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Brazilian Journal of Medical and... Dec 2005Acute rejection of a transplanted organ is characterized by intense inflammation within the graft. Yet, for many years transplant researchers have overlooked the role of... (Review)
Review
Acute rejection of a transplanted organ is characterized by intense inflammation within the graft. Yet, for many years transplant researchers have overlooked the role of classic mediators of inflammation such as prostaglandins and thromboxane (prostanoids) in alloimmune responses. It has been demonstrated that local production of prostanoids within the allograft is increased during an episode of acute rejection and that these molecules are able to interfere with graft function by modulating vascular tone, capillary permeability, and platelet aggregation. Experimental data also suggest that prostanoids may participate in alloimmune responses by directly modulating T lymphocyte and antigen-presenting cell function. In the present paper, we provide a brief overview of the alloimmune response, of prostanoid biology, and discuss the available evidence for the role of prostaglandin E2 and thromboxane A2 in graft rejection.
Topics: Acute Disease; Dinoprostone; Graft Rejection; Humans; Inflammation; Inflammation Mediators; Prostaglandins; Thromboxane A2
PubMed: 16302090
DOI: 10.1590/s0100-879x2005001200004 -
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 -
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 -
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 -
Cancer Immunology, Immunotherapy : CII Sep 1993The activity of cell-mediated defense systems is stimulated by consecutive formation of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2) and interferon gamma (IFN... (Review)
Review
The activity of cell-mediated defense systems is stimulated by consecutive formation of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2) and interferon gamma (IFN gamma). The system is inhibited by interleukin-4 (IL-4) and also by prostaglandin E2 (PGE2) and histamine, which are released when the immune system is activated. The inhibition is strong in cancer patients, because PGE2 is formed in many cancer cells and its formation is stimulated by IL-1 beta. The release of histamine is also stimulated by IL-1 beta. Thus PGE2 and histamine are feedback inhibitors of cell-mediated immunity. This inhibition can be abolished by inhibitors of the cyclo-oxygenase (e.g. indomethacin) and H-2 receptor antagonists (e.g. cimetidine). This may offer a new option to stimulate the immune system to kill cancer cells.
Topics: Dinoprostone; Histamine; Histamine H2 Antagonists; Humans; Immunotherapy; Neoplasms
PubMed: 8102321
DOI: 10.1007/BF01518519 -
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 -
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 -
Environmental Science and Pollution... Jun 2022Schistosomiasis, also known as snail fever or bilharziasis, is a worm infection caused by trematode called schistosomes that affects humans and animals worldwide.... (Review)
Review
Schistosomiasis, also known as snail fever or bilharziasis, is a worm infection caused by trematode called schistosomes that affects humans and animals worldwide. Schistosomiasis endemically exists in developing countries. Inflammatory responses elicited in the early phase of infection represent the rate limiting step for parasite migration and pathogenesis and could be a valuable target for therapeutic interventions. Prostaglandin E2 (PGE2) and interleukin (IL)-10 were found to be differentially affected in case of immune-modulation studies and cytokine analysis of hosts infected with either normal or radiation-attenuated parasite (RA) which switches off the development of an effective immune response against the migrating parasite in the early phase of schistosomiasis. Normal parasites induce predominantly a T helper 2 (Th2)-type cytokine response (IL-4 and IL-5) which is essential for parasite survival; here, we discuss in detail the downstream effects and cascades of inflammatory signaling of PGE2 and IL10 induced by normal parasites and the effect of blocking PGE2 receptors. We suggest that by selectively constraining the production of PGE2 during vaccination or therapy of susceptible persons or infected patients of schistosomiasis, this would boost IL-12 and reduce IL-10 production leading to a polarization toward the anti-worm Thl cytokine synthesis (IL-2 and Interferon (IFN)-γ).
