dinoprost and Diabetes--Gestational

Circulating endothelial progenitor cells (EPCs) play important roles in vascular repair. However, the mechanisms of high-glucose- (HG-) induced cord blood EPC senescence and the role of B2 receptor (B2R) remain unknown.. Cord blood samples from 26 patients with gestational diabetes mellitus (GDM) and samples from 26 healthy controls were collected. B2R expression on circulating CD34. B2R expression on circulating CD34. BK, acting through PI3K-AKT-eNOS signalling pathways, reduced hTERT translocation, increased the relative length of telomeres while reducing mtDNA copy number, and finally protected against EPC senescence induced by HG.

Topics: Bradykinin; Case-Control Studies; Cells, Cultured; Cellular Senescence; Diabetes, Gestational; Dinoprost; DNA, Mitochondrial; Endothelial Progenitor Cells; Female; Fetal Blood; Gene Dosage; Glucose; Humans; Infant, Newborn; Nitric Oxide; Nitric Oxide Synthase Type III; Pregnancy; Proto-Oncogene Proteins c-akt; Receptor, Bradykinin B2; Signal Transduction; Telomerase; Telomere

Background The primary objective of this study was to compare the fetal cardiac performance index (Tei index) between the fetuses of gestational diabetes mellitus (GDM) mothers and non-GDM mothers; and the secondary objective was to compare various other parameters of fetal cardiac function as well as maternal oxidative stress levels between the groups of GDM and non-GDM mothers. Methods A cross-sectional study was conducted on pregnant women at 24-28 weeks of gestation. All of the participants underwent 100 g, 3-h oral glucose tolerance test (OGTT) as a diagnostic test for GDM and were categorized as non-GDM and GDM group. All participants had fetal echocardiography performed for cardiac function, and then maternal blood samples were collected for biomarker measurements. Results A total of 80 pregnant women, including 43 in the GDM group and 37 in the non-GDM group, were included in the study. The maternal serum 8-isoprostane (8IsoP), tumor necrosis factor-α (TNF-α) and interleukin (IL)-10 levels were significantly higher in the GDM group than those in the non-GDM group (P: 0.028, P: 0.019 and P: 0.031, respectively). The fetal cardiac function parameters were not significantly different between the two groups. Regardless of the GDM status, the fetuses with high levels of oxidative stress (8Isop ≥1000 pg/mg protein) had a significantly higher rate of impaired shortening fraction (SF) of the left ventricle (P: 0.001). Conclusion GDM is significantly associated with an increase in the oxidative stress process, and a high level of oxidative stress was significantly associated with left ventricular (LV) function impairment. Though a correlation between GDM and fetal cardiac function impairment was not clearly demonstrated in this study, this study suggests that GDM patients with a high level of oxidative stress should be evaluated for fetal cardiac function.

Topics: Adult; Blood Glucose; Diabetes, Gestational; Dinoprost; Echocardiography; Female; Fetal Heart; Glucose Tolerance Test; Humans; Interleukin-10; Oxidative Stress; Pregnancy; Pregnancy Trimester, Second; Prenatal Care; Tumor Necrosis Factor-alpha; Ultrasonography, Prenatal

To evaluate serum concentration of 8-isoprostane, nitrotyrosine (NT), and total antioxidant capacity (TAC) in pregnant women with diabetes mellitus (DM) considering preconception planning and method of diabetes correction in 11-14 and 30-34 weeks.. The study included 130 women: T1DM (n = 40), T2DM (n = 35), gestational diabetes (GDM, n = 40) and the control group (n = 15). The serum concentrations of NT, 8-isoprostane, and TAC were measured by ELISA methods.. Elevated 8-isoprostane levels were observed in all patients with DM, but this biomarker's maximum values have been seen in T1DM and T2DM on insulin groups. A similar tendency was observed for the concentration of NT in both the 1st and 3rd trimesters. TAC levels showed a statistically relevant decrease in all DM groups compared to the control. The correlation analysis showed a direct correlation between HbA1c and serum 8-isoprostane levels in the 1st (r = .27) and 3rd (r = .3) pregnancy trimesters as well as inverse correlation with TAC level (r = -.48). Direct (NT, 8-isoprostane) and inverse correlations (TAC) were fixated for this biomarker concentration and preeclampsia rates.. DM in pregnancy is related to oxidative stress activation, which might lead to the development of adverse perinatal outcomes.

