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Immunity, Inflammation and Disease Jul 2022Prostaglandin E2 (PGE2) is a potent lipid mediator of inflammation that modulates immune cell function by binding to unique G protein-coupled receptors (EP receptors)....
Prostaglandin E2 (PGE2) is a potent lipid mediator of inflammation that modulates immune cell function by binding to unique G protein-coupled receptors (EP receptors). PGE2 production increases during microbial infection and inflammation. In this study, we assessed the effect of PGE2 on the phagocytosis of bacteria by neutrophils, which are key players during infection and inflammation. We also looked for specific EP receptor signaling pathways that contributed to the neutrophil phagocytic activity. PGE2 (50-1000 ng/ml) inhibited the phagocytosis of Escherichia coli by HL-60 human neutrophils in a concentration-dependent manner. Inhibition of neutrophil phagocytosis by PGE2 correlated with increased intracellular cyclic adenosine monophosphate (cAMP) production, and forskolin, an adenosyl cyclase agonist, confirmed the inhibitory effect of cAMP stimulation on neutrophil phagocytosis. The expression of EP2 receptors by HL-60 cells was confirmed by western blot analysis, and selective agonism of EP2 receptors mimicked the inhibition of phagocytosis by PGE2. The EP2 receptor antagonist AH-6089 partially blocked the inhibition of neutrophil phagocytosis PGE2. Specific inhibition of phosphatase and tensin homolog (PTEN) enzyme attenuated the inhibition of neutrophil phagocytosis by PGE2, and both PGE2 and increased intracellular cAMP increased neutrophil PTEN activity, which was associated with decreased PTEN phosphorylation. The results support negative regulation of the antimicrobial activity of neutrophils (i.e., phagocytosis), which has important implications for the future management of bacterial infections.
Topics: Cyclic AMP; Dinoprostone; Humans; Inflammation; Neutrophils; PTEN Phosphohydrolase; Phagocytosis; Receptors, Prostaglandin E, EP2 Subtype
PubMed: 35759236
DOI: 10.1002/iid3.662 -
The Journal of Maternal-fetal &... May 2019The objective of this study is to compare the uterine activity response between women administered dinoprostone (prostaglandin E2) and misoprostol (prostaglandin E1) for... (Comparative Study)
Comparative Study Observational Study
OBJECTIVE
The objective of this study is to compare the uterine activity response between women administered dinoprostone (prostaglandin E2) and misoprostol (prostaglandin E1) for induction of labour (IOL) by analysing not only the traditional obstetric data but also the parameters extracted from uterine electrohysterogram (EHG).
METHODS
Two cohorts were defined: misoprostol (25-µg vaginal tablets; 251 women) and dinoprostone cohort (10 mg vaginal inserts; 249 women). All the mothers were induced by a medical indication of a Bishop Score < = 6.
RESULTS
The misoprostol cohort was associated with a shorter time to achieve active labour (p = .017) and vaginal delivery (p = .009) and with a higher percentage of vaginal delivery in less than 24 h in mothers with a very unfavourable cervix score (risk ratio (RR): 1.41, IC95% 1.17-1.69, p = .002). Successful inductions with misoprostol showed EHG parameter values significantly higher than basal state for amplitude and pseudo Montevideo units (PMU) 60' after drug administration, while spectral parameters significantly increased after 150'. This response was not observed in failed inductions. In the successful dinoprostone group, the duration and number of contractions increased significantly after 120', PMU did so after 180', and no significant differences were found for spectral parameters, possibly due to the slower pharmacokinetics of this drug.
CONCLUSION
Successful inductions of labour by misoprostol are associated with earlier effective contractions than in labours induced by dinoprostone.
Topics: Administration, Intravaginal; Adult; Cervical Ripening; Cohort Studies; Delivery, Obstetric; Dinoprostone; Electromyography; Female; Humans; Labor, Induced; Misoprostol; Oxytocics; Pregnancy; Pregnancy Outcome; Time Factors; Uterine Contraction; Uterine Monitoring
PubMed: 29251182
DOI: 10.1080/14767058.2017.1410791 -
International Journal of Molecular... Dec 2022(1) Interest in the family has risen as some members have shown anti-inflammatory properties and interesting compounds. In this regard, we decided to investigate the...
