The naturally occurring prostaglandin E2 (PGE2) is known in medicine as dinoprostone. It has important effects in labour (softens cervix and causes uterine contraction) and also stimulates osteoblasts to release factors that stimulate bone resorption by osteoclasts. PGE2 is also the prostaglandin that ultimately induces fever. It works by binding and activating the prostaglandin E2 receptor.
It is sold under the trade name of Cervidil (by Forest Laboratories, Inc.), Prostin E2 (by Pfizer Inc.), Propess (by Ferring Pharmaceuticals) and Glandin (by Nabiqasim Pharmaceuticals Pakistan) as a vaginal suppository, to prepare the cervix for labour; it is used to induce labour.
|Prostaglandin metabolism in human hair follicle.||Prostaglandins regulate a wide number of physiological functions. Recently PGF(2alpha) analogue such as latanoprost was shown to have a real impact on hair regrowth. The aim of this study was to investigate and describe the expression profile in human hair follicle of prostaglandin metabolism key enzymes, i.e. carbonyl reductase-1 (CBR1), microsomal prostaglandin E synthase-1 (mPGES-1) and microsomal prostaglandin E synthase-2 (mPGES-2), cytosolic prostaglandin E synthase (cPGES), the aldoketoreductase AKR1C1 and the prostaglandin F synthase AKR1C3. Quantitative RT-PCR on plucked hair follicles revealed some sex-related differences, mPGES-2 and AKR1C3 expression levels being higher in women. Cell and hair follicle compartment specificity was investigated using Western blot, PGE(2) and PGF(2alpha) ELISA assays and immunohistochemistry. Most of the hair cell types were endowed with prostaglandin metabolism machinery and were thus able to produce PGE(2) and/or PGF(2alpha). The epithelial part of the hair bulb was identified by immunohistology and EIA assays as the main source of prostaglandin synthesis and interconversion. All these observations support the concept that prostaglandins might be involved in hair growth and differentiation control.|
|Prostaglandin e2 stimulates estradiol synthesis in the cerebellum postnatally with associated effects on purkinje neuron dendritic arbor and electrophysiological properties.||Prostaglandins (PGs) are ubiquitous membrane-derived, lipid-signaling molecules with wide ranging effects throughout the body. In the brain, PGE(2) is the key regulator of fever after inflammation but is also implicated in neural development and synaptic plasticity. The steroid hormone estradiol is also a key regulator of neural development and synaptic plasticity. Recently, we showed that administering cyclooxygenase (COX) inhibitors to block PGE(2) production increased the total length of Purkinje cell dendrites, the number of dendritic spines, and the level of spinophilin protein, which is enriched in dendritic spines. Correspondingly, PGE(2) administration into the cerebellum decreased spinophilin protein content. We now report that PGE(2) stimulates estradiol synthesis in the immature rat cerebellum via enhanced activity of the aromatase enzyme. Treatment with cyclooxygenase inhibitors reduced cerebellar aromatase activity and estradiol content whereas PGE(2) administration increased both. Treatment with either PGE(2) or estradiol stunted Purkinje neuron dendritic length and complexity and produced a corresponding reduction in spinophilin content. Treatment with formestane to inhibit aromatase activity led to excessive sprouting of the dendritic tree, whereas elevated estradiol had the opposite effect. Electrophysiological measurements from Purkinje neurons revealed novel sex differences in input resistance and membrane capacitance that were abolished by estradiol exposure, whereas a sex difference in the amplitude of the afterhyperpolarization after an action potential was not. Correlated changes in action potential threshold suggest that prolonged alterations in neuronal firing activity could be a consequence of increased estradiol content during the second week of life. These findings reveal a previously unappreciated role for PG-stimulated steroidogenesis in the developing brain and a new potential route for inflammation-mediated disruption of neuronal maturation.|
