A prospective and comparative investigation of blood sFlt-1, P1GF, and niacin concentrations in women with premature ovarian insufficiency.

OBJECTIVE: Endothelial dysfunction is an important component of preeclampsia like premature ovarian insufficiency (POI), and it is reported that placental growth factor (P1GF) and soluble fms-like tyrosine kinase receptor-1 (sFlt-1) levels are important in preeclampsia. Extra-placental sources for P1GF and sFlt-1 have also been identified, including various cell types. In animal models of POI, niacin treatment inhibited follicular apoptosis under hazardous conditions while significantly reducing cumulus cell apoptosis. The number of developing follicles also increased after niacin was given. This study was designed to determine blood sFlt-1, P1GF, and niacin concentrations in women with idiopathic POI (iPOI) compared with those of healthy women. METHODS: The study comprised 45 women with iPOI and 45 healthy women. Blood was obtained and analyzed at the early follicular phase of the menstrual cycle and sFlt-1, P1GF, and niacin levels were measured using a commercially available enzyme-linked immunosorbent assay kit. RESULTS: No significant differences were observed in the two groups according to the gravidity numbers, parity, abortion, live births, and menarche ages (p ≥ 0.05). In the iPOI group, the mean anti-mullerian hormone value was 0.03 ± 0.04 (min-max, 0.00-0.21) ng/ml. sFlt-1, P1GF, niacin levels, and also the sFlt-1/P1GF ratio were lower in the iPOI group (p < 0.01). A significant discriminative role of sFlt-1, P1GF, niacin levels, and the sFlt-1/P1GF ratio for the presence of iPOI, with cut-off values of 5.13, 10.28, 37.17, and 0.61 ng/ml, respectively, were reported in the receiver operating characteristics curve analysis. CONCLUSIONS: Lower levels of P1GF, sFlt-1, niacin, and sFlt-1/P1GF ratios may be associated with the development of POI/iPOI. Further studies are required to better understand the etiopathogenesis of POI/iPOI. CLINICAL TRIAL NUMBER: NCT04641624 (clinicaltrials.gov).

Analyses of interleukin-6, presepsin and pentraxin-3 in the diagnosis and severity of late-onset preeclampsia.

INTRODUCTION: The etiology/pathophysiology of preeclampsia remains an enigma. Maternal inflammation (humoral and cellular) is a key factor in the etiology of late-onset preeclampsia (L-PrE). Presepsin is split out from the phagocytes membranes after phagocytosis. It is known as a novel inflammation marker. To our knowledge, this is the first study in literature in English to investigate maternal blood concentrations of presepsin in preeclampsia and healthy pregnant women. METHODS: We examined maternal plasma interleukin-6, presepsin and pentraxin-3 concentrations in pregnant women with (n = 44) and without L-PrE (n = 44). These three inflammatory markers concentrations measured using enzyme-linked immunosorbent assays were compared. RESULTS: The mean maternal age and gestational age at sampling are similar in the both groups (p ≥ .05). Interleukin-6, presepsin and pentraxin-3 concentrations differed between the groups (p < .05). There was no difference between the three inflammatory markers concentrations in patients with mild (22 patients) and severe (22 patients) preeclampsia in L-PrE (p ≥ .05). A significant discriminative role of interleukin-6, presepsin and pentraxin-3 for presence of L-PrE, with cutoff values of 39.74 pg/mL, 309.88 mg/L and 34.96 ng/mL, respectively, were reported in a ROC curve analysis. When the patients with and without small for gestational age infants (12 patients and 76 patients, respectively) were compared, it was determined that there was no differences between the interleukin-6, but there were differences between the presepsin and pentraxin-3 concentrations (p = .016, p = .008, respectively). CONCLUSION: Lower concentrations of interleukin-6/presepsin and higher concentrations of pentraxin-3 were associated with the development of preeclampsia. Further investigations of inflammatory/immunity markers in pregnancy are required and may ultimately lead to novel therapeutic approaches to treat complications of pregnancy.

Analyses of maternal plasma cadmium, lead, and vanadium levels in the diagnosis and severity of late-onset preeclampsia: a prospective and comparative study.