(1) Interest in the family has risen as some members have shown anti-inflammatory properties and interesting compounds. In this regard, we decided to investigate the antioxidant and anti-inflammatory properties of , a not yet extensively studied, in the context of osteoarthritis. (2) The Ethanol extract (LS-E) was used to test the production of reactive oxygen species (ROS) by leucocytes, the IL1β and PGE2 production by peripheral blood mononuclear cells (PBMCs), the production of EP4, and the activation of NFκB in THP-1, as well as the IL1β-activated normal human knee articular chondrocytes (NHAC-Kn) gene expression, grown in monolayers or maintained in alginate beads. (3) Organic acids, caffeoylquinic acids, quercetin and luteolin, compounds frequently found in this family were identified. The LS-E exhibited inhibited ROS formation. The LS-E did not affect NFκB activation and IL1β secretion but dampened the secretion of PGE2 by PBMCs and the presence of EP4 in THP-1. It also modulated the expression of NHAC-Kn in both models and inhibited the expression of several proteases and inflammatory mediators. (4) might supply interesting antioxidant protection against cartilage damages and lessen joint inflammation, notably by decreasing PGE2 secretion in the synovial fluid. Moreover, it could act directly on chondrocytes by decreasing the expression of proteases and, thus, preventing the degradation of the extracellular matrix.
Topics: Humans; Anti-Inflammatory Agents; Antioxidants; Cartilage, Articular; Cells, Cultured; Chondrocytes; Dinoprostone; Leukocytes, Mononuclear; Peptide Hydrolases; Reactive Oxygen Species; Plant Extracts; Magnoliopsida
PubMed: 36613576
DOI: 10.3390/ijms24010127 -
Prostaglandins & Other Lipid Mediators Apr 2021The triplication of human chromosome 21 results in Down syndrome (DS), the most common genetic form of intellectual disability. This aneuploid condition also results in...
The triplication of human chromosome 21 results in Down syndrome (DS), the most common genetic form of intellectual disability. This aneuploid condition also results in an enhanced risk of a spectrum of comorbid conditions, such as leukemia, early onset Alzheimer's disease, and diabetes. Individuals with DS also display an increased incidence of wound healing complications and resistance to solid tumor development. Due to this unique phenotype and the involvement of eicosanoids in key comorbidities like poor healing and tumor development, we hypothesized that cells from DS individuals would display altered eicosanoid production. Using age- and sex-matched dermal fibroblasts we interrogated this hypothesis. Briefly, assessment of over 90 metabolites derived from cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome p450 systems revealed a possible deficiency in the COX system. Basal gene expression and Western blotting experiments showed significantly decreased gene expression of COX1 and 2, and COX2 protein abundance in DS fibroblasts compared to euploid controls. Further, using two different stressors, scratch wound or LPS, we found that DS fibroblasts could not upregulate COX2 abundance and prostaglandin E2 production. Together, these findings show that dermal fibroblasts from DS individuals have a deficient COX2 response, which may contribute to wound healing complications and tumor resistance in DS.
