequently, disturbances of blood flow between mother and fetus, which can then serve as a factor in the development of fetal hypoxia.


Author(s):  
N. A. Ishutina ◽  
I. A. Andrievskaya ◽  
N. G. Prikhodko

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.


2018 ◽  
Vol 3 (4) ◽  
pp. 9-14 ◽  
Author(s):  
I. A. Andrievskaya ◽  
N. A. Ishutina ◽  
O. L. Kutepova

The aim of the study was to assess free radical processes and their effect on oxygenation of hemoglobin in the blood of 18-21 weeks  pregnant women with exacerbation of cytomegalovirus infection. We  examined 40 pregnant women with exacerbation of cytomegalovirus  infection and various levels of specific antibodies (IgM) at 18-21  weeks and 30 pregnant women without cytomegalovirus. The  spectrophotometric method was used to determine the content of oxyhemoglobin, methemoglobin, thiobarbituric acid (TBA)-active  products, superoxide dismutase in blood erythrocytes; thin layer  chromatography – phosphotidylcholine, lysophosphatidylcholine;  gas-liquid chromatography – arachidonic acid. Exacerbation of  cytomegalovirus infection changes the activity of free radical  oxidation processes, the severity of which is determined by the level  of IgM antibodies and is manifested by a decrease in superoxide  dismutase (p = 0.000) and phosphatidylcholine (p = 0.000), an  increase in phospholipase A2 (p = 0.000), lysophosphatidylcholine (p  = 0.000), arachidonic acid (p = 0.000) and TBA-active products  (p = 0.000). Accumulation of superoxide anion radical and products of lipoperoxidation in erythrocytes decreases  oxyhemoglobin (p = 0.000) and increases methemoglobin (p =  0.000). Exacerbation of cytomegalovirus infection at 18-21 weeks is  associated with the enhancement of free radical lipid oxidation and a  deficiency in the antioxidant activity of superoxide dismutase. It  decreases oxygen transport properties and increases phagocytosis  by red blood monocytes; and pregnant women develop further  hemic hypoxia.


Author(s):  
Peter G. Kremsner ◽  
Philipp Mann ◽  
Arne Kroidl ◽  
Isabel Leroux-Roels ◽  
Christoph Schindler ◽  
...  

Summary Background We used the RNActive® technology platform (CureVac N.V., Tübingen, Germany) to prepare CVnCoV, a COVID-19 vaccine containing sequence-optimized mRNA coding for a stabilized form of SARS-CoV‑2 spike (S) protein encapsulated in lipid nanoparticles (LNP). Methods This is an interim analysis of a dosage escalation phase 1 study in healthy 18–60-year-old volunteers in Hannover, Munich and Tübingen, Germany, and Ghent, Belgium. After giving 2 intramuscular doses of CVnCoV or placebo 28 days apart we assessed solicited local and systemic adverse events (AE) for 7 days and unsolicited AEs for 28 days after each vaccination. Immunogenicity was measured as enzyme-linked immunosorbent assay (ELISA) IgG antibodies to SARS-CoV‑2 S‑protein and receptor binding domain (RBD), and SARS-CoV‑2 neutralizing titers (MN50). Results In 245 volunteers who received 2 CVnCoV vaccinations (2 μg, n = 47, 4 μg, n = 48, 6 μg, n = 46, 8 μg, n = 44, 12 μg, n = 28) or placebo (n = 32) there were no vaccine-related serious AEs. Dosage-dependent increases in frequency and severity of solicited systemic AEs, and to a lesser extent local AEs, were mainly mild or moderate and transient in duration. Dosage-dependent increases in IgG antibodies to S‑protein and RBD and MN50 were evident in all groups 2 weeks after the second dose when 100% (23/23) seroconverted to S‑protein or RBD, and 83% (19/23) seroconverted for MN50 in the 12 μg group. Responses to 12 μg were comparable to those observed in convalescent sera from known COVID-19 patients. Conclusion In this study 2 CVnCoV doses were safe, with acceptable reactogenicity and 12 μg dosages elicited levels of immune responses that overlapped those observed in convalescent sera.


2014 ◽  
Vol 89 (4) ◽  
pp. 428-432 ◽  
Author(s):  
A.A. Marchioro ◽  
C.M. Colli ◽  
É.C. Ferreira ◽  
B.M. Viol ◽  
S.M. Araújo ◽  
...  

AbstractThis study investigated the epidemiological factors that contribute to the seroprevalence of Toxoplasma gondii and Toxocara spp. in children from Paraná state, Brazil. Immunoglobulin G (IgG) antibodies to T. gondii were detected using indirect immunofluorescence, and IgG antibodies to Toxocara were detected using an enzyme-linked immunosorbent assay. For each individual, a questionnaire was completed that contained epidemiological and clinical data. The data analysis was performed using multiple logistic regression. Of the 544 children investigated, 3.2% presented co-infection with T. gondii and Toxocara spp. Of this total, 7.4% were positive for antibodies to T. gondii, and 25% were positive for antibodies to Toxocara spp. The presence of antibodies to Toxocara spp. increased the risk of T. gondii infection (P= 0.029). Children who were 1–8 years of age were less infected by T. gondii than those who were 9–12 years of age. The variables that influenced positivity for anti-Toxocara spp. were the origin of the children and contact with sand. Children with positive serology for Toxocara spp. presented more eosinophilia compared with those with non-reactive serology. Infection with both parasites reveals the need for preventive measures, such as guidance about modes of infection, parasite control and monitoring recreational areas.


2011 ◽  
Vol 18 (5) ◽  
pp. 578-586 ◽  
Author(s):  
Woojun Kim ◽  
Ji-Eun Lee ◽  
Xue Feng Li ◽  
Su-Hyun Kim ◽  
Byeong-Gu Han ◽  
...  

Background: Antibodies to aquaporin-4 (AQP4-Ab), known as NMO-IgG, are a sensitive and specific marker for neuromyelitis optica (NMO). Methods: To develop an enzyme-linked immunosorbent assay (ELISA) for AQP4-Ab, we expressed M23 isoform of human AQP4 in a baculovirus system, and used it as an antigen. We measured AQP4-Ab in the sera of 300 individuals: 64 with definite NMO, 31 with high-risk NMO, 105 with multiple sclerosis (MS), 57 with other neurological diseases (ONDs), and 43 healthy controls. We also performed longitudinal measurements of AQP4–Ab in 787 samples collected from 51 patients with definite or high-risk NMO. Results: AQP4-Abs were positive in 72% with definite NMO, 55% with high-risk NMO, and 4% with MS, but none of the OND patients and the healthy individuals. The longitudinal measurement showed AQP4-Ab levels correlating with disease activity. Out of 38 initially seropositive patients, 21 became seronegative under effective immunosuppressive therapy. During most relapses, the serum AQP4-Ab levels were either high or rising compared with the previous value, although rising AQP4-Ab levels did not always lead to acute exacerbation. Two of the 13 initially seronegative patients converted to seropositive following acute exacerbations. Conclusions: We established an AQP4-Ab ELISA, which could be a potential monitoring tool of disease activity.


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