|Dinoprostone vaginal pessary for induction of labour: Safety of use for up to 24 h.||BACKGROUND: Cervidil(®) (dinoprostone) intravaginal pessaries are used for induction of labour and maintain serum prostaglandin levels for up to 24 h. The Therapeutic Goods Administration approves Cervidil(®) for 12-h use. However, twenty-four-hour use of Cervidil(®) is supported in Europe, New Zealand, America and some Australian hospitals. AIM: To assess the safety of Cervidil(®) use for up to 24 h for induction of labour in nulliparous women. METHODS: A retrospective cohort study of 269 consecutive women receiving Cervidil(®) at the Royal Brisbane and Women's Hospital (RBWH) between July 2007 and December 2008 was performed. The primary outcome measures were frequency of, and time to, uterine tachysystole with or without fetal heart rate (FHR) changes. Secondary outcome measures included frequency of maternal (intrapartum temperature, postpartum haemorrhage) and neonatal (low Apgars, resuscitation, nursery admission) morbidity. Morbidity outcomes of those who received Cervidil(®) for less than or equal to 12 h were compared with those who received Cervidil(®) for more than 12 h. RESULTS: Uterine tachysystole occurred in 9.3% of patients receiving Cervidil(®) , with a mean time to tachysystole of 10 h. The majority of cases (68%) occurred within 12 h of use. There was no increase in maternal or neonatal morbidity for those who received Cervidil(®) for longer than 12 h. CONCLUSION: Twenty-four-hour use of Cervidil(®) is likely as safe as 12-h use for induction of labour in nulliparous women.|
|Comparison of Misoprostol versus Dinoprostone for pre-induction cervical ripening at-term.||BACKGROUND: The purpose of this study was to compare the efficacy and safety of 25 μg Misoprostol vs. 0.5 mg Dinoprostone for pre-labour ripening of the cervix at-term. METHODS: Nullipara or Para one women with unfavourable cervices after 37 completed weeks with live foetuses were randomized to received either 25 μg intravaginal Misoprostol or 0.5 mg intracervical Dinoprostone. The doses were repeated after 6 hrs if the Bishop Score was less than 6. In cases, in which cervical ripening was not reached even after two doses of ripening agents, oxytocin induction was started at least 6 hours apart. Insertion delivery interval (IDI), complications and pregnancy outcome associated with the use of drugs were compared. RESULTS: Two hundred women--100 in each group were evaluated. Comparatively more women (62% vs. 58%) in the Misoprostol group achieved cervical ripening (BS≥6) after one dose. The mean IDI was significantly shorter (3.91 hrs) in the Misoprostol group. The difference was marked more among the multipara at 5.72 hrs, mean difference (p=0.045). In the Misoprostol group 76.92% delivered within 24 hrs whereas, only 70.4% in the Dinoprostone group. Vaginal deliveries were achieved more in the Misoprostol group (78% vs. 71%). No significant differences found in terms of intrapartum complications and foetal outcome. Meconium stained liquor was found more in the Dinoprostone group (23% vs. 32%). CONCLUSIONS: A 25 μg dose of Misoprostol is superior in promoting cervical ripening, significantly shortened the insertion delivery interval. It is safe and effective for cervical ripening when applied in the hospital setting with close monitoring.|
|Activation of cytoprotective prostaglandin synthase-1 by minoxidil as a possible explanation for its hair growth-stimulating effect.||Data from the literature indicate that nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, naproxen, piroxicam, or ibuprofen, induce hair loss in vivo. These NSAIDs are well-known inhibitors of both the cytoprotective isoform of prostaglandin endoperoxide synthase-1 (PGHS-1) and of the inducible form (PGHS-2). By immunohistochemical staining, we found that PGHS-1 is the main isoform present in the dermal papilla from normal human hair follicle (either anagen or catagen), whereas PGHS-2 was only faintly and exclusively expressed in anagen dermal papilla. Thus, PGHS-1 might be the primary target of the hair growth-inhibitory effects of NSAIDs. We thus speculated that activation of PGHS-1 might be a mechanism by which minoxidil (2,4-diamino-6-piperidinopyrimidine-3-oxyde) stimulates hair growth in vivo. We demonstrate here that minoxidil is a potent activator of purified PGHS-1 (AC50 = 80 microM), as assayed by oxygen consumption and PGE2 production. This activation was also evidenced by increased PGE2 production by BALB/c 3T3 fibroblasts and by human dermal papilla fibroblasts in culture. Our findings suggest that minoxidil and its derivatives may have a cytoprotective activity in vivo and that more potent second-generation hair growth-promoting drugs might be designed, based on this mechanism.|