Topics: Cyclooxygenase 1; Cyclooxygenase 2; Dinoprostone; Down Syndrome; Humans
PubMed: 33418267
DOI: 10.1016/j.prostaglandins.2020.106524 -
Sheng Li Xue Bao : [Acta Physiologica... Aug 2021Prostaglandin E (PGE) is an important lipid mediator derived from arachidonic acid. It is widely distributed in various tissues and involved in numerous physiological... (Review)
Review
Prostaglandin E (PGE) is an important lipid mediator derived from arachidonic acid. It is widely distributed in various tissues and involved in numerous physiological and pathophysiological processes. Based on the inhibition of inflammatory PGE production, non-steroidal anti-inflammatory drugs (NSAIDs) are considered as the most commonly used drugs to treat pain and inflammation. However, clinical trials have revealed that NSAIDs, especially cyclooxygenase-2 (COX-2) selective inhibitors, may predispose patients to a remarkably increased cardiovascular risk, including hypertension, myocardial infarction, and heart failure. This promotes scientists to develop new drugs to not only afford pain relief but also have cardiovascular efficacy. Microsomal prostaglandin E synthase-1 (mPGES-1), the key terminal enzyme catalyzing the synthesis of inflammatory PGE, and the four PGE receptors (EP1-4) have gained more attention as the promising alternative drug targets for the development of novel NSAIDs. The role of mPGES-1 and EP receptors in cardiovascular diseases also has been widely studied. In this review, we highlight the most recent advances from our and other studies on the role of PGE, particularly mPGES-1 and the four PGE receptors, in cardiovascular diseases.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Cyclooxygenase 2; Dinoprostone; Humans; Prostaglandin-E Synthases; Receptors, Prostaglandin E
PubMed: 34405222
DOI: No ID Found -
Chinese Medical Journal Mar 2022At present, there is no consensus on the induction methods in term pregnancy with borderline oligohydramnios. This study aimed to compare the effectiveness and pregnancy...
Comparison of the effectiveness and pregnancy outcomes of labor induction with dinoprostone or single-balloon catheter in term nulliparous women with borderline oligohydramnios.
BACKGROUNDS
At present, there is no consensus on the induction methods in term pregnancy with borderline oligohydramnios. This study aimed to compare the effectiveness and pregnancy outcomes of labor induction with dinoprostone or single-balloon catheter (SBC) in term nulliparous women with borderline oligohydramnios.
METHODS
We conducted a retrospective cohort study from January 2016 to November 2018. During the study period, a total of 244 cases were enrolled. Of these, 103 cases were selected for induction using dinoprostone and 141 cases were selected for induction with SBC. The pregnancy outcomes between the two groups were compared. Primary outcomes were successful vaginal delivery rates. Secondary outcomes were maternal and neonatal adverse events. Multivariate logistic regression was used to assess the risk factors for vaginal delivery failure in the two groups.
RESULTS
The successful vaginal delivery rates were similar between the dinoprostone group and the SBC group (64.1% [66/103] vs. 59.6%, [84/141] P = 0.475), even after adjustment for potential confounding factors (adjusted odds ratio [aOR]: 1.07, 95% confidence interval [CI]: 0.57-2.00, P = 0.835). The incidence of intra-amniotic infection was lower in the dinoprostone group than in the SBC group (1.9% [2/103] vs. 7.8%, [11/141] P < 0.001), but the presence of non-reassuring fetal heart rate was higher in the dinoprostone group than in the SBC group (12.6% [13/103] vs. 0.7%, [1/141] P < 0.001). Multivariate logistic regression showed that nuchal cord was a risk factor for vaginal delivery failure after induction with dinoprostone (aOR: 6.71, 95% CI: 1.96-22.95). There were three factors related to vaginal delivery failure after induction with SBC, namely gestational age (aOR: 1.51, 95% CI: 1.07-2.14), body mass index (BMI) >30 kg/m2 (aOR: 2.98, 95% CI: 1.10-8.02), and fetal weight >3500 g (aOR: 2.49, 95% CI: 1.12-5.50).
CONCLUSIONS
Term nulliparous women with borderline oligohydramnios have similar successful vaginal delivery rates after induction with dinoprostone or SBC, with their advantages and disadvantages. In women with nuchal cord, the risk of vaginal delivery failure is increased if dinoprostone is used in the induction of labor. BMI >30 kg/m2, large gestational age, and estimated fetal weight >3500 g are risk factors for vaginal delivery failure after induction with SBC.
Topics: Administration, Intravaginal; Catheters; Dinoprostone; Female; Fetal Weight; Humans; Infant, Newborn; Labor, Induced; Nuchal Cord; Oligohydramnios; Oxytocics; Pregnancy; Pregnancy Outcome; Retrospective Studies
PubMed: 34935691
DOI: 10.1097/CM9.0000000000001881 -
American Journal of Obstetrics &... Jul 2022Induction of labor is a commonly performed obstetrical intervention. Vaginal prostaglandin E2 (dinoprostone) is a first-choice agent. Mechanical methods of induction are... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Induction of labor is a commonly performed obstetrical intervention. Vaginal prostaglandin E2 (dinoprostone) is a first-choice agent. Mechanical methods of induction are slower in achieving cervical ripening but have a lower risk of adverse effects.