Topics: Adult; Antioxidants; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Dinoprost; Female; Humans; Pre-Eclampsia; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Russia; Tyrosine

We have shown that some markers of oxidative stress were higher in women with gestational diabetes mellitus (GDM). This study examines the relationship between adipokines and oxidative stress and their potential effects in pregnant women.. Three markers of oxidative stress (malondialdehyde, 8-isoprostane and xanthine oxidase) and three adipokines (leptin, adiponectin and resistin) were measured in maternal plasma, cord plasma and placenta of 208 pregnant women.. Among all these women, 105 were diagnosed with GDM while the other 103 were controls. Leptin, resistin, malondialdehyde, xanthine oxidase and 8-isoprostane in maternal plasma, cord plasma and placenta were significantly higher while maternal adiponectin significantly lower in women with GDM (P < 0.05). Adipokines in maternal plasma, cord plasma and placenta were positively correlated with markers of oxidative stress. Both markers of oxidative stress and adipokines were correlated inversely with homeostasis model assessment of insulin resistance whereas positively with quantitative insulin sensitivity check index (P < 0.01). Adiponectin is negatively correlated with leptin and resistin. Placental/cord leptin and cord resistin levels were higher in the macrosomia while maternal adiponectin level was lower (P < 0.05) than normal birthweight newborns. Both markers of oxidative stress and adipokines in maternal and cord plasma are negatively correlated with newborn birthweight (P < 0.05).. Adipokines interact with markers of oxidative stress, both of which lead to insulin resistance, GDM and macrosomia. It has long been known that placenta involves in the development of GDM. Adipokines might participate in this process and need to be confirmed by further studies.

Topics: Adiponectin; Adult; Diabetes, Gestational; Dinoprost; Female; Fetal Blood; Fetal Macrosomia; Humans; Infant, Low Birth Weight; Infant, Newborn; Leptin; Male; Malondialdehyde; Placenta; Pregnancy; Resistin; Xanthine Oxidase

In response to oxidative stress, gestational diabetes mellitus (GDM) placenta releases less 8-isoprostane and tumour necrosis factor (TNF) alpha. The effect of oxidative stress on other cytokines and antioxidant gene expressions are unknown. The aim of this study is to further explore the antioxidant status and effect of oxidative stress in GDM tissue. Human placenta, omental and subcutaneous adipose tissue from women with and without GDM were exposed to hypoxanthine (HX)/xanthine oxidase (XO). Cytokine release was analysed by ELISA and cytokine and antioxidant gene expression by RT-PCR. Catalase (CAT) and glutathione reductase (GSR) mRNA expression was higher in GDM (n=18) compared with normal (n=23) placenta. There was no difference in glutathione peroxidase and superoxide dismutase mRNA expression. Antioxidant gene expression was unaltered between normal (n=18) and GDM (n=10) adipose tissue. HX/XO treatment significantly stimulated cytokine release (13/16 cytokines) and cytokine mRNA expression, and decreased antioxidant gene expression (CAT and GSR) in human placenta from normal pregnant women. In GDM placenta, HX/XO only significantly increased the release of 3/16 cytokines, while there was no effect on antioxidant gene expression. In normal and GDM adipose tissues, HX/XO increased proinflammatory cytokine and 8-isoprostane release, while there was no change in antioxidant gene expression. GDM placenta is characterised by increased antioxidant gene expression, and is less responsive to exogenous oxidative stress than tissues obtained from normal pregnant women. This may represent a protective or adaptive mechanism to prevent damage from further oxidative insult in utero as indicated by increased tissue antioxidant expression.

Topics: Adipose Tissue; Catalase; Cytokines; Diabetes, Gestational; Dinoprost; Female; Gene Expression; Glutathione Reductase; Humans; Inflammation Mediators; Oxidative Stress; Oxidoreductases; Placenta; Pregnancy; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Subcutaneous Tissue; Superoxide Dismutase; Xanthine Oxidase

Preeclampsia (PE) and diabetes mellitus (DM) are associated with oxidative stress. DM is complicated with formation of advanced glycation end products (AGEs), which are associated with oxidative stress. We hypothesized that elevated serum AGE would be found in pregnancies complicated by PE or DM.. Circulating AGEs, 8-isoprostane, vitamin E, and antioxidant capacity were analyzed from study patients.. Serum AGE was elevated both in patients with type 1 DM and gestational DM, but not in PE, compared with controls. 8-isoprostane was elevated in patients with type 1 DM and PE compared with controls.. AGEs and 8-isoprostane are not elevated in parallel in pregnancies complicated with PE or DM, suggesting biological heterogeneity.

Topics: Adult; Biomarkers; Case-Control Studies; Diabetes, Gestational; Dinoprost; Female; Ferric Compounds; Glycation End Products, Advanced; Humans; Lysine; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy in Diabetics; Vitamin E; Young Adult

Oxidative stress has been clearly linked to type 2 diabetes mellitus, however, limited data are available on the involvement of oxidative stress in gestational diabetes mellitus (GDM), a disease of similar pathophysiology. The aim of this study was to investigate the status of placental oxidative stress in healthy pregnant women and women with GDM. The hypothesis to be tested was that tissue markers of oxidative stress are significantly increased in GDM compared to normal placental tissues. Markers of oxidative stress measured were the release of 8-isoprostane (8-epi-prostaglandin F(2alpha)) from human term placental explants (n=11), the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase (n=10), and protein carbonyl content (n=12). Placental release of 8-isoprostane was 2-fold greater from women with GDM (P<0.001) compared to healthy pregnant women. Superoxide dismutase activity and protein carbonyl content were elevated in placentae obtained from women with GDM (P<0.04 and P<0.004 respectively), whilst there was no significant difference in the activity of glutathione peroxidase. These data demonstrate the presence of oxidative stress in the placenta from women with GDM, in addition to the induction of a key antioxidant, collectively indicating a state of existing oxidative stress in this condition.

