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Drugs Oct 2018Dinoprostone vaginal insert (Cervidil; Propess), a retrievable vaginal pessary containing 10 mg of dinoprostone [prostaglandin E (PGE)] in a controlled-release drug... (Review)
Review
Dinoprostone vaginal insert (Cervidil; Propess), a retrievable vaginal pessary containing 10 mg of dinoprostone [prostaglandin E (PGE)] in a controlled-release drug delivery device, is approved in many countries worldwide for the initiation (or continuation) of cervical ripening in patients at term prior to labour induction. The device is designed to provide a constant and sustained release of dinoprostone to the cervix to promote the complex processes involved in cervical ripening. The vaginal insert is attached to a retrieval system that facilitates easy removal of the device at the onset of labour or in the event of complications. The effectiveness of dinoprostone vaginal insert has been demonstrated in a vast range of randomized clinical trials in women at term. The agent is well tolerated, with a generally favourable safety profile, both maternal and foetal/neonatal. As with all prostaglandin agents used in cervical ripening, dinoprostone vaginal insert is associated with a risk of uterine hyperstimulation. However, this is generally rapidly reversible upon removal of the insert. The demonstrated effectiveness and safety of the device, combined with the benefits of controlled drug release from a simple, single application, and efficient dose control, suggest that dinoprostone vaginal insert is a valuable option for promoting cervical ripening in patients with an unfavourable cervix at term.
Topics: Cervical Ripening; Dinoprostone; Dose-Response Relationship, Drug; Drug Delivery Systems; Drug Liberation; Female; Humans; Pregnancy; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 30317521
DOI: 10.1007/s40265-018-0995-2 -
Theranostics 2021Tissue regeneration following injury from disease or medical treatment still represents a challenge in regeneration medicine. Prostaglandin E2 (PGE2), which involves... (Review)
Review
Tissue regeneration following injury from disease or medical treatment still represents a challenge in regeneration medicine. Prostaglandin E2 (PGE2), which involves diverse physiological processes via E-type prostanoid (EP) receptor family, favors the regeneration of various organ systems following injury for its capabilities such as activation of endogenous stem cells, immune regulation, and angiogenesis. Understanding how PGE2 modulates tissue regeneration and then exploring how to elevate the regenerative efficiency of PGE2 will provide key insights into the tissue repair and regeneration processes by PGE2. In this review, we summarized the application of PGE2 to guide the regeneration of different tissues, including skin, heart, liver, kidney, intestine, bone, skeletal muscle, and hematopoietic stem cell regeneration. Moreover, we introduced PGE2-based therapeutic strategies to accelerate the recovery of impaired tissue or organs, including 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitors boosting endogenous PGE2 levels and biomaterial scaffolds to control PGE2 release.
Topics: Animals; Dinoprostone; Humans; Regeneration; Signal Transduction; Wound Healing
PubMed: 34522214
DOI: 10.7150/thno.63396 -
African Journal of Reproductive Health Apr 2023Induction of labor (IOL) is the stimulation of the uterus during pregnancy to begin the onset of labour. Nearly two of five pregnancies require IOL. We compared the... (Meta-Analysis)
Meta-Analysis Review
Induction of labor (IOL) is the stimulation of the uterus during pregnancy to begin the onset of labour. Nearly two of five pregnancies require IOL. We compared the effectiveness of double-balloon catheter (DBC) with dinoprostone (PGE-2) insert for labour induction from previous studies. We included randomized controlled trials (RCTs) that compared the safety and efficacy of DBC to PGE-2. To evaluate the studies, we utilized the Cochrane tool for risk of bias assessment. The rates of vaginal birth and cesarean section were the primary outcomes. We included ten RCTs in this meta-analysis with a total sample of 2493 singleton pregnancies. After 24 hours, there was no significant difference in the delivery rates between DBC and PGE-2 s [R.R=1.08, 95% CI, (0.77, 1.52), P.value=0.65], and the rate of cesarean delivery [R.R=1.03, 95% CI, (0.90; 1.18), P.value=0.65]. The DBC showed a significantly higher oxytocin use rate compared to the PGE-2 group [R.R=1.77, 95% CI, (1.41; 2.32), P.value<0.0001]. In the PGE-2 group, there was a significantly higher risk of uterine hyperstimulation, tachysystole, and umbilical artery PH levels below 7. There was no significant difference in the efficacy between the PGE-2 and DBC in terms of delivery rate in 24 hours and the rate of cesarean delivery except for a slight BISHOP score improvement with DBC. However, DBC showed a higher rate of oxytocin use compared to the PGE-2, the DBC seems to be safer with a lower risk of umbilical artery PH < 7, uterine hyperstimulation, and tachysystole incidence than PGE-2.
