Evaluation of Proteasome and Immunoproteasome Levels in Plasma and Peritoneal Fluid in Patients with Endometriosis.

Endometriosis is a chronic disease in which the endometrium cells are located outside the uterine cavity. The aim of this study was to evaluate circulating 20S proteasome and 20S immunoproteasome levels in plasma and peritoneal fluid in women with and without endometriosis in order to assess their usefulness as biomarkers of disease. Concentrations were measured using surface plasmon resonance imaging biosensors. Patients with suspected endometriosis were included in the study-plasma was collected in 112 cases and peritoneal fluid in 75. Based on the presence of endometriosis lesions detected during laparoscopy, patients were divided into a study group (confirmed endometriosis) and a control group (patients without endometriosis). Proteasome and immunoproteasome levels in both the plasma (p = 0.174; p = 0.696, respectively) and the peritoneal fluid (p = 0.909; p = 0.284, respectively) did not differ between those groups. There was a statistically significant difference in the plasma proteasome levels between patients in the control group and those with mild (Stage I and II) endometriosis (p = 0.047) and in the plasma immunoproteasome levels in patients with ovarian cysts compared to those without (p = 0.017). The results of our study do not support the relevance of proteasome and immunoproteasome determination as biomarkers of the disease but suggest a potentially active role in the pathogenesis of endometriosis.

Investigation of the Changes in Concentrations of Vitamin D-Binding Protein and Lactoferin in Plasma and Peritoneal Fluid of Patients with Endometriosis.

An evaluation of the association between the concentrations of vitamin D-binding protein and lactoferrin in the plasma and peritoneal fluid may facilitate the elucidation of molecular mechanisms in endometriosis. Vitamin D-binding protein and lactoferrin concentrations were measured by ELISA in plasma and peritoneal fluid samples from 95 women with suspected endometriosis as classified by laparoscopy into groups with (n = 59) and without endometriosis (n = 36). There were no differences (p > 0.05) in the plasma and peritoneal fluid concentrations of vitamin D-binding protein and lactoferrin between women with and without endometriosis. In women with endometriosis, there was a significant correlation between plasma and peritoneal fluid vitamin D-binding protein concentrations (r = 0.821; p = 0.000), but there was no correlation between lactoferrin concentrations in those compartments (r = 0.049; p > 0.05). Furthermore, in endometriosis, lactoferrin was found to correlate poorly with vitamin D-binding protein (r= -0.236; p > 0.05) in plasma, while in the peritoneal fluid, the correlation between those proteins was significant (r = 0.399; p = 0.002). The characteristic properties of vitamin D-binding protein and lactoferrin and the associations between their plasma and peritoneal fluid concentrations found in women with endometriosis may provide a novel panel of markers to identify high-risk patients in need of further diagnostic measures.

The Influence of Lactoferrin in Plasma and Peritoneal Fluid on Iron Metabolism in Women with Endometriosis.

The aim of this study was to investigate the relationship between lactoferrin and iron and its binding proteins in women with endometriosis by simultaneously measuring these parameters in plasma and peritoneal fluid. Ninety women were evaluated, of whom 57 were confirmed as having endometriosis. Lactoferrin was measured by ELISA, transferrin, ferritin and iron on a Cobas 8000 analyser. Lactoferrin and transferrin in peritoneal fluid were lower compared to plasma, in contrast to ferritin and iron. In plasma, lactoferrin showeds associations with iron and transferrin in endometriosis and with ferritin in the group without endometriosis. Lactoferrin in peritoneal fluid correlated with lactoferrin, iron and transferrin of plasma in patients without endometriosis. The ratio of lactoferrin concentration in peritoneal fluid to plasma differentiated stage I versus IV of endometriosis and was negatively correlated with the iron ratio in patients without endometriosis. The ferritin ratio differentiated women with and without endometriosis. The very high ferritin ratios, especially in advanced stages of endometriosis, suggest the protective involvement of this protein in peritoneal fluid and the loss of this role by lactoferrin. The results demonstrate the validity of assessing iron metabolism in women with endometriosis, which may be useful as a marker of the disease and its progression.

Plasma and Peritoneal Fluid Fibronectin and Collagen IV Levels as Potential Biomarkers of Endometriosis.