|Effect of minoxidil on platelet function and the synthesis of prostaglandins in platelets.||At the 12.5 micrograms level, minoxidil prevents the irreversible aggregation of platelets by 2 x 10(-6) mol/L adenosine diphosphate (ADP). Levels of minoxidil greater than 12.5 micrograms cause a reversal of primary aggregation by 2 x 10(-6) mol/L ADP. Aggregation of platelets in response to 125 micrograms of arachidonic acid is measurably reduced by 12.5 micrograms of minoxidil and totally suppressed by 30 micrograms. Concurrent with the inhibition of platelet aggregation, increasing concentrations of minoxidil cause a gradual reduction in the synthesis of prostaglandin E2 (PGE2) and thromboxane B2 (TxB2). In the presence of 100 micrograms of minoxidil, PGE2 is reduced from a control value of 87.7 +/- 2.2 pg/ml to 23.9 +/- 3.2 pg/ml. At this level of minoxidil, TxB2 drops from 105 +/- 3.3 ng/ml to 10.5 +/- 2.6 ng/ml. The effect of minoxidil on platelet aggregation is not associated with increased cyclic adenosine monophosphate synthesis. All data support the conclusion that minoxidil functions (in platelet metabolism) primarily as a cyclooxygenase inhibitor.|
|Selective inhibition by minoxidil of prostacyclin production by cells in culture.||The effect of minoxidil on arachidonic acid metabolism by cells in culture was studied. In bovine aorta endothelial cells, treatment with minoxidil in the presence of various stimulators of arachidonic acid metabolism was accompanied by a dose-dependent inhibition of prostacyclin production (measured as 6-keto-prostaglandin F1 alpha). Synthesis of the other cyclooxygenase products (prostaglandins E2, F2 alpha and thromboxane) was not inhibited. When the bovine aorta endothelial cells were stimulated by the Ca2+ ionophore A-23187, the inhibition was seen as early as 2 min. Minoxidil also inhibited prostacyclin production by a second cell line of bovine aorta endothelial cells (the established CPAE cell line), bovine aorta smooth muscle cells, porcine aorta endothelial cells, and rat liver cells (the C-9 cell line)--the latter, less effectively. Again, formation of all the other cyclooxygenase products studied was not inhibited. Minoxidil did not affect significantly prostaglandin E2 and F2 alpha production by newborn rat keratinocytes (the NBR cell line)--a cell that does not produce PGI2. The clinical, biochemical, and pharmacologic implications are discussed.|
|The beneficial and detrimental effects of linoleic acid on autoimmune disorders.||Type 1, or cellular, immune response is characterized by overproduction of IL-1, IL-2, IFN-gamma and TNF-alpha and is the underlying immune mechanism of some autoimmune disorders such as psoriasis, alopecia areata, rheumatoid arthritis, Crohn's disease, multiple sclerosis, insulin-dependent diabetes mellitus and experimental autoimmune uveitis. Type 2 immune response is seen in allergic and antibody-mediated autoimmune diseases and is characterized by IL-4, IL-6 and IL-10 overproduction. Linoleic acid is a precursor of prostaglandin E2 (PGE2) and its intake results in tissue production of PGE2, especially in the absence of other polyunsaturated fatty acids (PUFAS) which inhibit this conversion. PGE2 decreases the production of IL-1, IL-2, IFN-gamma and TNF-alpha and proliferation of TH1 cells and increases the production of IL-4, leading to suppression of the type 1 immune response. Taken together, linoleic acid, the major PUFA of maize oil, could have therapeutic efficacy against cellular autoimmune disorders. On the other hand, excessive intake of linoleic acid may aggravate type 2 autoimmune disorders.|
|Prostaglandin analogs for hair growth: greater expectations.||An interesting paper has recently appeared in Dermatology Online Journal that introduced prostaglandin analogs as nonspecific stimulators of hair growth and predicted their use as the next agents for treatment of forms of alopecia . Prostaglandin analogs not only may stimulate human hair growth, but also may exert an inhibitory effect on the pathomechanism behind alopecia areata (AA) and therefore could be invaluable agents for this condition. The exact mechanism underlying the pathology of AA is currently unknown, although it is believed to be an autoimmune disorder. Increased expression of ICAM-1 and MHC class II molecules (such as HLA-DR on follicular epithelial cells) and also intense expression of E-selectin, VCAM-1, and ICAM-1 on the perifollicular