Topics: Pregnancy; Female; Humans; Dinoprostone; Oxytocics; Oxytocin; Labor, Induced; Catheters
PubMed: 37584912
DOI: 10.29063/ajrh2023/v27i4.10 -
Clinical Immunology (Orlando, Fla.) Jun 2006Prostaglandin E2 (PGE2) is a principal mediator of inflammation in diseases such as rheumatoid arthritis and osteoarthritis. Nonsteroidal anti-inflammatory medications... (Review)
Review
Prostaglandin E2 (PGE2) is a principal mediator of inflammation in diseases such as rheumatoid arthritis and osteoarthritis. Nonsteroidal anti-inflammatory medications (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors reduce PGE2 production to diminish the inflammation seen in these diseases, but have toxicities that may include both gastrointestinal bleeding and prothrombotic tendencies. In cells, arachidonic acid is transformed into PGE2 via cyclooxygenase (COX) enzymes and terminal prostaglandin E synthases (PGES). Accumulating data suggest that the interaction of various enzymes in the PGE2 synthetic pathway is complex and tightly regulated. In this review, we summarize the synthesis and secretion of PGE2. In particular, we focus on the three isoforms of the terminal PGES, and discuss the potential of targeting PGES as a more precise strategy for inhibiting PGE2 production.
Topics: Animals; Dinoprostone; Humans; Intramolecular Oxidoreductases; Phospholipases A; Prostaglandin-E Synthases; Prostaglandin-Endoperoxide Synthases
PubMed: 16540375
DOI: 10.1016/j.clim.2006.01.016 -
Medical Archives (Sarajevo, Bosnia and... Feb 2022Induction of labor (IOL) is a technique to establish vaginal delivery when the risks for continuing the pregnancy for mother or baby are higher than the risks of...
BACKGROUND
Induction of labor (IOL) is a technique to establish vaginal delivery when the risks for continuing the pregnancy for mother or baby are higher than the risks of delivery. It is usually performed in high-risk pregnancies, but can also be beneficial in low-risk populations, as shown in the ARRIVE trial.
OBJECTIVE
To evaluate the effectiveness and safety of slow-release vaginal dinoprostone (prostaglandin E2 10 mg) for labor induction in women with low-risk pregnancies.
METHODS
A prospective study was performed at Hanoi Obstetrics and Gynecology Hospital, Vietnam. We recruited women with low-risk pregnancies from 39 weeks + 0 days to 40 weeks + 6 days of gestation and an unfavorable cervix. Women who participated received 10 mg intravaginal slow-release dinoprostone (Propess) for induction of labor. Labor, deliveries, and post-partum management were performed according to the local protocol.
RESULTS
From September 2020 to March 2021, 102 low-risk women were eligible to participate in the study. Among these women, 67.6% had vaginal deliveries, 6.9% had postpartum bleeding, and 3.9% experienced tachysystole. All newborns were healthy, with good APGAR scores. None of the women needed respiratory support or intensive care unit admission. All other maternal or fetal complications were explored. The rate of cesarean section was 3.8 higher in nulliparous than multiparous women and 2.2 times higher in women who did not receive epidural analgesia than in those who did. The risk of cesarean section increased if the time between labor induction and active labor was greater than 12.5 hours.
CONCLUSION
Slow-release dinoprostone insert is safe and effective for the induction of labor in low-risk pregnant women. The risk of cesarean section was elevated in nulliparous patients and those who did not receive epidural analgesia during labor. As the time from labor induction to active labor increased, the risk of cesarean section increased.
Topics: Cesarean Section; Dinoprostone; Female; Humans; Infant, Newborn; Labor, Induced; Oxytocics; Pregnancy; Prospective Studies
PubMed: 35422562
DOI: 10.5455/medarh.2022.76.39-44 -
The Journal of Obstetrics and... Jul 2023The study purposed to evaluate the success rate of cervical ripening using dinoprostone controlled-release vaginal insert and reveal some factors relating to successful...
AIMS
The study purposed to evaluate the success rate of cervical ripening using dinoprostone controlled-release vaginal insert and reveal some factors relating to successful cervical ripening.
