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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 -
International Journal of Biological... 2023Prostaglandins are lipid mediators involved in physiological processes, such as constriction or dilation of blood vessels, but also pathophysiological processes, which... (Review)
Review
Prostaglandins are lipid mediators involved in physiological processes, such as constriction or dilation of blood vessels, but also pathophysiological processes, which include inflammation, pain and fever. They are produced by almost all cell types in the organism by activation of Prostaglandin endoperoxide synthases/Cyclooxygenases. The inducible Prostaglandin Endoperoxide Synthase 2/Cyclooxygenase 2 (PTGS2/COX2) plays an important role in pathologies associated with inflammatory signaling. The main product derived from expression and activation is Prostaglandin E (PGE), which promotes a wide variety of tissue-specific effects, pending environmental inputs. One of the major sources of PGE are infiltrating inflammatory cells - the production of this molecule increases drastically in damaged tissues. Immune infiltration is a hallmark of type 1 diabetes mellitus, a multifactorial disease that leads to autoimmune-mediated pancreatic beta cell destruction. Controversial effects for the -PGE signaling cascade in pancreatic islet cells subjected to diabetogenic conditions have been reported, allocating PGE as both, cause and consequence of inflammation. Herein, we review the main effects of this molecular pathway in a tissue-specific manner, with a special emphasis on beta cell mass protection/destruction and its potential role in the prevention or development of T1DM. We also discuss strategies to target this pathway for future therapies.
Topics: Humans; Dinoprostone; Cyclooxygenase 2; Diabetes Mellitus, Type 1; Signal Transduction; Inflammation
PubMed: 37705740
DOI: 10.7150/ijbs.86492 -
PloS One 2022Emerging evidence implicates the eicosanoid molecule prostaglandin E2 (PGE2) in conferring a regenerative phenotype to multiple organ systems following tissue injury. As...
Emerging evidence implicates the eicosanoid molecule prostaglandin E2 (PGE2) in conferring a regenerative phenotype to multiple organ systems following tissue injury. As aging is in part characterized by loss of tissue stem cells' regenerative capacity, we tested the hypothesis that the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) contributes to the diminished organ fitness of aged mice. Here we demonstrate that genetic loss of 15-PGDH (Hpgd) confers a protective effect on aging of murine hematopoietic and gastrointestinal (GI) tissues. Aged mice lacking 15-PGDH display increased hematopoietic output as assessed by peripheral blood cell counts, bone marrow and splenic stem cell compartments, and accelerated post-transplantation recovery compared to their WT counterparts. Loss of Hpgd expression also resulted in enhanced GI fitness and reduced local inflammation in response to colitis. Together these results suggest that 15-PGDH negatively regulates aged tissue regeneration, and that 15-PGDH inhibition may be a viable therapeutic strategy to ameliorate age-associated loss of organ fitness.
Topics: Aging; Animals; Dinoprostone; Hydroxyprostaglandin Dehydrogenases; Mice
PubMed: 35587945
DOI: 10.1371/journal.pone.0268787 -
American Journal of Physiology.... Mar 2021Prostaglandins are critical lipid mediators involved in the wound healing response, with prostaglandin E (PGE) being the most complex and exhibiting the most diverse... (Review)
Review
Prostaglandins are critical lipid mediators involved in the wound healing response, with prostaglandin E (PGE) being the most complex and exhibiting the most diverse physiological outputs. PGE signals via four G protein-coupled receptors, termed EP-receptors 1-4 that induce distinct signaling pathways upon activation and lead to an array of different outputs. Recent studies examining the role of PGE and EP receptor signaling in wound healing following various forms of tissue damage are discussed in this review.
Topics: Dinoprostone; Humans; Male; Receptors, Prostaglandin E; Signal Transduction; Wound Healing
PubMed: 33296281
DOI: 10.1152/ajpregu.00185.2020 -
Pharmacological Reviews Oct 2020Prostaglandins are derived from arachidonic acid metabolism through cyclooxygenase activities. Among prostaglandins (PGs), prostacyclin (PGI) and PGE are strongly...
International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin E Receptors (EP1-4) and Prostacyclin Receptor (IP): Specific Roles in Pathophysiologic Conditions.