Laparoscopy as a diagnostic tool for patients with suspected endometriosis is associated with several potentially life-threatening complications. Therefore, it is imperative to identify reliable, non-invasive biomarkers of the disease. The aim of this study was to analyse the concentrations of fibronectin and type IV collagen in peritoneal fluid and plasma to assess their role as potential biomarkers in the diagnosis of endometriosis. Fibronectin and collagen IV protein levels were assessed by surface plasmon resonance imaging (SPRi) biosensors with the usage of monoclonal antibodies. All patients enrolled in the study were referred for laparoscopy for the diagnosis of infertility or chronic pelvic pain (n = 84). The study group included patients with endometriosis confirmed during surgery (n = 49). The concentration of fibronectin in the plasma (329.3 ± 98.5 mg/L) and peritoneal fluid (26.8 ± 11.1 µg/L) in women with endometriosis was significantly higher than in the control group (251.2 ± 84.0 mg/L, 7.0 ± 5.9 µg/L). Fibronectin levels were independent of endometriosis stage (p = 0.874, p = 0.469). No significant differences were observed in collagen IV levels (p = 0.385, p = 0.465). The presence of elevated levels of fibronectin may indicate abnormalities in cell-ECM signalling during the course of endometriosis, and may be a potential biomarker for early detection.

Recommendations of the Polish Society of Gynaecologists and Obstetricians, Polish Paediatric Society, Polish Society of Family Medicine, Polish Society of Vaccinology, Polish Society of Oncological Gynaecology and Polish Society of Colposcopy and Pathophysiology of the Uterine Cervix on prophylactic vaccinations against infections with human papillomaviruses in Poland.

Several hundred million people are infected with genital genotypes of the human papillomavirus (HPV) annually in the world. The infections transmitted mainly through sexual routes are usually asymptomatic, but can lead to the development of cervical, vulvar, vaginal, anal, penile cancers, some head and neck cancers and genital warts (condylomas). The fraction HPV-related cancers range from nearly 100% in the case of cervical cancer to several/over a dozen percent in the case of other cancers and diseases. There are no effective drugs against HPV, but prophylactic HPV vaccines are available free of charge in immunization programmes in many countries around the world. In Poland, HPV vaccinations have so far been executed out on the pocket or in free-of-charge, local-governmental prevention programs, but the vaccination coverage of the target population does not exceed 10%. From November 2021, one of the vaccines is available with a 50% reimbursement, work is underway to reimburse the next ones, and the National Oncology Strategy assumes the implementation of the HPV immunization programmes and vaccination of 60% of the teen population by 2028. Three prophylactic HPV vaccines are registered. All of them are safe and their effectiveness in the prevention of diseases caused by vaccine genotypes reaches almost 100%, provided that full post-vaccination immunity is obtained before the contact with the virus. Girls aged 11-13 are the priority target cohort for HPV vaccination in Poland. The implementation of routine, free-of-charge HPV immunization in the Preventive Immunization Program (PIP) for all adolescents should be pursued. Persons over the age of 13 may also benefit from HPV vaccination and should be vaccinated according to product specifications. In addition to free access under the PIP, the key element for the success of the implementation of HPV vaccinations in Poland will be the education of medical personnel and parents of adolescents to be vaccinated.

Influence of human Papilloma Virus (hPV) infection on early pregnancy.

OBJECTIVES: HPV infection in early pregnancy may be a cause of miscarriage. Pregnancy significantly increases the risk of HPV infection. While ascending intrauterine infection with colonization of the trophoblast is commonly observed, descend- ing hematogenous infection should also be considered. The aim of the study is to assess the prevalence of HPV infection and its influence on pregnancy. MATERIAL AND METHODS: The study was conducted in the years 2010-2015 on a group of 143 pregnant women. The study group consisted of 84 women with abnormal course of the first trimester of pregnancy. The control group consisted of 59 women with normal pregnancy who delivered healthy neonates. Samples of cervix tissue along with samples of tropho- blast or placenta were taken for the study. The presence and genotype of the HPV virus were detected using a BIOTOOL B&M Labs set. Statistical analysis was conducted using R software. RESULTS: The rate of HPV infection in the entire studied population was 13% (19/143): the virus was confirmed in 18% (15/84) of patients in the study group and in 7% (4/59) of the control group. HR HPV was detected in 13 patients in the study group and three patients in the control group. HR HPV infection was more frequent in patients with an abnormal course of the first trimester of pregnancy (p = 0.03). HR HPV trophoblast infection was found only in patients in the study group (p = 0.02). In two members of the study group, the HPV virus was found in the trophoblast only. CONCLUSIONS: The obtained results may confirm the presence of adverse effects of HPV infection on early pregnancy. HR HPV trophoblast infection was observed only in women with 1st trimester complications. The presence of HPV only in trophoblast samples in some patients may suggest a descending - hematogenous route of primary infection.