METHODS
This cross-sectional study was conducted at Tu Du Hospital in Vietnam from December 2021 to August 2022. The study enrolled 200 pregnant women with gestational age ≥37 weeks diagnosed with oligohydramnios. These candidates underwent dinoprostone cervical ripening (DCR) according to the local protocol. The Bishop score ≥7 after 24 h was determined for the successful cervical ripening (SCR).
RESULTS
In total, the success rate of DCR achieved at 57.5% and the cesarean delivery rate was 46.5%. None of the severe side-effects and complications was present. Using multivariable logistic regression, the study found that the body mass index ≥25 kg/m and oxytocin infusion drip related to SCR with adjusted odds ratio (aOR): 3.67 (95% confidence intervals [CI]: 1.78-7.57) and aOR: 4.68 (95% CI: 1.84-11.93), p < 0.001. Using the Kaplan-Meier curve, the present study revealed a significant difference between Bishop <3 and ≥3 following the duration time of cervical ripening, with hazard ratio: 1.38 (95% CI: 1.19-1.59), p < 0.001. The time duration of cervical ripening was not significantly different following amniotic fluid index from 3 to 5 cm.
CONCLUSIONS
Cervical ripening using a dinoprostone vaginal insert is a potentially acceptable method in term pregnancy accompanying with oligohydramnios. The probability of SCR can be predicted on a careful assessment of relative factors by obstetricians. Further studies are required to strengthen these findings.
Topics: Female; Humans; Infant; Pregnancy; Administration, Intravaginal; Cervical Ripening; Cross-Sectional Studies; Dinoprostone; Labor, Induced; Oligohydramnios; Oxytocics; Delayed-Action Preparations
PubMed: 37245054
DOI: 10.1111/jog.15665 -
Cellular and Molecular Life Sciences :... May 2022The pathogenesis of liver fibrosis in nonalcoholic fatty liver disease (NAFLD) remains unclear and the effective treatments have not been explored yet. The activation of...
The pathogenesis of liver fibrosis in nonalcoholic fatty liver disease (NAFLD) remains unclear and the effective treatments have not been explored yet. The activation of hepatic stellate cells (HSCs) is considered as the most critical factor in the progression of liver fibrosis and cirrhosis. Autophagy has recently been identified as a new mechanism to regulate HSC activation. Here, we found that liver macrophages were polarized toward type 2 (M2) during the progression of nonalcoholic steatohepatitis (NASH) and liver fibrosis in both patients and NAFLD mice. Using the methionine-choline-deficient (MCD) diet NAFLD murine model and the in vitro cell culture system, we identified that the M2 macrophages promoted HSC autophagy by secreting prostaglandin E2 (PGE2) and binding its receptor EP4 on the surface of HSCs, which consequently enhanced HSC activation, extracellular matrix deposition, and liver fibrosis. Mechanistically, PGE2/EP4 signals enhanced HSC autophagy through the Erk pathway. A specific PGE2/EP4 antagonist E7046 significantly inhibited M2 macrophage-mediated HSC autophagy and improved liver fibrosis and histopathology in NAFLD mice. Our study provides novel mechanistic insights into the regulation of HSC activation and liver fibrosis. Our findings suggest that the PGE2/EP4 pathway is a promising therapeutic target to prevent NASH progression into cirrhosis.
Topics: Animals; Autophagy; Benzoates; Dinoprostone; Fibrosis; Hepatic Stellate Cells; Humans; Liver; Liver Cirrhosis; Macrophages; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Pyrazoles
PubMed: 35588334
DOI: 10.1007/s00018-022-04319-w -
Archives of Gynecology and Obstetrics Jun 2020Nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (COXibs) inhibit the progression of endometrial cancer, ovarian cancer and cervical cancer.... (Review)
Review
PURPOSE
Nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (COXibs) inhibit the progression of endometrial cancer, ovarian cancer and cervical cancer. However, concerning the adverse effects of NSAIDs and COXibs, it is still urgent and necessary to explore novel and specific anti-inflammation targets for potential chemoprevention. The signaling of cyclooxygenase 2-prostaglandin E-prostaglandin E receptors (COX-2-PGE-EPs) is the central inflammatory pathway involved in the gynecological carcinogenesis.
METHODS
Literature searches were performed to the function of COX-2-PGE-EPs in gynecological malignancies.