Prostaglandins are derived from arachidonic acid metabolism through cyclooxygenase activities. Among prostaglandins (PGs), prostacyclin (PGI) and PGE are strongly involved in the regulation of homeostasis and main physiologic functions. In addition, the synthesis of these two prostaglandins is significantly increased during inflammation. PGI and PGE exert their biologic actions by binding to their respective receptors, namely prostacyclin receptor (IP) and prostaglandin E receptor (EP) 1-4, which belong to the family of G-protein-coupled receptors. IP and EP1-4 receptors are widely distributed in the body and thus play various physiologic and pathophysiologic roles. In this review, we discuss the recent advances in studies using pharmacological approaches, genetically modified animals, and genome-wide association studies regarding the roles of IP and EP1-4 receptors in the immune, cardiovascular, nervous, gastrointestinal, respiratory, genitourinary, and musculoskeletal systems. In particular, we highlight similarities and differences between human and rodents in terms of the specific roles of IP and EP1-4 receptors and their downstream signaling pathways, functions, and activities for each biologic system. We also highlight the potential novel therapeutic benefit of targeting IP and EP1-4 receptors in several diseases based on the scientific advances, animal models, and human studies. SIGNIFICANCE STATEMENT: In this review, we present an update of the pathophysiologic role of the prostacyclin receptor, prostaglandin E receptor (EP) 1, EP2, EP3, and EP4 receptors when activated by the two main prostaglandins, namely prostacyclin and prostaglandin E, produced during inflammatory conditions in human and rodents. In addition, this comparison of the published results in each tissue and/or pathology should facilitate the choice of the most appropriate model for the future studies.
Topics: Animals; Autoimmune Diseases; Dinoprostone; Epoprostenol; Humans; Inflammation; Mice; Polymorphism, Single Nucleotide; Protein Multimerization; Rats; Receptors, Prostaglandin E; Species Specificity
PubMed: 32962984
DOI: 10.1124/pr.120.019331 -
Cancer Science Apr 2016Cyclooxygenase-2 (COX-2) and its downstream product prostaglandin E2 (PGE2 ) play a key role in generation of the inflammatory microenvironment in tumor tissues. Gastric... (Review)
Review
Cyclooxygenase-2 (COX-2) and its downstream product prostaglandin E2 (PGE2 ) play a key role in generation of the inflammatory microenvironment in tumor tissues. Gastric cancer is closely associated with Helicobacter pylori infection, which stimulates innate immune responses through Toll-like receptors (TLRs), inducing COX-2/PGE2 pathway through nuclear factor-κB activation. A pathway analysis of human gastric cancer shows that both the COX-2 pathway and Wnt/β-catenin signaling are significantly activated in tubular-type gastric cancer, and basal levels of these pathways are also increased in other types of gastric cancer. Expression of interleukin-11, chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL2, and CXCL5, which play tumor-promoting roles through a variety of mechanisms, is induced in a COX-2/PGE2 pathway-dependent manner in both human and mouse gastric tumors. Moreover, the COX-2/PGE2 pathway plays an important role in the maintenance of stemness with expression of stem cell markers, including CD44, Prom1, and Sox9, which are induced in both gastritis and gastric tumors through a COX-2/PGE2 -dependent mechanism. In contrast, disruption of Myd88 results in suppression of the inflammatory microenvironment in gastric tumors even when the COX-2/PGE2 pathway is activated, indicating that the interplay of the COX-2/PGE2 and TLR/MyD88 pathways is needed for inflammatory response in tumor tissues. Furthermore, TLR2/MyD88 signaling plays a role in maintenance of stemness in normal stem cells as well as gastric tumor cells. Accordingly, these results suggest that targeting the COX-2/PGE2 pathway together with TLR/MyD88 signaling, which would suppress the inflammatory microenvironment and maintenance of stemness, could be an effective preventive or therapeutic strategy for gastric cancer.
Topics: Animals; Cyclooxygenase 2; Dinoprostone; Humans; Inflammation; Mice; Myeloid Differentiation Factor 88; Neoplasm Proteins; Signal Transduction; Stomach Neoplasms; Toll-Like Receptor 2; Tumor Microenvironment
PubMed: 27079437
DOI: 10.1111/cas.12901 -
Prostaglandins & Other Lipid Mediators Jun 2022Inflammatory signaling pathways involving eicosanoids and other regulatory lipid mediators are a subject of intensive study, and a role for these in acute lung injury is...
Inflammatory signaling pathways involving eicosanoids and other regulatory lipid mediators are a subject of intensive study, and a role for these in acute lung injury is not yet well understood. We hypothesized that oxylipin release from lung injury could be detected in bronchoalveolar lavage fluid and in plasma. In a porcine model of surfactant depletion, ventilation with hyperinflation was assessed. Bronchoalveolar lavage and plasma samples were analyzed for 37 different fatty acid metabolites (oxylipins). Over time, hyperinflation altered concentrations of 4 oxylipins in plasma (TXB, PGE, 15-HETE and 11-HETE), and 9 oxylipins in bronchoalveolar lavage fluid (PGF, PGE, PGD, 12,13-DiHOME, 11,12-DiHETrE, 13-HODE, 9-HODE, 15-HETE, 11-HETE). Acute lung injury caused by high tidal volume ventilation in this porcine model was associated with rapid changes in some elements of the oxylipin profile, detectable in lavage fluid, and plasma. These oxylipins may be relevant in the pathogenesis of acute lung injury by hyperinflation.