dermal vessels are demonstrated in this condition . Several observations suggest the involvement of TH1-type cytokines in inflammatory responses observed in AA. For example, IFN-γ and TNF-α have been shown to participate in the pathology of AA. In patients with AA, a TH2 cytokine profile may indicate a good prognostic value; a TH1 cytokine profile appears to indicate a poor prognosis. Prostaglandin E2 (PGE2) increases intracellular cAMP levels and has important immunoregulatory functions. It exerts a suppressive effect on macrophage functions such as antigen presentation and MHC class II expression [3, 4]. It also decreases the proliferation of TH1 cells and expression or synthesis of the TH1 cytokines, IL-1, IL-2, IFN-γ, and TNF-α, and it increases the production of IL-4, which counterregulates the effects of type 1 cytokines. Although PGE2 inhibits the production of TH1 lymphokines, it does not inhibit that of Th2 lymphokines and its production by macrophages explains why presentation of antigens by these cells leads to generation of Th2 cells. Whereas B cells, which do not produce PGE2, induce generation of TH1 cells. Therefore, PGE2 suppresses cellular immune response generated by TH1 cells. An illustration of this process is the depression of cellular immunity following hemorrhage and burns, a depression that is associated with overproduction of PGE2 and is inhibited by ibuprofen. Given that PGE2 exerts an inhibitory influence on type 1 immune response, which is the underlying immunopathology of AA, PGE2 analogs may prove to be invaluable in the treatment of this clinical conundrum.|
|Topical or systemic 16, 16 dm prostaglandin E2 or WR-2721 (WR-1065) protects mice from alopecia after fractionated irradiation.||Our previous studies in mice demonstrated that systemic or topical 16,16 dm PGE2 protected against single dose radiation-induced hair loss. We have now investigated prostaglandin, or WR-2721, protection against murine alopecia produced by varying doses and schedules of fractionated radiation. On days one to eight after hair was plucked from the thighs of B6D2F1 mice, groups of 6 animals each were given daily exposures of 4.0 or 4.5 Gy for 5 days; 2.5, 3.5, 4.5 or 5.5 Gy for 10 days; or 2 Gy for 15 days. One hour before irradiation each mouse received 10 microgram 16,16 dm PGE2, either by subcutaneous injection into the neck or topical application, 8 mg WR-2721 by injection, or 0.3 mg WR-1065 by topical application. Three weeks later counts of regrowing hairs were recorded from excised skin samples. For the radioprotectors used, hair regrowth was increased 25-100% in the various radiation groups in comparison to irradiated-only control sites. In some studies with the radioprotector given systemically, WR-2721 afforded slightly greater radioprotection than 16,16 dm PGE2. The two compounds were essentially equally radioprotective in the topical application studies. Since both systemic and topical applications of the agents tested enhanced hair regrowth following radiation, we conclude that clinical use of these compounds may provide some protection of hair follicles, and perhaps other tissues, lying within a radiation therapy field.|
|Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term.||Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term First published: October 7, 2009; This version published: 2012; Review content assessed as up-to-date: May 31, 2009. Plain language summary Vaginal prostaglandins are a safe and effective way of bringing on labour. The use of these medications is not associated with an increase in operative deliveries. Prostaglandins are produced naturally by the body. They are involved in ripening the cervix and bringing on labour. Safety concerns for the mother or baby sometimes make it necessary to bring on labour artificially. Synthetic prostaglandins can be used and are available as vaginal tablets, gels, suppositories and pessaries. The induction regimens with number of applications, dosages, and time intervals between doses vary considerably. Sustained release pessaries reduce the number of applications needed and so the number of vaginal examinations. This review set out to determine the effectiveness and safety of vaginal prostaglandins for third trimester cervical ripening and induction of labour in comparison with placebo or no treatment, or other vaginal prostaglandins (except misoprostol). We identified 63 randomised controlled studies involving a total