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American Journal of Obstetrics and... Mar 1989This report summarizes the cumulative experience of 3313 pregnancies represented in 59 prospective clinical trials in which intracervical or intravaginal prostaglandin... (Clinical Trial)
Clinical Trial Review
This report summarizes the cumulative experience of 3313 pregnancies represented in 59 prospective clinical trials in which intracervical or intravaginal prostaglandin E2 gel was used for cervical ripening before induction of labor. Results indicate that local prostaglandin E2 is superior to placebo or no therapy in enhancing cervical effacement and dilation, reducing initial induction failures, shortening the induction-delivery interval, reducing oxytocin use, and lowering the rate of cesarean section because of failure to progress. Certain advantages also exist for labor induction in the presence of a favorable cervical state. Uterine hyperstimulation or pathologic fetal heart rate patterns before oxytocin administration occur in less than 1% of reported cases and are usually dose related, self contained, and reversible with the use of beta-adrenergic tocolytic therapy. Maternal systemic effects in these low doses are negligible. Worldwide clinical experience has clearly demonstrated that prostaglandin E2 gel administered before induction of labor is of major therapeutic benefit and should become commercially available for more than investigational use.
Topics: Cervix Uteri; Clinical Trials as Topic; Dinoprostone; Female; Gels; Humans; Injections; Labor, Induced; Pregnancy; Vagina
PubMed: 2648830
DOI: 10.1016/s0002-9378(89)80020-1 -
Metabolomics : Official Journal of the... Aug 2018Nitroproston® is a novel multi-target drug bearing natural prostaglandin E (PGE) and nitric oxide (NO)-donating fragments for treatment of inflammatory and obstructive...
INTRODUCTION
Nitroproston® is a novel multi-target drug bearing natural prostaglandin E (PGE) and nitric oxide (NO)-donating fragments for treatment of inflammatory and obstructive diseases (i.e., asthma and obstructive bronchitis).
OBJECTIVES
To investigate the effects of Nitroproston® administration on plasma metabolomics in vivo.
METHODS
Experimental in vivo study randomly assigning the target drug (treatment group) or a saline solution without the drug (vehicle control group) to 12 rabbits (n = 6 in each group). Untargeted (5880 initial features; 1869 negative-4011 positive ion peaks; UPLC-IT-TOF/MS) and 84 targeted moieties (Nitroproston® related metabolites, prostaglandins, steroids, purines, pyrimidines and amino acids; HPLC-QQQ-MS/MS) were measured from plasma at 0, 2, 4, 6, 8, 12, 18, 24, 32 and 60 min after administration.
RESULTS
PGE, 13,14-dihydro-15-keto-PGE, PGB, 1,3-GDN and 15-keto-PGE increased in the treatment group. Steroids (i.e., cortisone, progesterone), organic acids, 3-oxododecanoic acid, nicotinate D-ribonucleoside, thymidine, the amino acids serine and aspartate, and derivatives pyridinoline, aminoadipic acid and uric acid increased (p < 0.05 AUCROC curve > 0.75) after treatment. Purines (i.e., xanthine, guanine, guanosine), bile acids, acylcarnitines and the amino acids L-tryptophan and L-phenylalanine were decreased. Nitroproston® impacted steroidogenesis, purine metabolism and ammonia recycling pathways, among others.
CONCLUSION
Nitroproston®, a multi action novel drug based on natural prostaglandins, altered metabolites (i.e., guanine, adenine, cortisol, cortisone and aspartate) involved in purine metabolism, urea and ammonia biological cycles, steroidogenesis, among other pathways. Suggested mechanisms of action, metabolic pathway interconnections and useful information to further understand the metabolic effects of prostaglandin administration are presented.
Topics: Animals; Dinoprostone; Metabolomics; Nitric Oxide; Prostaglandins; Rabbits
PubMed: 30830378
DOI: 10.1007/s11306-018-1413-1 -
ACS Biomaterials Science & Engineering Aug 2023Cell-generated contraction force is the primary physical drive for fibrotic densification of biological tissues. Previous studies using two-dimensional culture models...