Usefulness of saline infusion sonohysterography and feeding artery imaging in endometrial polyp diagnosis.

OBJECTIVES: The aim of this study was to assess the usefulness of sonohysterography with feeding artery visualization using transvaginal sonography to diagnose endometrial polyps. MATERIAL AND METHODS: We conducted an observational study of 60 perimenopausal patients referred to the Department of Fetal Medicine and Gynaecology, Medical University of Lodz with abnormal uterine bleeding or suspicion of endometrial pathology based on sonography scan. In all 60 patients transvaginal sonography scan showed a possibility of an endometrial polyp. Of these, 46 underwent saline infusion sonohysterography with sonography visualization of a feeding artery. Pathological examination was performed on material collected during hysteroscopy. RESULTS: Sonography detection of endometrial polyp based on feeding artery visualization had a 40% sensitivity, whereas sonohysterographic polyp detection had a sensitivity of 75% and a specificity of 100%. The positive and negative predictive values of saline infusion sonohysterography in diagnosing endometrial polyps were estimated at 75% and 72% (95% CI: 52-86%), respectively. The combination of sonohysterography and feeding artery imaging in transvaginal sonography was 84% sensitive and 95% specific in detecting endometrial polyps. The positive and negative predictive values were: PPV = 96% and NPV = 89%. CONCLUSION: Saline infusion sonohysterography with feeding artery visualization may become a standard method in the diagnostics of endometrial polyps in perimenopausal women.

The evaluation of the predictive value of TNF-alpha concentration in maternal serum in the prediction of neonatal and maternal infection.

INTRODUCTION: The consequences of uncomplicated PPROM are serious, and the presence of overt intraamniotic infection (IAI) is associated with a significant increase in both, the maternal and fetal morbidity and mortality rate. TNF-alpha is a cytokine involved in systemic inflammation and plays an important role in modulating the acute phase reaction. AIM: The aim of this study was to evaluate the predictive value of TNF-alpha levels in maternal serum within 6 hours after pprom and in the period of up to 12 hours after delivery in the prediction of neonatal and maternal infection. MATERIAL AND METHODS: The investigation was conducted on a group of 56 women diagnosed with PPROM between 30+0 and 36+6 weeks gestational age. In the period of up to 6 hrs from pprom first sample of 10 ml of maternal venous blood for laboratory testing was taken and the level of TNF-alpha was measured. A second sample of venous blood was taken within 12 hrs from delivery to reassess the TNF-alpha levels. All the participants were divided retrospectively into four groups depending on the occurrence of adverse neonatal and maternal outcome. Measuring the concentration of TNF-alpha in maternal serum was performed using the elisa method (enzyme-linked immunosorbent assay). RESULTS: A statistically significant difference in the second assay (up to 12 hours after delivery) between the patients with and without signs of maternal infection was observed concerning the TNF-alpha serum level. The concentration of this cytokine in maternal serum after delivery was 1.79 and 1.36 pg/ml (p < 0.05) respectively whereas within 6 hours from the PPROM in those two groups it was comparable (1.25 vs. 7.37 pg/ml - ns). Analogous observations were made in case of adverse neonatal outcome, where the TNF-alpha serum level within 12 hours after delivery was 1.70 and 1.45 pg/ml (p < 0.05) and in the period of up to 6 hours from pprom was 1.25 vs. 1.38 pg/ml (ns) respectively CONCLUSIONS: 1. In our investigation the maternal serum TNF-alpha concentration testing within 6 hours from PPROM between 30+0 and 36+6 weeks of gestation did not allow for the identification of patients who are more likely to develop signs of maternal infection and whose infant was at risk of neonatal infection after delivery 2. In case of pprom between 30+0 and 36+6 weeks of gestation maternal serum TNF-alpha concentration testing in the period of up to 12 hours after delivery may be a useful diagnostic tool for identification of patients with an increased risk of maternal and neonatal infection. 3. The lower the gestational age at PPROM and at delivery the risk of neonatal infection was greater.