OBJECTIVE
This study aimed to compare the efficacy, maternal and neonatal safety, and maternal satisfaction of a synthetic osmotic cervical dilator (Dilapan-S) with those of dinoprostone.
STUDY DESIGN
This was an open-label superiority randomized controlled trial in 4 English hospitals. Eligible participants were women ≥16 years of age undergoing induction of labor for a singleton pregnancy at ≥37 weeks' gestation with vertex presentation and intact membranes. The women were randomly assigned to receive either Dilapan-S or dinoprostone using a telephone randomization system minimized by hospital, parity, body mass index, and maternal age. The induction agent was replaced as required until the cervix was assessed as favorable for labor by the Bishop score. The primary outcome was failure to achieve vaginal delivery (ieor a cesarean delivery being performed). The secondary outcome measures included maternal and neonatal adverse events. Analysis was by intention-to-treat, adjusting for design variables where possible.
RESULTS
Between December 19, 2017 and January 26, 2021, 674 women were randomized (337 to Dilapan-S, and 337 to dinoprostone). The trial did not reach its planned sample size of 860 participants because of restrictions on research during the COVID-19 pandemic. The primary outcome was missing for 2 women in the dinoprostone group. Failure to achieve vaginal delivery (or a cesarean delivery being performed) occurred in 126 women (37.4%) allocated to Dilapan-S and in 115 (34.3%) women allocated to dinoprostone (adjusted risk difference, 0.02; 95% confidence interval, -0.05 to 0.10). There were similar maternal and neonatal adverse events between the groups.
CONCLUSION
Women undergoing induction of labor with Dilapan-S have similar rates of cesarean delivery and maternal and neonatal adverse events compared with dinoprostone.
Topics: COVID-19; Cervix Uteri; Dinoprostone; Female; Humans; Infant; Infant, Newborn; Labor, Induced; Male; Oxytocics; Pandemics; Pregnancy
PubMed: 35358740
DOI: 10.1016/j.ajogmf.2022.100628 -
Scientific Reports Sep 2022The modalities of induction of labor in the event of premature rupture of membranes are controversial. The main purpose of this study was to compare the modalities of...
The modalities of induction of labor in the event of premature rupture of membranes are controversial. The main purpose of this study was to compare the modalities of delivery after the use of dinoprostone or misoprostol for labor induction in the preterm rupture of membranes after 35 weeks in women with an unfavorable cervix. We then studied maternal and fetal morbidity for the two drugs. Retrospective, single-center, comparative cohort study in a level 3 maternity unit in France from 2009 to 2018 comparing vaginal administration of misoprostol 50 µg every six hours (maximum 150 µg) and administration of dinoprostone 10 mg, a slow-release vaginal insert, for 24 h (maximum 20 mg), for labor induction in the preterm rupture of membranes after 35 weeks in women with an unfavorable cervix (Bishop score < 6). We included 904 patients, 656 in the misoprostol group and 248 in the dinoprostone group. Vaginal delivery rate was significantly higher in the dinoprostone group (89% vs. 82%, p = 0.016). There were more cesarean sections for abnormal fetal heart rate in the misoprostol group (p = 0.005). The time interval from induction to the beginning of the active phase of labor and the duration of labor were shorter in the misoprostol group than in the dinoprostone group (437 min vs. 719 min, p < 0.001 and 335 min vs. 381 min, p = 0.0023, respectively). Maternal and neonatal outcomes were not significantly different in the two groups. Vaginal dinoprostone used for labor induction in preterm rupture of membranes seems to be more effective for vaginal delivery than vaginal misoprostol (50 µg).