Cell-generated contraction force is the primary physical drive for fibrotic densification of biological tissues. Previous studies using two-dimensional culture models have shown that epithelial cells inhibit the myofibroblast-derived contraction force via the regulation of the fibroblast/myofibroblast transition (FMT). However, it remains unclear how epithelial cells interact with fibroblasts and myofibroblasts to determine the mechanical consequences and spatiotemporal regulation of fibrosis development. In this study, we established a three-dimensional microtissue model using an NIH/3T3 fibroblast-laden collagen hydrogel, incorporated with a microstring-based force sensor, to assess fibrosis mechanics. When Madin-Darby canine kidney epithelial cells were cocultured on the microtissue's surface, the densification, stiffness, and contraction force of the microtissue greatly decreased compared to the monocultured microtissue without epithelial cells. The key fibrotic features, such as enhanced protein expression of α-smooth muscle actin, fibronectin, and collagen indicating FMT and matrix deposition, respectively, were also significantly reduced. The antifibrotic effects of epithelial cells on the microtissue were dependent on the intercellular signaling molecule prostaglandin E2 (PGE2) with an effective concentration of 10 μM and their proximity to the fibroblasts, indicating paracrine cellular signaling between the two types of cells during tissue fibrosis. The effect of PGE2 on microtissue contraction was also dependent on the time point when PGE2 was delivered or blocked, suggesting that the presence of epithelial cells at an early stage is critical for preventing or treating advanced fibrosis. Taken together, this study provides insights into the spatiotemporal regulation of mechanical properties of fibrosis by epithelial cells, and the cocultured microtissue model incorporated with a real-time and sensitive force sensor will be a suitable system for evaluating fibrosis and drug screening.
Topics: Animals; Dogs; Dinoprostone; Fibroblasts; Myofibroblasts; Epithelial Cells; Fibrosis
PubMed: 37418666
DOI: 10.1021/acsbiomaterials.2c01502 -
Cardiology in the Young Mar 2018This is a case review of two infants who received a prolonged course of prostaglandin-E2 therapy for congenital cardiac lesions while awaiting corrective surgery. These...
This is a case review of two infants who received a prolonged course of prostaglandin-E2 therapy for congenital cardiac lesions while awaiting corrective surgery. These cases highlight an association between prolonged prostaglandin-E2 therapy with periosteal reactions and elevated C-reactive protein levels. Failure to recognise this association may lead to multiple courses of antibiotics for presumed sepsis and further prolongation of prostaglandin-E2 therapy.
Topics: C-Reactive Protein; Dinoprostone; Female; Heart Septal Defects, Ventricular; Humans; Infant; Infant, Newborn; Male; Surgical Procedures, Operative; Time Factors
PubMed: 29183404
DOI: 10.1017/S1047951117002426 -
ChemMedChem Sep 2021Water solubility is one of the key features of potential therapeutic agents. In order to enhance the low water solubility of the parent...
Water solubility is one of the key features of potential therapeutic agents. In order to enhance the low water solubility of the parent 5-butyl-4-(4-methoxyphenyl)-6-phenylpyrimidin-2-amine, a potent inhibitor of prostaglandin E (PGE ) production, we synthesized and evaluated a new series of derivatives in which the butyl group at the C5 position of the pyrimidine ring was replaced with a less lipophilic substituent, preferably with a hydrophilic aliphatic moiety. Except for the 5-cyanopyrimidine derivative, all target compounds exhibited increased (2.7-87-fold) water solubility relative to the parent compound. Although nontoxic in mouse peritoneal cells, the prepared compounds were either equipotent or weaker inhibitors of PGE production than the parent compound. The most promising compound from the series was found to be the 5-(2,5,8,11-tetraoxadodecyl)pyrimidine derivative (with three polyethylene glycol units at the C5 position), which exhibited 32-fold higher water solubility and only slightly weaker inhibitory activity (22 % of remaining PGE production) compared with the parent compound (15 % of remaining PGE production).