INTRODUCTION: Cadmium, lead, and vanadium, important pollutants produced from anthropogenic activities, have been suggested to be embryotoxic and fetotoxic in many studies. However, the causes of preeclampsia are little known and heavy metals merit further investigation. We tested whether late-onset preeclampsia (L-PrE) was associated with exposure to these metals. METHODS: This study was designed to determine maternal plasma cadmium, lead, and vanadium concentrations in women with L-PrE (n = 46) compared with those of normotensive women (n = 46). The concentrations of the metals were measured using inductively coupled plasma-mass spectrometry and compared. RESULTS: The groups were matched for maternal age, gestational age, and gravidity (p ≥ 0.05). Vanadium concentrations differed between the groups (p = 0.007). In contrast, there were no significant differences in the concentrations of cadmium and lead between the groups (p ≥ 0.05). There was no difference between the concentrations of the metals in patients with mild (n = 23) and severe (n = 23) preeclampsia in L-PrE (p ≥ 0.05). A significant discriminative role of vanadium for the presence of L-PrE, with a cutoff value of 1.84 µg/L, was found in ROC curve analysis. When the patients with and without small-for-gestational-age infants were compared (n = 12, and n = 80, respectively), it was determined that there were no differences between cadmium, lead, and vanadium concentrations (p ≥ 0.05). CONCLUSION: Lower levels of vanadium might be associated with the development of L-PrE. Our findings require further investigation in other populations.

Analyses of soluble endoglin and matrix metalloproteinase 14 using enzyme-linked immunosorbent assay in the diagnosis and assessment of severity of early- and late-onset pre-eclampsia

Objective: Abnormal trophoblastic invasion and impaired placentation have a crucial role in the etiopathogenesis of preeclampsia (PrE). Trophoblastic cells are involved in invading the maternal decidua and remodelling of the spiral arteries with matrix metalloproteinase-14 (MMP-14). MMP-14 cleavage of endoglin releases its extracellular region, the soluble form of endoglin (s-ENG), into the maternal circulation. In PrE, there is a relationship between endothelial dysfunction and s-ENG concentration. The aim was to determine and compare the serum levels of s-ENG and MMP-14 in different groups of PrE patients and healthy subjects. Material and Methods: The study included 30 patients with late-onset preeclampsia (L-PrE) (group 1; gestational age ≥34 weeks), 33 patients with normal pregnancy (group 2; gestational age ≥34 weeks), 31 patients early-onset preeclampsia (E-PrE) (group 3; gestational age <34 weeks), and 31 patients with normal pregnancy (group 4; gestational age <34 weeks). s-ENG and MMP-14 concentrations measured using enzyme-linked immunosorbent assays were compared. Results: In all groups, MMP-14 concentrations decreased with increasing gestational age. s-ENG concentrations were highest in the E-PrE group. In groups 1 and 3, 29 had mild PrE while 32 suffered severe PrE and s-ENG concentrations did not differ between mild and severe preeclampsia (p=0.133). However, there was a significant difference in MMP-14 concentration comparing mild with severe PrE (3.11±0.61 vs 3.54±1.00; p=0.047, respectively). There was no correlation between s-ENG and MMP-14 concentrations. Conclusion: MMP-14 and s-ENG concentrations can be predictive biomarkers for the diagnosis of PrE. Maternal serum MMP-14 concentration may be a biomarker for determining the severity of PrE.

Maternal serum endothelial cell-specific molecule-1 level and its correlation with severity of early-onset preeclampsia.

Preeclampsia (PE), the primary pathology of which is endothelial cell (EC) dysfunction, has long-lasting effects such as cardiovascular disease. Therefore, it was decided to investigate the maternal serum concentrations of EC-specific molecule-1 in patients with early-onset preeclampsia (E-PE). This study was conducted on 33 pregnant women with E-PE and 35 healthy pregnant women matched for gestational age. EC-specific molecule-1 level was measured using a commercially available enzyme-linked immunosorbent assay kit. The mean EC-specific molecule-1 concentrations were not significantly different between the groups (651.7 ± 632.2 pg/mL vs. 425.9 ± 263.0 pg/mL, p=.056). Among women with E-PE, the median EC-specific molecule-1 concentration did not differ significantly by disease severity (p=.115). EC-specific molecule-1 is not involved in the pathogenesis of E-PE. However, some studies in the literature report that EC-specific molecule-1 concentrations increased during the diagnosis of PE. Therefore, well-designed studies with a large sample are needed in cases of E-PE.Impact StatementWhat is already known on this subject? There is an increased risk of cardiovascular disease (CVD) in early-onset preeclampsia (E-PE) which is linked with endothelial dysfunction. Endothelial cell (EC)-specific molecule-1 stands out as an important marker in EC dysfunction related conditions such as preeclampsia.What the results of this study add? This study showed that EC-specific molecule-1 is not associated with the CVDs risk linked with endothelial dysfunction in E-PE. Additionally, there was also no significant relationship was detected between the severity of E-PE and EC-specific molecule-1 concentrations.What the implications are of these findings for clinical practice and/or further research? Endothelial cell-specific molecule-1 is not involved in the pathogenesis of E-PE. Moreover, advantageous and easy-to-measure markers are needed in larger sample studies to better understand the aetiology of E-PE.