Topics: Acute Lung Injury; Animals; Bronchoalveolar Lavage Fluid; Dinoprostone; Eicosanoids; Oxylipins; Swine
PubMed: 35307566
DOI: 10.1016/j.prostaglandins.2022.106636 -
Mediators of Inflammation 2017
Topics: Acute Lung Injury; Animals; Dinoprostone; Endothelium; Epithelium; Humans; Leukotriene B4; Peptides
PubMed: 28392632
DOI: 10.1155/2017/9081521 -
Scientific Reports Jun 2022Intestinal organoids are advanced cellular models, which are widely used in mammalian studies to mimic and study in vivo intestinal function and host-pathogen...
Intestinal organoids are advanced cellular models, which are widely used in mammalian studies to mimic and study in vivo intestinal function and host-pathogen interactions. Growth factors WNT3 and RSPO1 are crucial for the growth of intestinal organoids. Chicken intestinal organoids are currently cultured with mammalian Wnt3a and Rspo1, however, maintaining their longevity has shown to be challenging. Based on the limited homology between mammalian and avian RSPO1, we expect that chicken-derived factors are required for the organoid cultures. Isolated crypts from embryonic tissue of laying hens were growing in the presence of chicken WNT3 and RSPO1, whereas growth in the presence of mammalian Wnt3a and Rspo1 was limited. Moreover, the growth was increased by using Prostaglandin E2 (PGE) and a Forkhead box O1-inhibitor (FOXO1-inhibitor), allowing to culture these organoids for 15 passages. Furthermore, stem cells maintained their ability to differentiate into goblets, enterocytes and enteroendocrine cells in 2D structures. Overall, we show that chicken intestinal organoids can be cultured for multiple passages using chicken-derived WNT3 and RSPO1, PGE, and FOXO1-inhibitor.
Topics: Animals; Chickens; Dinoprostone; Female; Intestinal Mucosa; Intestines; Mammals; Organoids; Stem Cells
PubMed: 35732901
DOI: 10.1038/s41598-022-14875-7 -
Frontiers in Endocrinology 2022Prematurity is the leading cause of childhood death under the age of five. The aetiology of preterm birth is multifactorial; however, inflammation and infection are the...
BACKGROUND
Prematurity is the leading cause of childhood death under the age of five. The aetiology of preterm birth is multifactorial; however, inflammation and infection are the most common causal factors, supporting a potential role for immunomodulation as a therapeutic strategy. 15-Deoxy-Delta-12,14-prostaglandin J2 (15dPGJ2) is an anti-inflammatory prostaglandin and has been shown to delay lipopolysaccharide (LPS) induced preterm labour in mice and improve pup survival. This study explores the immunomodulatory effect of 15dPGJ2 on the transcription factors NF-κB and AP-1, pro-inflammatory cytokines, and contraction associated proteins in human cultured myocytes, vaginal epithelial cell line (VECs) and primary amnion epithelial cells (AECs).
METHODS
Cells were pre-incubated with 32µM of 15dPGJ2 and stimulated with 1ng/mL of IL-1β as an model of inflammation. Western immunoblotting was used to detect phosphorylated p-65 and phosphorylated c-Jun as markers of NF-κB and AP-1 activation, respectively. mRNA expression of the pro-inflammatory cytokines IL-6, IL-8, and TNF-α was examined, and protein expression of COX-2 and PGE2 were detected by western immunoblotting and ELISA respectively. Myometrial contractility was examined using a myograph.
RESULTS
15dPGJ2 inhibited IL-1β-induced activation of NF-κB and AP-1, and expression of IL-6, IL-8, TNF-α, COX-2 and PGE2 in myocytes, with no effect on myometrial contractility or cell viability. Despite inhibiting IL-1β-induced activation of NF-κB, expression of IL-6, TNF-α, and COX-2, 15dPGJ2 led to activation of AP-1, increased production of PGE2 and increased cell death in VECs and AECs.
CONCLUSION
We conclude that 15dPGJ2 has differential effects on inflammatory modulation depending on cell type and is therefore unlikely to be a useful therapeutic agent for the prevention of preterm birth.
Topics: Amnion; Animals; Anti-Inflammatory Agents; Cyclooxygenase 2; Cytokines; Dinoprostone; Epithelial Cells; Female; Humans; Infant, Newborn; Inflammation; Interleukin-6; Interleukin-8; Lipopolysaccharides; Mice; Muscle Cells; NF-kappa B; Premature Birth; Prostaglandin D2; RNA, Messenger; Transcription Factor AP-1; Tumor Necrosis Factor-alpha
PubMed: 36213265
DOI: 10.3389/fendo.2022.983924