Topics: Animals; Cell Line; Dinoprostone; Dose-Response Relationship, Drug; Mice; Molecular Structure; Pyrimidines; Solubility; Structure-Activity Relationship; Water
PubMed: 34056858
DOI: 10.1002/cmdc.202100263 -
Fish & Shellfish Immunology May 2014Lepeophtheirus salmonis produces pharmacologically active substances that have been shown to modify genetic expression of inflammatory mediators in SHK-1 cells and head...
Lepeophtheirus salmonis produces pharmacologically active substances that have been shown to modify genetic expression of inflammatory mediators in SHK-1 cells and head kidney macrophages of salmon. Differences in genetic expression among genera of Oncorhynchus and Salmo reflect different susceptibilities to L. salmonis. This study was conducted to determine if the presence of L. salmonis secretory products (SEPs)(1) alters the cellular innate immune response (specifically macrophage function) among several salmonids. Phagocytic assays were performed using SHK-1 cells and macrophages isolated from pink (Oncorhynchus gorbuscha), chum (Oncorhynchus keta) and Atlantic (Salmo salar) salmon following incubation with SEPs and Aeromonas salmonicida. Respiratory burst assays were analyzed using pink, chum and Atlantic salmon macrophages after exposure to SEPs. For SHK-1 cells, incubation with SEPS led to dose-dependent increases in phagocytosis. Following incubation with SEPs, chum salmon macrophages had the highest phagocytic index (55.1%) followed by Atlantic (26.4%) and pink (15.8%) salmon. In contrast, respiratory burst response was greatest in pink salmon and minimal in the other two species. Our results suggest that the cellular innate immune response of salmon is modified in the presence of L. salmonis secretions and differences observed among species provide insight into species-specific consequences of sea lice infection.
Topics: Animals; Cells, Cultured; Colorimetry; Copepoda; Dinoprostone; Female; Immunity, Cellular; Macrophages; Male; Phagocytosis; Proteins; Respiratory Burst
PubMed: 24657318
DOI: 10.1016/j.fsi.2014.03.014 -
Farmaco (Societa Chimica Italiana :... 1999We synthesized and evaluated the anti-inflammatory activity of a series of 4-quinazolinone derivatives. Two approaches were used to yield the title compounds. A first...
We synthesized and evaluated the anti-inflammatory activity of a series of 4-quinazolinone derivatives. Two approaches were used to yield the title compounds. A first group of quinazolinone derivatives was obtained by the appropriate substituted anthranilates. A second group of quinazolinone compounds was prepared through the benzoxazin-4-ones intermediate. The pharmacological results reveal that the synthesized derivatives exhibit a significant anti-inflammatory effect in an experimental ocular inflammation model. In fact, all the tested compounds lowered the prostaglandin E2 (PGE2) production with respect to the control group (P < 0.05). The 3-cyclohexyl-6-chloro-quinazolin-4(3H)-one and 3-cyclohexyl-quinazolin-4(3H)-one derivatives were the most active compounds. These compounds significantly reduced PGE2 levels even more than the reference drug tolmetin and significantly lower protein concentration and polymorphonuclear leukocytes number compared to the control group (P < 0.05). Therefore, these compounds may be useful to prevent ocular inflammatory reactions.
Topics: Animals; Dinoprostone; Female; Prostaglandin Antagonists; Quinazolines; Rabbits
PubMed: 10668179
DOI: 10.1016/s0014-827x(99)00102-0 -
Bioengineered May 2022Microglia acts as a critical player in neuroinflammation and neuronal injury. Remifentanil (Rem) has been reported to exert anti-inflammatory activity in several types...