Topics: Animals; Cytokines; Dinoprostone; Humans; Immunity; Interferon-gamma; Larva; Schistosomiasis
PubMed: 35396684
DOI: 10.1007/s11356-022-20108-1 -
Journal of Physiology and Pharmacology... Feb 2014Endogenous prostaglandins (PGs) play a role in modulating mucosal integrity and have various functions in the stomach, with E type PGs being the most effective. PGE₂... (Review)
Review
Endogenous prostaglandins (PGs) play a role in modulating mucosal integrity and have various functions in the stomach, with E type PGs being the most effective. PGE₂ provides gastric cytoprotection against damage induced in rats by HCl/ethanol, indomethacin, or acid back-diffusion after barrier disruption. These effects were mimicked by EP1 agonists and/or attenuated by an EP1 antagonist, and disappeared in EP1 (-/-) mice. Furthermore, the adaptive cytoprotection induced by a mild irritant was attenuated by the EP1 antagonist and indomethacin. Capsaicin also provides gastric protection against HCl/ethanol, and its action was mitigated by indomethacin and sensory deafferentation, but not by the EP1 antagonist. Similar results were obtained using mice lacking various EP receptor subtypes; i.e., PGE₂ failed to provide both direct and adaptive cytoprotection in EP1 (-/-) mice, while capsaicin-induced protection was observed in EP1 (-/-) mice, but disappeared in IP (-/-) mice. The effects of PGE₂ on various gastric functions are mediated by different EP receptor subtypes; inhibition of acid secretion (EP3) and motility (EP1), stimulation of mucus secretion (EP4) and HCO₃⁻ secretion (EP1), and an increase in mucosal blood flow (EP2/EP4). In conclusion, the presence of EP1 receptors is essential to the protective action of PGE₂, either generated endogenously or administered exogenously, against HCl/ ethanol or indomethacin, and this action is functionally associated with the inhibition of gastric motility. Endogenous PGs also contribute to maintaining mucosal integrity after barrier disruption through an increase in mucosal blood flow, which occurs via sensory neurons influenced by activation of the EP1 receptor.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cytoprotection; Dinoprostone; Epoprostenol; Ethanol; Gastric Mucosa; Humans; Receptors, Prostaglandin
PubMed: 24622825
DOI: No ID Found -
Reproductive Biology and Endocrinology... May 2018Infertility in mammalian females has been a challenge in reproductive medicine. The causes of female infertility include anovulation, ovulated oocyte defects, abnormal... (Review)
Review
BACKGROUND
Infertility in mammalian females has been a challenge in reproductive medicine. The causes of female infertility include anovulation, ovulated oocyte defects, abnormal fertilization, and insufficient luteal support for embryo development, as well as early implantation. Ovulation induction, in vitro fertilization and luteal support regimens have been performed for decades to increase fertility rates. The identification of proteins and biochemical factors involved in female reproduction is essential to further increase female fertility rates. Evidence has shown that prostaglandins (PGs) might be involved in the female reproductive process, mainly ovulation, fertilization, and implantation. However, only a few studies on individual PGs in female reproduction have been done so far. This review aimed to identify the pivotal role of prostaglandin E2 (PGE2), a predominant PG, in female reproduction to improve fertility, specifically ovulation, fertilization, embryo development and early implantation.
RESULTS
Prostaglandin E2 (PGE2) was shown to play a relevant role in the ovulatory cascade, including meiotic maturation, cumulus expansion and follicle rupture, through inducing ovulatory genes, such as Areg, Ereg, Has2 and Tnfaip6, as well as increasing intracellular cAMP levels. PGE2 reduces extracellular matrix viscosity and thereby optimizes the conditions for sperm penetration. PGE2 reduces the phagocytic activity of polymorphonuclear neutrophils (PMNs) against sperm. In the presence of PGE2, sperm function and binding capacity to oocytes are enhanced. PGE2 maintains luteal function for embryo development and early implantation. In addition, it induces chemokine expression for trophoblast apposition and adhesion to the decidua for implantation.
CONCLUSION
It has been shown that PGE2 positively affects different stages of female fertility. Therefore, PGE2 should be taken into consideration when optimizing reproduction in infertile females. We suggest that in clinical practice, the administration of non-steroidal anti-inflammatory drugs, which are PGE2 synthesis inhibitors, should be reasonable and limited in infertile women. Additionally, assessments of PGE2 protein and receptor expression levels should be taken into consideration.
Topics: Animals; Dinoprostone; Embryo Implantation; Embryonic Development; Female; Fertility; Fertilization; Humans; Mammals; Ovulation
PubMed: 29716588
DOI: 10.1186/s12958-018-0359-5