of 10,441 women. Vaginal prostaglandin E2 is an effective induction agent as it increases the likelihood of vaginal birth within 24 hours with no evidence of an effect on the rate of caesarean section. Requirements for oxytocin augmentation were reduced. Prostaglandin E2 tablets, gels, or pessaries appear to be as effective as each other. Sustained release inserts were associated with a reduction in instrumental vaginal deliveries compared to vaginal PGE2 gel or tablet, an effect that was greater in women with an unfavourable cervix. Comparing vaginal prostaglandin E2 to placebo or no treatment, the risk of uterine hyperstimulation with fetal heart rate changes was increased. Sustained release pessaries were associated with trends of increased hyperstimulation, with and without fetal heart rate changes, compared to gel or tablets. Lower dose regimens, as defined in the review, appear as efficacious as higher dose regimens. Very limited data were available in the included trials on time in labour and patient satisfaction. Few studies have addressed issues relating to the safety of using vaginal prostaglandins for induction of labour as an outpatient. Abstract Background: Prostaglandins have been used for induction of labour since the 1960s. Initial work focused on prostaglandin F2a as prostaglandin E2 was considered unsuitable for a number of reasons. With the development of alternative routes of administration, comparisons were made between various formulations of vaginal prostaglandins. Objectives: To determine the effects of vaginal prostaglandins E2 and F2a for third trimester cervical ripening or induction of labour in comparison with placebo/no treatment or other vaginal prostaglandins (except misoprostol). Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (May 2009) and bibliographies of relevant papers. We updated this search on 24 February 2012 and added the results to the awaiting classification section. Selection criteria: Clinical trials comparing vaginal prostaglandins used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods. Data collection and analysis: We assessed studies and extracted data independently. Main results: Sixty‐three (10,441 women) have been included. Vaginal prostaglandin E2 compared with placebo or no treatment reduced the likelihood of vaginal delivery not being achieved within 24 hours (18.1% versus 98.9%, risk ratio (RR) 0.19, 95% confidence interval (CI) 0.14 to 0.25, two trials, 384 women). The risk of the cervix remaining unfavourable or unchanged was reduced (21.6% versus 40.3%, RR 0.46, 95% CI 0.35 to 0.62, five trials, 467 women); and the risk of oxytocin augmentation reduced (35.1% versus 43.8%, RR 0.83, 95% CI 0.73 to 0.94, 12 trials, 1321 women) when PGE2 was compared to placebo. There was no evidence of a difference between caesarean section rates, although the risk of uterine hyperstimulation with fetal heart rate changes was increased (4.4% versus 0.49%, RR 4.14, 95% CI 1.93 to 8.90, 14 trials, 1259 women). PGE2 tablet, gel and pessary appear to be as efficacious as each other and the use of sustained release PGE2 inserts appear to be associated with a reduction in instrumental vaginal delivery rates (9.9 % versus 19.5%, RR 0.51, 95% CI 0.35 to 0.76, NNT 10 (6.7 to 24.0), five trials, 661 women) when compared to vaginal PGE2 gel or tablet. Authors' conclusions: PGE2 increases successful vaginal delivery rates in 24 hours and cervical favourability with no increase in operative delivery rates. Sustained release vaginal PGE2 is superior to vaginal PGE2 gel with respect to some outcomes studied. Further research is needed to assess the best vehicle for delivering vaginal prostaglandins and this should, where possible, include some examination of the cost‐analysis.|
|Prostaglandin E2 in prostatitis and prostatic adenoma.||The measurement of prostaglandin E2 (PGE2) concentrations in the serum and prostatic fluid of healthy men, patients with prostatic hyperplasia and of patients with prostatitis was attempted and correlated to the state of disease, respectively. PGE2-concentrations with prostatic fluid of healthy men were found to be significantly lower than in patients with prostatitis. Corresponding to the course of treatment concentrations normalized, being favorably influenced by sitosterin as an adjuvant medication. Compared to healthy men, PGF2 concentrations in the prostatic fluid of patients with hyperplasia of the prostate incline to lower levels.|