Topics: Administration, Intravaginal; Cohort Studies; Dinoprostone; Female; Humans; Infant, Newborn; Labor, Induced; Misoprostol; Oxytocics; Pregnancy; Pregnancy Outcome; Retrospective Studies
PubMed: 36056056
DOI: 10.1038/s41598-022-18948-5 -
Molecules (Basel, Switzerland) Jan 2022The formation of prostaglandin E2 (PGE2) is associated with adverse inflammatory effects. However, long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs)...
The formation of prostaglandin E2 (PGE2) is associated with adverse inflammatory effects. However, long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) comes with risk of severe side effects. Therefore, alternative ways to inhibit PGE2 are warranted. We have investigated the effects of tea extracts and the polyphenols epigallocatechin gallate (EGCG) and quercetin on PGE2 formation, determined by immunoassay, and protein expression, determined by immunoblotting, of cytosolic phospholipase A2 (cPLA2), cyclooxygenase 2 (COX-2) and microsomal PGE synthase-1 (mPGES-1) in human monocytes. Green and black tea extracts, and with a lower potency, Rooibos tea extract, inhibited lipopolysaccharide (LPS) and calcium ionophore-induced PGE2 formation. In addition, all tea extracts inhibited the LPS-induced expression of mPGES-1, and the green and black tea extracts also inhibited, to a lesser extent, COX-2 expression. The tea extracts only marginally reduced cPLA2 expression and had no effect on COX-1 expression. EGCG, present in green and black tea, and quercetin, present in all three teas, also inhibited PGE2 formation and expression of mPGES-1, COX-2 and cPLA2. Cell-based and cell-free assays were also performed to evaluate direct effects on the enzymatic activity of COX and PGE synthases. Mainly, the cell-free assay demonstrated partial inhibition by the tea extracts and polyphenols. However, the inhibition required higher doses compared to the effects demonstrated on protein expression. In conclusion, green and black tea, and to a lesser extent Rooibos tea, are potent inhibitors of PGE2 formation in human monocytes, and mediate their effects by inhibiting the expression of the enzymes responsible for PGE2 formation, especially mPGES-1.
Topics: Dinoprostone
PubMed: 35056712
DOI: 10.3390/molecules27020397 -
American Journal of Perinatology Aug 2021The aim of study is to compare, in a pilot study, combined dinoprostone vaginal insert and Foley catheter (DVI + Foley) with Foley alone (Foley) for cervical... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
The aim of study is to compare, in a pilot study, combined dinoprostone vaginal insert and Foley catheter (DVI + Foley) with Foley alone (Foley) for cervical ripening and labor induction at term.
STUDY DESIGN
In this open-label pilot randomized controlled trial, women not in labor, with intact membranes, no prior uterine incision, an unfavorable cervix, gestational age ≥37 weeks, and a live, nonanomalous singleton fetus in cephalic presentation were randomly assigned, stratified by parity, to DVI + Foley or Foley. Oxytocin was used in both groups after cervical ripening. Primary outcome was time to vaginal delivery.
RESULTS
From April 2017 to January 2018, 100 women were randomized. Median (25-75th percentile) time to vaginal delivery for nulliparous women was 21.2 (16.6-38.0) hours with DVI + Foley ( = 26) compared with 31.3 (23.3-46.9) hours with Foley ( = 24) (Wilcoxon = 0.05). Median time to vaginal delivery for parous women was 17.1 (13.6-21.9) hours with DVI + Foley ( = 25) compared with 14.8 (12.7-19.5) hours with Foley ( = 25) (Wilcoxon = 0.21). Results were also analyzed to consider the competing risk of cesarean using cumulative incidence functions.
CONCLUSION
Compared with Foley alone, combined use of the dinoprostone vaginal insert and Foley for cervical ripening may shorten time to vaginal delivery for nulliparous but not parous women.
Topics: Female; Humans; Pregnancy; Administration, Intravaginal; Catheters; Cervical Ripening; Delayed-Action Preparations; Dinoprostone; Kaplan-Meier Estimate; Labor, Induced; Oxytocics; Oxytocin; Parity; Pilot Projects; Time Factors; Urinary Catheterization
PubMed: 32120419
DOI: 10.1055/s-0040-1705113