RESULTS
This review provides an overview of the current knowledge of COX-2-PGE-EPs signaling in endometrial cancer, ovarian cancer and cervical cancer. Many studies demonstrated the upregulated expression of the whole signaling pathway in gynecological malignancies and some focused on the function of COX-2 and cAMP-linked EP2/EP4 and EP3 signaling pathway in gynecological cancer. By contrast, roles of EP1 and the exact pathological mechanisms have not been completely clarified. The studies concerning EP receptors in gynecological cancers highlight the potential advantage of combining COX enzyme inhibitors with EP receptor antagonists as therapeutic agents in gynecological cancers.
CONCLUSION
EPs represent promising anti-inflammation biomarkers for gynecological cancer and may be novel treatment targets in the near future.
Topics: Cyclooxygenase 2; Dinoprostone; Female; Genital Neoplasms, Female; Humans
PubMed: 32363546
DOI: 10.1007/s00404-020-05559-6 -
Obstetrics and Gynecology May 2001To compare dinoprostone 10 mg controlled-release vaginal insert with other forms of vaginal or cervical prostaglandin for cervical ripening. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare dinoprostone 10 mg controlled-release vaginal insert with other forms of vaginal or cervical prostaglandin for cervical ripening.
DATA SOURCES
Literature search strategy included review of the Cochrane database of randomized trials, on-line searching of MEDLINE, hand searching of bibliographies, and contact with authors of relevant reports.
METHODS OF STUDY SELECTION
Randomized trials were included if they compared a dinoprostone slow-release vaginal insert with an alternative vaginal or cervical prostaglandin for cervical ripening and labor induction in women at term with singleton gestations. Primary end points were delivery by 24 hours postinsertion, uterine hypertonus with fetal heart change, and cesarean delivery rate. Study inclusion, validity assessment, and data extraction were carried out independently by two reviewers, and cross-checked for consistency. Data were combined when appropriate, using the Mantel-Haenszel fixed-effects method. Statistical heterogeneity was assessed using chi-square statistics.
TABULATION, INTEGRATION, AND RESULTS
Nine relevant trials were identified, seven comparing the dinoprostone 10 mg vaginal insert with dinoprostone gel and two with misoprostol. Five trials reported adequate methods for randomization concealment. None were double blind. The likelihood of delivery by 24 hours was similar with the vaginal insert and alternatives: common odds ratio (OR) 0.80 (95% confidence interval [CI] 0.56, 1.15). Uterine hypertonus with change in fetal heart and cesarean delivery rate were also similar: common OR 1.19 (95% CI 0.56, 2.54) and 0.78 (95% CI 0.56, 1.08), respectively. The secondary end points of mean time to delivery and delivery by 12 hours appeared to favor misoprostol-dinoprostone gel. However, data for these end points were heterogeneous and their combination is therefore of limited value and potentially misleading.
CONCLUSION
No clinically significant differences were identified between the vaginal insert and alternatives used for cervical ripening at term.
Topics: Administration, Intravaginal; Cervical Ripening; Dinoprostone; Female; Humans; Pregnancy; Prostaglandins; Randomized Controlled Trials as Topic
PubMed: 11336776
DOI: 10.1016/s0029-7844(00)01216-3 -
Journal of Medicinal Chemistry Jul 2023Cyclooxygenase-1 and -2 (COX1 and COX2) derived endogenous ligand prostaglandin-E (PGE) triggers several physiological and pathological conditions. It mediates signaling... (Review)
Review
Cyclooxygenase-1 and -2 (COX1 and COX2) derived endogenous ligand prostaglandin-E (PGE) triggers several physiological and pathological conditions. It mediates signaling through four G-protein coupled receptors, EP1, EP2, EP3, and EP4. Among these, EP2 is expressed throughout the body including the brain and uterus. The functional role of EP2 has been extensively studied using EP2 gene knockout mice, cellular models, and selective small molecule agonists and antagonists for this receptor. The efficacy data from in vitro and in vivo animal models indicate that EP2 receptor is a major proinflammatory mediator with deleterious functions in a variety of diseases suggesting a path forward for EP2 inhibitors as the next generation of selective anti-inflammatory and antiproliferative agents. Interestingly in certain diseases, EP2 action is beneficial; therefore, EP2 agonists seem to be clinically useful. Here, we highlight the strengths, weaknesses, opportunities, and potential threats (SWOT analysis) for targeting EP2 receptor for therapeutic development for a variety of unmet clinical needs.
Topics: Animals; Mice; Receptors, Prostaglandin E; Dinoprostone; Cyclooxygenase 2; Drug Discovery; Receptors, Prostaglandin E, EP2 Subtype; Receptors, Prostaglandin E, EP4 Subtype
PubMed: 37458373
DOI: 10.1021/acs.jmedchem.3c00655