Surfactant administration without intubation in preterm infants with respiratory distress syndrome--our experiences.

BACKGROUND: Surfactant replacement therapy is crucial in the management of respiratory distress syndrome (RDS) in preterm infants. Classic strategies of surfactant administration required intubation. To reduce the need of intubation and mechanical ventilation (MV), we applied surfactant via a thin endotracheal catheter without intubation. PATIENTS AND METHODS: We compared 26 preterm infants threatened by RDS treated with surfactant via a thin endotracheal catheter without intubation (studied group - SG) with a retrospective group of preterm infants managed on MV with early surfactant treatment using INtubation SURfactant Extubation (INSURE) method (control group - CG). Study had an approval from the ethics committee (RNN/6/14/KE). RESULTS: In the SG, 26 preterm infants were treated with one dose of surfactant (Curosurf®) administered via endotracheal catheter without intubation while receiving nasal continuous positive airway pressure (nCPAP)/SiPAP (Infant Flow). After surfactant administration, significantly less patients in SG required intubation and MV (19.2%) versus 65% necessity of second intubation in the CG. The median of time of MV in SG was 5 d versus 3.5 d in CG. Median time spent on nCPAP was 5.5 d versus 4.0 d in CG. The incidence of intraventricular hemorrhage (IVH) in the SG was 53.9%, including 50% with ≥ IVH II versus 36.7% (30% ≥ IVH II) in CG. The incidence of other complications of prematurity in the SG, such as necrotizing enterocolitis was 11.5% versus 23.3% in CG, the hemodynamically important patent ductus arteriosus was observed in 53.9% in SG versus 45% in CG. Bronchopulmonary dysplasia level in SG was significantly lower (15.4%) than in CG (40%), and the incidence of retinopathy of prematurity in SG was also lower (3.9%) versus 11.7% in MV group. CONCLUSION: Surfactant application via a thin endotracheal catheter without intubation seems to be a beneficial therapy for preterm infants with slight and mild degree of RDS. This new method of surfactant application was associated with a lower prevalence of intubation and MV and better pulmonary outcome than implementation of traditional surfactant therapy (INSURE) and MV. Prospective randomized controlled trial is required.

Assessment of interleukin-6, interleukin-8 and interleukin-18 count in the serum of IUGR newborns.

AIM: Aim of this study was to assess concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-18 (IL-18) in the serum of newborns with diagnosed intrauterine growth restriction (IUGR) in comparison to concentrations in serum of newborns with weight appropriate for gestational age (AGA). MATERIALS: Research was conducted at the Lodz Medical University Clinic of Neonatology during 2010-2011. Surveyed group consisted of 50 hypotrophic full-term infants of single pregnancies (average weight: 2329 ± 287 g); control group, enclosing 50 infants AGA (average weight: 3544 ± 2161 g). Both groups received average Apgar score of 9 points. Concentrations of analysed cytokines were marked between 4-6 hours after birth. The enzyme-linked immunosorbent assay (ELISA) test was used to determine interleukins concentrations. Study was prospective. Statistics on the data were conducted with the Kolmogorov-Smirnov test. Significance level: p < 0.05. RESULTS: Concentrations of IL-6 and IL-18 were elevated in the IUGR group in a statistically significant manner in comparison to the control group. CONCLUSIONS: An elevated level of IL-6 and IL-18 in the IUGR group, comparing to control group, signifies the existence of inflammation in the process of developing IUGR, therefore, screening tests estimating levels of interleukins as IL-6 and IL-18 might be clinically useful in predicting the occurrence of IUGR and help preventing it.

[Prognostic significance of subchorionic hematoma for the course of pregnancy]. / Znaczenie prognostyczne ultrasonograficznego rozpoznania krwiaka podkosmówkowego dla przebiegu ciazy.