Microglia acts as a critical player in neuroinflammation and neuronal injury. Remifentanil (Rem) has been reported to exert anti-inflammatory activity in several types of diseases. However, the role of Rem in microglia-mediated neuroinflammation is unclear. The present study was designed to investigate the effects of Rem against lipopolysaccharide (LPS)-activated BV2 microglial and PC12 cell induced by activated BV2 microglia. Cell proliferative ability was assessed with cell counting kit-8 assay and cellular morphology was observed. ELISA assay was used to measure the expressions of PGE2 and inflammatory factors. The contents of p-NF-KB p65, p-IKKα/β, and COX2 were evaluated with the aid of western blot. The levels of NO and iNOS were assessed with Griess assay, qRT-PCR, and western blot. In addition, Tunel assay and western blot were performed to assess cell apoptosis. The data revealed that Rem alleviated BV2 microglial morphological injury induced by LPS. Furthermore, Rem suppressed inflammatory releases, iNOS, NO and PGE2 stimulated by LPS in activated BV2 cells. Moreover, Rem suppressed PC12 cell injury, the generations of inflammatory factors and cell apoptosis triggered by inflammatory mediators secreted from activated BV2 cells. These results suggest that Rem exhibited anti-neuroinflammatory activity in protecting PC12 cells against injury derived from LPS-stimulated BV2 microglia.
Topics: Animals; Dinoprostone; Lipopolysaccharides; Microglia; PC12 Cells; Rats; Remifentanil
PubMed: 35726401
DOI: 10.1080/21655979.2022.2080421 -
Redox Biology May 2019Overproduction of prostaglandin E (PGE) has been linked to enhanced tumor cell proliferation, invasiveness and metastasis as well as resistance to apoptosis. 15-Keto...
Overproduction of prostaglandin E (PGE) has been linked to enhanced tumor cell proliferation, invasiveness and metastasis as well as resistance to apoptosis. 15-Keto prostaglandin E (15-keto PGE), a product formed from 15-hydroxyprostaglandin dehydrogenase-catalyzed oxidation of PGE, has recently been shown to have anti-inflammatory and anticarcinogenic activities. In this study, we observed that 15-keto PGE suppressed the phosphorylation, dimerization and nuclear translocation of signal transducer and activator of transcription 3 (STAT3) in human mammary epithelial cells transfected with H-ras (MCF10A-ras). 15-Keto PGE inhibited the migration and clonogenicity of MCF10A-ras cells. In addition, subcutaneous injection of 15-keto PGE attenuated xenograft tumor growth and phosphorylation of STAT3 induced by breast cancer MDA-MB-231 cells. However, a non-electrophilic analogue, 13,14-dihydro-15-keto PGE failed to inhibit STAT3 signaling and was unable to suppress the growth and transformation of MCF10A-ras cells. These findings suggest that the α,β-unsaturated carbonyl moiety of 15-keto PGE is essential for its suppression of STAT3 signaling. We observed that the thiol reducing agent, dithiothreitol abrogated 15-keto PGE-induced STAT3 inactivation and disrupted the direct interaction between 15-keto PGE and STAT3. Furthermore, a molecular docking analysis suggested that Cys251 and Cys259 residues of STAT3 could be preferential binding sites for this lipid mediator. Mass spectral analysis revealed the covalent modification of recombinant STAT3 by 15-keto PGE at Cys259. Taken together, thiol modification of STAT3 by 15-keto PGE inactivates STAT3 which may account for its suppression of breast cancer cell proliferation and progression.
Topics: Animals; Biomarkers; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chromatography, Liquid; Dinoprostone; Disease Models, Animal; Disease Progression; Female; Humans; Mice; Phosphorylation; Protein Binding; Proteomics; STAT3 Transcription Factor; Signal Transduction; Structure-Activity Relationship; Tandem Mass Spectrometry; Xenograft Model Antitumor Assays
PubMed: 31129031
DOI: 10.1016/j.redox.2019.101175 -
American Journal of Health-system... Mar 1995
Topics: Cervix Uteri; Dinoprostone; Female; Gels; Humans; Labor, Induced; Pregnancy; Pregnancy Outcome
PubMed: 7606580
DOI: 10.1093/ajhp/52.6.646