Endothelial cell-specific-molecule-1 (endocan) levels in women with premature ovarian insufficiency: a prospective comparative study.

There is an increased risk of cardiovascular disease in women with premature ovarian insufficiency (POI). A relationship between cardiovascular disease and endocan levels has been shown. Endocan is a marker that is prominent in many diseases caused by endothelial dysfunction and can be measured in the blood. POI is also associated with endothelial dysfunction. The causes of POI include chromosomal and genetic defects, autoimmune processes, chemotherapy, radiation, infections and surgery, but many are unidentified (idiopathic). This study aimed to evaluate serum endocan levels in women with idiopathic POI. The blood for analysis was obtained at the early follicular phase of the menstrual cycle and endocan levels were measured using a commercially available enzyme-linked immunosorbent assay kit. There were 38 patients with idiopathic POI in the study group and 39 healthy subjects in the control group. The median ages of the women were not significantly different between the groups 34 [7] years vs. 34 [7] years, respectively (p = .862). The median endocan level was not different in the POI and control group 769 [727] vs. 1077 [403] pg/mL, respectively (p = .603). Endocan is not associated with the cardiovascular diseases risk linked with endothelial dysfunction in idiopathic POI. Clinical trial number: NCT03932877 (Clinicaltrials.gov)IMPACT STATEMENTWhat is already known on this subject? There is an increased risk of cardiovascular disease in premature ovarian insufficiency (POI) due to the decreased level of oestrogen, which is linked with endothelial dysfunction.What do the results of this study add? This study showed that endocan is not associated with the cardiovascular disease risk linked with endothelial dysfunction in idiopathic POI.What are the implications of these findings for clinical practice and/or further research? A marker to be used to predict the risk of cardiovascular disease in patients with POI could facilitate in improving the quality of life of these patients. Moreover, advantageous and easy-to-measure markers are needed in larger sample studies to better understand the cardiovascular diseases risk in POI.

The effect of vascular complications of diabetes mellitus on human umbilical cord tissue and the number of Wharton Jelly's mesenchymal stem cells.

The current study investigated the change in umbilical cord tissue and the number of markers of Wharton's jelly mesenchymal stem cells (WJ-MSC) in pregnant women with gestational diabetes (GDM), with chronic diabetes who developed nephropathy as vascular complication (VC-PGDM), and healthy pregnant women as the control. The umbilical cords (UC) were investigated by the histomorphological method and the number of WJ-MSC were detected by flow-cytometry using the CD90, CD44, CD105, and CD73 markers in Wharton's jelly (WJ) isolated from fresh umbilical cords. The number of positive cells for CD 90, CD44, CD105, and CD73 were found to be elevated in the GDM group, whereas it was significantly diminished in the VC-PGDM group (p = 0.001, p = 0.001, p = 0.001, and p = 0.001). The only histopathological sign in the GDM group were an increased number of pores in the Wharton jelly. Artery wall thickness/cord diamater ratio was increased, which indicates an increase of the artery wall thickness in the VC- PGDM group (p = 0.039 and p = 0.048). The increase in umbilical cord diameter and number of Wharton jelly mesenchymal stem cells in babies of gestational diabetic mothers was considered as an effect of macrosomia seen in babies of mothers with gestational diabetes. Vasculopathy, a long-term complication of diabetes, is known to affect all tissues by causing marked lower perfusion and hypoxia, as well as a decrease in the MSC number in our study.

Amniotic fluid concentrations of soluble endoglin and endothelial cell-specific molecule-1 in pregnancies complicated with neural tube defects.

Objective To determine the concentrations of soluble endoglin (sCD105) and endothelial cell-specific molecule-1 (ESM-1) in the amniotic fluid (AF) of pregnant women, and to investigate the relationship between these concentrations and neural tube defects (NTDs). Methods AF concentrations of sCD105 and ESM-1 were measured in the study group, which included 60 pregnant women complicated with NTDs, and 64 pregnant women with unaffected healthy fetuses (control group). The AF concentrations of sCD105 and ESM-1 in both groups were measured using enzyme-linked immunosorbent assay and compared. Results There were no significant differences in terms of the mean AF concentrations of sCD105 and ESM-1 between the groups (P=0.141, P=0.084, respectively). There was a significant difference between the AF sCD105 concentrations in those with gestational age <24 weeks (n=101) and ≥24 weeks (n=23) (X̅<24=76.35±126.62 vs. X≥24=39.87±58.32, P=0.041). AF ESM-1 concentrations were found to be statistically significant in the gestational age <22 weeks (n=90) and ≥22 weeks (n=34) groups (X̅<22=135.91±19.26 vs. X̅≥22=148.56±46.85, P=0.035). A positive and low-level relation at a statistically significant level was determined between the gestational age and AF ESM-1 concentration in the study group (r=0.257; P=0.048). Conclusion AF concentrations of sCD105 and ESM-1 were not associated with the development of NTDs. Unlike studies that reported that ESM-1 concentrations decreased in maternal plasma with increased gestational age, we determined an increase that was proportionate to gestational age in AF.