OBJECTIVES: the aim of this retrospective study was to assess if a first trimester subchorionic hematoma (SCH) influences the pregnancy outcome and whether pv bleeding can be a prognostic factor for the pregnancy course. MATERIAL AND METHODS: the study included 185 pregnant women hospitalized due to symptoms of a threatening miscarriage. Patients were divided into 2 groups: 119 women with SCH (study group) and 66 patients with normal prenatal scan (control group), further subdivided into cases with and without pv bleeding, irrespectively of the outcome of the ultrasound scan. Obstetric and neonatal data were analyzed. RESULTS: 1. A pregnancy complicated by SCH is more often associated with a poor outcome -- 23.78% of the study group patients had a miscarriage versus 7.62% of the controls. 2. Pregnancy with SCH is more likely to be lost before 9 weeks of gestation. 3. The "N" ratio, that expresses the maximal length of the hematoma to the maximal length of the fetus, equal to 2.5 or more, is associated with a risk of miscarriage. 4. The surface area of SCH equal to 280mm(2) or more is more likely to reveal with vaginal bleeding. 5. Vaginal bleeding can be a prognostic factor for the mode of delivery -- a higher rate of the Cesarean section is observed in patients with pv bleeding. 6. SCH is a complication that occurs in older women, with the limit of 30 years of age. 7. In this study there were no significant correlations between subchorionic hematoma or pv bleeding and PTL, IUGR, PIH, abnormal volume of the amniotic fluid, parity and order of gestation and delivery CONCLUSIONS: subchorionic hematoma can be associated with poor pregnancy outcome and the "N" index may be a useful predictor of the further course of a pregnancy Pv bleeding may be a prognostic factor for the delivery mode.

[Concentration of selected cytokines in women with premature rupture of membranes and preterm delivery--preliminary study]. / Stzenie wybranych cytokin u kobiet z przedwczesnym peknieciem blon plodowych i porodem przedwczesnym--badane wstepne.

INTRODUCTION: For years much attention has been paid to the possible role of cytokines in the etiology of preterm delivery (PTD) in relation to anticipation of delivery in women with premature rupture of membranes (PROM). There are no clear indications introducing this observation to clinical practice. The goal of this study was to evaluate interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), G-colony stimulating factor (G-CSF) concentration in serum of women with PROM in connection with the occurrence of the delivery MATERIAL AND METHODS: 35 patients with PROM (average age 29.6 +/- 3.8 years, average time of gestation 35.2 +/- 1.5 weeks) were analyzed. The pregnant women were divided into 2 groups: 15 women delivered < 24 h and 20 women delivered > 24 h since the appearance of PROM. In both analyzed subgroups, the levels of IL-6, TNF-alpha, G-CSF CRP and leucocytosis have been compared. The concentration of IL-6, TNF-alpha and G-CSF in serum was measured by immunoenzymatic ELISA method, CRP concentration by immunoturbimetric method. RESULTS: In the whole group of women with PROM, the differences in average serum concentration of IL-6 before and after delivery (6.01 +/- 3.71 pg/mL and 7.98 +/- 3.44 pg/mL p < 0.05) and G-CSF (130.92 +/- 110.32 pg/mL and 79.59 +/- 52, 13 pg/mL, p < 0,05) have been observed. Moreover, average TNF-alpha concentration before and after the delivery was 1.43 +/- 0.63 pg/mL and 1.72 +/- 1.06 pg/mL (p > 0.05), respectively. It is particularly interesting that the authors have observed higher concentration of G-CSF in women who delivered within 24 h since PROM (147.05 +/- 103.88 pg/mL), if compared to the women who delivered after 24 h since PROM (118.81 +/- 115.71 pg/mL, without statistically significant difference p > 0.05). The same remark was connected with difference of IL-6 concentration in analogical groups of women (6.42 +/- 4.14 pg/mL vs 5.71 +/- 3.42 pg/mL, p > 0.05). Equally interesting observation were statistically significant differences in G-CSF concentration before and after delivery (147.06 +/- 103,88 vs 74.67 +/- 46.84, p < 0.05) in the event of the delivery < 24 h since PROM, such as in IL-6 concentration (5.71 +/- 3.42 vs 8.11 +/- 3.41, p < 0.05) in case of the delivery > 24 h since PROM. CONCLUSIONS: Statistically significant differences in IL-6, G-CSF, and CRP concentration before and after the delivery suggest the participation of these factors in the etiology of preterm delivery in women with PROM. The higher IL-6 and G-CSF concentration in women delivering within 24 h since the appearance of PROM suggest that these cytokines could be involved in the processes leading to delivery Statistically significant differences in IL-6 and G-CSF concentration before and after the delivery in a group of women delivering < 24 h or > 24 could indicate an important contribution of changes in proportions of these cytokines in PTD the etiology in PROM.