Topics: Biomarkers; Cell Survival; Cesarean Section; Culture Techniques; Diabetes, Gestational; Dinoprost; Female; Glucose Tolerance Test; Glutathione Peroxidase; Humans; Oxidative Stress; Placenta; Pregnancy; Superoxide Dismutase

The aim of this study was to 1) profile the basal release of TNF-alpha, IL-6, IL-8, and 8-isoprostane (a marker of oxidative stress); and 2) investigate the effect of stimulation on the release of cytokines from sc adipose tissue and skeletal muscle from normal pregnant women and women with gestational diabetes mellitus (GDM). Placenta, sc adipose tissue, and skeletal muscle were incubated in the absence (control) or presence of lipopolysaccharide (LPS; 10 microg/ml), TNF-alpha (10 ng/ml), IL-6 (10 ng/ml), or IL-8 (10 ng/ml). After an 18-h incubation, the medium was collected, and the release of TNF-alpha, IL-6, IL-8, and 8-isoprostane was quantified by ELISA. In all three tissues, 8-isoprostane release was greater in women with GDM, and stimulation with LPS increased 8-isoprostane release from adipose and skeletal muscle, but not placenta, obtained from women with GDM. However, in tissues obtained from normal pregnant women, LPS stimulation increased 8-isoprostane release in placenta and had no effect in adipose tissue and skeletal muscle. Their was no difference in the release of TNF-alpha, IL-6, and IL-8 from placenta, adipose tissue, and skeletal muscle obtained from normal pregnant women and women with GDM. Stimulation of placenta, adipose tissue, and skeletal muscle with LPS and TNF-alpha resulted in greater release of IL-6 and IL-8, whereas only LPS increased TNF-alpha release from all three tissues. The data presented in this study demonstrate that there is a differential release of 8-isoprostane from fetal (placenta) and maternal (adipose tissue and skeletal muscle) tissues obtained from normal pregnant women and women with GDM. These data are consistent with the hypothesis that oxidative stress may be involved in the progression and/or pathogenesis of GDM.

Topics: Adipose Tissue; Adult; Cytokines; Diabetes, Gestational; Dinoprost; Female; Humans; L-Lactate Dehydrogenase; Lipopolysaccharides; Muscle, Skeletal; Oxidative Stress; Placenta; Pregnancy

This study has used an in vitro perfusion method to investigate the mechanism by which CRH causes vasodilatation in the human fetal-placental circulation. In normal term placentas, vasodilatory responses to human CRH (24-7000 pmol/L) were examined during submaximal vasoconstriction (100-120 mm Hg) of the fetal-placental vasculature induced by prostaglandin F2 alpha (0.7-2 mumol/L), KCl (50-100 mmol/L), or the thromboxane A2 mimetic, U46619 (0.05-0.5 mumol/L). Infusion of CRH caused a concentration-dependent vasodilatation that was similar in the presence of each constrictor agent (P > 0.05). The CRH antagonist, alpha-helical CRH-(9-41) (200 pmol/L), and a polyclonal CRH antiserum significantly inhibited CRH-induced vasodilatation during constriction with prostaglandin F2 alpha (P < 0.05). Vasodilatory responses to CRH were attenuated by the nitric oxide synthase inhibitor, N omega-nitro-L-arginine (100 mumol/L; P < 0.05), and the guanylate cyclase inhibitor, LY 83583 (1 mumol/L; P < 0.05), but not by the cyclooxygenase inhibitor, indomethacin (3 mumol/L; P > 0.05). In placentas of women with increased fetal vascular resistance, as demonstrated by Doppler ultrasound waveforms in vivo, CRH-induced vasodilatation was significantly reduced (P < 0.05). These results indicate that in the human fetal-placental circulation, CRH causes a vasodilatory response via a nitric oxide-/cGMP-dependent pathway. CRH may play a role in the control of vascular resistance to blood flow in the normal human placenta, and there may be a deficiency in the CRH signaling pathway of placentas with increased fetal vascular resistance.

Topics: Adult; Birth Weight; Corticotropin-Releasing Hormone; Cyclic GMP; Diabetes, Gestational; Dinoprost; Dose-Response Relationship, Drug; Female; Fetal Growth Retardation; Fetus; Humans; In Vitro Techniques; Infant, Newborn; Maternal-Fetal Exchange; Muscle, Smooth, Vascular; Nitric Oxide; Placenta; Potassium Chloride; Pregnancy; Pregnancy Complications; Reference Values; Regression Analysis; Signal Transduction; Vascular Resistance; Vasoconstriction; Vasodilation