Amniotic fluid levels of selected trace elements and heavy metals in pregnancies complicated with neural tube defects.

The aims of this study were to determine the levels of trace elements and heavy metals, namely aluminum (Al), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), molybdenum (Mo), cadmium (Cd), tin (Sn), antimony (Sb), mercury (Hg), and lead (Pb), in the amniotic fluid of pregnant women, and to investigate their relationship with neural tube defects (NTDs). The study included 36 pregnant women whose fetuses were complicated with NTDs (study group) and 39 pregnant women with unaffected healthy fetuses (control group), who were matched for body mass index and gestational weeks. The amniotic fluid levels of trace elements and heavy metals were measured using inductively coupled plasma-mass spectrometry and compared between the two groups. Significantly lower mean levels of Zn and Mo and significantly higher levels of Al, Sn, Sb, and Hg in the study group than in the healthy control group were observed, which implied that these elements are possibly correlated with risk factors for the occurrence of NTDs. In contrast, there were no significant differences in the levels of Cr, Mn, Co, Ni, Cu, As, Cd, and Pb between the groups (P ≥ .05).

Maternal serum endocan concentrations are elevated in patients with preterm premature rupture of membranes.

Objectives To evaluate the maternal serum endocan levels in pregnant women complicated by preterm premature rupture of membranes (PPROM) and to compare the results with healthy pregnancies. Methods This cohort study included 31 pregnant women with PPROM and 34 gestational age-matched healthy subjects in the third trimester of pregnancy. The blood for analysis was obtained on the day of diagnosis and serum endocan levels were measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. The pregnant women were observed until the delivery and perinatal data were noted. Results No significant differences regarding maternal age, body mass index, gravidity, parity and gestational age at sampling were observed (P > 0.05). Mean serum endocan level was significantly higher in the PPROM group than in healthy controls (1490 ± 632 pg/mL vs. 972 ± 586 pg/mL, respectively; P: 0.001). Serum endocan concentration was positively correlated with C-reactive protein (CRP) (r = 0.754, P < 0.001) and white blood cells count (WBC) (r = 0.712, P:0.001). The receiver operating characteristic (ROC) curve analysis showed that endocan with a cut-off point of 1198 ng/dL indicated women with PPROM with sensitivity of 64.5% and specificity of 35.1% (area under curve 0.731, confidence interval 0.61-0.85). Conclusion Serum endocan level was significantly elevated in the PPROM patients than in healthy controls. The endocan level may be a useful indicator of endothelial dysfunction/inflammation in PPROM cases.

The effect of resveratrol on prevention of the development of postoperative adhesions in a rat model.

OBJECTIVE: Our aim was to investigate the anti-adhesion potential of resveratrol, a phytoestrogen naturally found in wine, in a rat uterine horn model. METHODS: Lesions were created by laparotomy in the uterine horn of 70 rats, randomized before the operation into seven groups consisting of ten animals each: (1) control group, no adjuvant therapy; (2) intraperitoneal (IP) application of the resveratrol dilution vehicle, 10 mg/kg, before closing the laparotomy; (3) subcutaneous (SC) injection of dilution vehicle, 10 mg/kg, 30 min before the operation; (4) IP application of resveratrol, 10 mg/kg, before closing the laparotomy; (5) SC injection of resveratrol, 10 mg/kg, 30 min before the operation; (6) IP application of resveratrol, 10 mg/kg, before closing the laparotomy and continued SC daily for 5 days; and (7) SC injection of resveratrol, 10 mg/kg, 30 min before the operation and continued SC daily for 5 days. On the 14th postoperative day adhesion scores were determined. Levels of thiobarbituric acid-reactive substances and total antioxidant capacity (TAC) were also measured. RESULTS: In animals treated with repeated SC resveratrol, adhesions were graded as significantly less severe than in the vehicle control group or the groups treated with resveratrol IP or IP plus SC. TAC of control group rats was significantly lower than that of animals treated with repeated SC resveratrol. CONCLUSION: Repeated SC resveratrol significantly reduces adhesion formation.